ElsevierActa Medica Okayama0022-22754392002ω-Carboxyl variants of 7-ketocholesteryl esters are ligands for β2-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages14861495ENQingpingLiuDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryKazukoKobayashiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryJun-ichiFurukawaDivision of Bioscience, Graduate School of Environment Earth Science, Hokkaido UniversityJunkoInagakiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryNobuoSakairiDivision of Bioscience, Graduate School of Environment Earth Science, Hokkaido UniversityAkimasaIwadoGraduate School of Natural Science and Technology, Okayama UniversityTatsujiYasudaDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryTakaoKoikeDepartment of Medicine II, Hokkaido University Graduate School of MedicineDennis R.VoelkerProgram in Cell Biology, Department of Medicine, National Jewish Medical and Research CenterEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistrybeta(2)-Glycoprotein I (beta(2)-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome. We recently reported that beta(2)-GPI specifically binds to oxidized LDL (oxLDL) and that the beta(2)-GPI's major ligand, oxLig-1 is 7-ketocholesteryl-9-carboxynonanoate (Kobayashi, K, E. Matsuura, Q. P. Liu, J. Furukawa, K. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Welker, and T. Koike. 2001. A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. J Lipid Res. 42: 697-709). In the present study, we demonstrate that omega-carboxylated 7-ketocholesteryl esters are critical for beta(2)-GPI binding. A positive ion mass spectrum of a novel ligand, designated oxLig-2, showed fragmented ions at m/z 383 and 441 in the presence of acetone, which share features of oxLig-1 and 7-ketocholesterol. In the negative ion mode, ions at m/z 627, 625, and 243 were observed. oxLig-2 was most likely 7-ketocholesteryl-12-carboxy (keto) dodecanoate. These ligands were recognized by beta(2)-GPI. Liposome binding to macrophages was significantly increased depending on the ligand's concentration, in the presence of beta(2)-GPI and an anti-beta(2)-GPI Ab. Synthesized variant, 7-ketocholesteryl-13-carboxytxidecanoate (13-COOH-7KC), also showed a significant interaction with beta(2)-GPI and a similar binding profile with macrophages. Methylation of the carboxyl function diminished all of the specific ligand interactions with beta(2)-GPI. Thus, omega-carboxyl variants of 7-ketocholesteryl esters can mediate anti-beta(2)-GPI Ab-dependent uptake of oxLDL by macrophages, and autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0022-522316632023When to Intervene the Pulmonary Artery: Importance of Anatomical Assessment in the Diagnosis of Pulmonary Artery Coarctation926932ENEiriKisamoriDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalYasuhiroKotaniDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalHiroyukiSuzukiDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalJunkoKobayashiDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalTakuyaKawabataDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalYosukeKurokoDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalShingoKasaharaDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalObjective: Pulmonary artery coarctation (PACoA) is a major problem that increases the frequency of intervention. However, there is little evidence regarding the prediction of PACoA development.<br>
Methods: A retrospective chart review was performed on 42 patients who underwent modified Blalock-Taussig shunt and preoperative contrast-enhanced computed tomography. An uneven PA branching was defined as an abnormal ductus arteriosus connection to the left PA distal to the PA branching on contrast-enhanced computed tomography.<br>
Results: Nineteen (45.2%) of 42 patients were diagnosed with PACoA. The median diameters of the ductus on the aorta and PA sides were 4.1 mm and 3.6 mm in the PACoA group and 3.6 mm and 2.9 mm in the non-PACoA group, respectively (P = .07 and .28, respectively). Tortuous ductus was recognized in 7 (36.8%) patients in the PACoA group and 14 (60.8%) patients in the non-PACoA group (P = .12). PACoA was associated with pulmonary atresia (16 patients [84.2%] in the PACoA group and 12 patients [52.1%] in the non-PACoA group) (P = .02). All 19 patients had uneven PA branching in the PACoA group, whereas 5 of 23 (21.7%) patients had uneven PA branching in the non-PACoA group (P < .001).<br>
Conclusions: Uneven PA branching rather than the ductus arteriosus size was strongly associated with PACoA development; therefore, morphologic assessment by contrast-enhanced computed tomography should be considered in patients with pulmonary atresia.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama038776044252020Vitamin B6 in acute encephalopathy with biphasic seizures and late reduced diffusion402407ENTomoyukiAkiyamaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroTodaNobusukeKimuraDepartment of Pediatrics, Japanese Red Cross Otsu HospitalYukikoMogamiDepartment of Pediatric Neurology, Osaka Women’s and Children’s HospitalChihoTokorodaniDepartment of Pediatrics, Kochi Health Sciences CenterTomoshiroItoDepartment of Pediatrics, Sapporo City General HospitalHiroyukiMiyaharaDepartment of Pediatrics, Kurashiki Central HospitalYukiHyodoDepartment of Child Neurology, Okayama University HospitalKatsuhiroKobayashiDepartment of Child Neurology, Okayama University HospitalBackground</br>
The initial presentation of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is indistinguishable from that of complex febrile seizures (FS), which poses a great diagnostic challenge for clinicians. Excitotoxicity is speculated to be the pathogenesis of AESD. Vitamin B6 (VB6) is essential for the biosynthesis of gamma-aminobutyric acid, an inhibitory neurotransmitter. The aim of this study is to investigate our hypothesis that VB6 deficiency in the brain may play a role in AESD.</br>
Methods</br>
We obtained cerebrospinal fluid (CSF) samples from pediatric patients with AESD after early seizures and those with FS. We measured pyridoxal 5′-phosphate (PLP) and pyridoxal (PL) concentrations in the CSF samples using high-performance liquid chromatography with fluorescence detection.</br>
Results</br>
The subjects were 5 patients with AESD and 17 patients with FS. Age did not differ significantly between AESD and FS. In AESD, CSF PLP concentration was marginally lower (p = 0.0999) and the PLP-to-PL ratio was significantly (p = 0.0417) reduced compared to those in FS.</br>
Conclusions</br>
Although it is impossible to conclude that low PLP concentration and PLP-to-PL ratio are causative of AESD, this may be a risk factor for developing AESD. When combined with other markers, this finding may be useful in distinguishing AESD from FS upon initial presentation.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1052305728102019Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion104310ENXiaLiuDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruYamashitaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJingweiShangDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityXiaowenShiDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyutaMoriharaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYongHuangDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKotaSatoDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMamiTakemotoDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNozomiHishikawaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasuyukiOhtaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKojiAbeDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBACKGROUND:<br/>
The pathological impact of chronic cerebral hypoperfusion (CCH) on Alzheimer's disease (AD) is still poorly understood. In the present study, we investigated the role of CCH on an AD mouse model in phosphorylated tau and α-synuclein pathology, neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of a new antioxidant Twendee X (TwX).<br/>
METHODS:<br/>
APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors to gradually decrease the cerebral blood flow. The effects of the administration of TwX were evaluated by immunohistochemical analysis and Immunofluorescent histochemistry.<br/>
RESULTS:<br/>
The present study revealed that the expressions of phospho-tau and phospho-α-synuclein were significantly increased in the APP23 + CCH mice group as compared with wild type and APP23 mice groups (*P < .05 and ⁎⁎P < .01 versus WT; #P < .05 and ##P < .01 versus APP23). In addition, CCH significantly exacerbated MMP-9 activation relating to blood-brain barrier destruction (⁎⁎P < .01 versus WT; #P < .05, and ##P < .01 versus APP23), enhanced neurovascular remodeling, and impaired a neurovascular trophic coupling in the vascular endothelial BDNF expression of the APP23 + CCH group. TwX treatment (20 mg/kg/day, from 4.5 to 12 months) significantly reduced tau and α-synuclein pathologies, ameliorated neurovascular dysfunction compared with APP23 + CCH group.<br/>
CONCLUSIONS:<br/>
Our findings indicate that administration of a new antioxidative mixture TwX substantially reduced the above neuropathologic abnormalities, suggesting a potential therapeutic benefit of TwX for AD with CCH.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24680249592020Tubulointerstitial Nephritis Cases With IgM-Positive Plasma Cells15761580ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaokiTakahashiDepartment of Nephrology, Faculty of Medical Science, University of FukuiMasayukiIwanoDepartment of Nephrology, Faculty of Medical Science, University of FukuiJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1877-056810632020Transtibial pullout repair of the lateral meniscus posterior root tear combined with anterior cruciate ligament reconstruction reduces lateral meniscus extrusion: A retrospective study469473ENYukiOkazakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYusukeKamatsukiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshikiOkazakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinMasudaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakaakiHiranakaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuyaKodamaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinichiMiyazawaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground</br>
Lateral meniscus (LM) posterior root tear (PRT) is often associated with anterior cruciate ligament (ACL) injury and can result in rotational instability, joint overloading, and degenerative changes in the knee. Improved rotational stability and kinematics have been reported after LMPRT repair. However, it is unclear what repair technique can achieve the greatest reduction in LM extrusion (LME).</br>
Hypothesis</br>
We hypothesized that transtibial pullout repair would decrease LME to a greater extent than other repair techniques.</br>
Patients and methods</br>
Seventeen patients with ACL injury and complete LMPRT were evaluated. Nine underwent ACL reconstruction (ACLR) and transtibial pullout repair, and eight underwent ACLR and other repairs such as inside-out suturing. Double-bundle ACLR was performed using hamstring tendons, and LMPRT pullout repair was performed through the bone tunnel for the posterolateral bundle. Magnetic resonance imaging was performed immediately preoperatively and at > 6 months postoperatively, and LME was measured from coronal images only.</br>
Results</br>
A significantly greater decrease in the value of LME from pre- to postoperative measurement was observed in the transtibial pullout repair group (−0.5 ± 0.7 mm) than in the other-repair group (1.0 ± 0.9 mm, p < 0.01). Pre- and postoperative LME measurements were not significantly different between the two groups.</br>
Discussion</br>
The most important finding of this study was that transtibial pullout repair resulted in a greater decrease in LME than other repair techniques in patients with ACL injury and LMPRT. This technique might be useful for restoring hoop tension by decreasing LME.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1877056810512019Transtibial pullout repair of medial meniscus posterior root tear restores physiological rotation of the tibia in the knee-flexed position113117EN YukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YuyaKodamaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TomohitoHinoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YusukeKamatsukiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YoshikiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences ShinMasudaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences ShinichiMiyazawaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences HirosukeEndoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TomonoriTetsunagaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KazukiYamadaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBACKGROUND:<br/>
Medial meniscus posterior root tear (MMPRT) results in joint overloading and degenerative changes in the knee. Favorable clinical outcomes have been reported after transtibial pullout repair of MMPRT. To date, however, in vivo tibial rotational changes before and after root repair remain poorly understood. The purpose of this study was to investigate postoperative changes in tibial rotation following MMPRT pullout repair.<br/>
HYPOTHESIS:<br/>
Pathological external rotation of the tibia in the knee-flexed position is caused by MMPRT and is reduced after transtibial pullout repair.<br/>
PATIENTS AND METHODS:<br/>
Fifteen patients who underwent MMPRT pullout repair and 7 healthy volunteers were included. Magnetic resonance imaging examinations were performed in the 10° and 90° knee-flexed positions. The angles between the surgical epicondylar axis and a line between the medial border of the patellar tendon and the apex of the medial tibial spine were measured. Baseline was defined as a line lying at a right angle to the other, and a value was positive and negative when the tibia rotated internally and externally, respectively.<br/>
RESULTS:<br/>
In the volunteer's normal knees, tibial internal rotation was +1.00°±3.27° at 10° flexion and +4.14°±3.46° at 90° flexion. In the MMPRT preoperative knees, tibial internal rotation was +1.07°±3.01° at 10° flexion and +1.27°±2.96° at 90° flexion. In the postoperative knees, tibial internal rotation was +1.60°±2.85° at 10° flexion and +4.33°±2.89° at 90° flexion.<br/>
DISCUSSION:<br/>
This study demonstrates discontinuity of the MM posterior root may induce a pathological external rotation of the tibia during knee flexion and that MMPRT pullout repair reduces the pathological external rotation of the tibia in the knee-flexed position.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0914-50877712021Transcatheter closure of patent foramen ovale: Current evidence and future perspectives39ENTeijiAkagiDepartment of Cardiovascular Medicine, Okayama UniversityRecent prospective controlled studies have demonstrated that transcatheter closure of a patent foramen ovale (PFO) reduces recurrent stroke risk in select patients, especially in patients younger than 60 years with PFO and embolic-appearing infarct and where no other mechanism of stroke was identified. Detection of PFO depends on the intensity of the Valsalva maneuver, and not all PFOs can be diagnosed using transesophageal echocardiography. Transthoracic contrast echocardiography using abdominal compression during the Valsalva maneuver is an easy method that can increase the detection sensitivity of PFO shunt. PFO with two or more of the following factors is most likely considered a “high-risk PFO” and as such, has a significantly higher probability of cryptogenic stroke: (1) a long-tunnel PFO (≥10 mm in length), (2) atrial septal aneurysm and/or hypermobile interatrial septum, (3) prominent Eustachian valve or Chiari’s network, (4) large right-to-left shunt at rest and during the Valsalva maneuver, and (5) low-angle PFO. In order to establish the benefit of catheter-based PFO closure as a safe and effective treatment in clinical practice, the degree of accuracy of PFO diagnosis and its long-term safety need to be confirmed.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama030192683342019Tourmaline in a Mesoarchean pelagic hydrothermal system: Implications for the habitat of early life105475ENTsutomuOtaPheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityYuheiAiharaDepartment of Earth and Planetary Sciences, Kyushu UniversityShoichiKiyokawaDepartment of Earth and Planetary Sciences, Kyushu UniversityRyojiTanakaPheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityEizoNakamuraThe Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University The RNA World hypothesis requires the synthesis of RNA to allow the emergence of life on Earth. Hydrothermal systems have been proposed as potential candidates for constructing complex biomolecules. However, in order to successfully form RNA, it is necessary to stabilize ribose, a RNA carbohydrate component. Borate has been found to stabilize ribose. Therefore, boron rich hydrothermal systems are important environments concerning the origin of life on Earth.
<br/>
The 3.2-Ga Dixon Island Formation of the West Pilbara Superterrane, Western Australia, is a volcano-sedimentary sequence. The Formation represents a Mesoarchean pelagic hydrothermal system, which formed adjacent to an immature island arc. Fine-grained tourmaline, in addition to biogenic carbonaceous matter and spherulitic and tubular bacteriomorphs, are found in black chert. A boron-rich environment was responsible for the formation of these deposits. To explore the implications of such a boron enriched environment on microbial activity, modes of occurrence and chemical compositions of the tourmaline were examined.
<br/>
The tourmaline is schorl or dravite of the alkali tourmaline group and the boron isotope compositions range in δ11B from -7.3 to +2.6‰. The tourmaline occurs in microcrystalline quartz matrix of black chert veins that cross cut a volcanic unit and also in a bedded black chert, which overlays the volcanic unit. The volcanic unit contains highly altered zones with hydrothermal veins. The associated lithologic and stratigraphic features suggest that the black chert veins were the conduits for upward moving hydrothermal fluids, which reached the sea floor. Subsequently, the volcanic unit was covered by organic matter-rich cherty sediments that in part were fed, and/or altered, by the hydrothermal fluids.
<br/>
These results suggest that the origin of boron enrichment to form Dixon Island tourmaline is not the associated sedimentary mineral assemblage, which includes diagenetic clay, low-grade metamorphic mica, and organic matter. Instead, the tourmaline was directly precipitated from hydrothermal fluid, enriched in boron. Furthermore, the hydrothermal fluids had already concentrated the boron, in the Mesoarchean pelagic system, prior to the apex of organic matter production and microbial activity. Our findings support a hypothesis that the boron-enriched hydrothermal environment aided the survival and evolution of early life.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama003192013112021Thermocapillary effects in two-phase medium and applications to metal-silicate separation106640ENYanickRicardUniversité de Lyon, ENSL, UCBL, Laboratoire LGLTPEStéphaneLabrosseUniversité de Lyon, ENSL, UCBL, Laboratoire LGLTPEHidenoriTerasakiOkayama University, Department of Earth SciencesDavidBercoviciYale University, Department of Earth & Planetary Sciences The separation of a liquid phase from a solid but deformable matrix made of mineral grains is controlled at small scale by surface tension. The role of interfacial surface tension is twofold as it explains how a small volume of liquid phase can infiltrate the grain boundaries, be distributed and absorbed in the matrix, but after complete wetting of the grains, surface tension favors the self-separation of the liquid and solid phases. Another consequence of surface tension is the existence of Marangoni forces, which are related to the gradients of surface tension that are are usually due to temperature variations. In this paper, using a continuous multi-phase formalism we clarify the role of these different effects and quantify their importances at the scale of laboratory experiments and in planets. We show that Marangoni forces can control the liquid metal-solid silicate phase separation in laboratory experiments. The Marangoni force might help to maintain the presence of metal at the surface of asteroids and planetesimals that have undergone significant melting.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0141-6359652020Thermal influence on surface layer of carbon fiber reinforced plastic (CFRP) in grinding5363ENHiroyukiKodamaOkayama UniversityShingoOkazakiOkayama UniversityYifanJiangOkayama UniversityHiroyukiYodenIndustrial Technology Research Institute of Okayama Prefectural GovernmentKazuhitoOhashiOkayama UniversityIn this study, we investigated thermal influence on surface layer of CFRP in grinding with heat conduction analysis using grinding temperature at wheel contact area on dry and wet condition. Moreover, the thermal affected layer was analyzed through an experiment to examine the temperature of glass transition and thermal decomposition of the matrix resin that composes the CFRP used in this study. The influence of thermal effect on grinding of CFRP was verified based on observation of ground surface finish after grinding using SEM and the measurement of surface roughness. From the measurement result of DSC (Differential Scanning Calorimetry),TG-DTA (Thermogravimetry-Differential Thermal Analysis), It was found that the thermal affected layer of CFRP includes a layer in which the matrix resin is changed in quality by exceeding the glass transition temperature and a layer in which the matrix resin is thermally decomposed by exceeding the thermal decomposition temperature. In addition, it was found that the surface roughness was significantly reduced if the thermal affected layer with thermal decomposition was generated. In each grinding atmosphere, it tended to increase of grinding temperature at wheel contact area with increasing in the setting depth of cut. In the case of dry grinding, grinding temperature at wheel contact area increased up to t thermal decomposition temperature of the matrix resin. However, in the case of the wet grinding, grinding temperature at wheel contact area did not increase until thermally decomposition temperature. From the result of simulation about thermal affected layer, influence of grinding heat increased with increasing in the setting depth of cut. Ultimately, the thermal affected layer with thermal decomposition was generated in dry grinding. Moreover, from the results of SEM observation, it was confirmed that the surface finish properties deteriorated significantly due to thermal decomposition of the matrix resin in the case of Δ = 400 μm in the setting depth of cut at fiber angle θ = 0°. On the other hand, it was confirmed that the micro damage of carbon fiber was occurred in wet grinding at each setting depth of cut.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666548452021The usefulness and safety of the simultaneous parallel anterior and posterior combined lumbar spine surgery using intraoperative 3D fluoroscopy-based navigation (SPAPS)100047ENHisanoriIkumaDepartment of Orthopaedic Surgery, Kagawa Prefectural Central Hospital,TomohikoHiroseDepartment of Orthopaedic Surgery, Kagawa Prefectural Central Hospital,ShinichiroTakaoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceKazutoshiOtsukaOtsuka Orthopaedic Surgery ClinicKeisukeKawasakiDepartment of Orthopaedic Surgery, Kagawa Prefectural Central Hospital,Background<br/>
The combined anterior-posterior surgery in the lateral decubitus position generally needs the intraoperative repositioning. However, prolonged surgical time and increased medical costs due to intraoperative repositioning have been problematic. In recent years, there have been reports of combined anterior-posterior procedure with a single position performing anterior and posterior fixation consecutively where the patient remains in the lateral decubitus position (single surgeon method-SS method). We had further advanced this method, and have adopted the Simultaneous Parallel Anterior and Posterior combined lumbar spine Surgery using intraoperative 3D fluoroscopy-based navigation (SPAPS method), where anterior and posterior procedure are performed independently by two spine surgeons.<br/>
Methods<br/>
66 cases that underwent SPAPS method (n=37) and SS method (n=29) from 2015 to 2019 at single institution were concluded in this study. The pre- and post-operative changes in the following were compared retrospectively between the two groups: surgical factors and clinical evaluations including JOA back pain evaluation questionnaire (JOABPEQ), visual analogue scale (VAS) on lower back pain, buttock/lower limb pain, and buttock/lower limb numbness, and Roland-Morris disability questionnaire (RDQ). <br/>
Results<br/>
The SPAPS method was able to significantly reduce the surgical time (p=0.0025) compared to the SS method, and allowed a reduction of approximately 24.4 minutes per segment. The estimated blood loss were similar in both groups, and with regards to post-operative outcomes, both groups improved equally well. The rates of screw deviation and fusion were also similar. <br/>
Conclusions<br/>
In the case of performing the combined anterior-posterior surgery under a single position, the anterior and posterior procedure can be performed independently and simultaneously by two spine surgeons by utilizing the 3D fluoroscopy-based navigation. The surgical time can be significantly reduced by approximately 24.4 minutes per segment comparing to the SS method.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2468-8673202021The sweet taste receptor, glucose transporters, and the ATP-sensitive K+ (KATP) channel: sugar sensing for the regulation of energy homeostasis5763ENRyusukeYoshidaDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeikoYasumatsuTokyo Dental Junior CollegeYuzoNinomiyaDivision of Sensory Physiology and Medical Application Sensing, Research and Development Center for Five-Sense Devices, Kyushu UniversitySugar detection in the oral cavity does not solely depend on the TAS1R2 + TAS1R3 sweet receptor. Similar to gut, pancreas, and hypothalamic neurons, in the tongue glucose transporters and ATP-sensitive K+ (KATP) channels are also involved in sugar detection. Among them, the KATP channel is the target for the antiobesity hormone leptin, which inhibits sugar-sensitive cells such as sweet taste cells, pancreatic β-cells, and hypothalamic orexigenic neurons. Sugar signals from the taste organ elicit cephalic-phase insulin release, and those from the gut contribute to sweet preference for caloric sugars. All of these systems are indispensable for maintaining energy homeostasis. Thus, an exquisite system for sugar detection/signaling to regulate energy homeostasis exists in our body.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1567-5769832020The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1106429ENSakiNakagawaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOmoriDepartment of Periodontics and Endodontics, Okayama University HospitalMasaakiNakayamaDepartment of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiMandaiDepartment of Medical Technology, School of Health Science, Gifu University of Medical ScienceSatoshiYamamotoDepartment of Periodontics and Endodontics, Okayama University HospitalHiroyaKobayashiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitHidefumiSakoDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyosukeSakaidaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiYoshimuraivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversitySatokiIshiiDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversitySoichiroIbaragiDepartment of Oral Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKimitoHiraiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeYamashiroDepartment of Periodontics and Endodontics, Okayama University HospitalTadashiYamamotoDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversityShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama138824811092019The effects of BaTiO3 nanodots density support on epitaxial LiCoO2 thin-film for high-speed rechargeability106604ENSouYasuharaLaboratory for Materials and Structures, Tokyo Institute of TechnologyShintaroYasuiLaboratory for Materials and Structures, Tokyo Institute of TechnologyTakashiTeranishiGraduate School of Natural Science and Technology, Okayama UniversityYumiYoshikawaGraduate School of Natural Science and Technology, Okayama UniversityTomoyasuTaniyamaLaboratory for Materials and Structures, Tokyo Institute of TechnologyMitsuruItohLaboratory for Materials and Structures, Tokyo Institute of TechnologyLiCoO2 (LCO) is one of the most promising cathode materials for Li ion batteries (LIBs). However, LCO shows a rate-limiting step of Li+ migration between electrode and electrolyte interfaces, requiring LIBs to be charged under low-current conditions. For next generation batteries, it will be necessary to meet the demand for a shorter charging-time. We investigated a support method for the LCO surface to improve high C-rate performance, and revealed that the Li+ intercalation/de-intercalation reaction into/from LCO was accelerated by the introduction of a BaTiO3-LCO-electrolyte interface (triple-phase interface; TPI), due to the electric field concentration near the TPI. In this report, we investigate the dependence of high C-rate performance on the density of surface BaTiO3 nanodots using epitaxial LiCoO2 thin films created via pulsed laser deposition (PLD). As the number of nanodots increased, so did discharge capacity at 50C, becoming saturated at surface coverage over 22%. However, at 100C, the discharge capacity decreased at surface coverage over 40%. These results indicate that coalescence of nanodots reduces not only the TPI length but also the electrochemically active range at quite high C-rate. Therefore, we infer that optimal surface coverage should be varied depending on the C-rate.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0921-50937912020The effect of precipitations (NbC and carbide) in Fe–C–Mn-xNb steels on hydrogen embrittlement characteristics139598ENMitsuhiroOkayasuGraduate School of Natural Science and Technology, Okayama UniversityMasayaSatoGraduate School of Natural Science and Technology, Okayama UniversityDaikiIshidaGraduate School of Natural Science and Technology, Okayama UniversityTakehideSenumaGraduate School of Natural Science and Technology, Okayama UniversityHydrogen embrittlement (HE) characteristics in Fe–C–Mn-xNb steels were examined via various analyses, including electron backscatter diffraction analysis, scanning transmission electron microscopy and three-dimensional atom-probe tomography. For the investigation, the steel samples were prepared with varying Nb contents and heat treatment processes. The material properties of steel samples that were subjected to: (i) water quenching and (ii) quenching and tempering at 170 °C for 20 min, were determined to be nearly similar, although different degrees of HE were detected. After the tempering process, ε-carbide precipitated clearly in the matrix, which could act as a trapping site for hydrogen atoms and lead to improved HE resistance. Moreover, with addition of Nb, niobium base precipitates (e.g., NbC) with a diameter of a few nanometers were obtained in the martensite matrix, which could also function as hydrogen trapping sites. There was slight improvement in the HE resistance with NbC. Hydrogen-assisted failure mechanisms under both static and cyclic loading were observed with intergranular brittle cracking for the water quenched sample, even though the brittle and ductile mix failure mode was detected for the sample after the quenching and tempering process.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0949-26582242017The distribution of vascular endothelial growth factor in human meniscus and a meniscal injury model715721ENZhichaoLuDepartment of Orthopaedic Surgery, Okayama University Graduate SchoolTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate SchoolMasatakaFujiiDepartment of Orthopaedic Surgery, Okayama University Graduate SchoolAmiMaeharaDepartment of Orthopaedic Surgery, Okayama University Graduate SchoolToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate SchoolBACKGROUND:
The meniscus plays an important role in controlling the complex biomechanics of the knee. Meniscus injury is common in the knee joint. The perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Angiogenesis factors, such as vascular endothelial growth factor (VEGF), have important roles in promoting vascularization of various tissues. VEGF-mediated neovascularization is beneficial to the healing of injured tissues. However, the distribution and angiogenic role of VEGF remains unclear in the meniscus and injured meniscus. We hypothesized that VEGF could affect meniscus cells and modulate the meniscus healing process.
METHODS:
Menisci were obtained from total knee arthroplasty patients. Meniscal injury was created ex vivo by a microsurgical blade. VEGF mRNA and protein expression were detected by the polymerase chain reaction and immunohistochemical analyses, respectively.
RESULTS:
In native meniscal tissue, the expression of VEGF and HIF-1α mRNAs could not be detected. However, VEGF and HIF-1α mRNAs were found in cultured meniscal cells (VEGF: outer > inner; HIF-1α: outer = inner). Injury increased mRNA levels of both VEGF and HIF-1α, with the increase being greatest in the outer area. Immunohistochemical analyses revealed that VEGF protein was detected mainly in the outer region and around injured areas of the meniscus. However, VEGF concentrations were similar between inner and outer menisci-derived media.
CONCLUSIONS:
This study demonstrated that both the inner and outer regions of the meniscus contained VEGF. HIF-1α expression and VEGF deposition were high in injured meniscal tissue. Our results suggest that injury stimulates the expression of HIF-1α and VEGF that may be preserved in the extracellular matrix as the healing stimulator of damaged meniscus, especially in the outer meniscus.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-3409482023The dataset of de novo assembly and inferred functional annotation of the transcriptome of Heterosigma akashiwo, a bloom-forming, cosmopolitan raphidophyte109071ENMasanaoSatoDivision of Applied Bioscience, Graduate School of Agriculture, Hokkaido UniversityMasahideSekiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoYutakaSuzukiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoShokoUekiInstitute of Plant Science and Resources, Okayama UniversityHeterosigma akashiwo is a eukaryotic, cosmopolitan, and uni-cellular alga (class: Raphidophyceae), and produces fish -killing blooms. There is a substantial scientific and practical interest in its ecophysiological characteristics that determine bloom dynamics and its adaptation to broad climate zones. A well-annotated genomic/genetic sequence information en-ables researchers to characterize organisms using modern molecular technology. In the present study, we conducted H. akashiwo RNA sequencing, a de novo transcriptome assem-bly of 84,693,530 high-quality deduplicated short-read se-quences. <br>
Obtained RNA reads were assembled by Trinity assembler and 144,777 contigs were identified with N 50 values of 1085. Total 60,877 open reading frames with the length of 150 bp or greater were predicted. For further analy-ses, top Gene Ontology terms, pfam hits, and blast hits were annotated for all the predicted genes. The raw data were deposited in the NCBI SRA database (BioProject PR - JDB6241 and PRJDB15108), and the assemblies are available in NCBI TSA database (ICRV01). The annotation information can be obtained in Dryad and can be accessed via doi: 10.5061/dryad.m0cfxpp56.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-3409442022The dataset of Japanese patents and patents' holding firms in green vehicle powertrains field108524ENJiamingJiangGraduate School of Humanities and Social Science, Okayama UniversityKensukeBabaCyber-Physical Engineering Informatics Research Core, Okayama UniversityYuZhaoSchool of Management, Department of Management, Tokyo University of ScienceJunshiFengGraduate School of Humanities and Social Science, Okayama UniversitySouKumagaiDepartment of Electrical and Communication Engineering, Faculty of Engineering, Okayama UniversityIn 2020, the Government of Japan declared "2050 carbon neutral" and launched a long-term strategy to create a "virtuous cycle of economy and environment".(1) Japanese firms possess many technologies that contribute to decarbonization, which is important to expand investment for Green Technology (environmental technology) development. As automobiles are major contributors to greenhouse gas emissions [1], the technological shift towards vehicle powertrain systems is an attempt to lower problems like emissions of carbon dioxide, nitrogen oxides [2]. On the other hand, patent data are the most reliable business performance for applied research and development activities when investigating the knowledge domains or the technology evolution (Wand, 1997). Our paper describes a Japanese patents dataset of the vehicle powertrain systems for hybrid electric vehicle (HEV), battery electric vehicle (BEV) and fuel cell electric vehicles (FCEV). In this paper we create a method of bombinating international patent classification (IPC) and keywords to define "green" patents in vehicle powertrains field, using patent data which were applied to Japan Patent Office recorded on EPO's PATSTAT database during 2010 similar to 2019 year. When analyze patents, it is necessary to consider the social situation of each country including language background, we collect patents description documents (abstracts and titles) not only written in English but also in Japanese. Finally, we build a database includes 6025 green patents' description documents and 266 patents' holding firms. With which we then identify 3756 HEV patents, 1716 BEV patents, and 553 FCEV patents. Data about patent holding firms is also appended. The full dataset may be useful to researchers who would like to do further search like natural language processing and machine learning on patent description documents, statistical data analysis for empirical economics.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0001-87083052017The asymptotic behavior of Frobenius direct images of rings of invariants144164ENMitsuyasuHashimotoDepartment of Mathematics, Okayama UniversityPeterSymondsbUniversity of Manchester We define the Frobenius limit of a module over a ring of prime characteristic to be the limit of the normalized Frobenius direct images in a certain Grothendieck group. When a finite group acts on a polynomial ring, we calculate this limit for all the modules over the twisted group algebra that are free over the polynomial ring; we also calculate the Frobenius limit for the restriction of these to the ring of invariants. As an application, we generalize the description of the generalized F-signature of a ring of invariants by the second author and Nakajima to the modular case.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama22121374262021The HMGB1/RAGE axis induces bone pain associated with colonization of 4T1 mouse breast cancer in bone100330ENTatsuoOkuiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceMasahiroHiasaDepartment of Biomaterials and Bioengineerings, University of Tokushima Graduate School of DentistryShojiRyumonKishoOnoDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceYukiKunisadaDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceAkiraSasakiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceG. DavidRoodmanDepartment of Medicine, Hematology Oncology, Indiana University School of MedicineFletcher A.WhiteDepartment of Anesthesia, Paul and Carole Stark Neurosciences Research InstituteToshiyukiYonedaDepartment of Cellular and Molecular Biochemistry, Osaka University Graduate School of DentistryBone pain is a common complication of breast cancer (BC) bone metastasis and is a major cause of increased morbidity and mortality. Although the mechanism of BC-associated bone pain (BCABP) remains poorly understood, involvement of BC products in the pathophysiology of BCABP has been proposed. Aggressive cancers secrete damage-associated molecular patterns (DAMPs) that bind to specific DAMP receptors and modulate cancer microenvironment. A prototypic DAMP, high mobility group box 1 (HMGB1), which acts as a ligand for the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs), is increased in its expression in BC patients with poor outcomes. Here we show that 4T1 mouse BC cells colonizing bone up-regulate the expression of molecular pain markers, phosphorylated ERK1/2 (pERK) and pCREB, in the dorsal root ganglia (DRGs) innervating bone and induced BCABP as evaluated by hind-paw mechanical hypersensitivity. Importantly, silencing HMGB1 in 4T1 BC cells by shRNA reduced pERK and pCREB and BCABP with decreased HMGB1 levels in bone. Further, administration of a neutralizing antibody to HMGB1 or an antagonist for RAGE, FPS-ZM1, ameliorated pERK, pCREB and BCABP, while a TLR4 antagonist, TAK242, showed no effects. Consistent with these in vivo results, co-cultures of F11 sensory neuron-like cells with 4T1 BC cells in microfluidic culture platforms increased neurite outgrowth of F11 cells, which was blocked by HMGB1 antibody. Our results show that HMGB1 secreted by BC cells induces BCABP via binding to RAGE of sensory neurons and suggest that the HMGB1/RAGE axis may be a potential novel therapeutic target for BCABP.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1042-4431742021The Conditional Volatility Premium on Currency Portfolios101415ENJoseph P.ByrneEdinburgh Business School (Economics), School of Social Sciences, Heriot-Watt UniversityRyutaSakemotoGraduate School of Humanities and Social Sciences, Okayama UniversityOur paper examines conditional risk-return relations in a number of currency investment strategies, while modeling economic states using a large number of underlying risk factors. We identify a time-varying relationship between currency returns and volatility risk for most currency portfolios. In particular, value and momentum portfolios present risk-return relationships which switch sign, depending upon economic states. The positive relationship for the value portfolio is associated with “flight to quality” periods and the mean reversion for nominal exchange rates during financial crises. The positive relationship for the momentum portfolio is linked to the US and global business cycles and investors require positive compensation for risk in recessions.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2215-016172020Technique for single-step lymphocyte isolation from an endoscopic biopsy specimen for the diagnosis of gastrointestinal lymphoma101095ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahideTakahashiDivision of Medical Support, Okayama University HospitalNatsukiWatanabeDivision of Medical Support, Okayama University HospitalSizumaOmoteDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsunoriMatsuedaDepartment of Gastrointestinal Oncology, Osaka International Cancer InstituteTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadashiYoshinoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIn this paper, we introduce a simplified, one-step procedure for lymphocyte isolation from an endoscopically biopsied fragment. For lymphocyte isolation, an endoscopically harvested specimen and 5 mL of normal saline solution were placed in a wire mesh strainer set in a porcelain bowl. To obtain the lymphocyte suspension, the solid specimen was crushed using the rubber portion of a plunger of a 10 mL injection syringe. Flow cytometry was performed using the lymphocyte suspension. For validating our methods, the one-step lymphocyte isolation technique was used to perform flow cytometry on samples from 23 patients with (n = 12) or without (n = 11) gastrointestinal lymphoma. Flow cytometry of light chain expression was performed in all patient samples (feasibility: 100%). Sensitivity was 83.3% (10/12) and specificity was 100% (11/11). In conclusion, lymphocytes isolated from a single endoscopic biopsy specimen using our simplified and quick procedure are suitable for flow cytometry. Considering that flow cytometry has an important advantage of providing the results on the examination day itself, the results of this study suggest that flow cytometric analysis using our single-step lymphocyte isolation technique can be potentially used to diagnose lymphoma in the gastrointestinal mucosa.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0304-38354972021Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis13ENHirokiKajiokaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAteneItoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuichiSakamotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSurgery is the only curative treatment option for pancreatic cancer, but patients often develop postoperative recurrence. Surgical invasiveness might be involved in the mechanism of recurrence. The associations among inflammation caused by surgery, neutrophils, and cancer metastasis were investigated. At first, neutrophil extracellular traps (NETs) were examined in clinical specimens, and NETs were observed around metastatic tumors. To explore how NETs were induced, neutrophils were cultured with pancreatic cancer or in cancer-conditioned medium. Neutrophils formed NETs when they were cultured with pancreatic cancer or even its conditioned medium. The effects of NETs on cancer cells were further investigated in vitro and in vivo. NETs induced the epithelial to mesenchymal transition in cancer cells and thereby promoted their migration and invasion. HMGB1 derived from NETs appeared to potentiate the malignancy of cancer cells. In a mouse model of liver metastasis with inflammation, NETs participated in the metastatic process by enhancing extravasation. Interestingly, thrombomodulin degraded HMGB1 and consequently inhibited the induction of NETs, thereby preventing pancreatic cancer metastasis to the liver. In conclusion, NETs interact reciprocally with pancreatic cancer cells, which play a pivotal role in inflammation-associated metastasis. Targeting NETs with thrombomodulin can be a novel strategy to improve the surgical outcome of pancreatic cancer patients.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama092318119612019TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes2632ENSatoruSugiharaDepartments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSaekoSugimotoDepartments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKotaTachibanaDepartments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMinaKobashiDepartments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHayatoNomuraDepartments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoMiyakeDepartments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYojiHiraiDepartments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOsamuYamasakiDepartments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinMorizaneDepartments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBACKGROUND:<br/>
Serine proteases have important roles in skin barrier function and desquamation, and the aberrant expression or the dysfunction of serine proteases is associated with the pathogenesis of skin diseases. Serine protease activities are tightly regulated by serine proteases such as kallikrein-related peptidases (KLKs) and serine protease inhibitors such as lympho-epithelial Kazal-type related inhibitor (LEKTI). For a better understating of diseases' pathogenesis, the regulation mechanism of serine proteases and the inhibitors' expression in epidermal keratinocytes must be clarified.<br/>
OBJECTIVES:<br/>
To investigate the effects of the cytokines on the expression of LEKTI in epidermal keratinocytes.<br/>
METHODS:<br/>
Normal human epidermal keratinocytes (NHEKs) were stimulated with panels of inflammatory cytokines. The expression of serine protease inhibitors was analyzed using quantitative real-time PCR and ELISA. LEKTI expression in normal human skin and lesions from psoriasis or atopic dermatitis (AD) were analyzed by immunohistochemically and tape-stripping. Trypsin- and chymotrypsin-like serine protease activities in culture supernatants were measured by using specific substrates.<br/>
RESULTS:<br/>
TNF-α and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and AD lesions. Trypsin- and chymotrypsin-like protease activities in the culture media were upregulated 3-5 days later but attenuated 6-7 days later period by these cytokines.<br/>
CONCLUSIONS:<br/>
In epidermal keratinocytes, the Th1&Th17 cytokines TNF-α and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under inflammation.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0040-402064422008Synthesis and regioselective N- and O-alkylation of 3-alkyl-5-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones and 2-phenyl-9-propyl-9H-purin-6(1H)-one with evaluation of antiviral and antitumor activities98859894ENIslamRafiqulNoriyukiAshidaTomohisaNagamatsu<p>3-Alkyl-5-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones were prepared by nitrosative cyclization of the appropriate 5,6-diamino-2-phenylpyrimidin-4(3H)-ones with nitrous acid and were subjected to regioselective alkylation with several alkylating agents in aprotic solvent at different temperature. Simultaneous 6-N- and 7-O-alkylation were observed and the regioselectivity varied remarkably with size and shape of the alkylating agents as well as with the reaction temperature. Similarly, N- and O-alkylation as well as selectivity was also observed in the case of 2-phenyl-9-propyl-9H-purin-6(1H)-one. Some of the synthesized compounds showed moderate antiviral and antitumor activities.</p>
No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama122686152412021Swarming and mating behavior in Ephemera orientalis Mclachlan, 1875 (Ephemeroptera: Ephemeridae) with morphological analyses376382ENTakahisaMiyatakeGraduate School of Environmental and Life Science, Okayama UniversityTaichiSugeGraduate School of Environmental and Life Science, Okayama UniversityShunsukeSuzakiGraduate School of Environmental and Life Science, Okayama UniversityShintaroTanabeGraduate School of Environmental and Life Science, Okayama UniversityRyoIshiharaGraduate School of Environmental and Life Science, Okayama UniversityKentarouMatsumuraGraduate School of Environmental and Life Science, Okayama UniversitySwarming and mating behaviors of a mayfly species, Ephemera orientalis Mclachlan, 1875 were observed in 2015, 2016, and 2018 at a river bank of the Asahi River, Japan. Males started to make swarms between late April and middle May in 2016 and 2018. The numbers of mated pairs in a swarm correlated with the numbers of flying males in a swarm in 2016 and 2018. Swarms were formed during a limited period at dusk most probably because that interval is free from natural enemies. Males competed with each other to copulate with females in swarms. We clarified the function of the forelegs of males, which are significantly longer than those of females. Males used their forelegs to hold up a female from below. Besides forelegs, males have longer tails than females. We will discuss why sexual differences are found in these traits. Our results represent the first observation of swarm mating behavior in E. orientalis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama155876732020Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCCENYoshihikoTomitaDepartment of Urology, Niigata University Graduate School of Medical and Dental SciencesSeiNaitoDepartment of Urology, Yamagata University Faculty of MedicineNaotoSassaDepartment of Urology, Nagoya University Graduate School of MedicineAtsushiTakahashiDepartment of Urology, Hakodate Goryoukaku HospitalTsunenoriKondoDepartment of Urology, Tokyo Women's Medical University Medical Center EastTakuyaKoieDepartment of Urology, Hirosaki University Graduate School of MedicineWataruObaraDepartment of Urology, Iwate Medical UniversityYasuyukiKobayashiDepartment of Urology, Okayama University Graduate School of MedicineJunTeishimaDepartment of Urology, Graduate School of Biomedical Health Science, Hiroshima UniversityMasayukiTakahashi Department of Urology, Tokushima University Graduate School of Biomedical SciencesHideyasuMatsuyamaDepartment of Urology, Yamaguchi University Graduate School of MedicineTakeshiUeda Department of Urology, Chiba Cancer CenterKenyaYamaguchi Department of Urology, Nihon University School of MedicineTakeshiKishidaDepartment of Urology, Kanagawa Cancer CenterRyoichiShirokiDepartment of Urology, Fujita Health University School of MedicineTakashiSaika Department of Urology, Ehime UniversityNobuoShinoharaDepartment of Urology, Hokkaido University Graduate School of MedicineMototsuguOyaDepartment of Urology, Keio University School of MedicineHiro-omiKanayamaDepartment of Urology, Tokushima University Graduate School of Biomedical SciencesPurpose: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. <br/>
Patients and methods: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). <br/>
Results: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with < 5 metastatic sites). SO/SU was superior to SU/SO for patients without previous nephrectomy. <br/>
Conclusions: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870). No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2590152452021Structural basis of enzyme activity regulation by the propeptide of l-lysine α-oxidase precursor from Trichoderma viride100044ENMasakiKitagawaDepartment of Macromolecular Science, Graduate School of Science, Osaka UniversityNanakoItoDepartment of Macromolecular Science, Graduate School of Science, Osaka UniversityYuyaMatsumotoDepartment of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama UniversityMasayaSaitoDepartment of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama UniversityTakashiTamuraDepartment of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama UniversityHitoshiKusakabeEnzyme Sensor Co., Ltd.KenjiInagakiDepartment of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama UniversityKatsumiImadaDepartment of Macromolecular Science, Graduate School of Science, Osaka UniversityHarmuful proteins are usually synthesized as inactive precursors and are activated by proteolytic processing. l-Amino acid oxidase (LAAO) is a flavoenzyme that catalyzes the oxidative deamination of l-amino acid to produce a 2-oxo acid with ammonia and highly toxic hydrogen peroxide and, therefore, is expressed as a precursor. The LAAO precursor shows significant variation in size and the cleavage pattern for activation. However, the molecular mechanism of how the propeptide suppresses the enzyme activity remains unclear except for deaminating/decarboxylating Pseudomonasl-phenylalanine oxidase (PAO), which has a short N-terminal propeptide composed of 14 residues. Here we show the inactivation mechanism of the l-lysine oxidase (LysOX) precursor (prLysOX), which has a long N-terminal propeptide composed of 77 residues, based on the crystal structure at 1.97 Å resolution. The propeptide of prLysOX indirectly changes the active site structure to inhibit the enzyme activity. prLysOX retains weak enzymatic activity with strict specificity for l-lysine and shows raised activity in acidic conditions. The structures of prLysOX crystals that soaked in a solution with various concentrations of l-lysine have revealed that prLysOX can adopt two conformations; one is the inhibitory form, and the other is very similar to mature LysOX. The propeptide region of the latter form is disordered, and l-lysine is bound to the latter form. These results indicate that prLysOX uses a different strategy from PAO to suppress the enzyme activity and suggest that prLysOX can be activated quickly in response to the environmental change without proteolytic processing.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-8440582019Stroking hardness changes the perception of affective touch pleasantness across different skin sitese02141ENJiabinYuCognitive Neuroscience Laboratory, Graduate School of Natural Science and Technology, Okayama UniversityJiajiaYangCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityYinghuaYuCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityQiongWuCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversitySatoshiTakahashiCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityYoshimichiEjimaCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityJinglongWuCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityHuman unmyelinated tactile afferents (CT afferents) in hairy skin are thought to be involved in the transmission of affective aspects of touch. How the perception of affective touch differs across human skin has made substantial progress; however, the majority of previous studies have mainly focused on the relationship between stroking velocities and pleasantness ratings. Here, we investigate how stroking hardness affects the perception of affective touch. Affective tactile stimulation was given with four different hardness of brushes a three different forces, which were presented to either palm or forearm. To quantify the physical factors of the stimuli (brush hardness), ten naive, healthy participants assessed brush hardness using a seven-point scale. Based on these ten participants, five more participants were added to rate the hedonic value of brush stroking using a visual analogue scale (VAS). We found that pleasantness ratings over the skin resulted in a preference for light, soft stroking, which was rated as more pleasant when compared to heavy, hard stroking. Our results show that the hairy skin of the forearm is more susceptible to stroking hardness than the glabrous of the palm in terms of the perception of pleasantness. These findings of the current study extend the growing literature related to the effect of stroking characteristics on pleasantness ratings.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24058440582019Stroking hardness changes the perception of affective touch pleasantness across different skin sitese02141ENJiabinYuCognitive Neuroscience Laboratory, Graduate School of Natural Science and Technology, Okayama UniversityJiajiaYangCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityYinghuaYuCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityQiongWuCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversitySatoshiTakahashiCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityYoshimichiEjimaCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityJinglongWuCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary, Science and Engineering in Health Systems, Okayama UniversityHuman unmyelinated tactile afferents (CT afferents) in hairy skin are thought to be involved in the transmission of affective aspects of touch. How the perception of affective touch differs across human skin has made substantial progress; however, the majority of previous studies have mainly focused on the relationship between stroking velocities and pleasantness ratings. Here, we investigate how stroking hardness affects the perception of affective touch. Affective tactile stimulation was given with four different hardness of brushes at three different forces, which were presented to either palm or forearm. To quantify the physical factors of the stimuli (brush hardness), ten naïve, healthy participants assessed brush hardness using a seven-point scale. Based on these ten participants, five more participants were added to rate the hedonic value of brush stroking using a visual analogue scale (VAS). We found that pleasantness ratings over the skin resulted in a preference for light, soft stroking, which was rated as more pleasant when compared to heavy, hard stroking. Our results show that the hairy skin of the forearm is more susceptible to stroking hardness than the glabrous of the palm in terms of the perception of pleasantness. These findings of the current study extend the growing literature related to the effect of stroking characteristics on pleasantness ratings.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0040-60906982020Strain effects on spinodal decomposition in TiO2-VO(2)films on TiO2(100) substrates137854ENYujiMuraokaResearch Institute for Interdisciplinary Science (RIIS), Okayama UniversityFumiyaYoshiiGraduate School of Natural Science and Technology, Okayama UniversityTakahiroFukudaGraduate School of Natural Science and Technology, Okayama UniversityYujiManabeGraduate School of Natural Science and Technology, Okayama UniversityMikikoYasunoGraduate School of Natural Science and Technology, Okayama UniversityYoshitoTakemotoGraduate School of Natural Science and Technology, Okayama UniversityKenseiTerashimaResearch Institute for Interdisciplinary Science, Okayama UniversityTakanoriWakitaResearch Institute for Interdisciplinary Science (RIIS), Okayama UniversityTakayoshiYokoya We investigate the influence of lattice strain in the c-axis direction on spinodal decomposition in rutile TiO2-VO2 films on TiO2(100) substrates. The [100]-oriented Ti0.4V0.6O2 (TVO) solid-solution films are fabricated on rutile TiO2(100) substrates using a pulsed laser deposition with a KrF excimer laser, and are annealed inside the spinodal region. X-ray diffraction and scanning transmission electron microscopy are employed for characterization. Consequently, the in-plane tensile strain in the c-axis direction promotes the Ti-V interdiffusion in TVO/TiO2(100) under thermal annealing. In contrast, relaxation of the tensile strain results in the occurrence of spinodal decomposition along the c-axis direction in the film. These results indicate that the relaxation of the tensile strain in the c-axis direction is critically important for enabling spinodal decomposition in TVO/TiO2(100). Our work helps deepen the understanding of spinodal decomposition in the TVO film and provides information on achieving novel nanostructures via spinodal decomposition in TVO/TiO2(100).No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2090-1232352022Spred2 controls the severity of Concanavalin A-induced liver damage by limiting interferon-gamma production by CD4(+) and CD8(+) T cells7186ENCuimingSunDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityQiuyingLiuDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChenCaoDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityXuYangDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySteven L.KunkelDepartment of Pathology, University of Michigan Medical SchoolAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction: Mitogen-activated protein kinases (MAPKs) are involved in T cell-mediated liver damage. However, the inhibitory mechanism(s) that controls T cell-mediated liver damage remains unknown. Objectives: We investigated whether Spred2 (Sprouty-related, EVH1 domain-containing protein 2) that negatively regulates ERK-MAPK pathway has a biological impact on T cell-mediated liver damage by using a murine model. Methods: We induced hepatotoxicity in genetically engineered mice by intravenously injecting Concanavalin A (Con A) and analyzed the mechanisms using serum chemistry, histology, ELISA, qRT-PCR, Western blotting and flow cytometry. Results: Spred2-deficient mice (Spred2(-/-)) developed more sever liver damage than wild-type (WT) mice with increased interferon-gamma (IFNy) production. Hepatic ERK phosphorylation was enhanced in Spred2(-/-) mice, and pretreatment of Spred2(-/-) mice with the MAPK/ERK inhibitor U0126 markedly inhibited the liver damage and reduced IFN gamma production. Neutralization of IFNy abolished the damage with decreased hepatic Stat1 activation in Spred2(-/-) mice. IFN gamma was mainly produced from CD4(+) and CD8(+) T cells, and their depletion decreased liver damage and IFN gamma production. Transplantation of CD4(+) and/or CD8(+) T cells from Spred2(-/-) mice into RAG1(-/-) mice deficient in both T and B cells caused more severe liver damage than those from WT mice. Hepatic expression of T cell attractants, CXCL9 and CXCL10, was augmented in Spred2(-/-) mice as compared to WT mice. Conversely, liver damage, IFN gamma production and the recruitment of CD4(+) and CD8(+) T cells in livers after Con A challenge were lower in Spred2 transgenic mice, and Spred2-overexpressing CD4(+) and CD8(+) T cells produced lower levels of IFN gamma than WT cells upon stimulation with Con A in vitro. Conclusion: We demonstrated, for the first time, that Spred2 functions as an endogenous regulator of T cell IFNy production and Spred2-mediated inhibition of ERK-MAPK pathway may be an effective remedy for T cell-dependent liver damage.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0005-2728186172020Spectral tuning of light-harvesting complex II in the siphonous alga Bryopsis corticulans and its effect on energy transfer dynamics148191ENParveenAkhtarBiological Research CentrePaweł J.Nowakowskiivision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological UniversityWendaWangPhotosynthesis Research Centre, Chinese Academy of SciencesThanh NhutDoDivision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological UniversitySonghaoZhaoPhotosynthesis Research Centre, Chinese Academy of SciencesGiulianoSiligardiDiamond Light Source Ltd., Harwell Science and Innovation CampusGyőzőGarabBiological Research CentreJian-RenShenResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityHowe-SiangTanDivision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological UniversityPetar H.LambrevBiological Research CentreLight-harvesting complex II (LHCII) from the marine green macroalga Bryopsis corticulans is spectroscopically characterized to understand the structural and functional changes resulting from adaptation to intertidal environment. LHCII is homologous to its counterpart in land plants but has a different carotenoid and chlorophyll (Chl) composition. This is reflected in the steady-state absorption, fluorescence, linear dichroism, circular dichroism and anisotropic circular dichroism spectra. Time-resolved fluorescence and two-dimensional electronic spectroscopy were used to investigate the consequences of this adaptive change in the pigment composition on the excited-state dynamics. The complex contains additional Chl b spectral forms – absorbing at around 650 nm and 658 nm – and lacks the red-most Chl a forms compared with higher-plant LHCII. Similar to plant LHCII, energy transfer between Chls occurs on timescales from under hundred fs (mainly from Chl b to Chl a) to several picoseconds (mainly between Chl a pools). However, the presence of long-lived, weakly coupled Chl b and Chl a states leads to slower exciton equilibration in LHCII from B. corticulans. The finding demonstrates a trade-off between the enhanced absorption of blue-green light and the excitation migration time. However, the adaptive change does not result in a significant drop in the overall photochemical efficiency of Photosystem II. These results show that LHCII is a robust adaptable system whose spectral properties can be tuned to the environment for optimal light harvesting.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0944-50132152018Specific growth inhibitors of Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, X. campestris pv. campestris, and Clavibacter michiganensis subsp. michiganensis2935ENGraduate School of Environmental and Life Science, Okayama UniversityTakuSawaiGraduate School of Environmental and Life Science, Okayama UniversityYoshiteruNoutoshiGraduate School of Environmental and Life Science, Okayama UniversityYutaNishinaResearch Core for Interdisciplinary Sciences, Okayama UniversityHidenoriMatsuiGraduate School of Environmental and Life Science, Okayama UniversityMikihiroYamamotoGraduate School of Environmental and Life Science, Okayama UniversityKazuhiroToyodaGraduate School of Environmental and Life Science, Okayama UniversityYukiIchinoseGraduate School of Environmental and Life Science, Okayama University Plant pathogenic bacteria cause huge yield losses in crops globally. Therefore, finding effective bactericides to these pathogens is an immediate challenge. In this study, we sought compounds that specifically inhibit the growth of Ralstonia solanacearum. As a result, we identified one promising compound, 1-(4-bromophenyl)-6-methoxy-2,3,4,9-tetrahydro-1H-β-carboline, which inhibited the growth of R. solanacearum (Rs1002) from a pilot library of 376 chemicals provided from RIKEN. We further obtained its structural analogues and assessed their ability to inhibit Rs1002 growth. Then we identified five compounds, named ralhibitins A to E, that specifically inhibit growth of Rs1002 at >5 μg/ml final concentration. The most effective compounds, ralhibitins A, C, and E completely inhibited the growth of Rs1002 at 1.25 μg/ml. In addition, ralhibitins A to E inhibited growth of Xanthomonas oryzae pv. oryzae but not the other bacteria tested at a final concentration of 10 μg/ml. Whereas, ralhibitin E, besides inhibiting R. solanacearum and X. oryzae pv. oryzae, completely inhibited the growth of X. campestris pv. campestris and the Gram-positive bacterium Clavibacter michiganensis subsp. michiganensis at 10 μg/ml. Growth inhibition by these compounds was stable at pH 6–9 and after autoclaving. Because Rs1002 grew in the culture medium in which ralhibitins were incubated with the ralhibitin-insensitive bacteria, the unaffected bacteria may be able to inactivate the inhibitory effect of ralhibitins. These results suggest that ralhibitins might be potential lead compounds for the specific control of phytopathogenic bacteria.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama003991401222014Speciation of arsenic in a thermoacidophilic iron-oxidizing archaeon, Acidianus brierleyi, and its culture medium by inductively coupled plasma–optical emission spectroscopy combined with flow injection pretreatment using an anion-exchange mini-column240245ENNaokiHigashidaniTakashiKanetaNobuyukiTakeyasuShojiMotomizuNaokoOkibeKeikoSasakiThe thermoacidophilic iron-oxidizing archaeon Acidianus brierleyi is a microorganism that could be useful in the removal of inorganic As from wastewater, because it simultaneously oxidizes As(III) and Fe(II) to As(V) and Fe(III) in an acidic culture medium, resulting in the immobilization of As(V) as FeAsO4. To investigate the oxidation mechanism, speciation of the As species in both the cells and its culture media is an important issue. Here we describe the successive determination of As(III), As(V), and total As in A. brierleyi and its culture medium via a facile method based on inductively coupled plasma–optical emission spectroscopy (ICP–OES) with a flow injection pretreatment system using a mini-column packed with an anion-exchange resin. The flow-injection pretreatment system consisted of a syringe pump, a selection valve, and a switching valve, which were controlled by a personal computer. Sample solutions with the pH adjusted to 5 were flowed into the mini-column to retain the anionic As(V), whereas As(III) was introduced into ICP–OES with no adsorption on the mini-column due to its electrically neutral form. An acidic solution (1 M HNO3) was then flowed into the mini-column to elute As(V) followed by ICP–OES measurement. The same sample was also subjected to ICP–OES without being passed through the mini-column in order to determine the total amounts of As(III) and As(V). The method was verified by comparing the results of the total As with the sum of As(III) and As(V). The calibration curves showed good linearity with limits of detection of 158, 86, and 211 ppb for As(III), As(V), and total As, respectively. The method was successfully applicable to the determination of the As species contained in the pellets of A. brierleyi and their culture media. The results suggested that the oxidation of As(III) was influenced by the presence of Fe(II) in the culture medium, i.e., Fe(II) enhanced the oxidation of As(III) in A. brierleyi. In addition, we found that no soluble As species was contained in the cell pellets and more than 60% of the As(III) in the culture medium was oxidized by A. brierleyi after a 6-day incubation.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0013-46863632020Sophisticated rGO synthesis and pre-lithiation unlocking full-cell lithium-ion battery high-rate performances137257ENBenoît Denis Louis CampéonGraduate School of Natural Science and Technology, Okayama UniversityYumiYoshikawaGraduate School of Natural Science and Technology, Okayama UniversityTakashiTeranishiGraduate School of Natural Science and Technology, Okayama UniversityYutaNishinaGraduate School of Natural Science and Technology, Okayama UniversityFor the application to portable devices and storage of renewable energies, high-performance lithium-ion batteries are in great demand. To this end, the development of high-performance electrode materials has been actively investigated. However, even if new materials exhibit high performance in a simple evaluation, namely half-cell tests, it is often impossible to obtain satisfactory performance with an actual battery (full cell). In this study, the structure of graphene analogs is modified in various ways to change crystallinity, disorder, oxygen content, electrical conductivity, and specific surface area. These graphene analogs are evaluated as negative electrodes for lithium-ion batteries, and we found reduced graphene oxide prepared by combination of chemical reduction and thermal treatment was the optimum. In addition, a full cell is fabricated by combining it with LiCoO2 modified with BaTiO3, which is applicable to high-speed charge–discharge cathode material developed in our previous research. In general, pre-lithiation is performed for the anode when assembling full cells. In this study, we optimized a "direct pre-lithiation" method in which the electrode and lithium foil were in direct contact before assembling a full cell, and created a lithium-ion battery with an output of 293 Wh kg−1 at 8,658 W kg−1.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1882-7616592023Solid-state inorganic and metallic adhesives for soft biological tissues439445ENMasahiroOkadaDepartment of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakuyaMatsumotoDepartment of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCurrently, the soft-tissue adhesives used in clinical practice are glue-type organic adhesives. However, there is a demand for new types of adhesives, because the current organic adhesives present challenges in terms of their biocompatibility and adhesion strength. This review summarizes the discovery and development of inorganic and metallic adhesives designed for soft biological tissues while focusing on immobilization of medical divices on soft tissues. These new types of adhesives are in a solid state and adhere directly and immediately to soft tissues. Therefore, they are called "solid-state adhesives" to distinguish them from the currently used glue-type adhesives. In previous studies on inorganic solid-state adhesives, oxides and calcium phosphates were used as raw materials in the form of nanoparticles, nanoparticle-coated films, or nanoparticle-assembled porous plates. In previous studies on metallic solid-state adhesives, only Ti and its alloys were used as raw materials. This review also discusses the future perspectives in this active research area.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0141-39101792020Simultaneous degradation and dechlorination of poly (vinyl chloride) by a combination of superheated steam and CaO catalyst/adsorbent109225ENHarukaNishibataGraduate School of Environmental and Life Science, Okayama UniversityMd. AzharUddinGraduate School of Environmental and Life Science, Okayama UniversityYoshieiKatoGraduate School of Environmental and Life Science, Okayama UniversityIn order to explore the possibility of efficient chlorine removal from the poly (vinyl chloride) (PVC) containing waste plastics, simultaneous degradation and dechlorination of PVC at a relatively low temperature was investigated by changing the atmosphere gas and metal oxide as catalyst and/or adsorbent (catalyst/adsorbent). 5.0 g of PVC and various metallic oxides such as CaO, Fe3O4, SiO2, Al2O, Ca(OH)2, MgO were used under the superheated steam and nitrogen atmosphere of 473 K. The degradation rate of the PVC sample was small and the chlorine conversion to inorganic chloride was not observed without catalyst/adsorbent in the presence of either superheated steam or nitrogen atmosphere. Under the superheated steam atmosphere, the CaO catalyst/adsorbent resulted in much larger rates of degradation and dechlorination than any other metal oxides such as Fe3O4, SiO2, Al2O, Ca(OH)2, MgO compared with nitrogen atmosphere. The calcium compounds such as CaCl₂, CaClOH and Ca(OH)₂ were formed in the sample by the combination of CaO catalyst/adsorbent and superheated steam. The rates of PVC degradation and chlorine conversion to inorganic chlorides were dramatically enhanced beyond the stoichiometric CaO amount for the CaCl₂ formation reaction with PVC under the superheated steam atmosphere.
The CaO addition contributed to both of the PVC degradation as a catalyst and the reactant with HCl as an adsorbent, whereas the superheated steam played a role of the sample temperature increase to promote the PVC degradation through the exothermic reaction with CaO.
No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama009042951702022Simplified PADUA REnal (SPARE) Nephrometry System can Describe the Surgical Difficulty of Renal Masses With High Accuracy Even Without 3D Renal Models132138ENTomofumiWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaSadahiraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakanoriSekitoDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiMaruyamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiEdamuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuyukiKobayashiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjective: To evaluate whether a 2-dimensional(2D) model describes the surgical difficulty of a renal mass accurately comparable to that obtained using a 3D model with the Simplified PADUA REnal nephrometry system (SPARE).<br>
Methods: A total of 100 patients underwent RAPN in our hospital between October 2018 and May 2021. We excluded patients with CT images inappropriate for evaluation or for construction of 3D models, patients with multiple tumors, and those who underwent preoperative transcatheter arterial embolization. We conducted a retrospective analysis of the remaining patients using SPARE predictions from CT images (2D-SPARE) and SPARE predictions from 3D models (3D-SPARE). We evaluated the difference between the 2 nephrometry scores and compared them by their ability to predict the achievement of the desired surgical outcome: absence of positive margins, absence of ischemia, and absence of significant complications.<br>
Results: A total of 87 patients were included in this study. Total score, and risk categorization using 3D-SPARE was significantly different from those using 2D-SPARE (P <.05), but in their areas under the curve (AUC), the scores and categorizations were not significantly different (score, 0.763 vs 0.742; P = .501; categorization, 0.711 vs 0.701; P = .755).<br>
Conclusion: The SPARE system can describe the surgical difficulty of renal masses with high accuracy even without the use of 3D renal models.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama187940681452023Significance of the comprehensive geriatric assessment in the administration of chemotherapy to older adults with cancer: Recommendations by the Japanese Geriatric Oncology Guideline Committee101485ENKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalDaisukeInoueDepartment of Obstetrics and Gynecology, University of FukuiKenSugimotoDepartment of General Geriatric Medicine, Kawasaki Medical SchoolChieTanakaDepartment of Gastroenterological Surgery, Nagoya University Graduate School of MedicineKeikoMurofushiDivision of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalToruOkuyamaDepartment of Psychiatry / Palliative Care Center, Nagoya City University West Medical CenterShigeakiWatanukiNational Center for Global Health and Medicine, National College of NursingChiyo K.ImamuraAdvanced Cancer Translational Research Institute, Showa UniversityDaisukeSakaiDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of MedicineNaomiSakuraiCancer Solutions Co.,LtdKiyotakaWatanabeDivision of Medical Oncology, Department of Medicine, School of Medicine, Teikyo UniversityKazuoTamuraNPO Clinical Hematology/Oncology Treatment Study GroupToshiakiSaekiBreast Oncology Service, Saitama Medical University International Medical CenterHiroshiIshiguroBreast Oncology Service, Saitama Medical University International Medical CenterIntroduction: The number of older patients with cancer is expected to continue to increase owing to the aging population. Recently, the usefulness of geriatric assessment (GA) conducted by multiple staff members from different medical backgrounds has been reported; however, a consensus on the effectiveness of GA has not yet been achieved.<br>
Materials and Methods: We, as the Japanese Geriatric Oncology Guideline Committee for elderly patients with cancer, conducted a literature search of randomized controlled trials published before August 2021 that used GA or comprehensive GA (CGA) as an intervention for patients with cancer undergoing chemotherapy. As the key outcomes for answering the clinical question, we focused on survival benefit, adverse events, and quality of life (QOL). After a systematic review of these studies, the expert panel member developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.<br>
Results: For older patients with cancer, GA or CGA is suggested during or before chemotherapy (weakly recommended). Chemotherapy-induced adverse events were significantly reduced by GA/CGA interventions without any adverse effects on survival. Health-related QOL tended to improve with the GA/CGA interventions.<br>
Discussion: Although, in our opinion, GA/CGA does require time and resources, it poses no harm patients. Therefore, we suggest expanding the human resources and educating skills of medical providers for clinical implementation of GA/CGA.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama132389306822019Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis216224ENTakahisaKoyamaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinKariyaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuharuSatoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukaGionDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayaHigakiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakenoriHarunaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTazukoFujiwaraDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkiraMinouraDepartment of Public Health, Showa University School of MedicineSoshiTakaoDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYorihisaOritaDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto UniversityKengoKanaiDepartment of Otorhinolaryngology-Head & Neck Surgery, Kagawa Prefectural Central HospitalMasamiTaniguchiClinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National HospitalKazunoriNishizakiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMitsuhiroOkanoDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS).<br/>
Methods: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course.<br/>
Results: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field.<br/>
Conclusions: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama132389302020Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitisENAikoOkaDepartment of Otorhinolaryngology, International University of Health and Welfare Graduate School of MedicineTakahiroNinomiyaDepartment of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of FukuiTazukoFujiwaraDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoshiTakaoDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuharuSatoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukaGionDivision of Pathophysiology, Okayama University Graduate School of Health SciencesAkiraMinouraDepartment of Hygiene, Public Health and Preventive Medicine, Showa University School of MedicineShin-ichiHarunaDepartment of Otorhinolaryngology, Head & Neck Surgery, Dokkyo Medical UniversityNaohiroYoshidaDepartment of Otolaryngology, Jichi Medical University Saitama Medical CenterYasunoriSakumaDepartment of Otorhinolaryngology, Yokohama City Medical CenterKenjiIzuharaDivision of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical SchoolJunyaOnoShino-Test Co., Ltd.MasamiTaniguchiClinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National HospitalTakenoriHarunaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayaHigakiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinKariyaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahisaKoyamaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsujiTakabayashiDepartment of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of FukuiYoshimasaImotoDepartment of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of FukuiMasafumiSakashitaDepartment of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of FukuiMasanoriKidoguchiDepartment of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of FukuiKazunoriNishizakiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShigeharuFujiedaDepartment of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of FukuiMitsuhiroOkanoDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS.<br/>
Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence.<br/>
Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin.<br/>
Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1556086414122019Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC20712083ENYoshihiroOhueDepartment of Respiratory Medicine, Kawasaki Medical SchoolKojiKuroseDepartment of Respiratory Medicine, Kawasaki Medical SchoolTakahiroKarasakiDepartment of Thoracic Surgery, The University of TokyoMidoriIsobeDepartment of Respiratory Medicine, Kawasaki Medical SchoolTakaakiYamaokaDepartment of Respiratory Medicine, Kawasaki Medical SchoolJunichiroFutamiDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityIsaoIreiDepartment of Pathology, Kawasaki Medical SchoolTakeshiMasudaDepartment of Respiratory Internal Medicine, Hiroshima University HospitalMasaakiFukudaDepartment of Respiratory Medicine, The Japanese Red Cross Nagasaki Genbaku HospitalAkitoshiKinoshitaDepartment of Respiratory Medicine, Nagasaki Prefecture Shimabara HospitalHirokazuMatsushitaDepartment of Immunotherapeutics, Graduate School of Medicine, The University of TokyoKatsuhikoShimizuDepartment of General Thoracic Surgery, Kawasaki Medical SchoolMasaoNakataDepartment of General Thoracic Surgery, Kawasaki Medical SchoolNoboruHattoriDepartment of Respiratory Internal Medicine, Hiroshima University HospitalHiroyukiYamaguchiDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical SciencesMinoruFukudaDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical SciencesRyoheiNozawaFaculty of Health and Welfare Services Administration, Kawasaki University of Medical WelfareKazuhiroKakimiDepartment of Immunotherapeutics, Graduate School of Medicine, The University of TokyoMikioOkaDepartment of Immuno-Oncology, Kawasaki Medical SchoolIntroduction: Programmed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti-PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits.<br/>
Methods: We conducted a prospective study to explore whether serum antibody against NY-ESO-1 and/or XAGE1 cancer-testis antigens predicted primarily good clinical response and secondarily long survival with anti-PD-1 therapy for NSCLC. The serum antibody was detected by enzyme-linked immunosorbent assay, and tumor immune microenvironment and mutation burden were analyzed by immunohistochemistry and next-generation sequencing.<br/>
Results: In the discovery cohort (n = 13), six antibody-positive NSCLC cases responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC cases did not. Antibody positivity was associated with good response and survival, regardless of tumor programmed death ligand 1 (PD-L1) expression, mutation burden, and CD8+ T-cell infiltration. In the validation cohort (n = 75), 17 antibody-positive NSCLC cases responded well to anti-PD-1 therapy as compared with 58 negative NSCLC cases (objective response rate 65% versus 19%, p = 0.0006) and showed significantly prolonged progression-free survival and overall survival. Antibody titers highly correlated with tumor reduction rates. In the multivariate analysis, response biomarkers were tumor programmed death ligand 1 expression and antibody positivity, and only antibody positivity was a significantly better predictive biomarker of progression-free survival (hazard ratio = 0.4, p = 0.01) and overall survival (hazard ratio = 0.2, p = 0.004).<br/>
Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits in anti-PD-1 therapy for NSCLC and probably for other cancers.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama094926582021Semi-quantitative arthroscopic scoring system is related to clinical outcomes in patients after medial meniscus posterior root repairENXimingZhangDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKeisukeKintakaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHaoweiXueDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesShinichiMiyazawaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesBackground<br>
Different methods are available to assess the healing status of repaired root for medial meniscus posterior root tears (MMPRT) using second-look arthroscopy. However, few studies are comparing them or validating their usefulness. Therefore, it was hypothesized that the semi-quantitative arthroscopic score might correlate more with 1-year clinical outcomes in patients with MMPRT than the qualitative evaluation. <br>
Methods<br>
Data of 61 patients who underwent MMPRT pullout repair and second-look arthroscopy were retrospectively evaluated. The semi-quantitative arthroscopic scoring system was divided into three evaluation criteria: scores from 0 to 10 points include the width of the bridging tissue, stability of the repaired root, and synovial coverage. The qualitative evaluation was classified into 4 status; complete healing, lax healing, scar tissue healing, and failed healing according to the stability and mobility of the repaired root. Multivariate linear regression analyses were used to identify predictors of 1-year postoperative clinical outcomes, including Knee Injury and Osteoarthritis Outcome, Lysholm, or International Knee Documentation Committee scores. Spearman's correlation analysis was used to analyze the correlation between second-look arthroscopic score/qualitative evaluation and 1-year postoperative clinical outcomes. In addition, the optimal cutoff point of semi-quantitative arthroscopic score was determined by receiver operating characteristic (ROC) curve. The Mann–Whitney U test was used to compare clinical outcomes between patients with semi-quantitative arthroscopic scores ≥8 and scores <8. <br>
Results<br>
All clinical scores significantly improved at 1 year postoperatively. A good correlation was observed between the semi-quantitative score and clinical scores, but none between qualitative evaluation and clinical scores. The optimal cutoff point of semi-quantitative second-look arthroscopic score was 8 points. Significantly, better clinical outcomes were observed in patients with semi-quantitative scores ≥8 points. <br>
Conclusions<br>
All 1-year postoperative clinical scores were significantly improved. The semi-quantitative arthroscopic scores correlate more with 1-year clinical outcomes in patients with MMPRT than the qualitative evaluation. Level of evidence IV case series study.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-48476Suppl. 72020Self-assembly of Ni–Fe layered double hydroxide at room temperature for oxygen evolution reaction248254ENSeong HyunKimDepartment of Materials Science and Engineering, Pusan National UniversityYoo SeiParkDepartment of Materials Science and Engineering, Pusan National UniversityChihoKimDepartment of Materials Science and Engineering, Pusan National UniversityIl YeongKwonDepartment of Materials Science and Engineering, Pusan National UniversityJooyoungLeeMaterials Center for Energy Department, Surface Technology Division, Korea Institute of Materials Science,HyunsooJinDepartment of Mechanical Engineering, Worcester Polytechnic InstituteYoon-SeokLeeGraduate School of Natural Science and Technology, Okayama UniversitySung MookChoiMaterials Center for Energy Department, Surface Technology Division, Korea Institute of Materials ScienceYangdoKimDepartment of Materials Science and Engineering, Pusan National UniversityActive and stable electrocatalysts are the key to water electrolysis for hydrogen production. This paper reports a facile direct growth method to synthesize NiFe-layered double hydroxides (LDHs) on nickel foil as an electrocatalyst for the oxygen evolution reaction. The NiFe-LDH is synthesized by a galvanic process at room temperature without any additional energy for synthesis. The synthesized NiFe-LDH is a karst landform with abundant active sites and efficient mass diffusion. The NiFe-LDH with an oxygen defect show excellent electrocatalytic performance for the OER, with a low overpotential (272 mV at 10 mA/cm2), a small Tafel slope (43 mV/dec), and superior durability. Direct growth synthesis provide excellent electrical conductivity as well as strong bonding between the catalyst layer and the substrate. In addition, this synthesis process is simple to apply in the fabrication of a large size electrode and is believed to be applicable to commercialized alkaline water electrolysis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0168-36593302020Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture t (BNCT)788196ENHiroyukiMichiueNeutron Therapy Research Center, Okayama UniversityMizukiKitamatsuDepartment of Applied Chemistry, Kindai UniversityAsamiFukunagaDepartment of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobushigeTsuboiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAtsushiFujimuraDepartment of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroakiMatsushitaDepartment of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyoIgawaNeutron Therapy Research Center, Okayama UniversityTomonariKasaiNeutron Therapy Research Center, Okayama UniversityNatsukoKondoInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityHidekiMatsuiNeutron Therapy Research Center, Okayama UniversityShuichiFuruyaNeutron Therapy Research Center, Okayama UniversityBoron neutron capture therapy (BNCT) is a tumor selective therapy, the effectiveness of which depends on sufficient 10B delivery to and accumulation in tumors. In this study, we used self-assembling A6K peptide nanotubes as boron carriers and prepared new boron agents by simple mixing of A6K and BSH. BSH has been used to treat malignant glioma patients in clinical trials and its drug safety and availability have been confirmed; however, its contribution to BNCT efficacy is low. A6K nanotube delivery improved two major limitations of BSH, including absence of intracellular transduction and non-specific drug delivery to tumor tissue. Varying the A6K peptide and BSH mixture ratio produced materials with different morphologies—determined by electron microscopy—and intracellular transduction efficiencies. We investigated the A6K/BSH 1:10 mixture ratio and found high intracellular boron uptake with no toxicity. Microscopy observation showed intracellular localization of A6K/BSH in the perinuclear region and endosome in human glioma cells. The intracellular boron concentration using A6K/BSH was almost 10 times higher than that of BSH. The systematic administration of A6K/BSH via mouse tail vein showed tumor specific accumulation in a mouse brain tumor model with immunohistochemistry and pharmacokinetic study. Neutron irradiation of glioma cells treated with A6K/BSH showed the inhibition of cell proliferation in a colony formation assay. Boron delivery using A6K peptide provides a unique and simple strategy for next generation BNCT drugs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X2562019Second nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by Japanese Surveillance Committee from 2015 to 2016: antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus413422ENHiroshiHayamiThe Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID and the Japanese Society for Clinical Microbiology (JSCM)SatoshiTakahashiThe Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID and the Japanese Society for Clinical Microbiology (JSCM)KiyohitoIshikawaThe Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID and the Japanese Society for Clinical Microbiology (JSCM)MitsuruYasudaThe Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID and the Japanese Society for Clinical Microbiology (JSCM)ShingoYamamotoThe Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID and the Japanese Society for Clinical Microbiology (JSCM)KoichiroWadaThe Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID and the Japanese Society for Clinical Microbiology (JSCM)KanaoKobayashiThe Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID and the Japanese Society for Clinical Microbiology (JSCM)RyoichiHamasunaThe Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID and the Japanese Society for Clinical Microbiology (JSCM)ShinichiMinamitaniThe Urogenital Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID and the Japanese Society for Clinical Microbiology (JSCM)TetsuyaMatsumotoThe Surveillance Committee of JSC, JAID and JSCMHiroshiKiyotaThe Surveillance Committee of JSC, JAID and JSCMKazuhiroTatedaThe Surveillance Committee of JSC, JAID and JSCMJunkoSatoThe Surveillance Committee of JSC, JAID and JSCMHideakiHanakiInfection Control Research Center, Kitasato UniversityNaoyaMasumoriDepartment of Urology, Sapporo Medical University School of MedicineHiroyukiNishiyamaDepartment of Urology, University of TsukubaJunMiyazakiDepartment of Urology, University of TsukubaKiyohideFujimotoDepartment of Urology, Nara Medical UniversityKazushiTanakaDivision of Urology, Department of Surgery Related Faculty of Medicine, Kobe University Graduate School of MedicineShinyaUeharaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkioMatsubaraDepartment of Urology, Institute of Biomedical & Health Sciences, Hiroshima UniversityKenjiItoiClinicKenjiHayashiTomakomai Urology and Cardiology ClinicYuichiroKurimuraTomakomai Urology and Cardiology ClinicShinItoiClinicToshimiTakeuchiTakeuchi Urology and Dermatology ClinicHarunoriNaritaNarita ClinicMasanobuIzumitaniIzumitani Fureai ClinicHirofumiNishimuraNishimura Urology ClinicMotoshiKawaharaKawahara Urology ClinicMakotoHaraDepartment of Urology, Tsujinaka Hospital KashiwanohaTakahideHosobeHosobe ClinicKenjiTakashimaTakashima Urology ClinicHirofumiChokyuCyokyu Tenma ClinicMasaruMatsumuraMatsumura Urology ClinicHideariIharaIhara ClinicSatoshiUnoHirajima ClinicKoichiMondenAraki Urological ClinicToruSumii ShuichiKawaiSumii ClinicSatoruKariyaOotemachi ClinicTakashiSatoNissin Urological ClinicMasaruYoshiokaYoshioka Urology ClinicHitoshiKadenaKadena Urological ClinicShinjiMatsushitaDepartment of Urology, Kagoshima Prefectural Ohshima HospitalShoheiNishiNishi Urology and Dermatology Clinic YukinariHosokawaDepartment of Urology, Tane General HospitalTakeshiShiraneShirane Urology ClinicMutsumasaYohYoh Urology and Dermatology ClinicSyujiWatanabeDepartment of Urology, Saiseikai Chuwa HospitalShinichiMakinoseMakinose Urological ClinicTetsujiUemuraRemedy Kitakyushu Nephro ClinicHirokazuGotoDepartment of Urology, Fuji City Genaral HospitalThe Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16–40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified.</br>
In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0370-26937982019Search for heavy neutrinos in pi > mu nu decay134980ENA.Aguilar-ArevaloInstituto de Ciencias Nucleares, Universidad Nacional Autónoma de MexicoM.AokiGraduate School of Science, Osaka University,M.BlecherPhysics Department, Virginia Tech.D.I.BrittonSchool of Physics and Astronomy, University of GlasgowBruch, D.vom BruchDepartment of Physics and Astronomy, University of British ColumbiaD. A.BrymanDepartment of Physics and Astronomy, University of British ColumbiaS.ChenDepartment of Engineering Physics, Tsinghua UniversityJ.ComfortPhysics Department, Arizona State UniversityL.DoriaTRIUMF, 4004 Wesbrook MallS.Cuen-RochinDepartment of Physics and Astronomy, University of British ColumbiaP.GumplingerTRIUMF, 4004 Wesbrook MallA.HusseinUniversity of Northern British ColumbiaY.IgarashiKEKS.ItoGraduate School of Science, Osaka UniversityS. H.KettellBrookhaven National LaboratoryL.KurchaninovTRIUMF, 4004 Wesbrook MallL. S.LittenbergBrookhaven National LaboratoryC.MalbrunotDepartment of Physics and Astronomy, University of British ColumbiaR. E.MischkeTRIUMF, 4004 Wesbrook MallT.NumaoTRIUMF, 4004 Wesbrook MallD.ProtopopescuSchool of Physics and Astronomy, University of GlasgowA.SherTRIUMF, 4004 Wesbrook MallT.SullivanDepartment of Physics and Astronomy, University of British ColumbiaD.VavilovTRIUMF, 4004 Wesbrook MallIn the present work of the PIENU experiment, heavy neutrinos were sought in pion decays pi(+) -> mu(+)nu at rest by examining the observed muon energy spectrum for extra peaks in addition to the expected peak for a light neutrino. No evidence for heavy neutrinos was observed. Upper limits were set on the neutrino mixing matrix vertical bar U-mu i vertical bar(2) in the neutrino mass region of 15.7-33.8 MeV/c(2), improving on previous results by an order of magnitude. (C) 2019 The Authors. Published by Elsevier B.V.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1472-64832412012Screening of sperm velocity by fluid mechanical characteristics of a cyclo-olefin polymer microfluidic sperm-sorting device109115ENKojiMatsuuraMamiTakenamiYukaKurodaToruHyakutakeShinichiroYanaseKeijiNaruseThe microfluidic sperm-sorting (MFSS) device is a promising advancement for assisted reproductive technology. Previously, poly(dimethylsiloxiane) and quartz MFSS devices were developed and used for intracytoplasmic sperm injection. However, these disposable devices were not clinically suitable for assisted reproduction, so a cyclo-olefin polymer MFSS (COP-MFSS) device was developed. By micromachining, two microfluidic channels with different heights and widths (chip A: 0.3 x 0.5 mm; chip B: 0.1 x 0.6 mm) were prepared. Sorted sperm concentrations were similar in both microfluidic channels. Linear-velocity distribution using the microfluidic channel of chip B was higher than that of chip A. Using confocal fluorescence microscopy, it was found that the highest number of motile spermatozoa swam across the laminar flow at the bottom of the microfluidic channel. The time required to swim across the laminar flow was longer at the bottom and top of the microfluidic channels than in the middle because of the low fluid velocity. These results experimentally demonstrated that the width of microfluidic channels should be increased in the region of laminar flow from the semen inlet to the outlet for unsorted spermatozoa to selectively recover spermatozoa with high linear velocity.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0197-01861412020Scn1a and Cacna1a mutations mutually alter their original phenotypes in rats104859ENIoriOhmoriGraduate School of Education, Okayama UniversityKiyokaKobayashiDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMamoruOuchidaDepartment of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThis study aimed to examine the effects of Cacna1a mutation on the phenotype of Scn1a-associated epilepsy in rats. We used rats with an N1417H missense mutation in the Scn1a gene and others with an M251K mutation in the Cacna1a gene. Scn1a/Cacna1a double mutant rats were generated by mating both Scn1a and Cacna1a mutants. We investigated general health and the epileptic phenotype in all these genotypes. The onset threshold of hyperthermia-induced seizures was examined at 5 weeks and spontaneous seizures were monitored using video-EEG recordings from 6 to 12 weeks of age. Scn1a/Cacna1a double mutants showed significantly reduced threshold for hyperthermia-sensitive seizures onset compared with the Scn1a mutants and had absence seizures having 6–7 c/s spike-wave bursts with changes in the spike-wave pattern, whereas Cacna1a mutants had regular 6–7 c/s spike-wave bursts. In Scn1a/Cacna1a double mutants, 6–7 c/s spike-wave bursts were accompanied with eyelid myoclonia and continuously shifting generalized clonic seizures, which were not observed in either Scn1a or Cacna1a mutants. Although a curvature of the spine was observed in rats of all these genotypes, the degree of curvature was more pronounced in Scn1a/Cacna1a double mutants, followed by Cacna1a and Scn1a mutants. Our results indicate that Cacna1a and Scn1a mutations mutually alter their original phenotypes in rats. The phenotype of absence seizures with eyelid myoclonia, generalized clonic seizures, and of spine curvature in the Scn1a/Cacna1a double mutants were similar to that observed in patients with Dravet syndrome.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0019-10353592021Salt – A critical material to consider when exploring the solar system114328ENM.R.M.IzawaInstitute for Planetary Materials, Okayama UniversityP.L.KingResearch School of Earth Sciences, Australian National University CanberraP.VernazzaLab. d'Astrophys. de Marseille, Pôle de l'EtoileJ.A.BergerInst. Meteoritics, Univ. New MexicoW.A.McCutcheonInst. Meteoritics, Univ. New MexicoSalt-rich deposits may be more widespread on planetary surfaces than is generally appreciated. Remote observations, laboratory studies of meteorites, and cosmochemical constraints all point towards widespread occurrences of salts (including halides, sulfates, and (bi)carbonates) on asteroids, icy bodies, Mars, and elsewhere. We have investigated the mid-infrared (1.8–25 μm) reflectance spectral properties of mixtures of chondritic (ordinary, enstatite and carbonaceous) meteorites with potassium bromide; a mid-infrared transmissive salt like all halides. Our results demonstrate that halide-chondrite mixtures provide spectral signatures that either reveal the presence of transmissive materials or provide evidence for highly porous regolith. Previously, the nature of the surfaces of the asteroids 624 Hektor and 21 Lutetia was inferred using a limited range of spectra from halide-chondrite mixtures. Here, we provide an extensive dataset of halide-chondrite mixtures to encompass a wider set of possible surface compositions.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0006-291X48522017SRSF1-3 contributes to diversification of the immunoglobulin variable region gene by promoting accumulation of AID in the nucleus261266ENYukaKawaguchiDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityHiroakiNarikiDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityNaokoKawamotoDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityYuichiKanehiroDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversitySatoshiMiyazakiDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityMariSuzukiDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityMasakiMagariDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityHiroshiTokumitsuDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityNaokiKanayamaDepartment of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this study, we examined whether SRSF1-3 functions in IgV diversification by promoting nuclear localization of AID. AID expressed alone was localized predominantly in the cytoplasm. In contrast, co-expression of AID with SRSF1-3 led to the nuclear accumulation of both AID and SRSF1-3 and the formation of a protein complex that contained them both, although SRSF1-3 was dispensable for nuclear import of AID. Expression of either SRSF1-3 or a C-terminally-truncated AID mutant increased IgV diversification in DT40 cells. However, overexpression of exogenous SRSF1-3 was unable to further enhance IgV diversification in DT40 cells expressing the truncated AID mutant, although SRSF1-3 was able to form a protein complex with the AID mutant. These results suggest that SRSF1-3 promotes nuclear localization of AID probably by forming a nuclear protein complex, which might stabilize nuclear AID and induce IgV diversification in an AID C-terminus-dependent manner.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama193652331342020S100 Soil Sensor Receptors and Molecular Targeting Therapy Against Them in Cancer Metastasis100753ENNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe molecular mechanisms underlying the 'seed and soil' theory are unknown. S100A8/A9 (a heterodimer complex of S100A8 and S100A9 proteins that exhibits a 'soil signal') is a ligand for Toll-like receptor 4, causing distant melanoma cells to approach the lung as a 'seeding' site. Unknown soil sensors for S100A8/A9 may exist, e.g., extracellular matrix metalloproteinase inducer, neuroplastin, activated leukocyte cell adhesion molecule, and melanoma cell adhesion molecule. We call these receptor proteins 'novel S100 soil sensor receptors (novel SSSRs).' Here we review and summarize a crucial role of the S100A8/A9-novel SSSRs' axis in cancer metastasis. The binding of S100A8/A9 to individual SSSRs is important in cancer metastasis via upregulations of the epithelial-mesenchymal transition, cellular motility, and cancer cell invasiveness, plus the formation of an inflammatory immune suppressive environment in metastatic organ(s). These metastatic cellular events are caused by the SSSR-featured signal transductions we identified that provide cancer cells a driving force for metastasis. To deprive cancer cells of these metastatic forces, we developed novel biologics that prevent the interaction of S100A8/A9 with SSSRs, followed by the efficient suppression of S100A8/A9-mediated lung-tropic metastasis in vivo. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1882-76165612020Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation119126ENTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesCellular communication network factor 2 (CCN2) is a cysteine-rich secreted matricellular protein that regulates various cellular functions including cell differentiation. CCN2 is highly expressed under several types of mechanical stress, such as stretch, compression, and shear stress, in mesenchymal cells including chondrocytes, osteoblasts, and fibroblasts. In particular, CCN2 not only promotes cell proliferation and differentiation of various cells but also regulates the stability of mRNA of TRPV4, a mechanosensitive ion channel in chondrocytes. Of note, CCN2 behaves like a biomarker to sense suitable mechanical stress, because CCN2 expression is down-regulated when chondrocytes are subjected to excessive mechanical stress. These findings suggest that CCN2 is a mechano-sensing regulator. CCN2 expression is regulated by the activation of various mechano-sensing signaling pathways, e.g., mechanosensitive ion channels, integrin-focal adhesion-actin dynamics, Rho GTPase family members, Hippo-YAP signaling, and G protein-coupled receptors. This review summarizes the characterization of mechanoreceptors involved in CCN2 gene regulation and discusses the role of CCN2 as a mechano-sensing regulator of mesenchymal cell differentiation, with particular focus on chondrocytes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1882-76165612020Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation119126ENTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesCellular communication network factor 2 (CCN2) is a cysteine-rich secreted matricellular protein that regulates various cellular functions including cell differentiation. CCN2 is highly expressed under several types of mechanical stress, such as stretch, compression, and shear stress, in mesenchymal cells including chondrocytes, osteoblasts, and fibroblasts. In particular, CCN2 not only promotes cell proliferation and differentiation of various cells but also regulates the stability of mRNA of TRPV4, a mechanosensitive ion channel in chondrocytes. Of note, CCN2 behaves like a biomarker to sense suitable mechanical stress, because CCN2 expression is down-regulated when chondrocytes are subjected to excessive mechanical stress. These findings suggest that CCN2 is a mechano-sensing regulator. CCN2 expression is regulated by the activation of various mechano-sensing signaling pathways, e.g., mechanosensitive ion channels, integrin-focal adhesion-actin dynamics, Rho GTPase family members, Hippo-YAP signaling, and G protein-coupled receptors. This review summarizes the characterization of mechanoreceptors involved in CCN2 gene regulation and discusses the role of CCN2 as a mechano-sensing regulator of mesenchymal cell differentiation, with particular focus on chondrocytes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1015-958446102023Robotic surgery for congenital biliary dilatation using the scope switch technique (with video)43994402ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakahitoYagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTechnique: Minimally invasive congenital biliary dilatation (CBD) surgery is technically demanding. However, few studies have reported surgical approaches of robotic surgery for CBD. This report presents robotic CBD surgery using a scope-switch technique. Our robotic surgery technique for CBD consisted of four steps: step 1, Kocher's maneuver; step 2, dissection of the hepatoduodenal ligament using the scope switch technique; step 3, preparation for the Roux-en-Y loop; and step 4, hepaticojejunostomy. <br>
Results: The scope switch technique can provide different surgical approaches for dissecting the bile duct, including anterior approach by the standard position and right approach by the scope switch position. When approaching the ventral and left side of the bile duct, anterior approach with the standard position is suitable. In contrast, the lateral view by the scope switch position is preferable for approaching the bile duct laterally and dorsally. Using this technique, the dilated bile duct can be dissected circumferentially from four directions: anterior, medial, lateral, and posterior. Thereafter, complete resection of the choledochal cyst can be achieved. <br>
Conclusions: The scope switch technique in robotic surgery for CBD can be useful for dissecting around the bile duct with different surgical views, leading to the complete resection of the choledochal cyst.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X2672020Risk for the occupational infection by cytomegalovirus among health-care workers681684ENMiyukiTakaoDivision of Infection Control and Prevention, Osaka University HospitalNoriYoshiokaDivision of Infection Control and Prevention, Osaka University HospitalHideharuHagiyaOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMatsuoDeguchiDivision of Infection Control and Prevention, Osaka University HospitalMasanoriKagitaDivision of Infection Control and Prevention, Osaka University HospitalHirokoTsukamotoLaboratory for Clinical Investigation, Osaka University HospitalYohHidakaLaboratory for Clinical Investigation, Osaka University HospitalKazunoriTomonoDivision of Infection Control and Prevention, Osaka University HospitalToruTobeDepartment of Biomedical Informatics, Osaka University Graduate School of MedicineBackground</br>
Cytomegalovirus (CMV) are ubiquitously distributed worldwide, causing a wide range of clinical manifestations from congenital infection to a life-threatening disease in immunocompromised individuals. CMV can be transmitted via human-to-human contact through body fluids; however, the risk of CMV infection among healthcare workers (HCWs) has not been fully evaluated.</br>
Aim</br>
This study aimed to assess the risk of CMV infection among HCWs through daily medical practices.</br>
Methods</br>
Serum samples from HCWs at Osaka University Hospital (Japan) were analysed. Initially, we compared CMV IgG seropositivity among HCWs (medical doctors, nurses, and others) in 2017, which was examined after 1 year to evaluate seroconversion rates among those with seronegative results. Then, we examined CMV seroconversion rates in HCWs who were exposed to blood and body fluids.</br>
Findings</br>
We analysed 1153 samples of HCWs (386 medical doctors, 468 nurses, and 299 others), of which CMV seropositivity rates were not significantly different (68.9%, 70.3%, and 70.9%, respectively). Of these, 63.9% (221/346) of CMV seronegative HCWs were followed after 1 year, with CMV seroconversion rates of 3.2% (7/221). Among 72 HCWs who tested negative for CMV IgG when exposed to blood and body fluids, the CMV seroconversion rate was 2.8% (2/72). The CMV seroconversion rates between the two situations were not significantly different.</br>
Conclusion</br>
Our study indicated that CMV infection through daily patient care seems quite rare. Further well-designed studies with a large sample size are warranted to verify our finding.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-2612772020Retropharyngeal hematoma presenting airway obstruction: A case report321324ENAtsuyoshiIidaDepartment of Emergency Medicine, Okayama Red Cross HospitalAyumiNishidaepartment of Neurosurgery, Okayama Red Cross HospitalSeijiYoshitomiDepartment of Breast and Endocrine Surgery, Okayama Red Cross HospitalTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction</br>
Blunt neck trauma patients can suffer from an airway emergency and are necessary to careful observation.</br>
Presentation of cas</br>e
A 79-year-old man under anticoagulation therapy presented to our hospital three hours after a fall. Shortly after arrival, he developed dyspnea. Oral intubation was attempted, but with no success; therefore, an emergency tracheotomy was performed. Contrast-enhanced computed tomography (CT) and subsequent angiography revealed active bleeding from a branch of the right ascending cervical artery. Subsequently, the right thyrocervical trunk, which is upstream from the ascending cervical artery, was embolized and hemostasis was achieved. He was discharged 52 days after the emergency admission.</br>
Discussion</br>
This is the first case report of an ascending cervical artery injury due to blunt trauma that resulted in an airway emergency. Contrast-enhanced CT and cervical angiography are useful for confirming the area of injury and size of the hematoma. Half of patients with respiratory distress accompanied by a cervical spine injury require definitive airway management within five hours of the injury and all by 24 h. Neck trauma can lead to fatal airway obstruction and careful monitoring is warranted to detect any signs of impeding respiratory obstruction.</br>
Conclusion</br>
All emergency physicians need to keep their airway management skills updated in order to perform reliably and rapidly in difficult and urgent situations.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama097262922012020Repeated misclassifications of tachycardia by an implantable cardiac defibrillator3538ENAtsuyukiWatanabeDepartment of Cardiovascular Medicine, Okayama UniversityOsamuFujimuraDepartment of Cardiovascular Medicine, Okayama UniversityThis case describes repeated misclassifications of SVT due to AV node reentry as VT by an ICD. This case illustrates the limitations of SVT-VT discrimination algorithm. Careful analysis of the stored tracings is of critical importance to reach the correct diagnosis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama003808066122021Reliability-based design for earth-fill dams against severe natural disaster events271282ENShin-ichiNishimuraGraduate School of Environmental and Life Science, Okayama UniversityToshifumiShibataGraduate School of Environmental and Life Science, Okayama UniversityTakayukiShukuGraduate School of Environmental and Life Science, Okayama UniversityThe maintenance of geotechnical structures, such as earth-fill dams, is required as a countermeasure against severe natural disasters, particularly earthquakes and heavy rains. The reliability-based analysis introduced here is in response to the recent demand for low-cost improvements.First, a statistical model of N values was determined from Swedish weight sounding (SWS) tests to present the spatial variability of the soil strength. Then, a reliability-based analysis of embankments was conducted by considering the variability of the internal friction angle derived from N value, and the seismic hazard for the Nankai Trough. The next step was to evaluate the probability of the overflow of earth-fills during heavy rains. The rainfall intensity was considered as a probabilistic parameter, and the various rainfall patterns were tested by the proposed method. Finally, the total risk due to both earthquakes and heavy rains was evaluated for an earth-fill site. As a result, the possibility for the practical use of the proposed method in making plans for the maintenance of deteriorated earth-fill dams was verified.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X3032024Relevance of complement immunity with brain fog in patients with long COVID236241ENHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalKazukiTokumasuDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaruhikoSunadaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiHondaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasanoriFurukawaClinical Laboratory, Okayama University HospitalFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction<br>
This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50).<br>
<br>
Methods<br>
This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors.<br>
<br>
Results<br>
Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33–5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04–2.66).<br>
<br>
Conclusions<br>
High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1323-89306512016Regulatory effect of TLR3 signaling on staphylococcal enterotoxin-induced IL-5, IL-13, IL-17A and IFN-γ production in chronic rhinosinusitis with nasal polyps96102ENMitsuhiroOkanoDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTazukoFujiwaraDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinKariyaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayaHigakiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSei-ichiroMakiharaDepartment of Otorhinolaryngology, Kagawa Rosai HospitalTakenoriHarunaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuyukiNoyamaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahisaKoyamaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaroOmichiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYorihisaOritaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroMikiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKengoKanaiDepartment of Otorhinolaryngology, Kagawa Prefectural Central HospitalKazunoriNishizakiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBACKGROUND:
Toll-like receptor 3 (TLR3) is expressed in upper airways, however, little is known regarding whether Toll-like receptor 3 (TLR3) signals exert a regulatory effect on the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), especially on eosinophilic inflammation. We sought to investigate the effect of Poly(IC), the ligand for TLR3, on cytokine production by dispersed nasal polyp cells (DNPCs).
METHODS:
DNPCs were pretreated with or without Poly(IC), and were then cultured in the presence or absence of staphylococcal enterotoxin B (SEB), following which the levels of IL-5, IL-10, IL-13, IL-17A and interferon (IFN)-γ in the supernatant were measured. To determine the involvement of IL-10 and cyclooxygenase in Poly(IC)-mediated signaling, DNPCs were treated with anti-IL-10 monoclonal antibody and diclofenac, the cyclooxygenase inhibitor, respectively. Poly(IC)-induced prostaglandin E2 (PGE2) production was also determined.
RESULTS:
Exposure to Poly(IC) induced a significant production of IL-10, but not of IL-5, IL-13, IL-17A or IFN-γ by DNPCs. Pretreatment with Poly(IC) dose-dependently inhibited SEB-induced IL-5, IL-13 and IL-17A, but not IFN-γ production. Neutralization of IL-10 significantly abrogated the inhibitory effect of Poly(IC). Treatment with diclofenac also abrogated the inhibitory effect of Poly(IC) on SEB-induced IL-5 and IL-13 production. However, unlike exposure of diclofenac-treated DNPCs to lipopolysaccharide, the ligand for TLR4, exposure of these cells to Poly(IC) did not enhance IL-5 or IL-13 production. Poly(IC) did not significantly increase PGE2 production by DNPCs.
CONCLUSIONS:
These results suggest that TLR3 signaling regulates eosinophilia-associated cytokine production in CRSwNP, at least in part, via IL-10 production.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama134900796232020Regulation of cellular communication network factor 2 (CCN2) in breast cancer cells via the cell-type dependent interplay between CCN2 and glycolysis280288ENShoAkashi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomomiMizukawaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazumiKawataDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaharuTakigawaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiIida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjectives: Anti-osteoclastic treatments for breast cancer occasionally cause medication-related osteonecrosis of the jaw. Moreover, elevated glycolytic activity, which is known as the Warburg effect, is usually observed in these breast cancer cells. Previously, we found that cellular communication network factor 2 (CCN2) production and glycolysis enhanced each other in chondrocytes. Here, we evaluated the interplay between CCN2 and glycolysis in breast cancer cells, as we suspected a possible involvement of CCN2 in the Warburg effect in highly invasive breast cancer cells. <br/>
Methods: Two human breast cancer cell lines with a distinct phenotype were used. Glycolysis was inhibited by using 2 distinct compounds, and gene silencing was performed using siRNA. Glycolysis and the expression of relevant genes were monitored via colorimetric assays and quantitative RT-PCR, respectively. <br/>
Results: Although CCN2 expression was almost completely silenced when treating invasive breast cancer cells with a siRNA cocktail against CCN2, glycolytic activity was not affected. Notably, the expression of glycolytic enzyme genes, which was repressed by CCN2 deficiency in chondrocytes, tended to increase upon CCN2 silencing in breast cancer cells. Inhibition of glycolysis, which resulted in the repression of CCN2 expression in chondrocytic cells, did not alter or strongly enhanced CCN2 expression in the invasive and non-invasive breast cancer cells, respectively. <br/>
Conclusions: High CCN2 expression levels play a critical role in the invasion and metastasis of breast cancer. Thus, a collapse in the intrinsic repressive machinery of CCN2 due to glycolysis may induce the acquisition of an invasive phenotype in breast cancer cells. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama094926582020Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20–89 years: A cross-sectional nationwide study in JapanENKeikoYamadaDepartments of Sensory & Motor System Medicine, Faculty of Medicine, The University of TokyoYoichi M.ItoDepartment of Statistical Data Science, The Institute of Statistical MathematicsMasaoAkagiDepartment of Orthopedic Surgery, Kindai University HospitalEtsuoChosaDepartment of Orthopaedic Surgery, University of MiyazakiTakeshiFuji“Locomo Challenge!” Promotion CouncilKenichiHiranoHirano Orthopaedics ClinicShinichiIkedaDepartment of Orthopaedic Surgery, Oita University,HideakiIshibashi“Locomo Challenge!” Promotion CouncilYasuyukiIshibashiDepartment of Orthopaedic Surgery, Hirosaki University Graduate School of MedicineMuneakiIshijima“Locomo Challenge!” Promotion CouncilEijiItoiDepartment of Orthopaedic Surgery, Tohoku University Graduate School of MedicineNorimasaIwasaki“Locomo Challenge!” Promotion CouncilRyoichiIzumida“Locomo Challenge!” Promotion CouncilKenKadoyaDepartment of Advanced Medicine for Locomotor System, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityMasayukiKamimuraDepartment of Orthopaedic Surgery, Tohoku University Graduate School of MedicineArihikoKanaji“Locomo Challenge!” Promotion CouncilHiroyukiKatoDepartment of Orthopaedic Surgery, Shinshu University School of MedicineShunjiKishida“Locomo Challenge!” Promotion CouncilNaohikoMashimaDepartment of Bone and Joint Surgery, Ehime University Graduate School of MedicineShuichiMatsudaDepartment of Orthopaedic Surgery, Kyoto University Graduate School of MedicineYasumotoMatsuiCenter for Frailty and Locomotive Syndrome, National Center for Geriatrics and GerontologyToshikiMatsunagaDepartment of Rehabilitation Medicine, Akita University HospitalNaohisaMiyakoshiDepartment of Orthopedic Surgery, Akita University Graduate School of MedicineHiroshiMizutaDepartment of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto UniversityYutakaNakamuraSaiseikai Shonan Hiratsuka HospitalKenNakataMedicine for Sports and Performing Arts, Osaka University Graduate School of MedicineGoOmoriDepartment of Sports and Health, Faculty of Health and Science, Niigata University of Health and WelfareKojiOsukaOsuka ClinicYujiUchioDepartment of Orthopaedic Surgery, Shimane UniversityKazuteruRyuKanai HospitalNobuyukiSasakiSasaki Orthopedic and Anesthesiology ClinicKimihitoSato“Locomo Challenge!” Promotion CouncilMasuoSendaOkayama University Hospital, Division of Physical Medicine and RehabilitationAkihiroSudoDepartment of Orthopaedic Surgery, Mie University Graduate School of MedicineNaonobuTakahiraDepartment of Rehabilitation, Kitasato University School of Allied Health SciencesHiroshiTsumuraDepartment of Orthopaedic SurgerySatoshiYamaguchi“Locomo Challenge!” Promotion CouncilNoriakiYamamotoNigata Rehabilitation HospitalKozoNakamura“Locomo Challenge!” Promotion Council OheTakashi“Locomo Challenge!” Promotion Council, TBackground<br/>
The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex.<br/>
Methods<br/>
We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan.<br/>
Results<br/>
The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score.<br/>
Conclusion<br/>
The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-8440662020Rapid and specific detection of oxidized LDL/β2GPI complexes via facile lateral flow immunoassaye04114ENXian WenTanDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumiakiTakenakaCollaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironoriTakekawaFaculty of Medicine, Okayama UniversityEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciencesβ2-Glycoprotein I (β2GPI) forms indissociable complex with oxidized LDL (oxLDL) into proatherogenic oxLDL/β2GPI complex through a specific ligand known as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1). Recent discoveries have demonstrated the atherogenicity of these complexes in patients of both systemic and non-systemic autoimmune diseases. Hence, serological level of oxLDL/β2GPI complexes may represent one crucial clinical parameter for disease prognosis of atherosclerosis-related diseases. Herein, we established a simple, specific and rapid gold nanoparticle (GNP) based lateral flow immunoassay (LFIA) to quantify oxLDL/β2GPI complexes from test samples. Specificities of hybridoma cell-derived monoclonal antibodies against antigen, optimal conditions for conjugation of antibody with GNP, and sensitivity of oxLDL/β2GPI LFIA in comparison to an ELISA-based detection method were assessed accordingly. The established oxLDL/β2GPI LFIA was capable of detecting oxLDL/β2GPI specifically without interference from autoantibodies and solitary components of oxLDL/β2GPI present in test samples. A significant correlation (R2 > 0.8) was also obtained with the oxLDL/β2GPI LFIA when compared to the ELISA-based detection. On the whole, the oxLDL/β2GPI LFIA remains advantageous over the oxLDL/β2GPI ELISA. The unnecessary washing step, short developmental and analytical time support facile and rapid detection of oxLDL/β2GPI as opposed to the laborious ELISA system.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1556086414112019Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden20092018ENGoMakimotoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKadoakiOhashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShutaTomidaOkayama University Hospital Biobank, Okayama University HospitalKazuyaNishiiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakehiroMatsubaraOkayama University Hospital Biobank, Okayama University HospitalHiroeKayataniDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisaoHigoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKiichiroNinomiyaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkikoSatoDepartment of Respiratory Medicine, Okayama University HospitalHiromiWatanabeDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirohisaKanoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiNinomiyaDepartment of Respiratory Medicine, Okayama University HospitalToshioKuboCenter for Clinical Oncology, Okayama University HospitalKammeiRaiDepartment of Respiratory Medicine, Okayama University HospitalEikiIchiharaDepartment of Respiratory Medicine, Okayama University HospitalKatsuyukiHottaCenter of Innovative Clinical Medicine, Okayama University HospitalMasahiroTabataCenter for Clinical Oncology, Okayama University HospitalShinichiToyookaOkayama University Hospital Biobank, Okayama University HospitalMinoruTakataLaboratory of DNA Damage Signaling, Department of Late Effects Studies, Graduate School of Biostudies, Radiation Biology Center, Kyoto UniversityYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalIntroduction<br/>
The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. <br/>
Methods<br/>
Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction. <br/>Results<br/>
ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes. <br/>Conclusions<br/>
High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0960-9776552020Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer6368ENJunjiTsurutaniAdvanced Cancer Translational Research Institute, Showa UniversityFumikataHaraDepartment of Breast Medical Oncology, Cancer Institute Hospital of JFCRMasahiroKitadaDepartment of Breast Disease Center, Asahikawa Medical University HospitalMasatoTakahashiNHO Hokkaido Cancer CenterYuichiroKikawaDepartment of Breast Surgery, Kobe City Medical Center General HospitaHiroakiKatoTeine Keijinkai HospitalEikoSakataNiigata City General HospitalYoichiNaitoDepartment of Breast and Medical Oncology, National Cancer Center Hospital EastYoshieHasegawaDepartment of Breast Surgery, Hirosaki Municipal HospitalTsuyoshiSaitoJapanese Red Cross Saitama HospitalTsutomuIwasaDepartment of Medical Oncology, Kindai University Faculty of MedicineNarutoTairaOkayama University HospitalTsutomuTakashimaOsaka City University Graduate School of MedicineKosukeKashiwabaraClinical Research Promotion Center, The University of Tokyo HospitalTomohikoAiharaBreast Center, Aihara HospitalHirofumiMukaiNational Cancer Center Hospital East, KashiwaBackground</br>
Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX.</br>
Methods</br>
We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded.</br>
Results</br>
One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180.</br>
Conclusions</br>
Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0949-26582142016ROCK inhibition stimulates SOX9/Smad3-dependent COL2A1 expression in inner meniscus cells524529ENTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate SchoolAmiMaeharaDepartment of Orthopaedic Surgery, Okayama University Graduate SchoolToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate SchoolBACKGROUND:
Proper functioning of the meniscus depends on the composition and organization of its fibrocartilaginous extracellular matrix. We previously demonstrated that the avascular inner meniscus has a more chondrocytic phenotype compared with the outer meniscus. Inhibition of the Rho family GTPase ROCK, the major regulator of the actin cytoskeleton, stimulates the chondrogenic transcription factor Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. However, the crosstalk between ROCK inhibition, SOX9, and other transcription modulators on COL2A1 upregulation remains unclear in meniscus cells. The aim of this study was to investigate the role of SOX9-related transcriptional complex on COL2A1 expression under the inhibition of ROCK in human meniscus cells.
METHODS:
Human inner and outer meniscus cells were prepared from macroscopically intact lateral menisci. Cells were cultured in the presence or absence of ROCK inhibitor (ROCKi, Y27632). Gene expression, collagen synthesis, and nuclear translocation of SOX9 and Smad2/3 were analyzed.
RESULTS:
Treatment of ROCKi increased the ratio of type I/II collagen double positive cells derived from the inner meniscus. In real-time PCR analyses, expression of SOX9 and COL2A1 genes was stimulated by ROCKi treatment in inner meniscus cells. ROCKi treatment also induced nuclear translocation of SOX9 and phosphorylated Smad2/3 in immunohistological analyses. Complex formation between SOX9 and Smad3 was increased by ROCKi treatment in inner meniscus cells. Chromatin immunoprecipitation analyses revealed that association between SOX9/Smad3 transcriptional complex with the COL2A1 enhancer region was increased by ROCKi treatment.
CONCLUSIONS:
This study demonstrated that ROCK inhibition stimulated SOX9/Smad3-dependent COL2A1 expression through the immediate nuclear translocation of Smad3 in inner meniscus cells. Our results suggest that ROCK inhibition can stimulates type II collagen synthesis through the cooperative activation of Smad3 in inner meniscus cells. ROCKi treatment may be useful to promote the fibrochondrocytic healing of the injured inner meniscus.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama09445013223-2252019Quorum-dependent expression of rsmX and rsmY, small non-coding RNAs, in Pseudomonas syringae7278ENYukikoNakatsuGraduate School of Environmental and Life Science, Okayama UniversityHidenoriMatsuiGraduate School of Environmental and Life Science, Okayama UniversityMikihiroYamamotoGraduate School of Environmental and Life Science, Okayama UniversityYoshiteruNoutoshiGraduate School of Environmental and Life Science, Okayama UniversityKazuhiroToyodaGraduate School of Environmental and Life Science, Okayama UniversityYukiIchinoseGraduate School of Environmental and Life Science, Okayama UniversityPseudomonas syringae pathovars are known to produce N-acyl-homoserine lactones (AHL) as quorum-sensing molecules. However, many isolates, including P. syringae pv. tomato DC3000 (PtoDC3000), do not produce them. In P. syringae, psyI, which encodes an AHL synthase, and psyR, which encodes the transcription factor PsyR required for activation of psyI, are convergently transcribed. In P. amygdali pv. tabaci 6605 (Pta6605), there is one nucleotide between the stop codons of both psyI and psyR. However, the canonical stop codon for psyI in PtoDC3000 was converted to the cysteine codon by one nucleotide deletion, and 23 additional amino acids extended it to a C-terminal end. This resulted in overlapping of the open reading frame (ORF) for psyI and psyR. On the other hand, stop codons in the psyR ORF of P. syringae 7 isolates, including pv. phaseolicola and pv. glycinea, were found. These results indicate that many pathovars of P. syringae have genetically lost AHL production ability by the mutation of their responsible genes. To examine whether PtoDC3000 modulates the gene expression profile in a population-dependent manner, we carried out microarray analysis using RNAs prepared from low- and high-density cells. We found the expressions of rsmX and rsmY remarkably activated in high-density cells. The activated expressions of rsmX and rsmY were confirmed by Northern blot hybridization, but these expressions were abolished in a ΔgacA mutant of Pta6605. These results indicate that regardless of the ability to produce AHL, P. syringae regulates expression of the small noncoding RNAs rsmX/Y by currently unknown quorum-sensing molecules.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0304-38004642022Quantifying the GCM-related uncertainty for climate change impact assessment of rainfed rice production in Cambodia by a combined hydrologic - rice growth model109815ENK.TsujimotoGraduate School of Environmental and Life Science, Okayama UniversityN.KuriyaFaculty of Environmental Science and Technology, Okayama UniversityT.OhtaAssistance Unit for Research and Engineering Development (U-PRIMO)K.HommaGraduate School of Agricultural Science, Tohoku UniversityM.SoImMinistry of Water Resources and Meteorology (MOWRAM) of CambodiaThe effects of climate change on agriculture are a major concern for global food security. In this study, the impacts of climate change on rainfed rice production in the granary of Cambodia were examined on a basin scale by developing and applying a combined model consisting of a crop model and a basin-scale distributed hydrological model. The response of rice production to soil-water availability was simulated for past (1981–2000) and future (2041–2060, 2081–2100) periods. From 34 general circulation models (GCMs) that participated in the Coupled Model Intercomparison Project Phase 5 (CMIP5), 5 GCMs were selected by evaluating monthly rainfall in the past. Although annual rainfall was projected to increase by all five selected GCMs, notable decreases in rainfed rice production were projected with 3 GCMs, while small changes were projected with the other 2 GCMs. The main factor restricting future rice production was soil water availability, brought by the projected change in the seasonal distribution of rainfall and the projected more severe dry spells in the early monsoon season. The results suggest the importance of the selection and bias correction of GCMs to force rice crop models and of the simulation of soil water flow on a basin scale for the assessment of rain-fed rice production. In particular, improvements in projections of rainfall amounts over shorter periods rather than annual or seasonal periods, which fit within the time scales of rice plant growth, were suggested to be important.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1011-13441372014Quality control of Photosystem II: The molecular basis for the action of FtsH protease and the dynamics of the thylakoid membranes100106ENMihoYoshioka-NishimuraYasusiYamamotoThe reaction center-binding D1 protein of Photosystem II is damaged by excessive light, which leads to photoinhibition of Photosystem II. The damaged D1 protein is removed immediately by specific proteases, and a metalloprotease FtsH located in the thylakoid membranes is involved in the proteolytic process. According to recent studies on the distribution and organization of the protein complexes/supercomplexes in the thylakoid membranes, the grana of higher plant chloroplasts are crowded with Photosystem II complexes and light-harvesting complexes. For the repair of the photodamaged D1 protein, the majority of the active hexameric FtsH proteases should be localized in close proximity to the Photosystem II complexes. The unstacking of the grana may increase the area of the grana margin and facilitate easier access of the FtsH proteases to the damaged D1 protein. These results suggest that the structural changes of the thylakoid membranes by light stress increase the mobility of the membrane proteins and support the quality control of Photosystem II.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0887-89941132020Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate3341ENTomoyukiAkiyamaDepartment of Child Neurology, Okayama University HospitalYukiHyodoDepartment of Child Neurology, Okayama University HospitalKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalTaikanOboshiDepartment of Pediatric Neurology, Osaka Women’s and Children’s HospitalKatsumiImaiDepartment of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological DisordersNaokoIshiharaDepartment of Pediatrics, Fujita Health University School of MedicineYuriDowaDepartment of Neurology, Gunma Children’s Medical CenterTakayoshiKoikeDepartment of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological DisordersToshiyukiYamamotoInstitute of Clinical Genomics, Tokyo Women’s Medical UniversityJunShibasakiDepartment of Neonatology, Kanagawa Children’s Medical CenterHirokoShimboClinical Institute, Kanagawa Children’s Medical CenterTetsuhiroFukuyamaDepartment of Pediatrics, Shinshu UniversityKyokoTakanoCenter for Medical Genetics, Shinshu University HospitalHiroshiShirakuDepartment of Pediatrics, JA Toride Medical CenterSaokoTakeshitaDepartment of Pediatrics, Yokohama City University Medical CenterTohruOkanishiDepartment of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General HospitalShimpeiBabaDepartment of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General HospitalMasayaKubotaDivision of Neurology, National Center for Child Health and DevelopmentShin-ichiroHamanoDivision of Neurology, Saitama Children’s Medical CenterKatsuhiroKobayashiDepartment of Child Neurology, Okayama University HospitalBackground</br>
We aimed to demonstrate the biochemical characteristics of vitamin B6–dependent epilepsy, with a particular focus on pyridoxal 5′-phosphate and pyridoxal in the cerebrospinal fluid.</br>
Methods</br>
Using our laboratory database, we identified patients with vitamin B6–dependent epilepsy and extracted their data on the concentrations of pyridoxal 5′-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5′-phosphate concentrations.</br>
Results</br>
We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5′-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5′-phosphate concentrations were low in patients with vitamin B6–dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6–dependent epilepsy, suggestive of pyridoxal 5′-phosphate deficiency in the brain.</br>
Conclusions</br>
Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5′-phosphate deficiency in the brain in vitamin B6–dependent epilepsy than low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5′-phosphate homeostasis protein deficiency, which does not have known biomarkers.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama109671921251-22018Pyridoxal 5′-phosphate and related metabolites in hypophosphatasia: Effects of enzyme replacement therapy174180ENTomoyukiAkiyamaDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuoKubotaDepartment of Pediatrics, Osaka University Graduate School of MedicineKeiichiOzonoDepartment of Pediatrics, Osaka University Graduate School of MedicineToshimiMichigamiDepartment of Bone and Mineral Research, Osaka Women's and Children's HospitalDaisukeKobayashiDepartment of Food and Chemical Toxicology, School of Pharmaceutical Sciences, Health Sciences University of HokkaidoShinjiTakeyariDepartment of Pediatrics, Osaka University Graduate School of MedicineYuichiroSugiyamaDepartment of Pediatrics, Nagoya University Graduate School of MedicineMasahiroNodaDepartment of Pediatrics, Showa General HospitalDaisukeHaradaDepartment of Pediatrics, Osaka Hospital, Japan Community Healthcare OrganizationNoriyukiNambaDepartment of Pediatrics, Osaka Hospital, Japan Community Healthcare OrganizationAtsushiSuzukiDepartment of Neonatology and Pediatrics, Nagoya City University Graduate School of Medical SciencesMaikoUtoyamaDepartment of Pediatrics, Faculty of Medicine, University of MiyazakiSachikoKitanakaDepartment of Pediatrics, Graduate School of Medicine, University of TokyoMitsuguUematsuDepartment of Pediatrics, Tohoku University Graduate School of MedicineYusukeMitaniDepartment of Pediatrics, Kanazawa University HospitalKunihiroMatsunamiDepartment of Pediatrics, Gifu Prefectural General Medical CenterShigeruTakishimaDepartment of Pediatrics, Soka Municipal HospitalErikaOgawaDepartment of Pediatrics and Child Health, Nihon University School of MedicineKatsuhiroKobayashiDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjective
To investigate the utility of serum pyridoxal 5′-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) as a diagnostic marker of hypophosphatasia (HPP) and an indicator of the effect of, and patient compliance with, enzyme replacement therapy (ERT), we measured PLP, PL, and PA concentrations in serum samples from HPP patients with and without ERT.
Methods
Blood samples were collected from HPP patients and serum was frozen as soon as possible (mostly within one hour). PLP, PL, and PA concentrations were analyzed using high-performance liquid chromatography with fluorescence detection after pre-column derivatization by semicarbazide. We investigated which metabolites are associated with clinical phenotypes and how these metabolites change with ERT.
Results
Serum samples from 20 HPP patients were analyzed. The PLP-to-PL ratio and PLP concentration were elevated in all HPP patients. They correlated negatively with serum alkaline phosphatase (ALP) activity and showed higher values in more severe phenotypes (perinatal severe and infantile HPP) compared with other phenotypes. PL concentration was reduced only in perinatal severe HPP. ERT reduced the PLP-to-PL ratio to mildly reduced or low-normal levels and the PLP concentration was reduced to normal or mildly elevated levels. Urine phosphoethanolamine (PEA) concentration did not return to normal levels with ERT in most patients.
Conclusions
The serum PLP-to-PL ratio is a better indicator of the effect of ERT for HPP than serum PLP and urine PEA concentrations, and a PLP-to-PL ratio of <4.0 is a good indicator of the effect of, and patient compliance with, ERT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-2612732020Pulmonary resection for metachronous metastatic gastric cancer diagnosed using multi-detector computed tomography: Report of five cases342346ENNoriyukiNishiwakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideakiKojimaDivision of Thoracic Surgery, Shizuoka Cancer CenterMitsuhiroIsakaDivision of Thoracic Surgery, Shizuoka Cancer CenterEtsuroBandoDivision of Gastric Surgery, Shizuoka Cancer CenterMasanoriTerashimaDivision of Gastric Surgery, Shizuoka Cancer CenterYasuhisaOhdeDivision of Thoracic Surgery, Shizuoka Cancer CenterIntroduction</br>
As pulmonary resection for metastatic gastric cancer has been rarely reported on, the role of metastasectomy remains unclear in such settings. We reviewed the clinicopathological characteristics and surgical outcomes of patients with metachronous pulmonary metastasis from gastric cancer (MPMGC) diagnosed using multi-detector computed tomography (MDCT) who underwent pulmonary resection.</br>
Presentation of case</br>
From September 2002 to May 2018, five patients underwent pulmonary resection for MPMGC at Shizuoka Cancer Center. All patients received curative resection for initial gastric cancer. Three patients received adjuvant chemotherapy. The median age at pulmonary resection was 70 years. The median disease-free interval between initial gastrectomy and MPMGC diagnosis was 41 months. The first site of recurrence was the lung in all patients. All patients were diagnosed as having primary lung cancer using MDCT before pulmonary resection and fit the surgical indication for primary lung cancer. Lobectomy was performed in three patients, while wedge resection was performed in two. The median overall survival following pulmonary resection was 79 (range, 18–89) months. Two patients experienced recurrence. While one showed recurrence in the mediastinal lymph node, in the other it was observed in the remnant lung; the latter underwent repeated pulmonary resection followed by systemic chemotherapy. Four patients survived for longer than 4 years after pulmonary resection.</br>
Conclusions</br>
Of the five patients with MPMGC diagnosed using MDCT who underwent pulmonary resection, long-term survival was achieved after pulmonary resection in four. Thus, pulmonary resection may be considered for those diagnosed with lung nodules after surgery for gastric cancer, and who fit the surgical indication for primary lung cancer.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama096801602632019Pullout repair using modified Mason-Allen suture induces better meniscal healing and superior clinical outcomes: A comparison between two surgical methods653659ENTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Hospital YukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Hospital YuyaKodamaDepartment of Orthopaedic Surgery, Okayama University Hospital YoshikiOkazakiDepartment of Orthopaedic Surgery, Okayama University Hospital ShinMasudaDepartment of Orthopaedic Surgery, Okayama University Hospital YusukeKamatsukiDepartment of Orthopaedic Surgery, Okayama University Hospital ShotaTakihiraDepartment of Orthopaedic Surgery, Okayama University Hospital TakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University Hospital TadashiYamawakiDepartment of Orthopaedic Surgery, Kousei HospitalToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University HospitalBACKGROUND:<br/>
Pullout repairs of medial meniscus posterior root tears (MMPRTs) have many surgical options. However, there has been no reliable clinical study conducted to compare the superiority of each pullout repair technique. The current study hypothesized that pullout repairs using a modified Mason-Allen suture with FasT-Fix (F-MMA) would have several advantages in postoperative clinical outcomes and meniscal healing compared with single FasT-Fix. The aim of this study was to investigate the clinical usefulness of these two techniques in treating MMPRTs.<br/>
METHODS:<br/>
Thirty-eight patients who had complete MMPRTs were included. All patients underwent transtibial pullout repairs. To compare the clinical usefulness between pullout repairs using single FasT-Fix and F-MMA techniques, patients were divided into two groups. Second-look arthroscopic evaluations of meniscal healing were performed at one year postoperatively. Clinical outcomes were assessed using: Lysholm and visual analogue scale (VAS) pain scores, and Knee Injury and Osteoarthritis Outcome Score (KOOS).<br/>
RESULTS:<br/>
Single FasT-Fix and F-MMA pullout repairs improved clinical outcomes in patients with MMPRTs. At second-look arthroscopy, VAS pain, KOOS pain, and arthroscopic meniscal healing scores following F-MMA pullout repairs were superior to those after single FasT-Fix pullout repairs.<br/>
CONCLUSIONS:<br/>
This study demonstrated that F-MMA suture configuration obtained better meniscal healing and superior clinical outcomes compared with single FasT-Fix repairs in patients with MMPRTs. These results suggest that the F-MMA pullout repair may possibly reduce knee pain in arthroscopic treatments of MMPRTs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2212-62871012021Pullout Repair Associated With a Bridging Suture Using FiberLink for the Medial Meniscus Posterior Horn/Root Teare91e95ENTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University HospitalTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University HospitalTranstibial pullout repair for the medial meniscus (MM) posterior root tear has become the gold standard. However, an optimal repair technique has not yet been established for MM posterior horn (MMPH) tear with a sufficient root remnant. We describe a pullout repair technique associated with a bridging suture using FiberLink (Arthrex, Naples, FL) for the MMPH tear. In this bridging suture technique, the simple cinch stitch is applied to the root remnant and MMPH. The loop end of the FiberLink is inserted into the MMPH, and its free-end is inserted into the root remnant. Next, the suture is tensioned and tied on the superior surface of the MMPH. The bridging suture and the additional simple stitch applied to the MMPH are pulled out through the tibial tunnel and fixed to the tibia on an expected tension. This technique might lead to better meniscal healing of the tear site, because it involves bridging of the MMPH and root remnant, and lower risk of suture cut-out owing to the biomechanical strength.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama09609776562021Prospective cohort study of febrile neutropenia in breast cancer patients administered with neoadjuvant and adjuvant chemotherapies: CSPOR-BC FN study7077ENTakashiIshikawaDepartment of Breast Surgery and Oncology, Tokyo Medical UniversityKentaroSakamakiDepartment of Biostatistics, Yokohama City UniversityKazutakaNaruiDepartment of Biostatistics, Yokohama City UniversityHidekiNishimuraDepartment of Biostatistics, Yokohama City UniversityTakafumiSangaiDepartment of Breast and Thyroid Surgery, Chiba UniversityKentaroTamakiNaha-Nishi ClinicYoshieHasegawaDepartment of Breast Surgery, Hirosaki Municipal HospitaKen-ichiWatanabeDepartment of Breast Surgery, Hokkaido Cancer CenterNobuyasuSuganumaDepartment of Breast and Thyroid Surgery, Kanagawa Cancer CenterShintaroMichishitaDepartment of Breast Surgery, Yao Municipal HospitalSadatoshiSugaeDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of MedicineTomohikoAiharaBreast Center, Aihara HospitalKoichiroTsugawaDepartment of Breast and Thyroid Surgery, St. Marianna UniversityHiroseKaiseDepartment of Breast Surgery and Oncology, Tokyo Medical UniversityNarutoTairaDepartment of Breast and Endocrinology Surgery, Okayama University Graduate School of MedicineHirofumiMukaiDivision of Oncology/Hematology, National Cancer Center Hospital EastBackground<br/>
As Asians are more vulnerable to febrile neutropenia (FN) than Caucasians, evaluations of FN incidence and risk factors in Asians are important for the appropriate use of primary pegfilgrastim (PEG-G). <br/>
Patients and methods<br/>
Japanese breast cancer patients receiving standard adjuvant chemotherapies were prospectively enrolled in multicenter institutions from August 2015 to July 2017. FN was evaluated from 2 treatment policies: true FN (T-FN): ≥37.5 °C, grade 4 neutropenia, mandatory hospital visit (visiting); surrogate FN (S-FN): ≥37.5 °C, oral antibiotic, no mandatory visit (non-visiting). PEG-G was used at the physicians’ discretion. The primary endpoint was FN incidence during all cycles. Multivariate logistic regression analysis was performed to identify T-FN risk factors. <br/>
Results<br/>
Of 1005 enrolled patients, 980 women treated with FEC, E(A)C, and TC were analyzed. The FN incidence proportions in all patients were 22.5%, 27.5%, and 33.9% for FEC, E(A)C, and TC, respectively. Those of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5% with more frequent primary PEG-G usage. The relative dose intensity (RDI) of the 3 regimens was ≥0.85 in both groups. In the analysis of risk factors, TC (odds ratio = 2.67), age ≥ 65 years (2.24), and pretreatment absolute neutrophil count (ANC)/1000 μl (0.8) remained significant. <br/>
Conclusions<br/>
FN incidences were above 20% in the 3 regimens, with TC showing the highest. RDI was maintained at a high level in both visiting and non-visiting groups. Patient-related risk factors were age and pretreatment ANC.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama246812452021Profile of down syndrome–associated malignancies: Epidemiology, clinical features and therapeutic aspectsENAkiraShimadaDepartment of Pediatric Hematology, Okayama University HospitalDown syndrome (DS) is a congenital chromosomal abnormality caused by the presence of all or part of a third copy of chromosome 21 (+21). DS is frequently complicated by congenital heart or digestive tract diseases at birth. DS patients are prone to infections and have mental retardation, with dementia such as Alzheimer's disease showing in later life. Furthermore, malignancies with specific characteristics are also highly reported in DS patients compared with non-DS patients. Therefore, DS is believed to be a cancer predisposition syndrome due to the chromosomal instability. Acute myeloid leukemia (AML) and especially acute megakaryoblastic leukemia (AMKL) by French-American-British (FAB) classification are the most frequent hematological malignancies in DS patients, occurring at a rate that is 500 times higher than that in non-DS patients. Interestingly, transient abnormal myelopoiesis (TAM) is observed in approximately 10% of DS neonates with GATA1 mutations, and most TAM patients are asymptomatic and show spontaneous regression; however, about 10%–20% of TAM cases are fatal because of complications such as fetal effusion, liver fibrosis, and other complications.Acute lymphoblastic leukemia (ALL) is also associated with DS, occurring at a rate that is 20 times higher than that in non-DS patients. Furthermore, the prognosis of DS-ALL patients is poorer than that of non-DS-ALL patients. A recent genetic analysis revealed that more than half of DS-ALL cases have a mutation in the CRLF2–JAK pathway, indicating that JAK inhibitors might have a limited effect for DS-ALL patients.Notably, solid tumors such as neuroblastoma, Wilms tumor, and brain tumor, which are frequently observed in non-DS children, are rarely reported in DS children. The reason remains unknown, but it may be because of the triplication of the Down syndrome critical region 1 (DSCR1) gene on chromosome 21. In adult patients with DS, the expected age-adjusted incidence rates of solid tumors are low compared with age-matched euploid cohorts for most cancers except for testicular cancer. Although the average life expectancy of patients with DS will increase with advances in healthcare, the detailed health problems including cancer rates in older DS patients remain unknown. Therefore, these issues will be needed to be addressed in future studies.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama199179022021Prevention and early management of carotid blowout syndrome for patients receiving head and neck salvage boron neutron capture therapy (BNCT)ENTien-LiLanDivision of Radiotherapy, Department of Oncology, Taipei Veterans General HospitalFeng-ChiChangDepartment of Radiology, Taipei Veterans General HospitalChun-WeiWangDivision of Radiotherapy, Department of Oncology, Taiwan University HospitalKazuyoIgawaNeutron Therapy Research Center, Okayama UniversitySzu-HsienWuDivision of Plastic and Reconstructive Surgery, Taipei Veterans General HospitalWen-LiangLoDivision of Oral and Maxillofacial Surgery, Department of Stomatology, Taipei Veterans General HospitalYi-WeiChenDivision of Radiotherapy, Department of Oncology, Taipei Veterans General HospitalBackground/purpose<br/>
The incidence rate of oral and pharyngeal cancers in Taiwan has increased gradually over the past few decades. The standard treatment strategy for oral and pharyngeal cancers includes surgery or radiotherapy, with concurrent chemotherapy in certain types of tumors. Unfortunately, in-field recurrence is sometimes inexorable. Furthermore, re-irradiation of the recurrence site may cause severe complications due to the tolerance of normal tissue to radiation therapy. One fatal complication is carotid blowout syndrome (CBS). Boron neutron capture therapy (BNCT) is a new modality of radiation therapy, which is also mentioned as targeted radiotherapy. It is a feasible treatment that has the potential to spare normal tissue from being damaged by irradiation while simultaneously treating the primary tumor. In this presentation, we will share our experience with BNCT in treating recurrent head and neck cancers, as well as the prevention and management of CBS. <br/>
Materials and methods<br/>
We evaluated 4 patients with head and neck cancers treated by BNCT in Taiwan. All patients had undergone surgery previously and had received postoperative concurrent chemoradiotherapy. <br/>
Results<br/>
The 4 patients in this study were diagnosed with head and neck malignancies. The median follow-up period after the first course of BNCT was 15.1 months. After BNCT, 2 patients developed impending CBS, and 1 of them died. The remaining 3 patients survived until the last date of follow-up. <br/>
Conclusion<br/>
Pre-BNCT carotid artery evaluation through computed tomography angiography and early intervention if necessary is crucial when treating patients with recurrent head and neck cancers by BNCT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0168-160514332010Prevalence and antimicrobial resistance of Salmonella in retail foods in northern China230234ENHeYanLinLiM. JahangirAlamSumioShinodaShin-ichiMiyoshiLeiShiA total of 387 retail meat, seafood and milk powder samples were collected from nine cities in northern China in 2005 and screened for the presence of Salmonella. Salmonella strains isolated were subjected to serotyping and antimicrobial susceptibility testing. Salmonella was isolated from 81 (20.9%, 81/387) samples and classified into 23 serotypes. The isolates were frequently resistant to sulfamethoxazole (86.4%), sulfamethoxazole/trimethoprim (48.1%), nalidixic acid (30.9%), tetracycline (19.8%), carboxybenzylpenicillin (17.3%), amoxicillin (17.3%) and ampicillin (16.0%). The multiple resistance (resistance to ≥ 3 antibiotics) was found in 29.6% (n = 24) isolates. Additionally, 4 isolates from chicken displayed the ACSSuTNx profile, resistant to ampicillin, chloramphenicol, streptomycin, sulfonamide, tetracycline and nalidixic acid, in particular, strain HBS084 showing the resistance to as many as 20 antibiotics. Salmonella from chicken showed the higher frequency of antimicrobial resistance. Our findings indicate that in northern China food products of animal origin can be a source of exposure for consumers to multiresistant Salmonella strainsNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0032-38612022020Preparation of solution-grown lozenge-shaped poly(p-phenylene terephthalamide) single crystals and their structural stabilization by heat treatment122672ENTetsuyaUchidaGraduate School of Natural Science and Technology, Okayama UniversityYutaroHaraGraduate School of Natural Science and Technology, Okayama UniversityTomoyasuTakakiGraduate School of Natural Science and Technology, Okayama UniversityIn this study, the preparation of poly (p-phenylene terephthalamide) (PPTA) single crystals was examined using crystallization from dilute solutions in concentrated sulfuric acid. Lozenge-shaped PPTA single crystals were successfully prepared using a self-seeding method with a low degree of supercooling, and they consisted of modification I crystals. The a-axis direction of the crystal corresponded to the long diagonal direction of the rhombus, the b-axis direction with the short diagonal direction, and the PPTA molecular chain direction (the c-axis direction) with the crystal's thickness direction. In addition, the PPTA single crystals had a (110) growth plane, where the thickness of each single crystal was approximately equal to the molecular chain length of the PPTA. Upon heat treatment of the PPTA single crystals, the symmetry changed from P1a1 to the more stable P11n. In addition, the heat treatment caused a difference in the density of each symmetric crystal, resulting in crack formation along the b-axis direction, which is the hydrogen-bonding direction. However, the heat treatment did not change the thickness of the PPTA single crystals. Conversely, the isothermal crystallization of the PPTA caused progression in the crystallization only under a high degree of supercooling, thus yielding plate-like PPTA crystals that consisted of modification II crystals. In these plate-like PPTA crystals, the length corresponded to the crystal a-axis direction, and the electron diffraction pattern was broad. Furthermore, the equilibrium dissolution temperature of the PPTA single crystals was discussed.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama187854092142019Pregnancy with Fontan circulation: A report of case series in Japan161163ENErikoEtoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJotaMakiDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTeijiAkagiDepartment of Cardiovascular Medicine Field of Functional Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine Field of Functional Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisashiMasuyamaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOwing to new surgical procedures and medications, more women who have undergone the Fontan procedure reach childbearing ages. We report five cases of pregnancy with Fontan circulation. Case 1 had subchorionic hematoma (SCH), fetal growth restriction (FGR), and preterm labor (PTL). She delivered a 1073 g infant via cesarean section at gestation week 28 because of hemorrhagic shock. Case 2 delivered 2142 g and 2232 g infants at gestation weeks 37 and 36, respectively. She had FGR, PTL, and postpartum hemorrhage (PPH). Case 3 had SCH, PTL, and heart failure. At 36 weeks, labor was induced and she delivered a 2546 g infant by vacuum extraction with epidural analgesia. Cases 4 and 5 resulted in miscarriage. All subjects experienced obstetrical complications. This report discusses pregnant women with Fontan circulation by focusing on affected Japanese women. <Learning objective: More women who have undergone the Fontan procedure reach childbearing ages due to the new surgical procedures and medications. We report five cases and all of them experienced obstetrical complications. Anticoagulation might be one of the causes of postpartum hemorrhage. Labor epidural analgesia could contribute to minimized dynamic circulatory changes during labor. This report can be the literature regarding pregnant women with Fontan circulation in Japan.>No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1538-47211562016Predictive Factors of Rectal Toxicity After Permanent iodine-125 Seed Implantation: Prospective Cohort Study in 2339 Patients736745ENNorihisaKatayamaDepartment of Radiology, Okayama University Graduate School of MedicineAtsunoriYorozuDepartment of Radiation Oncology, National Hospital Organization Tokyo Medical CenterShinichiroMaruoTranslational Research Informatics CenterShinsukeKojimaTranslational Research Informatics CenterToshioOhashiDepartment of Radiation Oncology, Keio University School of MedicineNobumichiTanakaDepartment of Urology, Nara Medical University School of MedicineTakashiKikuchiTranslational Research Informatics CenterSatoshiHigashideTranslational Research Informatics CenterShiroSaitoDepartment of Urology, National Hospital Organization Tokyo Medical CenterTakushiDokiyaDepartment of Radiology, Kyoundo HospitalMasanoriFukushimaInstitutes of Preventive Medicine, Kurosawa HospitalHidetoshiYamanakaTranslational Research Informatics CenterPurpose: To evaluate the incidence and the associated factors of rectal toxicity in patients with prostate cancer undergoing permanent seed implantation (PI) with or without external beam radiation therapy (EBRT) in a nationwide prospective cohort study in Japan (J-POPS) during the first 2 years.<br/>
Methods and materials: A total of 2,339 subjects were available for the analyses. Rectal toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.<br/>
Results: The 3-year cumulative incidence for grade ≥2 rectal toxicity was 2.88%, 1.76%, and 6.53% in all subjects, PI group and EBRT combination therapy group, respectively. On multivariate analysis, among all subjects, grade ≥2 rectal toxicity was associated with rectal volumes receiving 100% of the prescribed dose (R100; p < 0.0001) and EBRT combination therapy (p = 0.0066). R100 in the PI group (p = 0.0254), and R100 (p = 0.0011) and interactive planning (p = 0.0267) in the EBRT combination therapy group were also associated with grade ≥2 toxicity. The 3-year cumulative incidence of grade ≥2 rectal toxicity was 3.80% and 1.37% for R100 ≥ 1 mL and R100 < 1 mL, respectively, in the PI group (p = 0.0068), and 14.09% and 5.52% for R100 ≥ 1 mL and R100 < 1 mL, respectively, in the EBRT combination therapy group (p = 0.0070).<br/>
Conclusions: Rectal toxicity was relatively rare in this study compared with previous reports. For Japanese prostate cancer patients, R100 < 1 mL in both PI and EBRT combination therapy groups and interactive planning in EBRT combination therapy group may be effective in decreasing the incidence of rectal toxicity.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1350-63071532023Prediction of slip activity of crystal grains around semi-circular and semi-elliptical notches in thin-sheet specimens of pure titanium using formulated macroscopic stress distribution and crystal orientation107623ENNaoyaTadaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityTakeshiUemoriFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityJunjiSakamotoFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityThin metal sheets and wires are important materials for various devices used in electrical, mechanical, and medical fields. With the downsizing of these devices, demand for thinner sheets and wires has increased. Amongst the many metals available, pure titanium has been attracting much attention for use in medical and dental devices because of its good biocompatibility in addition to its light weight and high corrosion resistance. However, thin metal sheets and wires are usually polycrystalline materials and, with the downsizing of materials, there is a loss of homogeneity during deformations. Inhomogeneous deformation becomes significant in thin sheets and wires, owing to the different crystal orientations and geometries of crystal grains. Furthermore, the shapes of such devices are not uniform, unlike, say, a simple rod. Therefore, macroscopic stress and strain concentrations should be taken into consideration when designing these devices as they affect the localization of deformation and the resultant fracture. In this study, semi-circular and semi-elliptical notched specimens made of thin-sheet polycrystalline pure titanium are subjected to tensile testing. Inhomogeneous deformation caused by crystallographic slip is observed near the notch root. Analysis of the crystal orientation and observation of the slip line show that the slip initiation in crystal grains is affected by the macroscopic stress distribution and can be predicted from the slip activity calculated from both the critical resolved shear stress on the slip systems and the resolved shear stress acting on prospective slip planes obtained from the macroscopic multiaxial stress distribution.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama094926582462019Posttraumatic cartilage degradation progresses following anterior cruciate ligament reconstruction: A second-look arthroscopic evaluation10581063ENTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeKamatsukiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhisaSugiuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshikiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinMasudaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTakihiraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiMiyazawaDepartment of Intelligent Orthopaedic System Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEijiNakataDepartment of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBACKGROUND:<br/>
Several studies have demonstrated that posttraumatic knee osteoarthritis progresses even after anterior cruciate ligament reconstruction. Few reports described zone-specific cartilaginous damages after anterior cruciate ligament reconstruction. This study aimed to compare the status of articular cartilage at anterior cruciate ligament reconstruction with that at second-look arthroscopy.<br/>
METHODS:<br/>
This study included 20 patients (20 knees, 10 males and 10 females, mean age 22.4 years, Body mass index 24.4 kg/m2) that underwent arthroscopic anatomic double-bundle anterior cruciate ligament reconstruction and second-look arthroscopy. Mean periods from injury to reconstruction and from reconstruction to second-look arthroscopy were 3.4 and 15.3 months, respectively. Cartilage lesions were evaluated arthroscopically in the 6 articular surfaces and 40 articular subcompartments independently, and these features were graded with the International Cartilage Repair Society articular cartilage injury classification; comparisons were made between the grades at reconstruction and at second-look arthroscopy. Furthermore, clinical outcomes were assessed at reconstruction and at second-look arthroscopy, using the Lysholm knee score, Tegner activity scale, International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, side-to-side difference of the KT-2000 arthrometer, and pivot shift test.<br/>
RESULTS:<br/>
Each compartment showed a deteriorated condition at second-look arthroscopy compared with the pre-reconstruction period. A significant worsening of the articular cartilage was noted in all compartments except the lateral tibial plateau and was also observed in the central region of the medial femoral condyle and trochlea after reconstruction. However, each clinical outcome was significantly improved postoperatively.<br/>
CONCLUSIONS:<br/>
Good cartilage conditions were restored in most subcompartments at second-look arthroscopy. Furthermore, posttraumatic osteoarthritic changes in the patellofemoral and medial compartments progressed even in the early postoperative period, although good knee stability and clinical outcomes were obtained. Care is necessary regarding the progression of osteoarthritis and the appearance of knee symptoms in patients undergoing anterior cruciate ligament reconstruction.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama004113455182019Postoperative Course of Serum Albumin Levels and Organ Dysfunction After Liver Transplantation27502754ENKazumasaHiroiDepartment of Anesthesiology and Resuscitology, Okayama University HospitalTakashiMatsusakiDepartment of Anesthesiology and Resuscitology, Okayama University HospitalRyujiKakuDepartment of Anesthesiology and Resuscitology, Okayama University HospitalYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahitoYagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University HospitalBackground and aims: Postoperative hypoalbuminemia, especially following liver transplantation, can lead to adverse multisystem effects and even death. We investigated the relationship between postoperative albumin levels and organ failure (assessed using Sequential Organ Failure Assessment [SOFA] scores).<br/>
Methods: Sixty liver transplant recipients admitted to the intensive care unit (ICU) from 2012 to 2015 were retrospectively divided into 2 groups: lower albumin (LA) (n=28) and higher albumin (HA) (n=32), using whether serum albumin level fell below 3.0 g/dL during the first postoperative week as the stratifying factor. The SOFA scores (primary endpoint) and associated complications (ascites amount, rejection, re-intubation, abdominal re-operation, thrombosis), additional treatment (dialysis, pleural effusion drainage), and duration of ICU stay (secondary endpoints) of the 2 groups were compared.<br/>
Results: Average serum albumin levels were significantly different between HA and LA groups (3.6 [3.4-3.8] vs 3.1 [2.9-3.3], respectively, P<.05), although the amounts of albumin infused in the 2 groups during the first postoperative week were not different (HA vs LA: 42 [30-71] vs 40 [30-58], respectively, P=.37). Mean daily SOFA scores were not significantly different between the HA and LA groups (8.3 [6.6-9.0] vs 7.2 [6.3-8.6], P=.73), although the HA group had lower mean cardiovascular SOFA sub-scores than the LA group (0.1 [0-0.4] vs 0.4 [0-1.3], P=.032). There were no significant differences between the groups with regard to complication rates and duration of ICU and hospital stays.<br/>
Conclusions: Serum albumin level might not influence cumulative organ function, but it decreases the amount of hemodynamic support required in liver transplant recipients.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0163-44538542022Poor vaccine responsiveness towards third-dose mRNA vaccine of COVID-19 in Japanese older people436480ENHideharuHagiyaDepartment of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakaoHikitaOffice of Innovative Medicine, Organization for Research Strategy and Development, Okayama UniversityTomohiroHabuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasakiAsadaDepartments of Medical Education, Kurashiki Central HospitalTakashiYorifujiDepartment of Epidemiology, Dentistry and Pharmaceutical Sciences, Graduate School of MedicineShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasanoriNakayamaOffice of Innovative Medicine, Organization for Research Strategy and Development, Okayama UniversityNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama26662507152022Physiologic biventricular repair in a patient with unrepaired adult congenital heart disease with severe cyanosis220223ENHiroyukiSuzukiDepartment of Cardiovascular Surgery, Okayama UniversityYosukeKurokoDepartment of Cardiovascular Surgery, Okayama UniversityYasuhiroKotaniDepartment of Cardiovascular Surgery, Okayama UniversityShingoKasaharaDepartment of Cardiovascular Surgery, Okayama UniversityNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0921-4534470S12010Photoemission study of Ca-intercalated graphite superconductor CaC<sub>6</sub>S637S638ENHiroyukiOkazakiRikiyaYoshidaKeisukeIwaiKengoNoamiTakayukiMuroTetsuyaNakamuraTakanoriWakitaYujiMuraokaMasaakiHiraiFumiakiTomiokaYoshihikoTakanoAsamiTakenakaMasahiroToyodaTamioOguchTakayoshiYokoyaIn this work, we have performed resonant photoemission studies of Ca-intercalated graphite superconductor CaC6. Using photon energy of the Ca 2p-3d threshold, the photoemission intensity of the peak at Fermi energy (E-F) is resonantly enhanced. This result provides spectroscopic evidence for the existence of Ca 3d states at E-F, and strongly supports that Ca 3d state plays a crucial role for the superconductivity of this material with relatively high T-c.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071312020Pediatric airway compromise due to thyroid storm associated with influenza A infection: A case report101182ENTaikiHigakiDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKoheiTsukaharaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakafumiObaraDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTsuyoshiNojimaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHirotsuguYamamotoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakaakiOsakoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHiromichiNaitouDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesThyroid storm is a potentially fatal intensification of thyrotoxicosis normally marked by tachycardia, hyperthermia, impaired mental status, and severe agitation. It can be initiated by numerous causes. Failure to promptly diagnose the condition may lead to high mortality. Early diagnosis and treatment of thyroid storm are essential to prevent further life-threatening complications. A 10-year-old girl was admitted to our emergency center for intensive care. The patient presented tachypnea with stridor, paradoxical abdominal breathing, and “barking” cough. The patient was diagnosed as upper airway obstruction complicated by thyroid storm associated with influenza infection. Following immediate airway management, the patient was administered a short-acting beta-blocker, hydrocortisone, thiamazole, and saturated solution of potassium iodide was initiated. The patient was extubated on day 8 and transferred to a local hospital on day 11 without adverse complications. When examining patients with influenza infection, emergency doctors should be more attentive not to miss other critical diagnoses. The present case was initially diagnosed as croup due to influenza infection. Sharing our experience may help emergency physicians treat similar cases of pediatric airway compromise due to thyroid storm.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama004113455222020Pediatric Living Donor Liver Transplantation for Congenital Absence of the Portal Vein With Pulmonary Hypertension: A Case Report630633ENNaohisaMatsumoto Department of Anesthesiology and Resuscitology, Okayama University HospitalTakashiMatsusaki Department of Anesthesiology and Resuscitology, Okayama University HospitalKazumasaHiroi Department of Anesthesiology and Resuscitology, Okayama University HospitalRyujiKaku Department of Anesthesiology and Resuscitology, Okayama University HospitalRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahitoYagiHiroshiMorimatsu Department of Anesthesiology and Resuscitology, Okayama University HospitalFew reports of liver transplantation exist in patients with congenital absence of the portal vein and pulmonary hypertension. Living donor liver transplantation is usually performed before exacerbation of pulmonary hypertension. A 7-year-old girl (height: 131.5 cm; weight: 27.4 kg) with congenital absence of the portal vein was diagnosed with pulmonary hypertension (mean pulmonary artery pressure 35 mm Hg), and liver transplantation was planned before exacerbation of pulmonary hypertension. We successfully managed her hemodynamic parameters using low-dose dopamine and noradrenaline under monitoring of arterial blood pressure, central venous pressure, cardiac output, and stroke volume variation. Anesthesia was maintained using air-oxygen-sevoflurane and remifentanil 0.1 to 0.6 μg∙kg-1∙min-1. It is necessary to understand the potential perioperative complications in such cases and to adopt a multidisciplinary team approach in terms of the timing of transplantation and readiness to deal with exacerbation of pulmonary hypertension. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0169-50021492020Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study4652ENJonathan W.GoldmanDavid Geffen School of Medicine at UCLAMarina ChiaraGarassinoFondazione IRCCS Istituto Nazionale dei TumoriYuanbinChenCancer & Hematology Centers of Western MichiganMustafaÖzgüroğluIstanbul University–Cerrahpaşa, Cerrahpaşa School of MedicineMikhailDvorkinBHI of Omsk Region Clinical Oncology DispensaryDmytroTrukhinOdessa National Medical UniversityGalinaStatsenkoOmsk Regional Cancer Center,KatsuyukiHottaOkayama University HospitalJun HoJiSamsung Changwon Hospital, Sungkyunkwan University School of MedicineMaximilian J.HochmairKarl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik FloridsdorfOleksandrVoitkoKyiv City Clinical Oncological CentreLiborHavelThomayer Hospital, First Faculty of Medicine, Charles UniversityArtemPoltoratskiyPetrov Research Institute of OncologyGyörgyLosonczySemmelweis UniversityNielsReinmuthAsklepios Lung ClinicNikunjPatelAstraZenecaPeter J.LaudStatistical Services Unit, University of SheffieldNorahShireAstraZenecaHaiyiJiangAstraZenecaLuisPaz-AresHospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense and CiberoncObjectives</br>
In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patient-reported outcomes (PROs).</br>
Materials and methods</br>
Treatment-naïve patients with ES-SCLC received 4 cycles of durvalumab plus EP every 3 weeks followed by maintenance durvalumab every 4 weeks until progression, or up to 6 cycles of EP every 3 weeks. PROs, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), were prespecified secondary endpoints. Changes from baseline to disease progression or 12 months in prespecified key disease-related symptoms (cough, dyspnea, chest pain, fatigue, appetite loss) were analyzed with a mixed model for repeated measures. Time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization was analyzed.</br>
Results</br>
In the durvalumab plus EP and EP arms, 261 and 260 patients were PRO-evaluable. Patients in both arms experienced numerically reduced symptom burden over 12 months or until progression for key symptoms. For the improvements from baseline in appetite loss, the between-arm difference was statistically significant, favoring durvalumab plus EP (difference, −4.5; 99% CI: −9.04, −0.04; nominal p = 0.009). Patients experienced longer TTD with durvalumab plus EP versus EP for all symptoms (hazard ratio [95% CI] for key symptoms: cough 0.78 [0.600‒1.026]; dyspnea 0.79 [0.625‒1.006]; chest pain 0.76 [0.575‒0.996]; fatigue 0.82 [0.653‒1.027]; appetite loss 0.70 [0.542‒0.899]), functioning, and global health status/QoL.</br>
Conclusion</br>
Addition of durvalumab to first-line EP maintained QoL and delayed worsening of patient-reported symptoms, functioning, and global health status/QoL compared with EP.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0142-96121922018Pancreatic stellate cells derived from human pancreatic cancer demonstrate aberrant SPARC-dependent ECM remodeling in 3D engineered fibrotic tissue of clinically relevant thickness355367ENHiroyoshi Y.TanakaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKentaroKitaharaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNaokiSasakiDepartment of Chemical and Biological Sciences, Japan Women's UniversityNatsumiNakaoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKaeSatoDepartment of Chemical and Biological Sciences, Japan Women's UniversityHirokazuNaritaDepartment of Anatomical Science, Hirosaki University Graduate School of MedicineHiroshiShimodaDepartment of Anatomical Science, Hirosaki University Graduate School of MedicineMichiyaMatsusakiDepartment of Frontier Biosciences, Osaka University Graduate School of Frontier BiosciencesHiroshiNishiharaGenomics Unit, Keio Cancer Center, Keio University School of Medicine, Institute of Integrated Medical ResearchAtsushiMasamuneDivision of Gastroenterology, Tohoku University Graduate School of MedicineMitsunobu R.KanoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityDesmoplasia is a hallmark of pancreatic cancer and consists of fibrotic cells and secreted extracellular matrix (ECM) components. Various in vitro three-dimensional (3D) models of desmoplasia have been reported, but little is known about the relevant thickness of the engineered fibrotic tissue. We thus measured the thickness of fibrotic tissue in human pancreatic cancer, as defined by the distance from the blood vessel wall to tumor cells. We then generated a 3D fibrosis model with a thickness reaching the clinically observed range using pancreatic stellate cells (PSCs), the main cellular constituent of pancreatic cancer desmoplasia. Using this model, we found that Collagen fiber deposition was increased and Fibronectin fibril orientation drastically remodeled by PSCs, but not normal fibroblasts, in a manner dependent on Transforming Growth Factor (TGF)-β/Rho-Associated Kinase (ROCK) signaling and Matrix Metalloproteinase (MMP) activity. Finally, by targeting Secreted Protein, Acidic and Rich in Cysteine (SPARC) by siRNA, we found that SPARC expression in PSCs was necessary for ECM remodeling. Taken together, we developed a 3D fibrosis model of pancreatic cancer with a clinically relevant thickness and observed aberrant SPARC-dependent ECM remodeling in cancer-derived PSCs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1936-52331412021PRRX1 promotes malignant properties in human osteosarcoma100960ENRyojiJokoDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeYamadaDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroNakamuraPrecision Health, Department of Bioengineering, Graduate School of Engineering, The University of TokyoAkiYoshidaDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTakihiraDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaTakaoDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMingLuDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiSatoDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsuoItoDepartment of Hygiene, Kawasaki Medical SchoolToshiyukiKunisadaDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEijiNakataDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakeshiTakaradaDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPaired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1476558621122019PODXL1 promotes metastasis of the pancreatic ductal adenocarcinoma by activating the C5aR/C5a axis from the tumor microenvironment11211132ENKenSaitoDivision of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental SciencesHidekazuIiokaDivision of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental SciencesSatoshiMaruyamaOral Pathology Section, Department of Surgical Pathology, Niigata University HospitalI. WayanSumardikaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEisakuKondoDivision of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental SciencesPancreatic invasive ductal adenocarcinoma (PDAC) is a representative intractable malignancy under the current cancer therapies, and is considered a scirrhous carcinoma because it develops dense stroma. Both PODXL1, a member of CD34 family molecules, and C5aR, a critical cell motility inducer, have gained recent attention, as their expression was reported to correlate with poor prognosis for patients with diverse origins including PDAC; however, previous studies reported independently on their respective biological significance. Here we demonstrate that PODXL1 is essential for metastasis of PDAC cells through its specific interaction with C5aR. In vitro assay demonstrated that PODXL1 bound to C5aR, which stabilized C5aR protein and recruited it to cancer cell plasma membranes to receive C5a, an inflammatory chemoattractant factor. PODXL1 knockout in PDAC cells abrogated their metastatic property in vivo, emulating the liver metastatic mouse model treated with anti-C5a neutralizing antibody. In molecular studies, PODXL1 triggered EMT on PDAC cells in response to stimulation by C5a, corroborating PODXL1 involvement in PDAC cellular invasive properties via specific interaction with the C5aR/C5a axis. Confirming the molecular assays, histological examination showed coexpression of PODXL1 and C5aR at the invasive front of primary cancer nests as well as in liver metastatic foci of PDAC both in the mouse metastasis model and patient tissues. Hence, the novel direct interaction between PODXL1 and the C5aR/C5a axis may provide a better integrated understanding of PDAC biological characteristics including its tumor microenvironment factors.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0960-98223112020Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord103114.e5ENTakumiOtiUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityKeitaSatohUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityDaisukeUtaDepartment of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of ToyamaJuntaNagafuchiUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversitySayakaTateishiUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityRyotaUedaUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityKeikoTakanamiUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityLarry J.YoungCenter for Translational Social Neuroscience, Silvio O. Conte Center for Oxytocin and Social Cognition, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory UniversityAntonyGalioneDepartment of Pharmacology, University of OxfordJohn F.MorrisDepartment of Physiology, Anatomy & Genetics, University of OxfordTatsuyaSakamotoUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityHirotakaSakamotoUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityOxytocinergic neurons in the paraventricular nucleus of the hypothalamus that project to extrahypothalamic brain areas and the lumbar spinal cord play an important role in the control of erectile function and male sexual behavior in mammals. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the “spinal ejaculation generator (SEG).” We have examined the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system in rats. Here, we show that SEG/GRP neurons express oxytocin receptors and are activated by oxytocin during male sexual behavior. Intrathecal injection of oxytocin receptor antagonist not only attenuates ejaculation but also affects pre-ejaculatory behavior during normal sexual activity. Electron microscopy of potassium-stimulated acute slices of the lumbar cord showed that oxytocin-neurophysin-immunoreactivity was detected in large numbers of neurosecretory dense-cored vesicles, many of which are located close to the plasmalemma of axonal varicosities in which no electron-lucent microvesicles or synaptic membrane thickenings were visible. These results suggested that, in rats, release of oxytocin in the lumbar spinal cord is not limited to conventional synapses but occurs by exocytosis of the dense-cored vesicles from axonal varicosities and acts by diffusion—a localized volume transmission—to reach oxytocin receptors on GRP neurons and facilitate male sexual function.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1566-07022282020Orexin A and B in the rat superior salivatory nucleus102712ENTadasuSatoDivision of Oral and Craniofacial Anatomy, Tohoku University Graduate School of DentistryTakehiroYajimaDivision of Oral and Craniofacial Anatomy, Tohoku University Graduate School of DentistryMasakoFujitaDepartment of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical SciencesMotoiKobashiDepartment of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical SciencesHiroyukiIchikawaDivision of Oral and Craniofacial Anatomy, Tohoku University Graduate School of DentistryRyusukeYoshidaDepartment of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical SciencesYoshihiroMitohDepartment of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical SciencesOrexin (OX), which regulates sleep and wakefulness and feeding behaviors has 2 isoforms, orexin-A and -B (OXA and OXB). In this study, the distribution of OXA and OXB was examined in the rat superior salivatory nucleus (SSN) using retrograde tracing and immunohistochemical and methods. OXA- and OXB-immunoreactive (-ir) nerve fibers were seen throughout the SSN. These nerve fibers surrounded SSN neurons retrogradely labeled with Fast blue (FB) from the corda-lingual nerve. FB-positive neurons had pericellular OXA- (47.5%) and OXB-ir (49.0%) nerve fibers. Immunohistochemistry for OX receptors also demonstrated the presence of OX1R and OX2R in FB-positive SSN neurons. The majority of FB-positive SSN neurons contained OX1R- (69.7%) or OX2R-immunoreactivity (57.8%). These neurons had small and medium-sized cell bodies. In addition, half of FB-positive SSN neurons which were immunoreactive for OX1R (47.0%) and OX2R (52.2%) had pericellular OXA- and OXB-ir nerve fibers, respectively. Co-expression of OX1R- and OX2R was common in FB-positive SSN neurons. The present study suggests a possibility that OXs regulate the activity of SSN neurons through OX receptors.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0377221729312020Optimal Investment under Ambiguous Technology Shocks304311ENTakaoAsanoFaculty of Economics, Okayama UniversityYusukeOsakiFaculty of Commerce, Waseda UniversityThis paper analyzes the behavior of a firm facing an ambiguous technology shock and the effects of the attitude toward ambiguity on optimal capital investment using the smooth ambiguity model of Klibanoffet al. (2005). Although it seems intuitive that an increase in ambiguity aversion always reduces the optimal capital investment, this is not necessarily true because the shape of the production function plays a key role in determining the effect. Under some conditions, we show that the optimal amount of capital investment increases (decreases) in ambiguity aversion if the production function is substitute (complement), and that this result is counterintuitive when the production function is substitute. Furthermore, our main results hold if we assume the alpha-maxmin preferences in Ghirardato et al. (2004). No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama221402715102019Open chest epicardial mapping in an asymptomatic patient with Brugada syndrome501504ENAtsuyukiWatanabeDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiMoritaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiKawadaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotomiTachibanaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshimasaMorimotoDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0003267011352020On-site analysis of paraquat using a completely portable photometric detector operated with small, rechargeable batteries99106ENSasikarnSeetasangDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityTakashiKanetaDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityThis work describes a methodology that can be used to achieve on-site analysis of paraquat in water samples by using a miniaturized portable photometer consisting of a couple of light-emitting diodes (LEDs). Paraquat produces a colored radical via a redox reaction with sodium dithionite, which is unstable against oxygen in solution. The steps taken to stabilize the reagent solution included control of the pH and the addition of organic solvents, but the most effective was the formation of an oil layer. Together, these steps stabilized the reagent solution for two days. An increase in the duration of reagent stability, however, is necessary in order to transport the reagent for on-site applications in remote locales. For the time being, an excess amount of solid sodium dithionite can be added directly to sample solutions because the unreacted dithionite shows no influence on absorbance of the paraquat radical. Orange LEDs with a maximum emission wavelength of 609 nm were employed in the portable photometer to measure the absorbance of paraquat radical produced by a redox reaction that has an absorption maximum of 603 nm. The developed photometer showed excellent performance with a linear range of from 2.0 mg L−1 to 40.0 mg L−1 and a linear regression (r2 = 1). The limits of detection and quantification were 0.5 mg L−1 and 1.5 mg L−1, respectively, intra-day precision (n = 3) and inter-day precision (n = 5) were both less than 5%, and accuracy based on the percentage of sample recovery ranged from 89 ± 0 to 105 ± 0% (n = 3). The proposed method was applied to the analysis of paraquat in water samples taken from rice fields. The results showed no paraquat in all thirteen samples, which could have been due to strong adsorption of paraquat by soil particles and/or to complications with the sampling conditions. To confirm the adsorption onto soil of paraquat contained in water, we constructed an artificial rice field where water containing paraquat was impounded above the soil layer. The results showed that paraquat in water gradually decreased within three days and could be measured in the soil on the fourth day. These results were confirmed by HPLC analysis, which underscores the utility of this portable photometer for the on-site monitoring of paraquat in water samples.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama187853521432021New metal complexes derived from diacetylmonoxime-n(4)antipyrinylthiosemicarbazone: Synthesis, characterization and evaluation of antitumor activity against Ehrlich solid tumors induced in mice102993ENBishoyEl-AaragDivision of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityFathyEl-SaiedDepartment of Chemistry, Faculty of Science, Menoufia UniversityTarekSalemDepartment of Biochemistry, College of Medicine, Qassim UniversityNesrinKhedrDepartment of Chemistry, Faculty of Science, Menoufia UniversityShaden A.M.KhalifaDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityHesham R.El-SeediDepartment of Chemistry, Faculty of Science, Menoufia University The present study aimed to synthesize new metal complexes of diacetylmonoxime-N(4)antipyrinylthiosemicarbazone ligand and evaluate their antitumor activity. New complexes with ferric, cobalt, nickel and copper ions were prepared. Elemental, 1H Nuclear magnetic resonance, Mass spectroscopy, Electron paramagnetic resonance, Fourier Transform InfraredSpectroscopy, Ultraviolet–visible and thermal gravimetricanalysis were used to characterize the obtained complexes 1–11. An in vivo tumor model was established to investigate the effect of the naked ligand and its metal complexes 2, 5 and 8. Ehrlich ascites carcinoma solid tumor was induced in mice through subcutaneous inoculation of Ehrlich ascites carcinoma cells. The volumes of the formed solid tumors, the alanine transaminase, aspartate transaminase, albumin concentration in the serum, as well as the levels of Ki67 and p53 proteins in tumor and liver tissues were detected. All the tested complexes, especially complex 5, possessed proliferative inhibition manifested as the reduction of the tumor volume, Alanine aminotransferase & Aspartate aminotransferase activity, and the level of the Ki67 protein. Additionally, they restored the albumin concentration to normal levels as well increased the level of pro-apoptotic p53 protein. In conclusion, the antitumor activity of the newly synthesized metal complexes against Ehrlich ascites carcinoma solid tumors was proved to be mediated by the inhibition of Ki67 and induction of p53 proteins.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24055808222020Neuroplastinβ-mediated upregulation of solute carrier family 22 member 18 antisense (SLC22A18AS) plays a crucial role in the epithelial-mesenchymal transition, leading to lung cancer cells' enhanced motility100768ENKarolinaBajkowskaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesI. WayanSumardikaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYouyiChenDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-ichiYamamotoDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiMurataDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNi LuhGede Yoni KomalasariDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFanJiangDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkiraYamauchiDepartment of Biochemistry, Kawasaki Medical SchoolI. MadeWinarsa RumaUniversity of SurreyCarlos IchiroKasano-CamonesFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityYusukeInoueFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOur recent study revealed an important role of the neuroplastin (NPTN)β downstream signal in lung cancer dissemination in the lung. The molecular mechanism of the signal pathway downstream of NPTNβ is a serial activation of the key molecules we identified: tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) adaptor, nuclear factor (NF)IA/NFIB heterodimer transcription factor, and SAM pointed-domain containing ETS transcription factor (SPDEF). The question of how dissemination is controlled by SPDEF under the activated NPTNβ has not been answered. Here, we show that the NPTNβ-SPDEF-mediated induction of solute carrier family 22 member 18 antisense (SLC22A18AS) is definitely required for the epithelial-mesenchymal transition (EMT) through the NPTNβ pathway in lung cancer cells. In vitro, the induced EMT is linked to the acquisition of active cellular motility but not growth, and this is correlated with highly disseminative tumor progression in vivo. The publicly available data also show the poor survival of SLC22A18AS-overexpressing lung cancer patients. Taken together, these data highlight a crucial role of SLC22A18AS in lung cancer dissemination, which provides novel input of this molecule to the signal cascade of NPTNβ. Our findings contribute to a better understanding of NPTNβ-mediated lung cancer metastasis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071452023Mycobacterium shinjukuense infection successfully treated with clarithromycin, rifampicin, and ethambutol101894ENKayoNakamuraDepartment of Medicine, Japanese Red Cross Society Himeji HospitalEtsukoMurakamiDepartment of Medicine, Japanese Red Cross Society Himeji HospitalDaizoKishinoDepartment of Medicine, Japanese Red Cross Society Himeji HospitalShukoMashimoDepartment of Medicine, Japanese Red Cross Society Himeji HospitalYusukeKuriokaDepartment of Medicine, Japanese Red Cross Society Himeji HospitalYusakuShibataDepartment of Medicine, Japanese Red Cross Society Himeji HospitalArihikoTaniguchiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalHisaoHigoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalYasushiHiramatsuDepartment of Medicine, Japanese Red Cross Society Himeji HospitalYoshinobuMaedaDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalWe present the case of a 59-year-old woman diagnosed with Mycobacterium shinjukuense infection using mass spectrometry of bronchioalveolar lavage fluid. We initiated treatment with clarithromycin, rifampicin, and ethambutol based on the results of drug susceptibility testing, which improved lung opacities. Most previous cases were treated with the standard regimen for Mycobacterium tuberculosis. However, our regimen may provide a therapeutic option for this rare nontuberculous Mycobacterium infection.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341321X2682020Mycobacterium chelonae bloodstream infection induced by osteomyelitis of toe: A case report843846ENYayoiUeda Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazukiTokumasuOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalTakumiFujimoriMicrobiology Division, Clinical Laboratory, Okayama University HospitalAyakaKakehiMicrobiology Division, Clinical Laboratory, Okayama University HospitalMamiOkuraMicrobiology Division, Clinical Laboratory, Okayama University HospitalHiroshiMinabeMicrobiology Division, Clinical Laboratory, Okayama University HospitalFumioOtsukaOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMycobacterium chelonae is a rapidly growing mycobacterium that has the potential to cause refractory infections in humans. Mycobacteremia resulting from the organism is extremely rare, and its clinical features are yet to be uncovered. We herein present a case of M. chelonae bloodstream infection involving an immunocompromised older patient. A 79-year-old woman, on a long-term treatment with prednisolone plus tacrolimus for rheumatoid arthritis, visited our outpatient department complaining of deteriorating pain and swelling at her right 1st toe. Laboratory parameters showed elevated C-reactive protein and leukocytosis, and magnetic resonance imaging indicated osteomyelitis at the proximal phalanx of her right 1st toe. Considering the refractory course, the infected toe was immediately amputated. M. chelonae was isolated from bacterial cultures of the resected tissue and blood (BD BACTEC™ FX blood culture system, Becton Dickinson, Sparks, MD, USA), leading to a diagnosis of disseminated M. chelonae infection. We treated the patient with an antibiotic combination of clarithromycin, minocycline, and imipenem (2 weeks), which was converted to oral therapy of clarithromycin, doxycycline, and levofloxacin. This case highlighted the potential pathogenesis of M. chelonae to cause mycobacteremia in an immunocompromised patient.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0924-42471641-22010Multiplex pneumatic control method for multi-drive system8894ENYasutakaNishiokaKoichiSuzumoriTakefumiKandaShuichiWakimotoPneumatic actuators have several advantages such as light weight safety low cost and high compliance However many pneumatic actuators have complicated systems that include a compressor air tubes and pneumatic valves with electrical wires This research proposes a new control method for a multiplex pneumatic transmission constructed with special resonant valves and air tubes with a control system driven by air vibration in air tubes without electrical wires The control is simplified and effective for pneumatic systems having many degrees of freedom In this paper the development of a primitive model of the resonant valve and a prototype valve is described In addition two control methods which are a superimposing method and a time-sharing method are shown and the independent driving of four actuators is realized by using one of the control methods with air tubes only.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0304-40171783-42011Molecular evidence for zoonotic transmission of Giardia duodenalis among dairy farm workers in West Bengal, India342345ENShahbaz ManzoorKhanChanchalDebnathAmiya KumarPramanikLihuaXiaoTomoyoshiNozakiSandipanGangulyNo study in the past has examined the genetic diversity and zoonotic potential of Giardia duodenalis in dairy cattle in India. To assess the importance of these animals as a source of human G. duodenalis infections and determine the epidemiology of bovine giardiasis in India, fecal samples from 180 calves, heifers and adults and 51 dairy farm workers on two dairy farms in West Bengal, India were genotyped by PCR-RFLP analysis of the β-giardin gene of G. duodenalis followed by DNA sequencing of the nested PCR products. The overall prevalence of G. duodenalis in cattle was 12.2% (22/180), the infection being more prevalent in younger calves than in adult cattle. Zoonotic G. duodenalis Assemblage A1 was identified in both calves and workers although the most prevalent genotype detected in cattle was a novel Assemblage E subgenotype. These findings clearly suggest that there is a potential risk of zoonotic transmission of G. duodenalis infections between cattle and humans on dairy farms in India.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0304-40171711-22010Molecular characterization and assessment of zoonotic transmission of Cryptosporidium from dairy cattle in West Bengal, India4147ENShahbaz ManzoorKhanChanchalDebnathAmiya KumarPramanikLihuaXiaoTomoyoshiNozakiSandipanGangulyFew studies in the past have examined the genetic diversity and zoonotic potential of Cryptosporidium in dairy cattle in India. To assess the importance of these animals as a source of human Cryptosporidium infections, fecal samples from 180 calves, heifers and adults and 51 farm workers on two dairy farms in West Bengal, India were genotyped by PCR-RFLP analysis of the 18S rRNA gene of Cryptosporidium followed by DNA sequencing of the PCR products. Phylogenetic analysis was carried out on the DNA sequences obtained in the study and those available in GenBank. The overall prevalence of Cryptosporidium in cattle was 11.7% though the infection was more prevalent in younger calves than in adult cattle. The occurrence of Cryptosporidium parvum, Cryptosporidium bovis, Cryptosporidium ryanae and Cryptosporidium andersoni in cattle followed an age-related pattern. A Cryptosporidium suis-like genotype was also detected in a calf. Farm workers were infected with Cryptosporidium hominis, C. parvum and a novel C. bovis genotype. These findings clearly suggest that there is a potential risk of zoonotic transmission of Cryptosporidium infections between cattle and humans on dairy farms in India.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0167-63931262021Model architectures to extrapolate emotional expressions in DNN-based text-to-speech3543ENKatsukiInoueGraduate school of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySunaoHaraGraduate school of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasanobuAbeGraduate school of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNobukatsuHojoNTT CorporationYusukeIjimaNTT CorporationThis paper proposes architectures that facilitate the extrapolation of emotional expressions in deep neural network (DNN)-based text-to-speech (TTS). In this study, the meaning of “extrapolate emotional expressions” is to borrow emotional expressions from others, and the collection of emotional speech uttered by target speakers is unnecessary. Although a DNN has potential power to construct DNN-based TTS with emotional expressions and some DNN-based TTS systems have demonstrated satisfactory performances in the expression of the diversity of human speech, it is necessary and troublesome to collect emotional speech uttered by target speakers. To solve this issue, we propose architectures to separately train the speaker feature and the emotional feature and to synthesize speech with any combined quality of speakers and emotions. The architectures are parallel model (PM), serial model (SM), auxiliary input model (AIM), and hybrid models (PM&AIM and SM&AIM). These models are trained through emotional speech uttered by few speakers and neutral speech uttered by many speakers. Objective evaluations demonstrate that the performances in the open-emotion test provide insufficient information. They make a comparison with those in the closed-emotion test, but each speaker has their own manner of expressing emotion. However, subjective evaluation results indicate that the proposed models could convey emotional information to some extent. Notably, the PM can correctly convey sad and joyful emotions at a rate of >60%.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1387-18113042020Mineralogical alterations in calcite powder flooded with MgCl2 to study Enhanced Oil Recovery (EOR) mechanisms at pore scale109402ENMona W.MindeThe National IOR Centre of NorwayMerete V.MadlandThe National IOR Centre of NorwayUdoZimmermannThe National IOR Centre of NorwayNinaEgelandThe National IOR Centre of NorwayReidar I.KorsnesThe National IOR Centre of NorwayEizoNakamuraInstitute for Planetary Materials, Okayama UniversityKatsuraKobayashiInstitute for Planetary Materials, Okayama UniversityTsutomuOtaInstitute for Planetary Materials, Okayama UniversitySeawater injection into chalk-reservoirs on the Norwegian Continental Shelf has increased the oil recovery and reduced seabed subsidence, but not eliminated it. Therefore, understanding rock–fluid interactions is paramount to optimize water injection, predict and control water-induced compaction.</br>
Laboratory experiments on onshore and reservoir chalks have shown the need to simplify the aqueous chemistry of the brine, and also the importance of studying the effect of primary mineralogy of chalk to understand which ions interact with the minerals present. In this study, the mineralogy of the samples tested, are simplified. These experiments are carried out on pure calcite powder (99.95%), compressed to cylinders, flooded with MgCl2, at 130 °C and 0.5 MPa effective stress, for 27 and 289 days.</br>
The tested material was analysed by scanning and transmission electron microscopy, along with whole-rock geochemistry. The results show dissolution of calcite followed by precipitation of magnesite. The occurrence and shape of new-grown crystals depend on flooding time and distance from the flooding inlet of the cylinder. Crystals vary in shape and size, from a few nanometres up to 2 μm after 27 days, and to over 10 μm after 289 days of flooding and may crystallize as a single grain or in clusters.</br>
The population and distribution of new-grown minerals are found to be controlled by nucleation- and growth-rates along with advection of the injected fluid through the cores. Our findings are compared with in-house experiments on chalks, and allow for insight of where, when, and how crystals preferentially grow.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama092150937902020Microstructure-dependent hydrogen diffusion and trapping in high-tensile steel139418ENMitsuhiroOkayasuGraduate School of Natural Science and Technology, Okayama UniversityJunMotojimaGraduate School of Natural Science and Technology, Okayama UniversityIn this work, the hydrogen embrittlement (HE) characteristics of high-tensile steel sheets with different microstructural characteristics were investigated. The sheets were fabricated via cold rolling (CR), water quenching (WQ), baking hardening (BH), and low-temperature annealing (LT), and their HE characteristics were clarified by examining the relationships between the microstructural characteristics and the severity of HE. Severe HE occurred in the WQ sample with hydrogen trapping at the boundaries of the retained austenite phases, resulting in intergranular and cleavage-like brittle failure. A reduction in HE was realized after the BH and LT processes. In these cases, hydrogen trapping was divided between the ε-carbide in the lattice spacings and at the boundaries of retained austenite, resulting in a mixed ductile/brittle failure mode. The extent of HE in the CR sample was similar to those in the BH and LT samples. However, the trapping sites were different; hydrogen trapping in the CR sample occurred in the slip band and around dislocations, resulting in delamination-like brittle failure on the slip planes. The extent of HE was also affected by the strain rate. More severe HE occurred in both the WQ and BH samples loaded slowly at 0.01 mm min−1 compared to the samples loaded 1.0 mm min−1 (i.e., intergranular failure). In this case, HE was affected by the large amount of hydrogen atoms trapped at the boundaries of the retained austenite phases. The hydrogen atoms in the lattice structure and ε-carbide migrated to the boundaries via dislocation movement. The extent of deterioration in tensile strength was two times higher in the samples loaded at the higher speed of 1.0 mm min−1 compared to those loaded at 0.01 mm min−1. Finally, the hydrogen trapping and failure mechanisms on the nano and atomic scales were discussed based on the results of the microstructural analyses.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama038581464662019Methotrexate-associated lymphoproliferative disorder with multiple pulmonary nodules and bilateral cervical lymphadenopathy927933ENSeiichiroMakiharaDepartment of Otolaryngology-Head & Neck Surgery, Kagawa Rosai HospitalShinKariyaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaiNoujima-HaradaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,NobuyaOharaDepartment of Pathology, Kagawa Rosai HospitalTomoyukiNaitoDepartment of Otolaryngology-Head & Neck Surgery, Kagawa Rosai HospitalJunyaMatsumotoDepartment of Otolaryngology-Head & Neck Surgery, Kagawa Rosai HospitalYoheiNodaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMitsuhiroOkanoDepartment of Otolaryngology, International University of Health and Welfare School of MedicineTadashiYoshinoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,KazunoriNishizakiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences As has been well recognized, methotrexate (MTX) leads to a state of immunosuppression and can provide a basis for the development of lymphoproliferative disorders (LPDs). MTX-associated LPDs can affect nodal sites as well as extranodal sites, though the manifestation of an LPD in the form of multiple pulmonary nodules is rare. Here, we report two cases of MTX-associated LPD with multiple bilateral pulmonary nodules, which was a finding suggestive of lung cancer, and bilateral cervical lymphadenopathy. After withdrawal of MTX, the multiple bilateral pulmonary nodules and bilateral cervical lymphadenopathy disappeared without chemotherapy in both cases. From these results, patients with pulmonary nodules and cervical lymphadenopathy should be examined for head and neck malignant tumors. Also, physicians should carefully check the administration of MTX. In patients with an MTX-associated LPD, we need to make an early diagnosis and consider discontinuing the administration of MTX as soon as possible.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0968-01602712020Medial meniscus posterior root repair decreases posteromedial extrusion of the medial meniscus during knee flexion132139ENYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University HospitalTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University HospitalYoshikiOkazakiDepartment of Orthopaedic Surgery, Okayama University HospitalShinMasudaDepartment of Orthopaedic Surgery, Okayama University HospitalTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University HospitalYuyaKodamaDepartment of Orthopaedic Surgery, National Hospital Organization Iwakuni Clinical CenterYusukeKamatsukiDepartment of Orthopaedic Surgery, Kochi Health Science CenterShinichiMiyazawaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomonoriTetsunagaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Hospital
Background
Medial meniscus (MM) medial extrusion in the coronal plane does not always improve, even after repair. This study aimed to determine the extent of posteromedial extrusion of the MM during knee flexion before and after MM pullout repair using three-dimensional magnetic resonance imaging (MRI).
Methods
Data from 14 patients (mean age, 63.4 years; 86% female) who had undergone MM pullout repair at the current institution between August 2017 and October 2018 were retrospectively reviewed. The MRIs were performed pre-operatively and ≥ 3 months postoperatively. Three-dimensional MRIs of the tibial surface and MM were evaluated using Tsukada's measurement method before and after pullout repair. The expected center of MM posterior root attachment (point A), the point on the extruded edge of the MM farthest away from point A (point E), and the point of intersection of a line through the posteromedial corner of the medial tibial plateau and a line connecting points A and E (point I) were identified. Subsequently, the pre-operative and postoperative AE and IE distances were calculated and compared.
Results
Point E was laterally shifted by the pullout repair, whereas point I showed no significant change. The postoperative IE distance (6.7 mm) was significantly shorter than the pre-operative one (9.1 mm, P < 0.01). The postoperative AE distance (29.3 mm) was significantly shorter than the pre-operative one (31.5 mm, P < 0.01).
Conclusions
The AE and IE distances significantly decreased after MM posterior root repair, suggesting that transtibial pullout repair may be useful in reducing posteromedial extrusion of the MM.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0014482738322019Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1111556ENTakashiOhtsukiDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityAkiraShinaokaDepartment of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKanaeKumagishi-ShinaokaDepartment of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiAsanoDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOmer FarukHatipogluDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityJunkoInagakiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenTakahashiDepartment of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshitakaOohashiDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiroNishidaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeijiNaruseDepartment of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiHirohataDepartment of Medical Technology, Graduate School of Health Sciences, Okayama University The synovial fluids of patients with osteoarthritis (OA) contain elevated levels of inflammatory cytokines, which induce the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and of the matrix metalloproteinase (MMP) in chondrocytes. Mechanical strain has varying effects on organisms depending on the strength, cycle, and duration of the stressor; however, it is unclear under inflammatory stimulation how mechanical strain act on. Here, we show that mechanical strain attenuates inflammatory cytokine-induced expression of matrix-degrading enzymes. Cyclic tensile strain (CTS), as a mechanical stressor, attenuated interleukin (IL)-1β and tumor necrosis factor (TNF)-α-induced mRNA expression of ADAMTS4, ADAMTS9, and MMP-13 in normal chondrocytes (NHAC-kn) and in a chondrocytic cell line (OUMS-27). This effect was abolished by treating cells with mechano-gated channel inhibitors, such as gadolinium, transient receptor potential (TRP) family inhibitor, ruthenium red, and with pharmacological and small interfering RNA-mediated TRPV1 inhibition. Furthermore, nuclear factor κB (NF-κB) translocation from the cytoplasm to the nucleus resulting from cytokine stimulation was also abolished by CTS. These findings suggest that mechanosensors such as the TRPV protein are potential therapeutic targets in treating OA.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071382022Massive hemoptysis in a post-operative patient with recurrent lung cancer successfully treated by the combination therapy of Endobronchial Watanabe Spigot and bronchial artery embolization101669ENMasatakaTaokaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalGoMakimotoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalNoriyukiUmakoshiDepartment of Radiology, Okayama University HospitalKiichiroNinomiyaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalHisaoHigoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalYukaKatoCenter for Innovative Clinical Medicine, Okayama University HospitalMasanoriFujiiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalToshioKuboCenter for Clinical Oncology, Okayama University HospitalEikiIchiharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKadoakiOhashiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalMasahiroTabataCenter for Clinical Oncology, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Allergy and Respiratory Medicine, Okayama University HospitalA 76-year-old woman who was treated with lorlatinib for postoperative recurrent anaplastic lymphoma kinase-positive lung adenocarcinoma visited our hospital with massive hemoptysis. Chest computed tomography showed massive bleeding from the right upper lobe; however, the cause of bleeding was unclear. After bronchial artery embolization (BAE), bronchial occlusion was performed using an Endobronchial Watanabe Spigot (EWS) that was easily placed because BAE had reduced the bleeding volume. Treatment with BAE alone was inadequate; however, additional therapy with EWS after BAE successfully controlled the massive hemoptysis, especially in this patient who underwent lobectomy to prevent respiratory dysfunction.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2214-4269252020Marked motor function improvement in a 32-year-old woman with childhood-onset hypophosphatasia by asfotase alfa therapy: Evaluation based on standardized testing batteries used in Duchenne muscular dystrophy clinical trials100643ENHitomiNishizawaFaculty of Health Sciences, Department of Medicine, Shinshu UniversityYoshihikoSatoDepartment of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, MatsumotoMasumiIshikawaCenter for Medical Genetics, Shinshu University HospitalYukoArakawaDepartment of Dentistry and Oral Surgery, Shinshu University School of MedicineMariIijimaDepartment of Clinical Nutrition, Shinshu University HospitalTomoyukiAkiyamaDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKyokoTakanoCenter for Medical Genetics, Shinshu University HospitalAtsushiWatanabeDivision of Clinical Genetics, Kanazawa University HospitalTomokiKoshoCenter for Medical Genetics, Shinshu University HospitalHypophosphatasia (HPP) is a rare disorder resulting from biallelic loss-of-function variants or monoallelic dominant negative variants in the ALPL gene. We herein describe the clinical outcome of a 32-year-old woman with childhood-onset HPP caused by compound heterozygous variants in ALPL. Her chief complaints were severe musculoskeletal pain, muscle weakness, and impaired daily activities necessitating assistance in housework and child-rearing in addition to a history of early tooth loss and mildly short stature. Asfotase alfa therapy produced a remarkable increase in muscle strength and daily activities and markedly reduced musculoskeletal pain. Drug efficacy was clearly demonstrated through multiple test batteries (muscle strength test using microFET®2, six-minute walking test, Stair Climb Test, rising-from-floor-time test, and number-of-steps test using Actigraph®) currently adopted as standardized evaluations in Duchenne muscular dystrophy clinical trials since no test batteries for HPP have been established to date. These tests may also be promising for the assessment of HPP.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0960-7404352020Low-grade soft-tissue sarcomas: What is an adequate margin for local disease control?303308ENTomohiroFujiwaraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoichiKaneuchiOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustYusukeTsudaOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustJonathanStevensonOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustMichaelParryOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustLeeJeysOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustBackground</br>
Whilst the resection margin is an established factor predictive of local control of soft-tissue sarcomas (STSs), the adequacy of margin width for low-grade STSs has been rarely described. We aimed to investigate the margin adequacy and its prognostic relevance in low-grade STSs.</br>
Methods</br>
109 patients who underwent surgical treatment for a low-grade STS were studied. The prognostic value of margin status was evaluated according to the R–, R+1–classification, and width in millimetres.</br>
Results</br>
The 10-year local recurrence (LR) rates were 6%, 27%, 54% in R0, R1, and R2, respectively (p < 0.001), according to the R–classification. The R+1–classification resulted in a decreased LR rate in R1, but no major differences in LR rates in R0 and R2; 7%, 14%, 54% in R0, R1, and R2, respectively (p < 0.001). When classified by metric distance, 10-year LR rates were 0%, 8%, and 38% by ≥ 2.0 mm, 0.1–1.9 mm, and 0 mm margins, respectively (p < 0.001). Patients with close margins (0.1–1.9 mm) who received adjuvant radiotherapy had a trend toward lower LR risk than those without radiotherapy (10-year, 4% vs. 12%; p = 0.406). The 5 and 10-year disease-specific mortality was 9% and 13%, respectively; margin width was not associated with disease-specific mortality but LR was a poor prognostic factor for survival (p = 0.003).</br>
Conclusion</br>
Whilst negative margin provided local control over 90%, excellent local control was achieved with microscopic margins ≥2 mm. The role of margins is more important than radiotherapy in local control. Margins do not determine survival, but LR is associated with a poor prognosis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama246864412021Low-Angle Patent Foramen Ovale (PFO): High-Risk PFO Morphology Associated with Paradoxical EmbolismENRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTeijiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNorihisaTohDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071282019Long-term spontaneous remission with active surveillance in IgG4-related pleuritis: A case report and literature review100938ENGoMakimotoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKadoakiOhashiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKoheiTaniguchiDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunichiSohDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihikoTaniguchiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalNobuakiMiyaharaDepartment of Medical Technology, Okayama University Graduate School of Health SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadashiYoshinoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Allergy and Respiratory Medicine, Okayama University HospitalPleural effusion is a relatively rare feature of IgG4-related disease (IgG4-RD). Here, we report a case of a 72-year-old woman who presented with pleural effusion. Although the pleural adenosine deaminase level was increased, surgical biopsy of the pleura and left inguinal lymph node indicated that the effusion was due to IgG4-RD. Active surveillance was initiated because serum IgG4 and pleural effusion naturally decreased and then completely disappeared. The patient has shown no recurrence for >4 years. This case suggests that pleural biopsy can be used to distinguish IgG4-RD from tuberculosis; moreover, some cases with pleural effusion could improve without treatment.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0048-969774112020Long-term exposure to nitrogen dioxide and natural-cause and cause-specific mortality in Japan140465ENTakashiYorifujiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySaoriKashimaEnvironmental Health Sciences Laboratory, Graduate School for International Development and Cooperation, Hiroshima UniversityBackground</br>
Long-term exposure to air pollution is linked with increased risk of adverse health outcomes, but the evidence for the association between nitrogen dioxide (NO2) and mortality is weak because of the inadequate adjustment of potential confounders and limited spatial resolution of the exposure assessment. Moreover, there are concerns about the independent effects of NO2. Therefore, we examined the association between NO2 long-term exposure and all-cause and cause-specific mortality.</br>
Methods</br>
We included participants who were enrolled in health checkups in Okayama City, Japan, in 2006 or 2007 and were followed until 2016. We used a land-use regression model to estimate the average NO2 concentrations from 2006 to 2007 and allocated them to the participants. We estimated hazard ratios (HRs) for a 10-μg/m3 increase in NO2 levels for all-cause or cause-specific mortality using Cox proportional hazard models.</br>
Results</br>
After excluding the participants who were assigned with outlier exposures, a total of 73,970 participants were included in the analyses. NO2 exposure was associated with increased risk of mortality and the HRs and their confidence intervals were 1.06 (95% CI: 1.02, 1.11) for all-cause, 1.02 (0.96, 1.09) for cardiopulmonary, and 1.36 (1.14, 1.63) for lung cancer mortality. However, the elevated risks became equivocal after the adjustment for fine particulate matter except lung cancer.</br>
Conclusion</br>
Long-term exposure to NO2 was associated with increased risk of all-cause, cardiopulmonary, and lung cancer mortality. The elevated risk for lung cancer was still observable even after adjustment for fine particulate matter.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0016-70372522019Lithium- and oxygen-isotope compositions of chondrule constituents in the Allende meteorite107125ENTakuyaKunihiroThe Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityTsutomuOtaThe Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityEizoNakamuraThe Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University We report in situ ion-microprobe analyses of Li- and O-isotope compositions for olivine, low-Ca pyroxene, high-Ca pyroxene, and chondrule mesostasis/plagioclase in nine chondrules from the Allende CV3 chondrite. Based on their mineralogy and O-isotope compositions, we infer that the chondrule mesostasis/plagioclase and ferroan olivine rims were extensively modified or formed during metasomatic alteration and metamorphism on the Allende parent asteroid. We excluded these minerals in order to determine the correlations between Li and both O and the chemical compositions of olivines and low-Ca pyroxenes in the chondrules and their igneous rims. Based on the O-isotope composition of the olivines, nine chondrules were divided into three groups. Average Δ17O of olivines (Fo>65) in group 1 and 2 chondrules are −5.3 ± 0.4 and −6.2 ± 0.4‰, respectively. Group 3 chondrules are characterized by the presence of 16O-rich relict grains and the Δ17O of their olivines range from −23.7 to −6.2‰. In group 1 olivines, as Fa content increases, variation of δ7Li becomes smaller and δ7Li approaches the whole-rock value (2.4‰; Seitz et al., 2012), suggesting nearly complete Li-isotope equilibration. In group 2 and 3 olivines, variation of δ7Li is limited even with a significant range of Fa content. We conclude that Li-isotope compositions of olivine in group 1 chondrules were modified not by an asteroidal process but by an igneous-rim formation process, thus chondrule olivines retained Li-isotope compositions acquired in the protosolar nebula. In olivines of the group 3 chondrule PO-8, we observed a correlation between O and Li isotopes: In relict 16O-rich olivine grains with Δ17O of ∼−25 to −20‰, δ7Li ranges from −23 to −3‰; in olivine grains with Δ17O > −20‰, δ7Li is nearly constant (−8 ± 4‰). Based on the Li-isotope composition of low-Ca pyroxenes, which formed from melt during the crystallization of host chondrules and igneous rims, the existence of a gaseous reservoir with a δ7Li ∼ −11‰ is inferred.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama17439191862021Learning curves of minimally invasive donor nephrectomy in a high-volume center: A cohort study of 1895 consecutive living donors712ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHendrikus J.A.N.KimenaiDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamTurkanTerkivatanDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamKhe T.C.TranDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamJan N.M.IjzermansDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamRobert C.MinneeDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamBackground<br/>
Few studies have investigated the learning curves of minimally invasive donor nephrectomy (MIDN) using the cumulative sum (CUSUM) analysis. In addition, no study has compared the learning curves of the different surgical MIDN techniques in one cohort study using the CUSUM analysis. This study aims to evaluate and compare learning curves for several MIDN using the CUSUM analysis. <br/>
Methods<br/>
A retrospective review of consecutive donors, who underwent MIDN between 1997 and 2019, was conducted. Three laparoscopic-assisted techniques were applied in our institution and included for analysis: laparoscopic (LDN), hand-assisted retroperitoneoscopic (HARP), and robot-assisted laparoscopic (RADN) donor nephrectomy. The outcomes were compared based on surgeon volume to develop learning curves for the operative time per surgeon. <br/>
Results<br/>
Out of 1895 MIDN, 1365 (72.0%) were LDN, 427 (22.5%) were HARP, and 103 (5.4%) were RADN. The median operative time and median blood loss were 179 (IQR, 139–230) minutes and 100 (IQR, 40–200) mL, respectively. The incidence of major complication was 1.2% with no mortality, and the median hospital stay was three (IQR, 3–4) days. The CUSUM analysis resulted in learning curves, defined by decreased operative time, of 23 cases in LDN, 45 cases in HARP, and 26 cases in RADN. <br/>
Conclusions<br/>
Our study shows different learning curves in three MIDN techniques with equal post-operative complications. The LDN and RADN learning curves are shorter than that of the hand-assisted donor nephrectomy. Our observations can be helpful for informing the development of teaching requirements for fellows to be trained in MIDN.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2451830162019Layer-specific expression of extracellular matrix molecules in the mouse somatosensory and piriform cortices117ENHiroshiUenoDepartment of Medical Technology, Kawasaki University of Medical WelfareShunsukeSuemitsuDepartment of Psychiatry, Kawasaki Medical SchoolShinjiMurakamiDepartment of Psychiatry, Kawasaki Medical SchoolNaoyaKitamuraDepartment of Psychiatry, Kawasaki Medical SchoolKentaWaniDepartment of Psychiatry, Kawasaki Medical SchoolYosukeMatsumotoDepartment of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotoiOkamotoDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityTakeshiIshiharaDepartment of Psychiatry, Kawasaki Medical SchoolIn the developing central nervous system (CNS), extracellular matrix (ECM) molecules have regulating roles such as in brain development, neural-circuit maturation, and synaptic-function control. However, excluding the perineuronal net (PNN) area, the distribution, constituent elements, and expression level of granular ECM molecules (diffuse ECM) present in the mature CNS remain unclear. Diffuse ECM molecules in the CNS share the components of PNNs and are likely functional. As cortical functions are greatly region-dependent, we hypothesized that ECM molecules would differ in distribution, expression level, and components in a region- and layer-dependent manner. We examined the layer-specific expression of several chondroitin sulfate proteoglycans (aggrecan, neurocan, and brevican), tenascin-R, Wisteria floribunda agglutinin (WFA)-positive molecules, hyaluronic acid, and link protein in the somatosensory and piriform cortices of mature mice. Furthermore, we investigated expression changes in WFA-positive molecules due to aging. In the somatosensory cortex, PNN density was particularly high at layer 4 (L4), but not all diffuse ECM molecules were highly expressed at L4 compared to the other layers. There was almost no change in tenascin-R and hyaluronic acid in any somatosensory-cortex layer. Neurocan showed high expression in L1 of the somatosensory cortex. In the piriform cortex, many ECM molecules showed higher expression in L1 than in the other layers. However, hyaluronic acid showed high expression in deep layers. Here, we clarified that ECM molecules differ in constituent elements and expression in a region- and layer-dependent manner. Region-specific expression of ECM molecules is possibly related to functions such as region-specific plasticity and vulnerability.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-2612732020Laparoscopic liver resection of segment seven: A case report and review of surgical techniques168171ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakashiKuiseDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakahitoYagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesIntroduction</br>
Laparoscopic liver resection of segment seven (LLR-S7) is a technically challenging procedure due to its anatomical location and difficult accessibility. Herein, we present our experience with LLR-S7, and demonstrate a literature review regarding surgical techniques.</br>
Presentation of case</br>
A 28-year-old female was diagnosed with rectosigmoid cancer and synchronous liver metastases at the segment three (S3) and S7, which were treated with laparoscopic procedure. After the completely mobilization of the right lobe, the Glissonean pedicle of S7 (G7) was intrahepatically transected. The right hepatic vein was exposed to identify the venous branch of S7 (V7). Finally the liver parenchyma between RHV and dissection line was divided.</br>
Discussion</br>
Various laparoscopic approaches for S7 have been reported including the Glissonian approach from the hilum, the intrahepatic Glissonean approach, the caudate lobe first approach, and the lateral approach from intercostal ports. To perform LLR-S7 safely, it is important to understand the advantage of each technique including the trocar placement and approaches to S7 by laparoscopy.</br>
Conclusion</br>
We present our experience of LLR-S7 for the tumor located at the top of S7, successfully performed with the intrahepatic Glissonean approach. LLR-S7 can be performed safely with advanced laparoscopic techniques and sufficient knowledge on various approaches for S7.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama002235491102021Lactosome-Conjugated siRNA Nanoparticles for Photo-Enhanced Gene Silencing in Cancer Cells17881798ENMelissa Siaw HanLimYukiNishiyamaTakashiOhtsukiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazunoriWatanabeGraduate School of Natural Science and Technology, Okayama UniversityHirotsuguKobuchiKazukoKobayashiCollaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEijiMatsuuraThe A3B-type Lactosome comprised of poly(sarcosine)3-block-poly(l-lactic acid), a biocompatible and biodegradable polymeric nanomicelle, was reported to accumulate in tumors in vivo via the enhanced permeability and retention (EPR) effect. Recently, the cellular uptake of Lactosome particles was enhanced through the incorporation of a cell-penetrating peptide (CPP), L7EB1. However, the ability of Lactosome as a drug delivery carrier has not been established. Herein, we have developed a method to conjugate the A3B-type Lactosome with ATP-binding cassette transporter G2 (ABCG2) siRNA for inducing in vitro apoptosis in the cancer cell lines PANC-1 and NCI-H226. The L7EB1 peptide facilitates the cellular uptake efficiency of Lactosome but does not deliver siRNA into cytosol. To establish the photoinduced cytosolic dispersion of siRNA, a photosensitizer loaded L7EB1-Lactosome was prepared, and the photosensitizer 5,10,15,20-tetra-kis(pentafluorophenyl)porphyrin (TPFPP) showed superiority in photoinduced cytosolic dispersion. We exploited the combined effects of enhanced cellular uptake by L7EB1 and photoinduced endosomal escape by TPFPP to efficiently deliver ABCG2 siRNA into the cytosol for gene silencing. Moreover, the silencing of ABCG2, a protoporphyrin IX (PpIX) transporter, also mediated photoinduced cell death via 5-aminolevulinic acid (ALA)-mediated PpIX accumulated photodynamic therapy (PDT). The synergistic capability of the L7EB1/TPFPP/siRNA-Lactosome complex enabled both gene silencing and PDT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0006291X51922019Jiadifenolide induces the expression of cellular communication network factor (CCN) genes, and CCN2 exhibits neurotrophic activity in neuronal precursor cells derived from human induced pluripotent stem cells309315ENMasakiShojiLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityMasakoUedaLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityMegumiNishiokaLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityHirokiMinatoLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityMasahideSekiKenichiHaradaLaboratory of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityMiwaKuboLaboratory of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityYoshiyasuFukuyamaLaboratory of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityYutakaSuzukiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of TokyoErikoAoyamaAdvanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School/Graduate School of Medicine Dentistry and Pharmaceutical SciencesMasaharuTakigawaAdvanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School/Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakashiKuzuharaLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University Jiadifenolide has been reported to have neurotrophin-like activity in primary rat cortical neurons, and also possesses neurotrophic effects in neuronal precursor cells derived from human induced pluripotent stem cells (hiPSCs), as we have previously reported. However, the molecular mechanisms by which jiadifenolide exerts its neurotrophic effects in rat and human neurons are unknown. Thus, we aimed to investigate the molecular mechanisms and pathways by which jiadifenolide promotes neurotrophic effects. Here, we found that jiadifenolide activated cellular communication network factor (CCN) signaling pathways by up-regulating mRNA level expression of CCN genes in human neuronal cells. We also found that CCN2 (also known as connective tissue growth factor, CTGF) protein promotes neurotrophic effects through activation of the p44/42 mitogen-activated protein kinase signaling pathway. This is the first discovery which links neurotrophic activity with CCN signaling.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama132389306932020Japanese guidelines for atopic dermatitis 2020.356369ENNoritoKatohDepartment of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical ScienceYukihiroOhyaAllergy Center, National Center for Child Health and DevelopmentMasanoriIkedaDepartment of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTamotsuEbiharaDepartment of Dermatology, Keio University School of MedicineIchiroKatayamaDepartment of Dermatology, Graduate School of Medicine, Osaka UniversityHidehisaSaekiDepartment of Dermatology, Graduate School of Medicine, Nihon Medical SchoolNaokiShimojoDepartment of Pediatrics, Graduate School of Medicine, Chiba UniversityAkioTanakaDepartment of Dermatology, Hiroshima University Graduate School of Biomedical SciencesTakeshiNakaharaDivision of Skin Surface Sensing, Department of Dermatology, Graduate School of Medical Sciences, Kyushu UniversityMizuhoNagaoDivision of Clinical Research, National Hospital Organization Mie National HospitalMichihiroHideDepartment of Dermatology, Hiroshima University Graduate School of Biomedical SciencesYujiFujitaDepartment of Pediatrics, Graduate School of Medicine, Chiba UniversityTakaoFujisawaDivision of Allergy, National Hospital Organization Mie National HospitalMasakiFutamuraDivision of Pediatrics, National Hospital Organization Nagoya Medical CenterKojiMasudaDepartment of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical ScienceHiroyukiMurotaDepartment of Dermatology, Nagasaki University Graduate School of Biomedical SciencesKiwakoYamamoto-HanadaAllergy Center, National Center for Child Health and DevelopmentAtopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama26663643212021Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations100107ENKiichiroNinomiyaDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShunsukeTeraokaInternal Medicine III, Wakayama Medical UniversityYoshitakaZenkeDepartment of Thoracic Oncology, National Cancer Center Hospital EastHirotsuguKenmotsuDivision of Thoracic Oncology, Shizuoka Cancer CenterYukikoNakamuraDepartment of Respiratory Medicine, Yokohama Municipal Citizen’s HospitalYusukeOkumaDepartment of Thoracic Oncology, National Cancer Center HospitalAkihiroTamiyaDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterKanameNosakiDepartment of Thoracic Oncology, National Cancer Center Hospital EastMasahiroMoriseDepartment of Respiratory Medicine, Nagoya University Graduate School of MedicineKeijuAokageDepartment of Thoracic Surgery, National Cancer Center Hospital EastYukoOyaDepartment of Thoracic Oncology, Aichi Cancer Center HospitalToshiyukiKozukiDepartment of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer CenterTomohiroSakamotoDivision of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori UniversityKentaroTanakaResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityHisashiTanakaDepartment of Respiratory Medicine, Hirosaki University Graduate School of MedicineJunkoTanizakiDepartment of Medical Oncology, Kishiwada City HospitalSatoruMiuraDepartment of Internal Medicine, Niigata Cancer Center HospitalHideakiMizutaniDepartment of Thoracic Oncology, Saitama Cancer CenterEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalOuYamaguchiDepartment of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical CenterNoriyukiEbiDepartment of Respiratory Oncology, Iizuka HospitalYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalTakaakiSasakiRespiratory Center, Asahikawa Medical UniversityHarukoDagaDepartment of Medical Oncology, Osaka City General HospitalSatoshiMoritaDepartment of Biomedical Statistics and Bioinformatics, Graduate School of Medicine Kyoto UniversityTakeharuYamanakaDepartment of Biostatistics, Yokohama City University School of MedicineShinsukeAmanoJapan Federation of Cancer Patient GroupsKazuoHasegawaJapan Lung Cancer AllianceChiyo K.ImamuraAdvanced Cancer Translational Research Institute, Showa UniversityKenichiSuzukiDivision of Applied Pharmaceutical Education and Research, Hoshi UniversityKazukoNakajimaDepartment of Nursing and The Division of Stem Cell Transplantation, Shizuoka Cancer CenterHitomiNishimotoDepartment of Nursing, Okayama University HospitalSatoshiOizumiDepartment of Respiratory Medicine, National Hospital Organization Hokkaido Cancer CenterToyoakiHidaDepartment of Thoracic Oncology, Aichi Cancer Center HospitalKatsuyukiHottaCenter for Clinical Oncology, Okayama University HospitalYuichiTakiguchiDepartment of Medical Oncology, Chiba University HospitalPatients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0278-4165602020Isotopic proveniencing at Classic Copan and in the southern periphery of the Maya Area: A new perspective on multi-ethnic society101228ENShintaroSuzukiGraduate School of Humanities and Social Sciences, Okayama UniversitySeiichiNakamuraCenter for Cultural Resource Studies, Institute of Human and Social Sciences, Kanazawa UniversityT. DouglasPriceLaboratory for Archaeological Chemistry, University of WisconsinStrontium, oxygen, and carbon isotopes were measured in human tooth enamel from 66 burials in 9L-22 and 9L-23 residential groups at the Classic Maya site of Copan in western Honduras. These results are discussed in relation to earlier studies at Copan and baseline measurements from the surrounding region and the Maya area in general. Nearly 50% of the individuals are identified as non-local based on combinations of strontium, oxygen, and carbon isotope ratios. They came from a variety of places in the Maya area. This migratory pattern at the 9L-22 & 9L-23 residential complex from the Early to Late Classic (ca. 400–800 CE) is compared with 10J-45 sector from the mainly Early Classic occupation (ca. 400–650 CE) and an interesting change is noted. The social privileges observed among the Early Classic immigrants from the north Maya Lowlands were apparently revoked in the Late Classic. New immigrants, probably from the “non-Maya” regions of Western/Central Honduras, appear to have gained those social privileges. High-status Honduran individuals in the urban core suggests a strategy by the Copan dynasty in the Late Classic that incorporated the emerging “non-Maya” elites from Western/Central Honduras.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0168-16053252020Isolation and identification of the antimicrobial substance included in tempeh using Rhizopus stolonifer NBRC 30816 for fermentation108645ENMasahiroItoDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiItoDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHideyukiAokiIkeda Food Research Co., Ltd.KoshiNishiokaIkeda Food Research Co., Ltd.TsugumiShiokawaDivision of Instrumental Analysis, Department of Instrumental Analysis and Cryogenics, Advanced Science Research Center, Okayama UniversityHirokoTadaDivision of Instrumental Analysis, Department of Instrumental Analysis and Cryogenics, Advanced Science Research Center, Okayama UniversityYukiTakeuchiDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityNobuyukiTakeyasuDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityTadashiYamamotoDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoTakashibaDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIn this study, we focus on the antimicrobial properties of tempeh, a soybean fermented food, against oral bacteria.</br>
Tempeh showed antimicrobial activity against dental caries pathogenic bacterium Streptococcus mutans at a final concentration of 1 mg/mL. An antimicrobial substance contained in tempeh was present in the 100 kDa or greater fraction generated by ultrafiltration, but it was found not to be proteinaceous by native-PAGE, SDS-PAGE and protein degradation tests. Next, when the fraction was purified with an ODS column, the 80% and 100% methanol eluates showed antimicrobial activity against S. mutans. The 100% methanol eluate was further subjected to a 2nd column purification, and isolation of the target was confirmed by HPLC. When the isolated material was analyzed by ESI-MS, the m/z was 279.234. Further analysis by Raman spectroscopy revealed a peak similar to linoleic acid. This substance also possessed antimicrobial properties equivalent to linoleic acid.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0038-109815282012Iron–platinum–arsenide superconductors Ca<sub>10</sub>(Pt<sub>n</sub>As<sub>8</sub>)(Fe<sub>2−x</sub>Pt<sub>x</sub>As<sub>2</sub>)<sub>5</sub>635639ENMinoruNoharaSatomiKakiyaKazutakaKudoYoshihiroOshiroShingoArakiTatsuo C.KobayashiKentaOkuEijiNishiboriHiroshiSawaAn overview of the crystal structures and physical properties of the recently discovered iron-platinum-arsenide superconductors, Ca-10(PtnAs8)(Fe2-xPtxAs2)(5) (n = 3 and 4), which have a superconducting transition temperature up to 38K, is provided. The crystal structure consists of superconducting Fe2As2 layers alternating with platinum-arsenic layers, PtnAs8. The upper critical field H-c2, hydrostatic pressure dependence of superconducting transition temperature T-c, and normal-state magnetic susceptibility are reported.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama240545692021Intravesical Therapy in Patients with Intermediate-risk Non–muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis of Disease RecurrenceENEkaterinaLaukhtinaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaMohammadAbufarajDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaAbdallahAl-AniDivision of Urology, Department of Special Surgery, Jordan University Hospital, The University of JordanMustafa RamiAliDivision of Urology, Department of Special Surgery, Jordan University Hospital, The University of JordanKeiichiroMoriDepartment of Urology, The Jikei University School of MedicineMarcoMoschiniDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaFahadQuhalDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaRezaSari MotlaghDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaBenjaminPradereDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaVictor M.SchuettfortDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaHadiMostafaeiDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaSatoshiKatayamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNico C.GrossmannDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaHarunFajkovicDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaFrancescoSoriaDivision of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of TorinoDmitryEnikeevInstitute for Urology and Reproductive Health, Sechenov UniversityShahrokh F.ShariatDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaContext<br/>
Patients with intermediate-risk non–muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment. <br/>Objective<br/>
To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC. <br/>
Evidence acquisition<br/>
The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy. <br/>Evidence synthesis<br/>
Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26–1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39–2.11 vs OR 0.93, 95% CI 0.40–2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666). <br/>
Conclusions<br/>
Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression. <br/>Patient summary<br/>
A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1877056810512019Injury patterns of medial meniscus posterior root tears107111ENTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School, YukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School, YoshikiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School, TomohitoHinoDepartment of Orthopaedic Surgery, Okayama University Graduate School, YusukeKamatsukiDepartment of Orthopaedic Surgery, Okayama University Graduate School, ShinMasudaDepartment of Orthopaedic Surgery, Okayama University Graduate School,ShinichiMiyazawaDepartment of Orthopaedic Surgery, Okayama University Graduate School, EijiNakataDepartment of Orthopaedic Surgery, Okayama University Graduate School, JoeHaseiDepartment of Orthopaedic Surgery, Okayama University Graduate School, ToshiyukiKunisadaDepartment of Orthopaedic Surgery, Okayama University Graduate School,ToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School,INTRODUCTION:<br/>
Medial meniscus posterior root tear (MMPRT) can occur in middle-aged patients who have a posteromedial painful popping during light activities. MMPRTs are more common in patients with increased age, female gender, sedentary lifestyle, obesity, and varus knee alignment. However, injury mechanisms of minor traumatic MMPRTs are still unclear. We hypothesized that high flexion activities are the major cause of MMPRTs. The aim of this study was to clarify injury patterns of MMPRTs.<br/>
MATERIALS AND METHODS:<br/>
One hundred patients were diagnosed having MMPRTs after posteromedial painful popping episodes. Details of posteromedial painful popping episode, situation of injury, and position of injured leg were obtained from the patients by careful interviews. Injury patterns were divided into 8 groups: descending knee motion, walking, squatting, standing up action, falling down, twisting, light exercise, and minor automobile accident.<br/>
RESULTS:<br/>
A descending knee motion was the most common cause of MMPRTs (38%) followed by a walking injury pattern (18%) and a squatting action related to high flexion activities of the knee (13%). The other injury patterns were less than 10%.<br/>
DISCUSSION:<br/>
Descending knee motions associated with descending stairs, step, and downhill slope are the most common injury pattern of MMPRTs. High flexion activities of the knee are not the greatest cause of MMPRTs. Our results suggest that the descending action with a low knee flexion angle may trigger minor traumatic MMPRTs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama091450877812020Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats1216ENKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesLuh Oliva SaraswatiSuastikaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuichiroHigashimotoDepartment of Chemistry, Kurume University School of MedicineKeiFukamiDivision of Nephrology, Department of Medicine, Kurume University School of MedicineHiromiMatsubaraDepartment of Cardiology, National Hospital Organization Okayama Medical CenterHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: The receptor for advanced glycation end products (RAGE), a transmembrane receptor belonging to the immunoglobulin superfamily, is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with pulmonary arterial hypertension (PAH) and is implicated in the etiology of PAH. Recently, we reported that RAGE-aptamer, a short and single-stranded DNA directed against RAGE, inhibited an inappropriate increase in cultured PASMCs in PAH. The aim of this study was to determine the efficacy of RAGEaptamer in monocrotaline-induced PAH in rats.<br><br>
Methods and Results: Rats were assigned to either an untreated control group, a group that received continuous subcutaneous administration of RAGE-aptamer immediately after monocrotaline injection, or a group that received control-aptamer immediately after monocrotaline injection. All rats survived 21 days after injection of monocrotaline and control-aptamer or RAGE-aptamer. Injection of monocrotaline with continuous subcutaneous delivery of control-aptamer resulted in higher right ventricular systolic pressure compared with controls. This increase was attenuated by continuous subcutaneous delivery of RAGE-aptamer. The proportion of small pulmonary arteries with full muscularization was greater in the monocrotaline and control-aptamer group than in the control group. Continuous subcutaneous delivery of RAGE-aptamer significantly reduced the percentage of small pulmonary arteries with full muscularization Conclusions: Continuous subcutaneous delivery of RAGE-aptamer suppresses development of monocrotaline-induced PAH in rats. Inhibition of RAGE ameliorates muscularization of 3 small pulmonary arteries. Treatment with RAGE-aptamer might be a new therapeutic option for PAH.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0927-77575202017Indocyanine green-laden poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules incorporating reverse micelles: Effects of PEG-b-PLA composition on the nanocapsule diameter and encapsulation efficiency764770ENTakaichiWatanabeDepartment of Applied Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityYuiSakamotoDepartment of Applied Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityTetsuyaInookaDivision of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityYukitakaKimuraDivision of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityTsutomuOnoDepartment of Applied Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityReverse micelles are thermodynamically stable systems, with a capacity to encapsulate hydrophilic molecules in their nanosized core, which is smaller than the core generally obtained with water-in-oil-emulsion droplets. Herein, we present a simple technique for the preparation of poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules encapsulating a hydrophilic photosensitizer (indocyanine green, ICG), which exploits reverse micelle formation and subsequent emulsion-solvent diffusion. We establish the effect of the PEG-b-PLA composition and the co-surfactant volume on the diameter and water content of the reverse micelles. We demonstrate that the composition of PEG-b-PLA affects also the diameter and encapsulation efficiency of the resulting nanocapsules. We show that the ICG-laden nanocapsules fabricated under the most optimal conditions have a diameter of approximately 100 nm and an ICG encapsulation efficiency of 58%. We believe that the method proposed here is a promising step towards the preparation of hydrophilic drug-laden polymer nanocapsules with a small diameter and therefore suitable for use in drug delivery applications based on enhanced permeability and retention (EPR) effect-driven passive targeting.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0168-36592302016Increased fibrosis and impaired intratumoral accumulation of macromolecules in a murine model of pancreatic cancer co-administered with FGF-2109115ENSatoshiSakaiGraduate School of Medicine, The University of TokyoCanameIwataGraduate School of Medicine, The University of TokyoHiroyoshi Y.Tanaka Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHoracioCabralGraduate School of Engineering, The University of TokyoYasuyukiMorishitaGraduate School of Medicine, The University of TokyoKoheiMiyazonGraduate School of Medicine, The University of TokyoMitsunobu R.KanoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityPancreatic cancer is notorious for its poor prognosis. The histopathologic characteristic of pancreatic ductal adenocarcinoma (PDAC), which is the most common type of pancreatic cancer, is fibrosis within tumor tissue. Although fibrosis within tumor tissue is thought to impede drug therapy by interfering with the intratumoral accumulation of anti-tumor drugs, this hypothesis has yet to be proven directly in preclinical models. Here, we evaluated the effect of enhanced fibrosis on intratumoral accumulation of macromolecular drugs by increasing fibrosis in a murine tumor model of subcutaneously xenografted BxPC-3, a human PDAC cell line. When fibroblast growth factor-2 (FGF-2) was co-administered upon BxPC-3 inoculation, stromal fibrotic area was increased and was characterized by augmented murine collagen accumulation compared to inoculation of BxPC-3 alone, which correlated with increased monocyte/macrophage contents in the tumor tissues. We further discovered that the intratumoral accumulation of intravenously administrated fluorescein isothiocyanate-dextran of 2,000,000 Da (2 MDa) was significantly reduced in the FGF-2 co-administered tumors despite unaltered hyaluronan accumulation and pericyte coverage of the tumor neovasculature and increased lymphangiogenesis. Finally, we found that FGF-2 co-administered tumors are more refractory to macromolecular drug therapy using nab-paclitaxel (Abraxane). The model established and analyzed in this study, characterized by increased fibrotic component, provides a preclinical animal model suited to predict the intratumoral accumulation of macromolecular drugs and to evaluate the efficacy of drugs targeting the tumor stroma.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0041-01015762011Inactivation of Vibrio vulnificus hemolysin through mutation of the N- or C-terminus of the lectin-like domain904908ENShin-ichiMiyoshiYukiAbeMitsutoshiSenohTamakiMizunoYokoMaeharaHiroshiNakaoVibrio vulnificus is an etiological agent causing serious systemic infections in the immunocompromised humans or cultured eels. This species commonly produces a hemolytic toxin consisting of the cytolysin domain and the lectin-like domain. For hemolysis, the lectin-like domain specifically binds to cholesterol in the erythrocyte membrane, and to form a hollow oligomer, the toxin is subsequently assembled on the membrane. The cytolysin domain is essential for the process to form the oligomer. Three-dimensional structure model revealed that two domains connected linearly and the C-terminus was located near to the joint of the domains. Insertion of amino acid residues between two domains was found to cause inactivation of the toxin. In the C-terminus, deletion, substitution or addition of an amino acid residue also elicited reduction of the activity. However, the cholesterol-binding ability was not affected by the mutations. These results suggest that mutation of the C- or N-terminus of the lectin-like domain may result in blockage of the toxin assembly.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0300-95721532020Improved outcomes for out-of-hospital cardiac arrest patients treated by emergency life-saving technicians compared with basic emergency medical technicians: A JCS-ReSS study report251257ENHiromichiNaitouHiromichi TetsuyaYumotoOkayama University HospitalTakashiYorifujiOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshioTaharaNational Cerebral and Cardiovascular Center, Department of Cardiovascular MedicineNaohiroYonemotoNational Center of Neurology and PsychiatryHiroshiNonogiShizuoka General Hospital, Intensive Care CenterKenNagaoNihon University Hospital, Cardiovascular CenterTakanoriIkedaToho University Faculty of Medicine, Department of Cardiovascular MedicineNaokiSatoKawaguchi Cardiovascular and Respiratory Hospital, Cardiovascular MedicineHiroyukiTsutsuiKyushu University Faculty of Medical Sciences, Department of Cardiovascular MedicineBackground</br>
Emergency life-saving technicians (ELSTs) are specially trained prehospital medical providers believed to provide better care than basic emergency medical technicians (BEMTs). ELSTs are certified to perform techniques such as administration of advanced airways or adrenaline and are considered to have more knowledge; nevertheless, ELSTs’ effectiveness over BEMTs regarding out-of-hospital cardiac arrest (OHCA) remains unclear. We investigated whether the presence of an ELST improves OHCA patient outcomes.</br>
Methods</br>
In a retrospective study of adult OHCA patients treated in Japan from 2011 to 2015, we compared two OHCA patient groups: patients transported with at least one ELST and patients transported by only BEMTs. The primary outcome measure was one-month favorable neurological outcomes, defined as Cerebral Performance Category ≤ 2. A multivariable logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs) to evaluate the effect of ELSTs.</br>
Results</br>
Included were 552,337 OHCA patients, with 538,222 patients in the ELST group and 14,115 in the BEMT group. The ELST group had a significantly higher odds of favorable neurological outcomes (2.5% vs. 2.1%, adjusted OR 1.39, 95% CI 1.17–1.66), one-month survival (4.9% vs. 4.1%, adjusted OR 1.37, 95% CI 1.22–1.54), and return of spontaneous circulation (8.1% vs. 5.1%, adjusted OR 1.90, 95% CI 1.72–2.11) compared with the BEMT group. However, ELSTs’ limited procedure range (adrenaline administration or advanced airway management) did not promote favorable neurological outcomes.</br>
Conclusions</br>
Compared with the BEMT group, transport by the ELST group was associated with better neurological outcomes in OHCA.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1472-64832032010Improved development of mouse and human embryos using a tilting embryo culture system358364ENKojiMatsuuraNobuyoshiHayashiYukaKurodaChisatoTakiueReiHirataMamiTakenamiYokoAoiNanakoYoshiokaToshihiroHabaraTetsunoriMukaidaKeijiNaruseMammalian embryos experience not only hormonal but also mechanical stimuli, such as shear stress, compression and friction force in the Fallopian tube before nidation. In order to apply mechanical stimuli to embryos in a conventional IVF culture system, the tilting embryo culture system (TECS) was developed. The observed embryo images from the TECS suggest that the velocities and shear stresses of TECS embryos are similar to those experienced in the oviduct. Use of TECS enhanced the development rate to the blastocyst stage and significantly increased the cell number of mouse blastocysts (P < 0.05). Although not statistically significant, human thawed embryos showed slight improvement in development to the blastocyst stage following culture in TECS compared with static controls. Rates of blastocyst formation following culture in TECS were significantly improved in low-quality embryos and those embryos cultured under suboptimal conditions (P < 0.05). The TECS is proposed as a promising approach to improve embryo development and blastocyst formation by exposing embryos to mechanical stimuli similar to those in the Fallopian tube.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2589-5370282020Impact of patient characteristics on the efficacy and safety of landiolol in patients with sepsis-related tachyarrhythmia: Subanalysis of the J-Land 3S randomised controlled study100571ENNaoyukiMatsudaDepartment of Emergency & Critical Care Medicine, Nagoya University Graduate School of MedicineOsamuNishidaDepartment of Anesthesiology & Critical Care Medicine, Fujita Health University School of MedicineTakumiTaniguchiDepartment of Anesthesiology & Intensive Care Medicine, Kanazawa UniversityMasakiOkajimaIntensive Care Unit, Kanazawa University HospitalHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiOguraDepartment of Traumatology and Acute Critical Medicine, Osaka University Graduate School of MedicineYoshitsuguYamadaDepartment of Anesthesiology and Pain Relief Center, The University of Tokyo HospitalTetsujiNaganoClinical Development Planning, Ono Pharmaceutical Co., Ltd.AkiraIchikawaClinical Development Planning, Ono Pharmaceutical Co., Ltd.YasuyukiKakihanaDepartment of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental SciencesJ-Land 3S Study GroupBackground</br>
The J-Land 3S trial demonstrated that landiolol is effective and tolerated for treating sepsis-related tachyarrhythmias. Patient characteristics (e.g. baseline heart rate [HR], type of tachyarrhythmia, and concomitant disorders) may impact the outcomes of landiolol therapy. We performed subanalyses of J-Land 3S to evaluate the impact of patient characteristics on the efficacy and safety of landiolol for treating sepsis-related tachyarrhythmia.</br>
Methods</br>
Patients (≥20 years old; N = 151) hospitalised with sepsis at 54 participating hospitals in Japan with HR ≥100 beats/min for ≥10 min accompanied by diagnosis of tachyarrhythmia were randomised 1:1 to conventional sepsis therapy alone (control group) or conventional sepsis therapy plus landiolol (landiolol group). The efficacy and safety of landiolol were assessed in prespecified analyses of patients divided into subgroups by baseline characteristics and in post hoc, multivariate analyses with adjustment for age and HR at baseline.</br>
Findings</br>
The percentage of patients with HR of 60–94 beats/min at 24 h after randomisation (primary endpoint) was greater in the landiolol group in most subgroups in univariate unadjusted analyses and in multivariate logistic regression. The incidence of new-onset arrhythmia by 168 h and mortality by 28 days were also lower in the landiolol group in most subgroups in univariate and multivariate Cox proportional hazards models. No subgroups showed a markedly higher incidence of adverse events in univariate or multivariate logistic regression analyses.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-8440652020Impact of heavy rains of 2018 in western Japan: disaster-induced health outcomes among the population of Innoshima Islande03942ENSrinivasBandaruDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShunjiSanoDepartment of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San FranciscoYurikaShimizuDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukaSekiDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshikazuOkanoHitz Hitachi Zosen Health Insurance Association Clinic at InnoshimaTamakiSasakiDepartment of Nephrology & Hypertension, Kawasaki Medical SchoolHidehoWadaDepartment of Hematology, Kawasaki Medical SchoolTakemiOtsukiDepartment of Hygiene, Kawasaki Medical SchoolTatsuoItoDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSouthwestern Japan suffered its worst rains in 2018 causing floods and mudslides, claiming 225 lives and forcing millions for evacuations. Referred as "Heisei san-ju-nenshichi-gatsugou", the disaster was the result of incessant precipitation caused by the interaction of typhoon "Prapiroon" with the seasonal rain front "Baiu". The present epidemiological study aims to investigate disaster-induced health issues in 728 residents of Innoshima island in the Hiroshima Prefecture by comparing their clinical data in pre-disaster (2017) and disaster-hit (2018) years which was obtained from annual health screening. Comparison of data showed a significant increase in the urine protein concentration in victims following the disaster. Probing further into the household conditions, showed that a total of 59,844 households were affected with water outage during the heavy rains, which was accompanied by severe damage of sewerage pipelines with complete recovery process taking two weeks. This two weeks of the crisis forced victims to refrain from using restrooms which in turn led to infrequent urination, thereby explaining the increased urine protein concentration in victims following the disaster. The present study addresses the acute health implications caused by the water crisis and serves as a precautionary measure for disaster management council to provide enhanced aftercare services in victims in further events of natural disasters. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-36434102023Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors100573ENHidekiIkedaChiba Cancer Center, Research InstituteJojiNagasakiChiba Cancer Center, Research InstituteDaikiShimizuDivision of Thoracic Surgery, Chiba Cancer CenterYukiKatsuyaDepartment of Experimental Therapeutics, National Cancer Center HospitalHidehitoHorinouchiDepartment of Thoracic Oncology, National Cancer Center HospitalYukioHosomiDepartment of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalEtsukoTanjiChiba Cancer Center, Research InstituteTakekazuIwataDivision of Thoracic Surgery, Chiba Cancer CenterMakikoItamiDepartment of Surgical Pathology, Chiba Cancer CenterMasahitoKawazuChiba Cancer Center, Research InstituteYuichiroOheDepartment of Thoracic Oncology, National Cancer Center HospitalTakujiSuzukiDepartment of Respirology, Graduate School of Medicine, Chiba UniversityYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs).<br>
Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II–expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo.<br>
Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti–programmed cell death protein 1 monoclonal antibody.<br>
Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama016801022020Immediate changes in transcription factors and synaptic transmission in the cochlea following acoustic trauma: A gene transcriptome studyENYukihideMaedaDepartment of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinKariyaDepartment of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKensukeUraguchiDepartment of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunkoTakaharaDepartment of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShoheiFujimotoDepartment of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkikoSugayaDepartment of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazunoriNishizakiDepartment of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPathologic mechanisms in cochleae immediately following the onset of noise-induced hearing loss (NIHL) remain unclear. In this study, mice were exposed to 120 dB of octave band noise for 2 h to induce NIHL. Three hours after noise exposure, expression levels of the whole mouse genome in cochleae were analyzed by RNA-seq and DNA microarray. Differentially expressed genes (DEGs) exhibiting >2-fold upregulation or downregulation in noise-exposed cochleae compared to controls without noise exposure were identified. RNA-seq and microarray analyses identified 273 DEGs regulated at 3 h post-noise (51 upregulated and 222 downregulated). Bioinformatic analysis revealed that these DEGs were associated with the functional gene pathway "neuroactive ligand-receptor interaction" and included 28 genes encoding receptors for neurotransmitters such as gamma-aminobutyric acid and glutamate. Other DEGs included 25 genes encoding transcription factors. Downregulation of 4 neurotransmitter receptors (Gabra3, Gabra5, Gabrb1, Grm1) and upregulations of 5 transcription factors (Atf3, Dbp, Helt, Maff, Nr1d1) were validated by RT-PCR. The differentially regulated transcription factor Atf3 immunolocalized to supporting cells and hair cells in the organ of Corti at 12-h post-noise. The present data serve as a basis for further studies aimed at developing medical treatments for acute sensorineural hearing loss. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1930-04331462019Imaging an intrapulmonary solitary fibrous tumor with CT and F-18 FDG PET/CT755758ENTakayoshiShinyaDepartment of Pediatric Radiology, Okayama University HospitalYoshihisaMasaokaDepartment of Radiology, Okayama University HospitalMotohiroSandoDepartment of Radiology, Okayama University HospitalShinTanabeDepartment of Radiology, Okayama University HospitalSoichiroOkamotoDepartment of Radiology, Okayama University HospitalHirokiIharaDepartment of Radiology, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiOtaniDepartment of General Thoracic Surgery, Okayama University HospitalTakaoHirakiDepartment of Radiology, Okayama University HospitalSusumuKanazawaDepartment of Radiology, Okayama University HospitalIntrapulmonary solitary fibrous tumors (SFTs) are extremely rare neoplasms. We report a case of an intrapulmonary SFT and describe the findings of computed tomography (CT) and F-18 fluorodeoxyglucose positron emission tomography. The case indicates that a benign intrapulmonary SFT can present as a ground-glass nodule in the early stages of disease and may appear as a well-defined, lobular, homogeneously enhanced mass with slow growth on chest CT images. To our knowledge, this is the first report describing the natural course of an intrapulmonary SFT over 16 years based on the findings of chest CT and F-18 fluorodeoxyglucose positron emission tomography/CT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama002191503112020Identification and visualization of oxidized lipids in atherosclerotic plaques by microscopic imaging mass spectrometry-based metabolomics112ENLianhuaShenCollaborative Research Center (OMIC)TakushiYamamotoAnalytical & Measuring Instruments Division, Shimadzu CorporationXian WenTanDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKoretsuguOgataAnalytical & Measuring Instruments Division, Shimadzu CorporationEijiAndoAnalytical & Measuring Instruments Division, Shimadzu CorporationEiichiOzekiTechnology Research Laboratory, Shimadzu CorporationEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground and aimsDysregulated lipid metabolism has emerged as one of the major risk factors of atherosclerosis. Presently, there is a consensus that oxidized LDL (oxLDL) promotes development of atherosclerosis and downstream chronic inflammatory responses. Due to the dynamic metabolic disposition of lipoprotein, conventional approach to purify bioactive lipids for subsequent comprehensive analysis has proven to be inadequate for elucidation of the oxidized lipids species accountable for pathophysiology of atherosclerotic lesions. Herein, we aimed to utilize a novel mass microscopic imaging technology, coupled with mass spectrometry (MS) to characterize oxidized lipids in atherosclerotic lesions. MethodsWe attempted to use MALDI-TOF-MS and iMScope to identify selected oxidized lipid targets and visualize their respective localizations in study models of atherosclerosis. ResultsBased on the MS analysis, detection of 7-K under positive ionization through product ion peak at m/z 383 [M+H-H2O] indicated the distinctive presence of targeted lipid within Cu2+-oxLDL and Cu2+-oxLDL loaded macrophage-like J774A.1 cell, along with other cholesterol oxidation products. Moreover, the application of two-dimensional iMScope has successfully visualized the localization of lipids in aortic atherosclerotic plaques of the Watanabe heritable hyperlipidemic (WHHL) rabbit. Distinctive lipid distribution profiles were observed in atherosclerotic lesions of different sizes, especially the localizations of lysoPCs in atherosclerotic plaques. ConclusionsTaken together, we believe that both MALDI-TOF-MS and iMScope metabolomics technology may offer a novel proposition for future pathophysiological studies of lipid metabolism in atherosclerosis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0272-63867562020Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials830846ENKätheGoossenInstitute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke UniversityMonikaBeckerInstitute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke UniversityMark R.MarshallBaxter Healthcare (Asia) Pte LtdStefanieBühnInstitute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke UniversityJessicaBreuingInstitute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke UniversityCatherine A.FiranekBaxter Healthcare InternationalSimoneHessnstitute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke UniversityHisanoriNariaiBaxter Japan LtdJames A.SloandBaxter Healthcare InternationalQiangYaoBaxter (China) Investment Co. LtdTae IkChangDepartment of Internal Medicine, NHIS Medical CenterJinBorChenDivision of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineRamónPaniaguaResearch Unit, Unidad de Investigación Médica en Enfermedades Nefrológicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS)YujiTakatoriInternal Medicine, Rijinkai Medical Foundation, Socio-Medical Corporation, Kohsei General HospitalJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDawidPiepernstitute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke UniversityRationale & Objective</br>
The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell icodextrin versus glucose among patients with kidney failure undergoing PD.</br>
Study Design</br>
Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies.</br>
Setting & Study Populations</br>
Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition.</br>
Selection Criteria for Studies</br>
Medline, Embase, CENTRAL, Ichushi Web, 10 Chinese databases, clinical trials registries, conference proceedings, and citation lists from inception to November 2018. Further data were obtained from principal investigators and industry clinical study reports.</br>
Data Extraction</br>
2 independent reviewers selected studies and extracted data using a prespecified extraction instrument.</br>
Analytic Approach</br>
Qualitative synthesis of demographics, measurement scales, and outcomes. Quantitative synthesis with Mantel-Haenszel risk ratios (RRs), Peto odds ratios (ORs), or (standardized) mean differences (MDs). Risk of bias of included studies at the outcome level was assessed using the Cochrane risk-of-bias tool for RCTs.</br>
Results</br>
19 RCTs that enrolled 1,693 participants were meta-analyzed. Ultrafiltration was improved with icodextrin (medium-term MD, 208.92 [95% CI, 99.69-318.14] mL/24 h; high certainty of evidence), reflected also by fewer episodes of fluid overload (RR, 0.43 [95% CI, 0.24-0.78]; high certainty). Icodextrin-containing PD probably decreased mortality risk compared to glucose-only PD (Peto OR, 0.49 [95% CI, 0.24-1.00]; moderate certainty). Despite evidence of lower peritoneal glucose absorption with icodextrin-containing PD (medium-term MD, −40.84 [95% CI, −48.09 to −33.59] g/long dwell; high certainty), this did not directly translate to changes in fasting plasma glucose (−0.50 [95% CI, −1.19 to 0.18] mmol/L; low certainty) and hemoglobin A1c levels (−0.14% [95% CI, −0.34% to 0.05%]; high certainty). Safety outcomes and residual kidney function were similar in both groups; health-related quality-of-life and pain scores were inconclusive.</br>
Limitations</br>
Trial quality was variable. The follow-up period was heterogeneous, with a paucity of assessments over the long term. Mortality results are based on just 32 events and were not corroborated using time-to-event analysis of individual patient data.</br>
Conclusions</br>
Icodextrin for once-daily long-dwell PD has clinical benefit for some patients, including those not meeting ultrafiltration targets and at risk for fluid overload. Future research into patient-centered outcomes and cost-effectiveness associated with icodextrin is needed.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0006-291X53132020High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4422430ENYumiSakamotoDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTatsuoOkuiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceToshiyukiYonedaDepartment of Cellular and Molecular Biochemistry, Osaka University Graduate School of DentistryShojiRyumonDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTomoyaNakamuraDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceHotakaKawaiDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukiKunisadaDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceMasanoriMasuiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKishoOnoDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKyoichiObataDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTsuyoshiShimoDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoAkiraSasakiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceBone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama094926582632020High body mass index is a risk factor for unfavorable clinical outcomes after medial meniscus posterior root repair in well-aligned knees430434ENXimingZhangDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuyaKodamaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHaoweiXueDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshikiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University HospitalBackgroundSevere chondral lesions and varus knee alignment are associated with poor outcomes following transtibial pullout repair for medial meniscus posterior root tears and meniscus tear is strongly associated with body mass index. The prognostic factors in well-aligned knees (femorotibial angle < 180°) with mild chondral lesions are unknown. Therefore, we investigated the prognostic factors in these patients. We hypothesized that high body mass index would lead to poor clinical outcomes following pullout repair of medial meniscus posterior root tears. <br>
MethodsWe retrospectively reviewed the files of 28 patients who had undergone pullout repair of medial meniscus posterior root tears between October 2016 and December 2017. We recorded the baseline characteristics (age, gender, height, weight, and body mass index) and the time between injury and surgery. We recorded the International Knee Documentation Committee scores, Knee injury and Osteoarthritis Outcome Scores, and pain visual analog scale scores. Using magnetic resonance imaging preoperatively and 1 year after surgery, we measured the medial meniscus body width and absolute and relative medial meniscus extrusion. Pearson correlation and multivariate linear regression analyses were used to assess potential associations between these factors and clinical outcomes. <br>
ResultsAge positively correlated (coefficient = 0.49, P < 0.01) and body mass index negatively correlated with the postoperative International Knee Documentation Committee score (coefficient = −0.64, P < 0.01). In multivariate linear regression analysis, body mass index was a significant factor leading to poor postoperative International Knee Documentation Committee score (R2 = 0.29, P < 0.05). <br>
ConclusionsBody mass index > 30 kg/m(2) is a risk factor for unfavorable clinical outcomes following pullout repair of medial meniscus posterior root tears in well-aligned knees. Level of evidenceIII, Comparative retrospective study.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0142-96122512020Heterotypic 3D pancreatic cancer model with tunable proportion of fibrotic elements120077ENHiroyoshi Y.TanakaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTsuyoshiKuriharaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakuyaNakazawaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMichiyaMatsusakiDepartment of Applied Chemistry, Graduate School of Engineering, Osaka UniversityAtsushiMasamuneDivision of Gastroenterology, Graduate School of Medicine, Tohoku UniversityMitsunobu R.KanoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityPancreatic ductal adenocarcinoma (PDAC) is an often lethal disease characterized by a dense, fibrotic stroma. However, the lack of relevant preclinical models that recapitulate the characteristic histopathology of human PDAC in vitro impedes the development of novel therapies. The amount of stromal elements differ largely within and between patients, but in vitro models of human PDAC often do not account for this heterogeneity. Indeed, analyses of human PDAC histopathology revealed that the proportion of stroma ranged from 40 to 80% across patients. We, therefore, generated a novel 3D model of human PDAC, consisting of co-cultured human PDAC tumor cells and fibroblasts/pancreatic stellate cells, in which the proportion of fibrotic elements can be tuned across the clinically observed range. Using this model, we analyzed the signaling pathways involved in the differentiation of myofibroblasts, a characteristic subpopulation of fibroblasts seen in PDAC. We show that both YAP and SMAD2/3 in fibroblasts are required for myofibroblastic differentiation and that both shared and distinct signaling pathways regulate the nuclear localization of these factors during this process. Our novel model will be useful in promoting the understanding of the complex mechanisms by which the fibrotic stroma develops and how it might be therapeutically targeted.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071262019Heat-not-burn cigarettes induce fulminant acute eosinophilic pneumonia requiring extracorporeal membrane oxygenation8790ENToshiyukiAokageDepartment of Geriatric Emergency Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiTsukaharaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasushiFukudaDepartment of Respiratory Medicine, Kurashiki Central HospitalFumiakiTokiokaDepartment of Respiratory Medicine, Kurashiki Central HospitalAkihikoTaniguchiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromichiNaitoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground</br>
Although the cause of acute eosinophilic pneumonia (AEP) has not yet been fully clarified, cigarette smoking is reported to be a risk factor for developing AEP. The heat-not-burn cigarette (HNBC) was developed to reduce the adverse effects of smoke on the user's surroundings. However, the health risks associated with HNBCs have not yet been clarified. We report a successfully treated case of fatal AEP presumably induced by HNBC use.</br>
Presentation of case</br>
A 16-year-old man commenced HNBC smoking two weeks before admission and subsequently suffered from shortness of breath that gradually worsened. The patient was transferred to emergency department and immediately intubated because of respiratory failure. Computed tomography showed mosaic ground-glass shadows on the distal side of both lungs with a PaO2/FIO2 ratio of 76. The patient required veno-venous extracorporeal membrane oxygenation (ECMO) for severe respiratory failure. He was diagnosed with AEP by clinical course and detection of eosinophils in sputum; thus, methylprednisolone was administrated. The patient was weaned off ECMO four days after initiation and extubated the day after. He fully recovered without sequelae.</br>
Conclusion</br>
As far as we know, our patient is the first case of AEP induced by HNBC use successfully treated with ECMO. Emergency physicians must be aware that HNBCs can induce fatal AEP.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2451-8654192020HAMAMATSU-ICG study: Protocol for a phase III, multicentre, single-arm study to assess the usefulness of indocyanine green fluorescent lymphography in assessing secondary lymphoedema100595ENShinsukeAkitaDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of MedicineNaokiUnnoDepartment of Vascular Surgery, Hamamatsu Medical CenterJiroMaegawaDepartment of Plastic and Reconstructive Surgery, Yokohama City University, Graduate School of MedicinYoshihiroKimataDepartment of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceHidekazuFukamizuDepartment of Plastic and Reconstructive Surgery, Hamamatsu University School of MedicineYuichiroYabukiDepartment of Plastic and Reconstructive Surgery, Yokohama City University, Graduate School of MedicineAkiraShinaokaDepartment of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceMasakiSanoSecond Department of Surgery, Hamamatsu University School of MedicineYoheiKawasakiClinical Research Center, Chiba University HospitalTadamiFujiwaraClinical Research Center, Chiba University HospitalHidekiHanaokaClinical Research Center, Chiba University HospitalNobuyukiMitsukawaDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of MedicineIntroduction</br>
Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery.</br>
Methods and analysis</br>
This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy—one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA.</br>
Ethics and dissemination</br>
The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0012821X5302019Grain boundary diffusion of W in lower mantle phase with implications for isotopic heterogeneity in oceanic island basalts by core-mantle interactions115887ENTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityYoshikiMakinoGeochemical Research Center, The University of TokyoToshihiroSuzukiGeochemical Research Center, The University of TokyoTakafumiHirataGeochemical Research Center, The University of TokyoTungsten isotopes provide important constraints on the ocean-island basalt (OIB) source regions. Recent analyses of μ182W in modern basalts with high 3He/4He originating from the core-mantle boundary region reveal two distinct features: positive μ182W in Phanerozoic flood basalts indicating the presence of primordial reservoir, and negative μ182W in modern OIBs. One possibility to produce large variations in μ182W is interaction between the mantle and outer core. Here, we report grain boundary diffusion of W in lower mantle phases. High pressure experimental results show that grain boundary diffusion of W is fast and strongly temperature dependent. Over Earth's history, diffusive transport of W from the core to the lowermost mantle may have led to significant modification of the W isotopic composition of the lower mantle at length scales exceeding one kilometer. Such grain boundary diffusion can lead to large variations in μ182W in modern basalts as a function of the distance of their source regions from the core mantle boundary. Modern oceanic island basalts from Hawaii, Samoa and Iceland exhibit negative μ182W and likely originated from the modified isotope region just above the core-mantle boundary, whereas those with positive μ182W could be derived from the thick Large Low Shear Velocity Provinces (LLSVPs) far from the core-mantle boundary (CMB). When highly-oxidized slabs accumulate at the CMB oxidizing the outer core at the interface, a large W flux with negative μ182W can be added to the silicate mantle. As a result, the source region of the OIB would be effectively modified to a negative μ182W.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1873-5061482020Generation of four induced pluripotent stem cell lines (FHUi003-A, FHUi003-B, FHUi004-A and FHUi004-B) from two affected individuals of a familial neurohypophyseal diabetes insipidus family101960ENSatoruYoshidaDepartment of Regenerative Medicine and Stem Cell Biology, Fujita Health University School of MedicineHanayukiOkuraDepartment of Regenerative Medicine Support Promotion Facility, Center for Research Promotion and Support, Fujita Health UniversityHidetakaSugaDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineMikaSoenDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineYoheiKawaguchiDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineJunkiKurimotoDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineTakashiMiyataDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineHiroshiTakagiDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineHiroshiArimaDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineTatsuyaFujikawaDepartment of General Internal Medicine, Mitoyo General HospitalFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry Pharmaceutical SciencesAkifumiMatsuyamaDepartment of Regenerative Medicine and Stem Cell Biology, Fujita Health University School of MedicineFour disease-specific induced pluripotent stem cell (iPSC) lines were respectively derived from peripheral blood mononuclear cells of two affected individuals in a family affected by familial neurohypophyseal diabetes insipidus carrying the c.314G>C mutation. The expression of pluripotency markers (NANOG, OCT4, and SOX2), maintenance of a normal karyotype, absence of episomal vectors used for iPSC generation, and presence of the original pathogenic mutation were confirmed for each iPSC line. The ability to differentiate into three germ layers was confirmed by a teratoma formation assay. These iPSC lines can help in disease recapitulation in vitro using organoids and elucidation of disease mechanisms.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2211-3355202020Gender differences in dietary behaviors among Japanese adolescents101203ENYuichiroOtsukaDivision of Public Health, Department of Social Medicine, Nihon University School of MedicineYoshitakaKaneitaDivision of Public Health, Department of Social Medicine, Nihon University School of MedicineOsamuItaniDivision of Public Health, Department of Social Medicine, Nihon University School of MedicineMakiJikeDivision of Public Health, Department of Social Medicine, Nihon University School of MedicineYoneatsuOsakiDivision of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of MedicineSusumuHiguchiNational Hospital Organization Kurihama Medical and Addiction CenterHideyukiKandaDepartment of Public Health, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, University Faculty of MedicineUnhealthy dietary behaviors in adolescence are an important public health problem. Gender differences in dietary behaviors have already appeared during adolescence. However, few studies have assessed a variety of adolescent dietary behaviors in Japan. We aimed to clarify gender differences in unhealthy dietary behaviors among Japanese adolescents. The participants consisted of 84,988 participants from seventh to 12th grades. Unhealthy dietary behaviors were defined according to the National Health and Nutrition Survey. Multivariable logistic regression was used to analyze a nationally representative sample of Japanese adolescents from the 2014 to 2015 Lifestyle Survey. The effective response rate was 51.4%. The prevalence of unhealthy dietary behaviors (skipping breakfast, snacking, eating out, skipping meals, eating alone at dinner, and subjectively poor diet quality) among boys and girls was 14.2% versus 12.4%, 19.6% versus 14.1%, 10.6% versus 7.0%, 7.9% versus 5.6%, 13.3% versus 12.1%, and 12.3% versus 15.8%, respectively. Compared with boys, girls were more negatively associated with skipping breakfast [OR = 0.76 (95% CI 0.73–0.79)], snacking [OR = 0.67 (95% CI 0.65–0.70)], eating out [OR = 0.62 (95% CI 0.59–0.66)], skipping meals [OR = 0.61 (95% CI 0.58–0.65)], and eating alone at dinner [OR = 0.79 (95% CI 0.76–0.83)]. However, girls were more positively associated with subjectively poor diet quality [OR = 1.19 (95% CI 1.14.1.24)]. The findings suggest that gender differences existed in dietary behaviors. Gender differences in dietary behaviors suggest opportunities for tailoring interventions related to dietary education in schools.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2059-7029642021Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study100191ENK.HottaCenter for Innovative Clinical Medicine, Okayama University HospitalS.SaekiDepartment of Respiratory Medicine, Kumamoto University HospitalM.YamaguchiDepartment of Thoracic Oncology, National Hospital Organization Kyushu Cancer CenterD.HaradaDepartment of Thoracic Oncology, National Hospital Organization Shikoku Cancer CenterA.BesshoDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalK.TanakaDepartment of Respiratory Medicine, Kyushu University HospitalK.InoueDepartment of Respiratory Medicine, Kitakyushu Municipal Medical CenterK.GembaDepartment of Respiratory Medicine, Chugoku Central HospitalM.ShiojiriDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalY.KatoCenter for Innovative Clinical Medicine, Okayama University HospitalT.NinomiyaDepartment of Respiratory Medicine, Okayama University HospitalT.KuboDepartment of Respiratory Medicine, Okayama University HospitalJ.KishimotoCenter for Clinical and Translational Research, Kyushu University HospitalY.ShioyamaClinical Radiology, Radiology Informatics and Network, Graduate School of Medical Sciences, Kyushu UniversityK.KatsuiDepartment of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJ.SasakiResearch and Development Center for New Medical Frontiers, Kitasato University School of MedicineK.KiuraDepartment of Respiratory Medicine, Okayama University HospitalK.SugioDepartment of Thoracic and Breast Surgery, Oita UniversityBackground: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting. <br>
Patients and methods: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m(2) each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%. <br>
Results: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade >= 3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade >= 3 or treatment-related death did not occur. <br>
Conclusions: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama159086585112019Gastric lanthanum phosphate deposition masquerading as white globe appearance168ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHaruoUrataCentral Research Laboratory, Okayama University Medical SchoolTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1567-13481112011Full genomic analysis of a simian SA11-like G3P[2] rotavirus strain isolated from an asymptomatic infant: Identification of novel VP1, VP6 and NSP4 genotypes5763ENSouvikGhoshZipporahGatheruJamesNyangaoNoriakiAdachiNorikoUrushibaraNobumichiKobayashiWe report here the full genomic analysis of a simian SA11-like G3P[2] group A rotavirus (GAR) strain, B10, isolated from an asymptomatic infant in Kenya in 1987. By nucleotide sequence identities and phylogenetic analyses, the VP7–VP4–VP2–VP3–NSP1–NSP2–NSP3–NSP5 genes of strain B10 exhibited maximum genetic relatedness to those of the different isolates of simian strain SA11, and were assigned to the G3–P[2]–C5–M5–A5–N5–T5–H5 genotypes, respectively. On the other hand, the VP1, VP6 and NSP4 genes of strain B10 did not belong to any of the established GAR genotypes, and therefore, were assigned to new genotype numbers R8, I16 and E13, respectively, by the Rotavirus Classification Working Group. These observations suggested that strain B10 might have originated from reassortment event/s involving simian SA11-like strains and GAR strains from unknown animal host species (possibly other wild animals) preceding transmission to humans. Alternatively, considering the lack of data on simian GARs, it might be also possible that the VP1, VP6 and NSP4 genes of strain B10 are those of unknown simian strains, and that strain B10 might be a typical simian strain that was directly transmitted to humans. Therefore, either hypothesis pointed towards a rare instance of possible direct transmission of GARs from an animal host (possibly a monkey or some other wild animal) to humans. This was corroborated by the presence of different species of wild animals including non-human primates, and unhygienic conditions at the sampling site. To our knowledge, the present study is the first report on the detection of a simian SA11-like G3P[2] GAR strain in humans.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0165-178121622014Four polymorphisms of the pericentriolar material 1 (PCM1) gene are not associated with schizophrenia in a Japanese population288289ENShinjiSakamotoDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOkahisaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutakaMizukiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasafumiKodamaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiUjikeDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeUchitomiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama001216064522019Fgf- and Bmp-signaling regulate gill regeneration in Ambystoma mexicanum104113EN NanamiSaitoOkayama University, Research Core for Interdisciplinary Sciences (RCIS) KokiNishimuraOkayama University, Research Core for Interdisciplinary Sciences (RCIS) AkiMakanaeOkayama University, Research Core for Interdisciplinary Sciences (RCIS)AkiraSatohOkayama University, Research Core for Interdisciplinary Sciences (RCIS) Gill regeneration has not been well studied compared to regeneration of other appendages, such as limb and tail regeneration. Here, we focused on axolotl gill regeneration and found that Fgf- and Bmp-signaling are involved in their gill regeneration mechanism. Axolotls have three pairs of gill rami, and each gill ramus has multiple gill filaments. The gills consist of mesenchyme rich in extracellular matrix and epidermis. The gill nerves are supplied from the trigeminal ganglia located in the head. Denervation resulted in no gill regeneration responses. Nerves and gills express Bmp and Fgf genes, and treating animals with Fgf- and Bmp-signaling inhibitors results in phenotypes similar to those seen in denervated gills. Inducing an accessory appendage is a standard assay in amphibian regeneration research. In our study, an accessory gill could be induced by lateral wounding, suggesting that thin axon fibers and mesenchymal Fgfs and Bmps contributed to the induction of the accessory structure. Such accessory gill induction was inhibited by the denervation. Exogenous Fgf2+Fgf8+Bmp7, which have been determined to function as a regeneration inducer in urodele amphibians, could compensate for the effects denervation has on accessory blastema formation. Our findings suggest that regeneration of appendages in axolotls is regulated by common Fgf- and Bmp-signaling cascades.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0021-86934842017F-rationality of the ring of modular invariants207223ENMitsuyasuHashimotoDepartment of Mathematics, Okayama University Using the description of the Frobenius limit of modules over the ring of invariants under an action of a finite group on a polynomial ring over a field of characteristic p>0 developed by Symonds and the author, we give a characterization of the ring of invariants with a positive dual F-signature. Combining this result and Kemper's result on depths of the ring of invariants under an action of a permutation group, we give an example of an F-rational, but non-F-regular ring of invariants under the action of a finite group.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071312020Extracorporeal membrane oxygenation in Stenotrophomonas maltophilia pneumonia during acute myeloid leukemia: A case report101224ENKenkiSaitoDepartment of Hematology/Oncology, Kurashiki Central HospitalToshiyukiAokageDepartment of Geriatric Emergency Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayukiSatoDepartment of Hematology/Oncology, Kurashiki Central HospitalKoheiTsukaharaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University HospitalFumiakiTokiokaDepartment of Respiratory Medicine, Kurashiki Central HospitalTakanaoOtakeDepartment of Anesthesiology, Kurashiki Central HospitalHiromasaIrieDepartment of Anesthesiology, Kurashiki Central HospitalYasunoriUedaDepartment of Hematology/Oncology, Kurashiki Central HospitalStenotrophomonas maltophilia (S. maltophilia) is a Gram-negative, multidrug-resistant organism that both opportunistically infects the bloodstream and leads to pneumonia in immunosuppressed patients, including those with hematologic malignancies. In patients with severe respiratory failure, venovenous extracorporeal membrane oxygenation (VV ECMO) can stabilize the respiratory status. However, whether ECMO in patients with hematologic malignancies improves the clinical outcomes is still controversial because ECMO increases the risk of the exacerbation of sepsis and bleeding. We report a case of a 46-year-old man with Stenotrophomonas maltophilia hemorrhagic pneumonia acquired during consolidation chemotherapy for acute myeloid leukemia in whom VV ECMO lead to a good clinical outcome. The stabilization of his respiratory status achieved with VV ECMO allowed time for trimethoprim-sulfamethoxazole antibiotic therapy to improve the pneumonia. We suggest the background of patients, including comorbidities and general conditions, should be taken into account when considering the clinical indications of ECMO.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1010-60304052021Exploring reaction pathways for the structural rearrangements of the Mn cluster induced by water binding in the S3 state of the oxygen evolving complex of photosystem II112905ENHiroshiIsobeResearch Institute for Interdisciplinary Science, Okayama UniversityMitsuoShojiCenter for Computational Science, University of TsukubaTakayoshiSuzukiResearch Institute for Interdisciplinary Science, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science, Okayama UniversityKizashiYamaguchiInstitute for NanoScience Design, Osaka UniversityPhotosynthetic oxidation of water to dioxygen is catalyzed by the Mn4CaO5 cluster in the protein-cofactor complex photosystem II. The light-driven catalytic cycle consists of four observable intermediates (S0, S1, S2, and S3) and one transient S4 state. Recently, using X-ray free-electron laser crystallography, two experimental groups independently observed incorporation of one additional oxygen into the cluster during the S2 to S3 transition, which is likely to represent a substrate. The present study implicates two competing reaction routes encountered during the structural rearrangement of the catalyst induced by the water binding and immediately preceding the formation of final stable forms in the S3 state. This mutually exclusive competition involves concerted versus stepwise conformational changes between two isomers, called open and closed cubane structures, which have different consequences on the immediate product in the S3 state. The concerted pathway involves a one-step conversion between two isomeric hydroxo forms without changes to the metal oxidation and total spin (Stotal = 3) states. Alternatively, in the stepwise process, the bound waters are oxidized and transformed into an oxyl–oxo form in a higher spin (Stotal = 6) state. Here, density functional calculations are used to characterize all relevant intermediates and transition structures and demonstrate that the stepwise pathway to the substrate activation is substantially favored over the concerted one, as evidenced by comparison of the activation barriers (11.1 and 20.9 kcal mol−1, respectively). Only after formation of the oxyl–oxo precursor can the hydroxo species be generated; this occurs with a slow kinetics and an activation barrier of 17.8 kcal mol−1. The overall thermodynamic driving force is likely to be controlled by the movements of two glutamate ligands, D1-Glu189 and CP43-Glu354, in the active site and ranges from very weak (+0.4 kcal mol−1) to very strong (–23.5 kcal mol−1).No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama000925415592021Experimental variable effects on laser heating of inclusions during Raman spectroscopic analysis119928ENYuukiHagiwaraGraduate School of Science, Hokkaido UniversityKentaYoshidaResearch Institute for Marine Geodynamics, Japan Agency for Marine-Earth Science and Technology (JAMSTEC)AkiraYonedaInstitute for Planetary Materials, Okayama UniversityJunjiTorimotoOre Genesis Research Unit, Project Team for Development of New-Generation Research Protocol for Submarine Resources, Japan Agency for Marine-Earth Science and Technology (JAMSTEC)JunjiYamamotoThe Hokkaido University Museum Raman spectroscopy for fluid, melt, and mineral inclusions provides direct insight into the physicochemical conditions of the environment surrounding the host mineral at the time of trapping. However, the obtained Raman spectral characteristics such as peak position are modified because of local temperature enhancement of the inclusions by the excitation laser, which might engender systematic errors and incorrect conclusions if the effect is not corrected. Despite the potentially non-negligible effects of laser heating, the laser heating coefficient (B) (°C/mW) of inclusions has remained unsolved. For this study, we found B from experiments and heat transport simulation to evaluate how various parameters such as experimental conditions, mineral properties, and inclusion geometry affect B of inclusions. To assess the parameters influencing laser heating, we measured B of a total of 19 CO2-rich fluid inclusions hosted in olivine, orthopyroxene, clinopyroxene, spinel, and quartz. Our results revealed that the measured B of fluid inclusions in spinel is highest (approx. 6 °C/mW) and that of quartz is lowest (approx. 1 × 10−2 °C/mW), consistent with earlier inferences. Our simulation results show that the absorption coefficient of the host mineral is correlated linearly with B. It is the most influential parameter when the absorption coefficient of the host mineral (αh) is larger than that of an inclusion (αinc). Furthermore, although our results indicate that both the inclusion size and depth have little effect on B if αh > αinc, the thickness and radius of the host mineral slightly influence B. These results suggest that the choice of inclusion size and depth to be analyzed in a given sample do not cause any systematic error in the Raman data because of laser heating, but the host radius and thickness, which can be adjusted to some degree at the time of sample preparation, can cause systematic errors between samples.Our results demonstrate that, even with laser power of 10 mW, which is typical for inclusion analysis, the inclusion temperature rises to tens or hundreds of degrees during the analysis, depending especially on the host mineral geometry and optical properties. Therefore, correction of the heating effects will be necessary to obtain reliable data from Raman spectroscopic analysis of inclusions. This paper presents some correction methods for non-negligible effects of laser heating.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24058440662020Evaluation of the simulator with automatic irrigation control system designed for countermeasures of internal contamination in dental unit water linese04132ENKeisukeOkuboDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiItoCenter for Innovative Clinical Medicine, Okayama University HospitalKentaroOkamotoDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIchiroYamamotoDental Department Marketing Division, TAKARA BELMONT CorporationHajimeMizutaniResearch and Development Department, TAKARA BELMONT CorporationYusukeKawataDepartment of Periodontics and Endodontics, Okayama University HospitalYasuyoshiShiotaDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroItoDepartment of Periodontics and Endodontics, Okayama University HospitalShinNakamuraDepartment of Periodontics and Endodontics, Okayama University HospitalMasakoTaiDepartment of Periodontics and Endodontics, Okayama University HospitalTadashiYamamotoDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShogoTakashibaDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceThe prevention of nosocomial infections is an imperative task. The dental chair unit (DCU) is an indispensable device used in dental treatment. However, it is known that the dental unit water line (DUWL) can become contaminated with biofilm, consisting mainly of heterotrophic bacteria (HB). Recently, the International Organization for Standardization specified the methods for testing DUWL contamination management. On these grounds, a simulator reproducing DUWL was prepared to standardize the examination method of the DUWL contamination.</br>
Objectives</br>
To evaluate the reproducibility of the DUWL simulator, monitor the DUWL contamination states, and test the efficacy of a commercial decontaminant for DUWL.</br>
Methods</br>
The DUWL simulator was assembled by a DCU manufacturing company. The simulator's DUWL was filled with tap water (TW), and left for approximately one year. Neutral electrolyzed water (NEW) was used as a decontaminant for DUWL. Both TW and NEW were passed through DUWL in a timely manner simulating daily dental treatment. Water was sampled from the air turbine hand piece weekly for 4 weeks and used for HB culture. Contamination status was evaluated by measuring bacterial adenosine triphosphate release and by culturing on Reasoner's 2A medium.</br>
Results</br>
The DUWL released contaminated water had a bacterial count of over 6 × 104 cfu/mL. After passing NEW through DUWL for 1 week, the count drastically decreased to its basal level and remained steady for 4 weeks. However, TW showed no effect on DUWL decontamination throughout the examination periods.</br>
Conclusions</br>
The DUWL simulator could be useful to examine the efficacy of the decontaminant for DUWL and development of new methods in DUWL contamination management.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama016890029592020Evaluation of gadolinium’s action on water Cherenkov detector systems with EGADS163549ENLl.MartiKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoM.IkedaKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoY.KatoKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoY.KishimotoKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoM.NakahataKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoY.NakajimaKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoY.NakanoKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoS.NakayamaKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoY.OkajimaKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoA.OriiKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoG.PronostKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoH.SekiyaKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoM.ShiozawaKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoH.TanakaKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoK.UenoKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoS.YamadaKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoT.YanoKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoT.YokozawaKamioka Observatory, Institute for Cosmic Ray Research, University of TokyoM.Murdoch Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo Institutes for Advanced StudyJ.Schuemann Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo Institutes for Advanced StudyM.R.Vagins Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo Institutes for Advanced StudyK.Bays Department of Physics and Astronomy, University of CaliforniaG.Carminati Department of Physics and Astronomy, University of CaliforniaN.J.Griskevich Department of Physics and Astronomy, University of CaliforniaW.R.Kropp Department of Physics and Astronomy, University of CaliforniaS.Locke Department of Physics and Astronomy, University of CaliforniaA.Renshaw Department of Physics and Astronomy, University of CaliforniaM.B.Smy Department of Physics and Astronomy, University of CaliforniaP.Weatherly Department of Physics and Astronomy, University of CaliforniaS.Ito Department of Physics, Okayama UniversityH.IshinoDepartment of Physics, Okayama UniversityA.KibayashiDepartment of Physics, Okayama UniversityY.KoshioDepartment of Physics, Okayama UniversityT.MoriDepartment of Physics, Okayama UniversityM.SakudaDepartment of Physics, Okayama UniversityR.YamaguchiDepartment of Physics, Okayama UniversityP.Fernandez Department of Theoretical Physics, University Autonoma MadridL.Labarga Department of Theoretical Physics, University Autonoma MadridI.BandacLaboratorio Subterraneo de CanfrancJ.PerezLaboratorio Subterraneo de CanfrancJ.AmeyDepartment of Physics, Imperial College LondonR.P.LitchfieldDepartment of Physics, Imperial College LondonA.SztucDepartment of Physics, Imperial College LondonY.UchidaDepartment of Physics, Imperial College LondonW.Y.MaDepartment of Physics, Imperial College LondonA.GoldsackDepartment of Physics, Oxford UniversityC.SimpsonDepartment of Physics, Oxford UniversityD.WarkDepartment of Physics, Oxford UniversityL.H.V.AnthonyDepartment of Physics, University of LiverpoolN.McCauleyDepartment of Physics, University of LiverpoolA.PritchardDepartment of Physics, University of LiverpoolF.Di Lodovico Department of Physics, King’s College LondonB.Richards Department of Physics, King’s College LondonA.ColeDepartment of Physics and Astronomy, University of SheffieldM.ThiesseDepartment of Physics and Astronomy, University of SheffieldL.ThompsonDepartment of Physics and Astronomy, University of SheffieldJ.Imber Ecole Polytechnique, IN2P3-CNRS, Laboratoire Leprince-RinguetS.V.CaoHigh Energy Accelerator Research Organization (KEK)K.ItoDepartment of Physics, Tokai UniversityY.Takeuchi Department of Physics, Kobe UniversityR.AkutsuResearch Center for Cosmic Neutrinos, Institute for Cosmic Ray Research, University of TokyoY.NishimuraResearch Center for Cosmic Neutrinos, Institute for Cosmic Ray Research, University of TokyoK.OkumuraResearch Center for Cosmic Neutrinos, Institute for Cosmic Ray Research, University of TokyoS.Hirota Department of Physics, Kyoto UniversityF.Muto Institute for Space-Earth Environmental Research, Nagoya UniversityM.YokoyamaDepartment of Physics, University of TokyoY.SudaDepartment of Physics, University of TokyoH.ZhangDepartment of Engineering Physics, Tsinghua University Used for both proton decay searches and neutrino physics, large water Cherenkov (WC) detectors have been very successful tools in particle physics. They are notable for their large masses and charged particle detection capabilities. While current WC detectors reconstruct charged particle tracks over a wide energy range, they cannot efficiently detect neutrons. Gadolinium (Gd) has the largest thermal neutron capture cross section of all stable nuclei and produces an 8 MeV gamma cascade that can be detected with high efficiency. Because of the many new physics opportunities that neutron tagging with a Gd salt dissolved in water would open up, a large-scale R&D program called EGADS was established to demonstrate this technique’s feasibility. EGADS features all the components of a WC detector, chiefly a 200-ton stainless steel water tank furnished with 240 photo-detectors, DAQ, and a water system that removes all impurities from water while keeping Gd in solution. In this paper we discuss the milestones towards demonstrating the feasibility of this novel technique, and the features of EGADS in detail.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1882-76165612020Evaluation of dental caries, tooth crack, and age-related changes in tooth structure using optical coherence tomography109118ENYasushiShimadaDepartment of Operative Dentistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasahiroYoshiyamaDepartment of Operative Dentistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJunjiTagamiDepartment of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityYasunoriSumiDepartment for Advanced Dental Research, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and GerontologyOptical coherence tomography (OCT) is an imaging technique that can visualize the internal biological structure without X-ray exposure. Swept-source OCT (SS-OCT) is one of the latest version of OCT, wherein the light source is a tunable laser that sweeps near-infrared wavelength light to achieve real-time imaging. The imaging depth of OCT is highly influenced by the translucency of the medium. The medium that does not transmit light and the deeper structure beyond the range of light penetration depth are not relevant for OCT imaging. In OCT, sound enamel is almost transparent at the OCT wavelength range, and enamel and dentin can be distinguished from each other as the dentin–enamel junction (DEJ) appears as a dark border. Demineralized enamel and dentin are imaged as bright zones because of the formation of numerous micro-porosities where the backscatter of OCT signal is increased. In cavitated caries at interproximal or occlusal hidden zone, the upper margin of the cavity reflects the signal showing a distinct bright border in the SS-OCT image. SS-OCT is capable of determining crack penetration depth even when the cracks extended beyond the DEJ. SS-OCT has a high degree of sensitivity and specificity for the detection of dental caries and tooth cracks. SS-OCT is also capable of detecting non-carious cervical lesions and occlusal tooth wear in cross-sectional views to estimate the amount of tooth structure loss.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1526-82092022020Evaluation of Therapeutic Target Gene Expression Based on Residual Cancer Burden Classification After Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer117124ENYukoTakahashiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityTakayukiIwamotoDepartments of Breast and Endocrine Surgery, Okayama University HospitalYokoSuzukiDepartments of Breast and Endocrine Surgery, Okayama University HospitalYukikoKajiwaraDepartments of Breast and Endocrine Surgery, Okayama University HospitalMinamiHatonoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityTakahiroTsukiokiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityKengoKawadaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityMarikoKochiDepartments of Breast and Endocrine Surgery, Okayama University HospitalHirokuniIkedaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityTadahikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityNarutoTairaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityJunjiMatsuokaDepartments of Palliative and Supportive Medicine, Okayama University HospitalHiroyoshiDoiharaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction</br>
Patients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy.</br>
Patients and Methods</br>
We retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III.</br>
Results</br>
Among hormone receptor–positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P < .01). The mRNA expressions of ESR1 and PGR were significantly higher, and that of MKI67 was lower in RCB-II and RCB-III than in RCB-0/I. The mRNA expression of cyclin D1 was up-regulated in RCB-III and that of CDKN2A was down-regulated in RCB-III (P = .027 and < .01). Among triple-negative (TN) samples, RCB-III had higher clinical stage and more lymph node–positive samples than RCB-0/1 and RCB-II (P < .01). In both subtypes, VEGF-C expression was significantly higher in RCB-III than in RCB-0/I and RCB-II.</br>
Conclusion</br>
In hormone receptor–positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama222541102019Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actionsEN Mohamed E.AbouelelaDepartment of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University Mohamed A.A.OrabiDepartment of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University Reda A.AbdelhamidDepartment of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University Mohamed S.AbdelkaderDepartment of Pharmacognosy, Faculty of Pharmacy, Sohag University Hafez R.MadkorDepartment of Biochemistry, Faculty of Pharmacy, Al-Azhar University Faten M.M.DarwishDepartment of Pharmacognosy, Faculty of Pharmacy, Assiut University TsutomuHatanoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Bakheet E.M.ElsadekDepartment of Biochemistry, Faculty of Pharmacy, Al-Azhar University Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects.Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, C. pentandra ethyl acetate extract showed powerful in vitro radical-scavenging potential (IC50 = 0.0716) comparable to those of the standard natural (ascorbic acid, IC50 = 0.045) and synthetic (BHA, IC50 = 0.056) antioxidants. The effect of C. pentandra ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.).C. pentandra showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. C. pentandra also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, C. pentandra inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture.Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (1), cinchonains 1a (2) and 1b (3), cis-clovamide (4), trans-clovamide (5), and glochidioboside (6); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that C. pentandra exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms. TaxonomyFunctional Disorder, Traditional Medicine, Herbal Medicine.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2214-5818362021Environmental flow sustainability in the Lower Limpopo River Basin, Mozambique100843ENOsvaldo SilvaZefanias NhassengoEscola Superior de Neg´ocios e Empreendedorismo de Chibuto, Universidade Eduardo MondlaneHiroakiSomuraGraduate School of Environmental and Life Science, Okayama UniversityJune IIIWolfeTexas A&M AgriLife, Blackland Research & Extension CenterStudy region: This study focuses on the Lower Limpopo River basin (LLRB) in Mozambique, Africa. Study focus: Maintaining environmental flows necessary for ecosystem sustainability represents a significant challenge to water resource management. In this study the sustainability of LLRB was evaluated by comparing hydrologic availability with ecological and anthropogenic needs. Current river ecological status was scored with a habitat integrity index verified through ground-truthing field surveys and aerial imagery data. Local stakeholder interviews were used to further evaluate the habitat index scores. Deficiencies between water availability and ecological-human requirements were assessed with a water scarcity index.<br>
New Hydrological Insights for the Region: Four environmental flow categories defined as "Excellent", "Fair", "Poor", and "Degraded" coincided to approximately 50 %, 39 %, 27 %, and 14 % of the natural mean annual flow, respectively. Stakeholder interview responses indicated annual water shortages currently occur between August and November and coincide with "Poor" and "Degraded" environmental flow conditions. Water supplies appear to meet consumption needs when calculated on an annual basis with the water scarcity index. However, when calculated monthly, there is not enough to meet human water demand between August and October. This deficit period will likely expand from June to November due to projected increases in future water demands. As the greatest water use in the basin is agricultural irrigation, long-term environmental flows sustainability will likely depend upon effective irrigation management.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0882-40105142011Enterotoxigenic Escherichia coli CS6 gene products and their roles in CS6 structural protein assembly and cellular adherence243249ENTakeakiWajimaSubrataSabuiMegumiFukumotoShigeyukiKanoThandavarayanRamamurthyNabendu SekharChatterjeeTakashiHamabataEnterotoxigenic Escherichia coli (ETEC) produces a variety of colonization factors necessary for attachment to the host cell, among which CS6 is one of the most prevalent in ETEC isolates from developing countries. The CS6 operon is composed of 4 genes, cssA, cssB, cssC, and cssD. The molecular mechanism of CS6 assembly and cell surface presentation, and the contribution of each protein to the attachment of the bacterium to intestinal cells remain unclear. In the present study, a series of css gene-deletion mutants of the CS6 operon were constructed in the ETEC genetic background, and their effect on adhesion to host cells and CS6 assembly was studied. Each subunit deletion resulted in a reduction in the adhesion to intestinal cells to the same level of laboratory E. coli strains, and this effect was restored by complementary plasmids, suggesting that the 4 proteins are necessary for CS6 expression. Bacterial cell fractionation and western blotting of the mutant strains suggested that the formation of a CssA–CssB–CssC complex is necessary for recognition by CssD and transport of CssA–CssB to the outer membrane as a colonization factor.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama016041201382020Enhanced expression of nicotinamide nucleotide transhydrogenase (NNT) and its role in a human T cell line continuously exposed to asbestos105654ENShokoYamamotoDepartment of Hygiene, Kawasaki Medical SchoolSuniLeeDepartment of Hygiene, Kawasaki Medical SchoolHidenoriMatsuzakiDepartment of Life Science, Faculty of Life and Environmental Science, Prefectural University of HiroshimaNaokoKumagai-TakeiDepartment of Hygiene, Kawasaki Medical SchoolKeiYoshitomeDepartment of Hygiene, Kawasaki Medical SchoolNagisaSadaDepartment of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYurikaShimizuDepartment of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTastsuoItoDepartment of Hygiene, Kawasaki Medical SchoolYasumitsuNishimuraDepartment of Hygiene, Kawasaki Medical SchoolTakemiOtsukiDepartment of Hygiene, Kawasaki Medical SchoolThe effects of asbestos fibers on human immune cells have not been well documented. We have developed a continuously exposed cell line model using the human T-lymphotropic virus 1 (HTLV-1)-immortalized human T cell line MT-2. Sublines continuously exposed to chrysotile (CH) or crocidolite (CR) showed acquired resistance to asbestos-induced apoptosis following transient and high-dose re-exposure with fibers. These sublines in addition to other immune cells such as natural killer cells or cytotoxic T lymphocytes exposed to asbestos showed a reduction in anti-tumor immunity. In this study, the expression of genes and molecules related to antioxidative stress was examined. Furthermore, complexes related to oxidative phosphorylation were investigated since the production of reactive oxygen species (ROS) is important when considering the effects of asbestos in carcinogenesis and the mechanisms involved in resistance to asbestos-induced apoptosis. In sublines continuously exposed to CH or CR, the expression of thioredoxin decreased. Interestingly, nicotinamide nucleotide transhydrogenase (NNT) expression was markedly enhanced. Thus, knockdown of NNT was then performed. Although the knockdown clones did not show any changes in proliferation or occurrence of apoptosis, these clones showed recovery of ROS production with returning NADPH/NADP+ ratio that increased with decreased production of ROS in continuously exposed sublines. These results indicated that NNT is a key factor in preventing ROS-induced cytotoxicity in T cells continuously exposed to asbestos. Considering that these sublines showed a reduction in anti-tumor immunity, modification of NNT may contribute to recovery of the anti-tumor effects in asbestos-exposed T cells.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0914-50877812021Efficacy of shear wave elastography for evaluating right ventricular myocardial fibrosis in monocrotaline-induced pulmonary hypertension rats1723ENRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoruKobayashiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOhnoKawasaki University of Medical WelfareNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiIto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Right ventricular (RV) function is important for outcomes in pulmonary hypertension. Evaluation of RV myocardial characteristics is useful to assess the disease severity. Shear wave elastography (SWE) provides information of shear wave (SW) elasticity, which is related to tissue hardness, and SW dispersion slope, which reflects tissue viscosity. This study aimed to test the hypothesis that SW elasticity is increased and SW dispersion slope is decreased in the right ventricle of monocrotaline (MCT)-induced pulmonary hypertension rats. <br>
<br>
Methods: Rats were divided into MCT-induced pulmonary hypertension group (n = 10) and control group (n = 10). SW elasticity and SW dispersion slope were measured on excised hearts. Myocardial fibrosis was evaluated histologically. <br>
<br>
Results: RV hypertrophy was observed in the MCT group. SW elasticity of right ventricle was higher in the MCT group than in the control group (3.5 ± 0.9 kPa vs. 2.5 ± 0.4 kPa, p < 0.01). SW dispersion slope of right ventricle was lower in the MCT group than in the control group (5.3 ± 1.7 m/s/kHz vs. 7.7 ± 1.5 m/s/kHz, p < 0.01). The fibrosis area of right ventricle was increased in MCT group compared with control group (18 ± 5% vs. 8 ± 3%, p < 0.01), and was positively related to SW elasticity and negatively related to SW dispersion slope. <br>
<br>
Conclusions: Higher SW elasticity and lower SW dispersion slope were observed in the fibrotic myocardium of right ventricle in MCT-induced pulmonary hypertension rats. SWE may have the potential to evaluate RV function by assessing myocardial characteristics. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0921-50938072021Effects of microstructural characteristics on the hydrogen embrittlement characteristics of austenitic, ferritic, and γ–α duplex stainless steels140851ENMitsuhiroOkayasuGraduate School of Natural Science and Technology, Okayama UniversityTakafumiFujiwaraGraduate School of Natural Science and Technology, Okayama UniversityHydrogen embrittlement (HE) characteristics of γ (AS), α (FS), and γ–α duplex (DS) stainless steels were examined experimentally and numerically. Severe HE occurred in the DS sample, whereas weak HE was detected in the AS and FS samples. This was attributed to the high hydrogen concentrations at the DS-trapping sites. Hydrogen trapping occurred in the low atomic density zones in the boundaries between α and γ phases in DS sample. The chemical bonding between atomic-scale phase boundaries was weakened by hydrogen penetration. This resulted in a crack growth along the DS α/γ phase boundaries. The ductility of DS decreased as the hydrogen content increased, especially when it exceeded 15 ppm. In contrast, the weak HE observed among AS and FS samples was attributed to the small hydrogen levels that infiltrated both samples. Finally, HE mechanism was proposed on the basis of these experimental results.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2214-5818442022Effects of local land-use policies and anthropogenic activities on water quality in the upstream Sesan River Basin, Vietnam101225ENVo Ngoc QuynhTramGraduate School of Environmental and Life Science, Okayama UniversityHiroakiSomuraGraduate School of Environmental and Life Science, Okayama UniversityToshitsuguMoroizumiGraduate School of Environmental and Life Science, Okayama UniversityMorihiroMaedaGraduate School of Environmental and Life Science, Okayama UniversityStudy region: This study focuses on the upstream Sesan River Basin in the Central Highlands of Vietnam. Study focus: Local land-use policies and human activities can significantly affect hydrology and increase the magnitude of erosion and nutrients in downstream areas. The effects in terrestrial regions on water quality of the target area were evaluated during the 2000-2018 period using the SWAT (Soil and Water Assessment Tool) with updated land-use conditions following the local policy decisions and agricultural practices in different periods. New hydrological insights for the regions: This study indicates that the implementation of the local land-use policies, along with extensive anthropogenic activities, has had significant effects on the downstream aquatic environment as compared with the period before the implementation of the land-use policies. Higher annual sediment, total nitrogen (TN), and total phosphorus (TP) load-ings were found upstream from the Poko Watershed, where range land predominated, and in southern and southwestern Dakbla Watershed, where arable land and permanent cropland pre-dominated. Arable land had the highest proportion of sediment and nutrient loadings into the reach, especially in the 2005-2009 period (conducting afforestation, agricultural expansion, and urbanization) and in the 2010-2014 period (applying crop conversion policy involving a shift from mixed forests to rubber forests). Understanding the watershed characteristics along with the combination of spatial land use, local land-use policies, and agricultural practices will support the implementation of regional land use and water resources management strategies more comprehensively.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0006-291X48042016Effects of induced Na+/Ca2+ exchanger overexpression on the spatial distribution of L-type Ca2+ channels and junctophilin-2 in pressure-overloaded hearts564569ENYoshihiroUjiharaDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiMohriaDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiKatanosakaDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe Na+/Ca2+ exchanger 1 (NCX1) is an essential Ca2+ efflux system in cardiomyocytes. Although NCX1 is distributed throughout the sarcolemma, a subpopulation of NCX1 is localized to transverse (T)-tubules. There is growing evidence that T-tubule disorganization is a causal event that shifts the transition from hypertrophy to heart failure (HF). However, the detailed molecular mechanisms have not been clarified. Previously, we showed that induced NCX1 expression in pressure-overloaded hearts attenuates defective excitation-contraction coupling and HF progression. Here, we examined the effects of induced NCX1 overexpression on the spatial distribution of L-type Ca2+ channels (LTCCs) and junctophilin-2 (JP2), a structural protein that connects the T-tubule and sarcoplasmic reticulum membrane, in pressure-overloaded hearts. Quantitative analysis showed that the regularity of NCX1 localization was significantly decreased at 8 weeks after transverse aortic constriction (TAC)-surgery; however, T-tubule organization and the regularities of LTCC and JP2 immunofluorescent signals were maintained at this time point. These observations demonstrated that release of NCX1 from the T-tubule area occurred before the onset of T-tubule disorganization and LTCC and JP2 mislocalization. Moreover, induced NCX1 overexpression at 8 weeks post-TAC not only recovered NCX1 regularity but also prevented the decrease in LTCC and JP2 regularities at 16 weeks post-TAC. These results suggested that NCX1 may play an important role in the proper spatial distribution of LTCC and JP2 in T-tubules in the context of pressure-overloading.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0304-39402020Effects of Bitter Receptor Antagonists on Behavioral Lick Responses of Mice135041ENMichimasaMasamotoDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihiroMitohDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotoiKobashiDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNoriatsuShigemuraSection of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu UniversityRyusukeYoshidaDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Bitter taste receptors TAS2Rs detect noxious compounds in the oral cavity. Recent heterologous expression studies reported that some compounds function as antagonists for human TAS2Rs. For examples, amino acid derivatives such as γ-aminobutyric acid (GABA) and Nα,Nα-bis(carboxymethyl)-L-Lysine (BCML) blocked responses to quinine mediated by human TAS2R4. Probenecid inhibited responses to phenylthiocarbamide mediated by human TAS2R38. In this study, we investigated the effects of these human bitter receptor antagonists on behavioral lick responses of mice to elucidate whether these compounds also function as bitter taste blockers. In short-term (10 s) lick tests, concentration-dependent lick responses to bitter compounds (quinine-HCl, denatonium and phenylthiourea) were not affected by the addition of GABA or BCML. Probenecid reduced aversive lick responses to denatonium and phenylthiourea but not to quinine-HCl. In addition, taste cell responses to phenylthiourea were inhibited by probenecid. These results suggest some bitter antagonists of human TAS2Rs can work for bitter sense of mouse.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1387-70031242021Effect of ultrasonic irradiation on γ-Fe2O3 formation by co-precipitation method with Fe3+ salt and alkaline solution108400ENHayatoKoizumiDepartment of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityMd. AzharUddinDepartment of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityYoshieiKatoDepartment of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityThe effect of ultrasonic irradiation on direct maghemite (γ-Fe2O3) preparation by a co-precipitation method with Fe3+ salt (Fe(NO3)3) and an excess amount of alkaline (KOH) solution without going through the conventional magnetite (Fe3O4) formation route was explored in comparison with impeller stirring. The preparation procedure for obtaining iron oxide nanoparticles was designed using the sequential processes of precipitation, decantation, drying and thermal dehydration, and ultrasonic irradiation or impeller stirring was done during the precipitation process. γ-ferric oxyhydroxide (γ-FeOOH) was partially formed in addition to α-ferric oxyhydroxide (α-FeOOH) and thermally dehydrated to γ-Fe2O3 and hematite (α-Fe2O3) by ultrasonic-assisted co-precipitation of Fe3+ salt and the excess KOH solution, whereas only α-FeOOH and α-Fe2O3 were synthesized by impeller stirring. The difference between the products of the two methods was explained by the Lamer model associated with the nucleation and growth of FeOOH. Magnetization increased as the crystallite diameter decreased, which is estimated to facilitate partial formation of magnetic γ-Fe2O3. Magnetization was enhanced by a lower ultrasonic frequency due to the stronger shock wave induced by the cavitation effect.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1323-8930 6542016Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts414419ENKengoKanaiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMitsuhiroOkanoDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTazukoFujiwaraDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinKariyaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakenoriHarunaDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaroOmichiDepartment of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSei-ichiroMakiharaDepartment Otorhinolaryngology, Kagawa Rosai HospitalYujiHirataDepartment Otorhinolaryngology, Kagawa Prefectural Central HospitalKazunoriNishizakiDepartment Otorhinolaryngology, Kagawa Prefectural Central HospitalBackground: Vascular endothelial growth factor (VEGF) is known to be associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). VEGF is produced by a variety of cells including fibroblasts. It was recently reported that prostaglandin (PG) E-2 induces VEGF release by nasal polyp fibroblasts. However, little is known regarding possible regulation of VEGF by other PGs. We have reported that molecules that regulate PGD(2) metabolism play roles in the pathogenesis of CRS including in local eosinophilia and type 2 cytokine production. In the present study, we sought to determine whether PGD(2) regulates VEGF release by nasal polyp fibroblasts. <br/>
Methods: Nasal polyp fibroblasts were established from nasal polyps. These fibroblasts were stimulated with serial dilutions of PGD(2) or PGD(2) receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. The concentration of VEGF in the culture supernatants was determined using ELISA. <br/>
Results: 5 mM of PGD(2) significantly induced VEGF release by nasal polyp fibroblasts. VEGF release was also obtained by stimulation with a DP receptor-selective, but not with a CRTH2 receptor-selective agonist. In addition, PGD(2)-induced VEGF release was significantly inhibited by pre-treatment with DP receptor-selective antagonists. In contrast, pre-treatment with a CRTH2 receptor-selective antagonist significantly enhanced PGD(2)-induced VEGF release. <br/>
Conclusions: PGD(2) stimulates VEGF production via DP but not CRTH2 receptors in nasal polyp fibroblasts. Copyright (C) 2016, Japanese Society of Allergology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama22146873202020Early chondral damage following meniscus repairs with anterior cruciate ligament reconstruction15ENTakaakiHiranakaDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University HospitalKamatsukiKamatsukiDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKazuhisaSugiuDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityShinichiiyazawaDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYoshikiOkazakiDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityShinMasudaDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYukiOkazakiDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University,YuyaKodamaDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityToshifumiOzakiDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBackground</br>
Meniscal tears are commonly observed in patients with anterior cruciate ligament (ACL) injuries. Meniscal repair has become a common procedure for the injured meniscus, and good clinical outcomes have been reported in such cases when used concurrently with ACL reconstruction. However, it is unclear whether early chondral damage progression can be prevented following meniscal repair with ACL reconstruction, as meniscal damage is a potential risk factor for the development of osteoarthritis. The purpose of this study was to evaluate the zone-specific chondral damage that occurs after arthroscopic meniscal repair with concomitant ACL reconstruction. Our hypothesis was that meniscal repair with ACL reconstruction would not decrease the rate of progression of chondral damage compared to that observed in isolated ACL reconstruction with intact menisci.</br>
Methods</br>
This study included 40 patients who underwent anatomic double-bundle ACL reconstruction. We divided the patients into the following two groups: Group A with an intact meniscus (20 knees) and Group M requiring meniscal repair (20 knees). Chondral damage was evaluated arthroscopically in six compartments and 40 sub-compartments, and these features were graded using the International Cartilage Repair Society lesion classification. The cartilage damage in each sub-compartment and compartment was compared between the two groups both at reconstruction and at second-look arthroscopy (average 16 months postoperatively). At the latest follow-up examination (average 37 months postoperatively), the International Knee Documentation Committee (IKDC) score was compared between the two groups.</br>
Results</br>
Group M had a significantly worse cartilage status than Group A in five sub-compartments (mainly in the medial compartment) at reconstruction and in nine sub-compartments (mainly in the bilateral compartments) at second-look arthroscopy. The mean IKDC score was better in Group A than in Group M (Group A; 90 vs. Group M; 86). The overall success rate of meniscal repairs was 92% (23 of 25 menisci) at second-look arthroscopy.</br>
Conclusion</br>
The progression of post-traumatic chondral damage may occur at a faster rate in patients who require ACL reconstruction and meniscal repair than in patients with intact menisci.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama004896976552019Early childhood exposure to maternal smoking and Kawasaki Disease: A longitudinal survey in Japan141146EN TakashiYorifujiDepartment of Human Ecology, Graduate School of Environmental and Life Science, Okayama University HirokazuTsukaharaDepartment of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HiroyukiDoiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kawasaki disease is the leading cause of acquired childhood heart disease in most developed countries, but the etiology of the disease is unknown. An aberrant immune response to some environmental triggers may play a role and involuntary exposure to tobacco smoke can alter immune functions. We thus prospectively examined the association between early childhood exposure to maternal smoking and the incidence of Kawasaki disease. We used a large, nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 38,444 children for whom information on maternal smoking was available. Maternal smoking status was ascertained at 6months of age, and responses to questions about hospital admission for Kawasaki disease between the ages of 6 and 30months were used as outcome. We conducted binomial log-linear regression analyses adjusting for children's, parental, and residential factors with children of non-smoking mothers as our reference group. Maternal smoking increased the risk of admission, in particular for the period between 6 and 18months of age, in a dose-dependent manner. Compared with children of non-smoking mothers, the children of mothers who smoked had a risk ratio of 1.83 (95% confidence interval: 1.06, 3.35) for hospital admissions between 6 and 30months of age and a risk ratio of 2.69 (95% confidence interval: 1.56, 4.64) for hospital admissions between 6 and 18months of age. Early childhood exposure to maternal smoking may increase the risk of Kawasaki disease hospitalizations in childhood.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama193004331632021Dysostosis in mucopolysaccharidosis type 2: A case of longitudinal follow up and literature review656660ENTomoakiSasakiDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityMikiOgataDepartment of Radiology, Asahikawa Medical UniversityAyaKajihamaDepartment of Pediatrics, Asahikawa Medical UniversityKouichiNakauDepartment of Pediatrics, Asahikawa Medical UniversityAtsutakaOkizakiDepartment of Radiology, Asahikawa Medical University Mucopolysaccharidosis type 2 is a congenital lysosomal disease characterized by iduronate-2-sulfatase deficiency, which leads to excessive accumulation of glycosaminoglycans in tissue. Dysostosis, which primarily involves decreased bone mineralization with morphological changes in the bone, is a major skeletal condition in mucopolysaccharidosis, but its pathophysiology is not well known. Here, we report a case of mucopolysaccharidosis type 2 diagnosed at the age of 2 years with longitudinal follow-up data for more than 15 years. Although the patient underwent bone marrow transplantation, the developmental quotient did not improve, and cranial hyperostosis progressed prominently with a faintly dilated perivascular space. Other dysostoses and contraction of the joints were observed but did not improve either.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama019701861322020Dopaminergic neuroprotective effects of rotigotine via 5-HT1A receptors: Possibly involvement of metallothionein expression in astrocytes104608ENNamiIsookaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIkukoMiyazakiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoKikuokaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKouichiWadaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesErikaNakayamaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKotaroShinDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaichiYamamotoDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaKitamuraDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoAsanumaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAstrocytes exert neuroprotective effects through production of antioxidant molecules and neurotrophic factors. A recent study showed that stimulation of astrocyte serotonin 1A (5-HT1A) receptors promotes astrocyte proliferation and upregulation of the antioxidant molecules metallothionein (MT)-1,2, which protect dopaminergic neurons against oxidative stress. Rotigotine, an anti-parkinsonian drug, can bind to dopamine and 5-HT1A receptors. In this study, we examined neuroprotective effects of rotigotine in models of Parkinson's disease and involvement of astrocyte 5-HT1A receptors in neuroprotective effects of rotigotine against dopaminergic neurodegeneration. Rotigotine increased the number of astrocytes and MT-1,2 expression in cultured astrocytes. Pretreatment with conditioned media from rotigotine-treated astrocytes significantly inhibited 6-hydroxydopamine (6-OHDA)-induced dopaminergic neurotoxicity. These effects were completely blocked by a 5-HT1A antagonist or MT-1,2 specific antibody. Subcutaneous administration of rotigotine increased MT-1,2 expression in striatal astrocytes and prevented reduction of dopaminergic neurons in the substantia nigra of a 6-OHDA-lesioned mouse model of Parkinson's disease. These effects were blocked by co-administration with a 5-HT1A antagonist. These results suggest that rotigotine exerts neuroprotective effects through upregulation of MT expression in astrocytes by targeting 5-HT1A receptors. Our findings provide a possible therapeutic application of rotigotine to prevent dopaminergic neurodegeneration in Parkinson's disease.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X26102020Disseminated Mycobacterium genavense infection mimicking TAFRO syndrome10951099ENKosukeOkaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaiYamaneDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuyaYokotaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMihoYasudaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKouHasegawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakumiFujimoriMicrobiology Division, Clinical Laboratory, Okayama University HospitalKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTAFRO syndrome is a rare variant of idiopathic multicentric Castleman's disease, for which disseminated non-tuberculous mycobacteria (NTM) infection must be excluded. However, due to the slow and fastidious growth of the organisms, identification of the pathogen is often challenging. We herein describe a case of disseminated Mycobacterium genavence infection, in which manifestations of the patient were confusingly similar to those of TAFRO syndrome. A 69-year-old Japanese man presented with prolonged fever accompanying pain in his back and ribs on the right side. Systemic investigations revealed thrombocytopenia, marked elevation of alkaline phosphatase, anasarca (pleural effusion and ascites), megakaryocytosis in the bone marrow, and hepatomegaly. Magnetic resonance imaging (MRI) showed diffuse, T1-and T2-low-intensity spotted lesions on his vertebral bodies, but biopsy showed inconclusive results. The patient met the diagnostic criteria of TAFRO syndrome and was started on prednisolone, which improved his general condition shortly thereafter. Blood culture after 42 days of incubation revealed the presence of Mycobacterium; however, we considered it a contamination at that time because no organisms grew on conventional agars, and the patient was discharged. Ten weeks after the isolation of Mycobacterium, he developed persistent fever and was readmitted. This time, vertebral bone mallow biopsy demonstrated a large amount of mycobacterium, which was later successfully identified as M. genavense by sequencing analysis. Under a final diagnosis of disseminated M. genavense infection, we treated the patient with clarithromycin, rifampicin, and ethambutol. This case highlighted that disseminated NTM infection may follow a similar clinical course as that of TAFRO syndrome.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama003808066012020Disaster report of 2018 July heavy rain for geo-structures and slopes in Okayama300314ENS.NishimuraOkayama UniversityY.TakeshitaOkayama UniversityS.NishiyamaOkayama UniversityS.SuzukiOkayama UniversityT.ShibataOkayama UniversityT.ShukuOkayama UniversityM.KomatsuOkayama UniversityB.KimOkayama UniversityIn July 2018, heavy rain and a large amount of damage to geo-structures and natural slopes were reported in Okayama, Japan. In particular, in the area surrounding the Oda River System, 52 people drowned due to the breach of river banks. Besides the flooding of rivers, the earth-fill dams of many water reservoirs were damaged. The stability of the large number of earth-fill dams in the Setouchi area is very important. Heavy rain is often associated with the collapse of slopes. In Okayama, many shallow slope failures or debris flows occurred over a wide area, particularly in the western part of the prefecture. Through detailed investigations, the mechanism of this geo-disaster was clarified.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama002016934982019Dinuclear lanthanoid(III) dithiocarbamato complexes bridged by (E)-N-benzylidenepicolinohydrazonate: Syntheses, crystal structures and spectroscopic properties119124ENAbdallahYakubuGraduate School of Natural Science and Technology, Okayama UniversityTakayoshiSuzukiResearch Institute for Interdisciplinary Science, Okayama UniversityMasakazuKitaFaculty of Education, Okayama University (E)-N-Benzylidenepicolinohydrazide (Hbphz) was used to synthesize a series of hydrazonato-bridged homodinuclear Ln(2)(III) dithiocarbamato (RR'dtc(-)) complexes of the form [{Ln(RR' dtc)(2)}(2)(mu-bphz)(2)] {Ln= La, Pr, Nd, Sm or Eu; RR'= dimethyl-(Me-2) or pyrrolidine-(pyr)}. X-ray crystallographic studies revealed that these complexes possessed a common head-to-tail type dinuclear structural motif in which two hydrazonato ligands bridged two Ln(III) centers in the mu- 1 kappa N-2(py),O:2 kappa O-2,N(imine) mode and two RR'dtc ligands coordinated to each Ln(III) center. Interestingly, while the Sm-III and Eu-III complexes crystallized as simple 8:8-coordinate dinuclear molecules, the lighter Ln(III) (i.e. La-III, Pr-III and Nd-III) complexes afforded in some cases 9:9-coordinate molecules, where the ninth coordination site was occupied by a solvent ethanol or methanol molecule. Even for the lighter Ln(III) complexes, the complexes were solved in dichloromethane or chloroform as the 8:8-coordinate dimer, as revealed by H-1 NMR spectroscopy. In the UV-visible absorption and magnetic circular dichroism (MCD) spectra of the complexes, similar spectral patterns for ligand-centered and Laporte forbidden f-f transitions were observed. The MCD spectral studies demonstrated the characteristic magneto-optical behavior of the complexes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0387-76044092018Differential diagnosis of nonepileptic twilight state with convulsive manifestations after febrile seizures781785ENHiroyukiMiyaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyukiAkiyamaDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiWakiDepartment of Pediatrics, Kurashiki Central HospitalYoshioArakakiDepartment of Pediatrics, Kurashiki Central HospitalBackground</br>
Nonepileptic twilight state with convulsive manifestations (NETC) is a nonepileptic state following a febrile seizure (FS), which may be misdiagnosed as a prolonged seizure and result in overtreatment. We aimed to describe clinical manifestations of NETC and to determine characteristics that are helpful to distinguish NETC from other pathological conditions.</br>
Methods</br>
We conducted a retrospective chart review from January 2010 to December 2016 and selected the patients who presented with symptoms resembling status epilepticus with fever and a confirmed diagnosis using an electroencephalogram (EEG). We compared the NETC clinical features and venous blood gas analysis results with those of other conditions that mimic NETC. We also compared the characteristics of NETC with past reports.</br>
Results</br>
Our NETC patients presented with short durations of the preceding generalized convulsions followed by tonic posturing, closed eyes, no cyanosis, responsiveness to painful stimulation, and no accumulation of CO2 in the venous blood gas. Most of these characteristics were consistent with past reports. Prolonged FS or acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) showed several of these features, but all the characteristics were not consistent with our study.</br>
Conclusions</br>
Prolonged FS and AESD need to be differentiated from NETC, and close clinical observation makes it possible to partially distinguish NETC from the other conditions. EEG is recommended for patients with symptoms that are inconsistent with these features.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama094926582622020Differences between the root and horn cells of the human medial meniscus from the osteoarthritic knee in cellular characteristics and responses to mechanical stress230236ENYukiOkazakiOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiFurumatsuOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYusukeKamatsukiOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKeiichiroNishidaOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshihisaNasuOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyuichiNakaharaOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTaichiSaitoOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshifumiOzakiOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground</br>
Many histological, mechanical, and clinical studies have been performed on the medial meniscus posterior root attachment, as it often tears in patients with osteoarthritic knee. Medial meniscal root repair is recommended in clinical situations; however, to date, no studies have examined the differences between meniscal root and horn cells. The aim of this study was, therefore, to investigate the morphology, reaction to cyclic tensile strain, and gene expression levels of medial meniscal root and horn cells.</br>
Methods</br>
Meniscal samples were obtained from the medial knee compartments of 10 patients with osteoarthritis who underwent total knee arthroplasty. Root and horn cells were cultured in Dulbecco's modified Eagle's medium without enzymes. The morphology, distribution, and proliferation of medial meniscal root and horn cells, as well as the gene and protein expression levels of Sry-type HMG box 9 and type II collagen, were determined after cyclic tensile strain treatment.</br>
Results</br>
Horn cells had a triangular morphology, whereas root cells were fibroblast-like. The number of horn cells positive for Sry-type HMG box 9 and type II collagen was considerably higher than that of root cells. Although root and horn cells showed similar levels of proliferation after 48, 72, or 96 h of culture, more horn cells than root cells were lost following a 2-h treatment with 5% and 10% cyclic tensile. Sry-type HMG box 9 and α1(II) collagen mRNA expression levels were significantly enhanced in both cells after 2- and 4-h cyclic tensile strain (5%) treatment.</br>
Conclusions</br>
Medial meniscal root and horn cells have distinct morphologies, reactions to mechanical stress, and cellular phenotypes. Our results suggest that physiological tensile strain is important to activate extracellular matrix production in horn cells.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-478X12020Dicer monitoring in a model filamentous fungus host, Cryphonectria parasitica100001ENAnnisaAuliaInstitute of Plant Science and Resources, Okayama UniversityMidoriTabaraTokyo University of Agriculture and Technology, Department of Applied Biological SciencesPaulTelengechInstitute of Plant Science and Resources, Okayama UniversityToshiyukiFukuharaTokyo University of Agriculture and Technology, Department of Applied Biological SciencesNobuhiroSuzukiInstitute of Plant Science and Resources, Okayama UniversityThe ascomycete Cryphonectria parasitica has served as a model filamentous fungus for studying virus host interactions because of its susceptibility to diverse viruses, its genetic manipulability and the availability of many biological and molecular tools. Cryphonectria prasitica is known to activate antiviral RNA silencing upon infection by some viruses via transcriptional up-regulation of key RNA silencing genes. Here, utilizing a newly developed GFP-based reporter system to monitor dicer-like 2 (dcl2) transcript levels, we show different levels of antiviral RNA silencing activation by different viruses. Some viruses such as mycoreovirus 1, a suppressor-lacking mutant of Cryphonectria hypovirus 1 (CHV1-Δp69) and Rosellinia necatrix partitivirus 11 (RnPV11) highly induced RNA silencing, while others such as CHV3, Rosellinia necatrix victorivirus 1 and RnPV19 did not. There was considerable variation in dcl2 induction by different members within the family Hypoviridae with positive-sense single-stranded RNA genomes or Partitiviridae with double-stranded RNA genomes. Northern blotting and an in vitro Dicer assay developed recently by us using mycelial homogenates validated the reporter assay results for several representative virus strains. Taken together, this study represents a development in the monitoring of Dicer activity in virus-infected C. parasitica.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-8440942023Diagnostic value of circulating microRNA-21 in chronic lung allograft dysfunction after bilateral cadaveric and living-donor lobar lung transplantatione14903ENToshioShiotaniOrgan Transplant Center, Okayama University HospitalSeiichiroSugimotoOrgan Transplant Center, Okayama University HospitalYasuakiTomiokaOrgan Transplant Center, Okayama University HospitalHaruchikaYamamotoDepartment of General Thoracic Surgery, Okayama University HospitalShinTanakaOrgan Transplant Center, Okayama University HospitalKentarohMiyoshiDepartment of General Thoracic Surgery, Okayama University HospitalKenSuzawaDepartment of General Thoracic Surgery, Okayama University HospitalKazuhikoShienDepartment of General Thoracic Surgery, Okayama University HospitalHiromasaYamamotoDepartment of General Thoracic Surgery, Okayama University HospitalMikioOkazakiDepartment of General Thoracic Surgery, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery, Okayama University HospitalBackground: MicroRNAs (miRNAs) involved in the pathogenesis of pulmonary fibrosis have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). We investigated the role of circulating miRNAs in the diagnosis of CLAD after bilateral LT, including cadaveric LT (CLT) and living-donor lobar LT (LDLLT). <br>
Methods: The subjects of this retrospective study were 37 recipients of bilateral CLT (n = 23) and LDLLT (n = 14), and they were divided into a non-CLAD group (n = 24) and a CLAD group (n = 13). The plasma miRNA levels of the two groups were compared, and correlations between their miRNAs levels and percent baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) values were calculated from one year before to one year after the diagnosis of CLAD. <br>
Results: The plasma levels of both miR-21 and miR-155 at the time of the diagnosis of CLAD were significantly higher in the CLAD group than in the non-CLAD group (miR-21, P = 0.0013; miR155, P = 0.042). The miR-21 levels were significantly correlated with the percent baseline FEV1, FVC, and TLC value of one year before and at the time of diagnosis of CLAD (P < 0.05). A receiver operating characteristic curve analysis of the performance of miR-21 levels in the diagnosis of CLAD yielded an area under the curve of 0.89. <br>
Conclusion: Circulating miR-21 appears to be of potential value in diagnosing CLAD after bilateral LT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0968-08962812020Development and characterization of a 68Ga-labeled A20FMDV2 peptide probe for the PET imaging of αvβ6 integrin-positive pancreatic ductal adenocarcinoma115189ENTakashiUiGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasashiUedaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYusukeHigakiGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversitShinichiroKaminoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKoheiSanoGraduate School of Pharmaceutical Sciences, Kyoto UniversityHiroyukiKimuraGraduate School of Pharmaceutical Sciences, Kyoto UniversityHideoSajiGraduate School of Pharmaceutical Sciences, Kyoto UniversityShuichiEnomotoRIKEN Center for Life Science TechnologiesPancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal cancers. Since the majority of patients are diagnosed at an advanced stage, development of a detection method for PDAC at an earlier stage of disease progression is strongly desirable. Integrin αVβ6 is a promising target for early PDAC detection because its expression increases during precancerous changes. The present study aimed to develop an imaging probe for positron emission tomography (PET) which targets αVβ6 integrin-positive PDAC. We selected A20FMDV2 peptide, which binds specifically to αvβ6 integrin, as a probe scaffold, and 68Ga as a radioisotope. A20FMDV2 peptide has not been previously labeled with 68Ga. A cysteine residue was introduced to the N-terminus of the probe at a site-specific conjugation of maleimide-NOTA (mal-NOTA) chelate. Different numbers of glycine residues were also introduced between cysteine and the A20FMDV2 sequence as a spacer in order to reduce the steric hindrance of the mal-NOTA on the binding probe to αVβ6 integrin. In vitro, the competitive binding assay revealed that probes containing a 6-glycine linker ([natGa]CG6 and [natGa]Ac-CG6) showed high affinity to αVβ6 integrin. Both probes could be labeled by 67/68Ga with high radiochemical yield (>50%) and purity (>98%). On biodistribution analysis, [67Ga]Ac-CG6 showed higher tumor accumulation, faster blood clearance, and lower accumulation in the surrounding organs of pancreas than did [67Ga]CG6. The αVβ6 integrin-positive xenografts were clearly visualized by PET imaging with [68Ga]Ac-CG6. The intratumoral distribution of [68Ga]Ac-CG6 coincided with the αVβ6 integrin-positive regions detected by immunohistochemistry. Thus, [68Ga]Ac-CG6 is a useful peptide probe for the imaging of αVβ6 integrin in PDAC.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-3409422022Developing a dataset for the expected anthropogenic mercury release in China in response to the Minamata convention on mercury108280ENHabuerGraduate School of Environmental and Life Science, Okayama UniversityTakeshiFujiwaraGraduate School of Environmental and Life Science, Okayama UniversityMasakiTakaokaGraduate School of Engineering, Kyoto UniversityThis paper contains supplementary data in support of a research paper published [1] regarding the expected anthropogenic mercury release in China in response to the Minamata Convention on Mercury (MCM). The dataset provided within this article contains a set of excel spreadsheets. Each spreadsheet contains filtered (collected) and analysed data, i.e., parameters, collected data, calculated and summarized results for mercury distribution by the category of mineral production, intentional uses, secondary metal production, extraction and combustion, and waste treatment in a specific year. The collected (filtered) data in this article consist of the input factor (IF), activity rate data (ARD), output scenario (OS), initial distribution factor (iDF), and redistribution factor (rDF). IF was from the default IF in the United Nations Environment Programme (UNEP) Toolkit Level 2 and published scientific papers. ARD was obtained from the U.S. Geological Survey database, China Statistical Yearbooks, and published scientific papers. The OS content was from the default OS in the UNEP Toolkit Level 2 and published scientific papers. iDF was from the default distribution factor (DF) in the UNEP Toolkit Level 2 and published scientific papers. rDF was from published scientific paper. The mercury input was calculated using IF and ARD. The mercury release to different media in the initial distribution step was calculated using the mercury input and iDF. The release of mercury to the final sinks in the redistribution step was calculated using the amount of sector-specific treatment/disposal, product or by-product, and rDF. The dataset with combination of the collected (filtered) and analyzed data can contribute to an understanding of differences in anthropogenic mercury release before and after implementation of the MCM, especially considering technology transformation in China. Government policymakers involved in hazardous waste management, especially those working on MCM, and engineers and scientists interested in hazardous waste management may benefit from these data. The data can be used for identifying the environmental impact of anthropogenic mercury release before and after the MCM in China. The data can facilitate the creation of strategic management policies for mercury as the MCM is implemented in China.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0003-267012782023Determination of mass-dependent chromium isotopic compositions in geological samples by double spike-total evaporation-thermal ionization mass spectrometry (DS-TE-TIMS)341723ENDilan M.RatnayakeThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityRyojiTanakaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityEizoNakamuraThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityBackground: Chromium isotopes have been used to trace geochemical and cosmochemical processes in the past. However, the presence of multivalent Cr species has made it difficult to isolate Cr from geological samples, particularly for samples with a low Cr mass fraction.<br>
Results: Here, a simple three-step ion exchange chromatography procedure is presented to separate Cr from various sample matrices, ranging from ultramafic to felsic rocks. Throughout each of the column chromatography step, 1 mL of cation exchange resin AG50W-X8 (200–400 mesh) was used as the stationary phase and oxalic acid as a chelating agent, was used in addition to the inorganic acids. This method yielded high recoveries of Cr [93 ± 8% (2SD, N = 7)] regardless of the lithology. The total procedural blank of Cr was <0.5 ng. We also developed a double spike-total evaporation-thermal ionization mass spectrometry (DS-TE-TIMS) technique that significantly reduced sample consumption to ∼20 ng of Cr per each measurement of mass-dependent 53Cr/52Cr.<br>
Significance: This study achieved a 2SD external precision of 0.02‰ for the analysis of NIST NBS3112a and of 0.01–0.07‰ for the geological samples. This study enabled high-precision Cr isotope analysis in geological samples with various matrix and Cr compositions using relatively small sample volumes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama221253455832020Deterioration of high-resolution computed tomography findings predicts disease progression after initial decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone185189ENHisaoHigoOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuakiMiyaharaOkayama University HospitalAkihikoTaniguchiOkayama University HospitalSatoruSenooOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJunkoItanoOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiromiWatanabeOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNaohiroOdaOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroeKayataniNational Hospital Organization Okayama Medical CenterHirohisaIchikawaKKR Takamatsu HospitaTakuoShibayamaNational Hospital Organization Okayama Medical CenterKazuhiroKajimotoKobe Red Cross HospitalYasushiTanimotoNational Hospital Organization Minami-Okayama Medical CenterArihikoKanehiroOkayama Rosai HospitalYoshinobuMaedaOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyukiKiuraOkayama University Hospital OKAYAMA respiratory disease study group (ORDSG)Background</br>
Pirfenidone suppresses the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF). However, IPF progresses in some patients despite treatment. We analyzed patients with meaningful FVC declines during pirfenidone treatment and explored the factors predictive of disease progression after FVC decline.</br>
Methods</br>
This study was a retrospective, multicenter, observational study conducted by the Okayama Respiratory Disease Study Group. We defined initial decline in %FVC as 5% or greater per 6-month period during pirfenidone treatment. IPF patients who were treated with pirfenidone and experienced an initial decline from December 2008 to September 2017 were enrolled.</br>
Results</br>
We analyzed 21 patients with IPF. After the initial decline, 4 (19.0%) patients showed improvement in disease, 11 (52.4%) showed stable disease, and 6 (28.6%) showed progressive disease. There was no significant correlation between %FVC reduction on initial decline and subsequent %FVC change (p = 0.475). Deterioration of high-resolution computed tomography (HRCT) findings on initial decline was observed significantly more often in the progressive versus improved/stable disease groups (100% vs 20.0%, p = 0.009).</br>
Conclusions</br>
We revealed that deterioration of HRCT findings may predict disease progression after the initial decline in %FVC in IPF patients treated with pirfenidone.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama23523409272019Dataset of characteristic remanent magnetization and magnetic properties of early Pliocene sediments from IODP Site U1467 (Maldives platform)104666ENLucaLanciDepartment of Pure and Applied Science, University of UrbinoElenaZanellaAlpine Laboratory of Paleomagnetism ALP - CIMaNLuigiJovaneInstituto Oceanográfico da Universidade de São PauloSimoneGaleottiDepartment of Pure and Applied Science, University of UrbinoMontserratAlonso-GarcíaDivisão de Geologia e Georecursos Marinhos, Instituto Portugues do Mar e da Atmosfera (IPMA)Carlos A.Alvarez-ZarikianInternational Ocean Discovery Program, Texas A&M UniversityNagender NathBejugamGeological Oceanography Division, CSIR-National Institute of OceanographyChristianBetzlerInstitute for Geology, CEN, University of HamburgOr M.BialikDr. Moses Strauss Department of Marine Geosciences, The Leon H. Charney School of Marine Sciences, University of HaifaClara L.BlättlerDepartment of the Geophysical Sciences, University of ChicagoGregor P.EberliDepartment of Marine Geosciences, Department of Marine Geosciences, Rosenstiel School of Marine and Atmospheric Science, University of Miami,Junhua AdamGuoDepartment of Geological Sciences, California State University BakersfieldSébastienHaffenPhysical Properties Specialist, Ecole Nationale Superieure de Geologie, Universite de LorraineSenayHorozalPetroleum and Marine Research Division, Korea Institute of Geoscience and Mineral Resources (KIGAM)MayuriInoueGraduate School of Natural Science and Technology, Okayama UniversityDickKroonDepartment of Geology and Geophysics, University of EdinburgJuan CarlosLayaDepartment of Geology and Geophysics, Texas A&M UniversityAnna LingHui MeeDepartment of Marine Geosciences, Department of Marine Geosciences, Rosenstiel School of Marine and Atmospheric Science, University of MiamiThomasLüdmannInstitute for Geology, CEN, University of HamburgMasatoshiNakakuniDepartment of Environmental Engineering for Symbiosis, Soka UniversityKaoruNiinoGraduate School of Science and Engineering, Yamagata UniversityLoren M.PetrunyEnvironmental Science and Policy Department, George Mason UniversitySanti D.PratiwiDepartment of Geosciences, Geological Engineering Faculty, Universitas PadjadjaranJohn J.G.ReijmerCollege of Petroleum Engineering and Geosciences, King Fahd University of Petroleum and MineralsJesúsReolidDepartamento de Estratigrafía y Paleontología, Universidad de GranadaAngela L.SlagleLamont-Doherty Earth Observatory, Columbia UniversityCraig R.SlossEarth and Environmental Sciences, University of Technology QueenslandXiangSuKey Laboratory of Marginal Sea Geology, South China Sea Institute of Oceanology, Chinese Academy of SciencesPeter K.SwartDepartment of Geological Sciences, Rutgers, The State University of New JerseyJames D.WrightDepartment of Marine Geology, First Institute of Oceanography (FIO) State Oceanic Administration (SOA)ZhengquanYaoLaboratory for Marine Geology, Qingdao National Laboratory for Marine Science and TechnologyJeremy R.YoungDepartment of Earth Sciences, University College LondonThis data article describes data of magnetic stratigraphy and anisotropy of isothermal remanent magnetization (AIRM) from "Magnetic properties of early Pliocene sediments from IODP Site U1467 (Maldives platform) reveal changes in the monsoon system" [1]. Acquisition of isothermal magnetization on pilot samples and anisotropy of isothermal remanent magnetization are reported as raw data; magnetostratigraphic data are reported as characteristic magnetization (ChRM).No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-3409302020Dataset for de novo transcriptome assembly of the African bullfrog Pyxicephalus adspersus105388ENNaokiYoshidaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityChikaraKaitoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityIn this article, we report the first de novo transcriptome assembly of the African bullfrog Pyxicephalus adspersus. In this data, 75,320,390 raw reads were acquired from African bullfrog mRNA using Illumina paired-end sequencing platform. De novo assembly resulted in a total of 136,958 unigenes. In the obtained unigenes, 30,039 open reading frames (ORFs) were detected. This dataset provides basic information for molecular level analysis of this species, which undergoes a state of dormancy under dry conditions at ordinary temperatures called estivation. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071372022Dasatinib-induced massive left chylothorax in a patient with chronic myeloid leukemia101662ENGoMakimotoDepartment of Allergy and Respiratory Medicine, Okayama University HospitaMahitoMisawaDepartment of Hematology, Ako Central HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Allergy and Respiratory Medicine, Okayama University HospitaDasatinib, an effective second-generation tyrosine kinase inhibitor, is used to treat breakpoint cluster region-Ableson-positive chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphocytic leukemia. One common adverse event associated with dasatinib use is fluid retention, including pleural effusion. Chylothorax, however, is a rare adverse event. Although the precise mechanism of dasatinib-induced chylothorax is unclear, almost all cases involve right or bilateral chylothorax, and mostly occur within 5 years of dasatinib initiation. Here, we report a rare case of a patient with dasatinib-induced massive left chylothorax 10 years after dasatinib initiation, which improved after dasatinib termination and a switch to bosutinib.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24054569552019Current Disease Management of Primary Urethral Carcinoma722734ENFlorianJanischDepartment of Urology, Medical University of ViennaMohammadAbufarajDepartment of Urology, Medical University of ViennaHarunFajkovicDepartment of Urology, Medical University of ViennaShojiKimuraDepartment of Urology, Medical University of ViennaTakehiroIwataDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPeterNyiradyDepartment of Urology, Semmelweis UniversityMichaelRinkDepartment of Urology, University Medical Center Hamburg-EppendorfShahrokh F.ShariatDepartment of Urology, Medical University of ViennaContext: Primary urethral cancer (PUC) is a rare cancer entity. Owing to the low incidence of this malignancy, the main body of literature consists mainly of case reports, making evidence-based management recommendations difficult.<br/>
Objective: To review reported disease management strategies of PUC and their impact on oncological outcomes.<br/>
Evidence acquisition: A systematic research was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement using Medline, Scopus, and Web of Science, to find studies of the past 10yr including ≥20 patients, and investigating treatment strategies and their impact on outcomes of the three most frequent histologies: urothelial carcinoma, adenocarcinoma, and squamous cell carcinoma.
Evidence synthesis: In localized PUC, penis-sparing surgery can be performed in males, while in females, complete urethrectomy with surrounding tissue is advised to minimize recurrence due to positive margins. Radiotherapy (RT) has worse survival and recurrence rates, as well as more adverse effects, than surgery, limiting its use in genital-preserving therapy. Locally advanced PUC should be treated with multimodal therapy, as monotherapies result in inferior recurrence and survival rates. Extent of surgery is still undecided, favoring radical cyst(oprostat)ectomy with total urethrectomy (RCU). Lymph node involvement is a predictor of survival, highlighting the role of lymph node dissection for disease control and staging. RT can improve survival in combination with surgery and/or chemotherapy (CHT). Neoadjuvant platinum-based CHT can improve overall and recurrence-free survival. At recurrence, salvage therapy with surgery and/or CHT can improve survival. Superficial urothelial carcinoma of the prostatic urethra can be treated with transurethral resection. Stromal invasion often features concomitant bladder cancer with a poor prognosis and requires RCU with or without systemic preoperative CHT.<br/>
Conclusions: PUC is a rare malignancy with an often poor natural course, requiring a stage- and gender-specific risk-based treatment strategy. The role of systematic perioperative CHT and the extent of surgery are becoming more important.<br/>
Patient summary: In this review, we looked at the treatment options for primary urethral cancer. We found that while an organ-confined disease can be managed with local resection, growth beyond the organ border makes a combination of different treatment modalities, such as surgery and systematic chemotherapy, necessary to improve outcomes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0260-87742922021Crystallization characteristics of amorphous trehalose dried from alcohol110325ENTakanariSekitohDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityTakashiOkamotoDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityAkihoFujiokaDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityTomohikoYoshiokaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityShinjiTeruiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHiroyukiImanakaDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityNaoyukiIshidaDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityKoreyoshiImamuraDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityTrehalose forms a glass that can be used to preserve labile substances under desiccation. The crystallization characteristics, namely crystallization temperature (Tcry) and isothermal crystallization behavior of amorphous trehalose, dried from alcohol (methanol, ethanol), was analyzed and the results were compared with those for the amorphous trehalose freeze-dried from water. The use of alcohol as a solvent lowered the Tcry from 184 ± 6 °C for the case of an aqueous solvent to 103 ± 5 °C/methanol and 120 ± 8 °C/ethanol. The formation of multiple forms of crystals and partial melting were suggested by the thermal analysis. Isothermal crystallization experiments showed that the alcohol-originated amorphous trehalose was eventually exclusively converted into β-form crystals. The induction period (tind) before the start of isothermal crystallization was markedly shortened when alcohol was used as the solvent compared to water. The tind values for various amorphous sugar samples including the alcohol-originated ones could be correlated with difference between Tcry and the sample temperature.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1083-351X298122022Crystal structures of photosystem II from a cyanobacterium expressing psbA2 in comparison to psbA3 reveal differences in the D1 subunit102668ENYoshikiNakajimaResearch Institute for Interdisciplinary Science, Okayama UniversityNatsumiUgai-AmoGraduate School of Natural Science and Technology, Okayama UniversityNaokiToneGraduate School of Natural Science and Technology, Okayama UniversityAkikoNakagawaProteo-Science Research Center, Ehime UniversityMasakoIwaiGraduate School and College of Arts and Sciences, The University of TokyoMasahikoIkeuchiGraduate School and College of Arts and Sciences, The University of TokyoMiwaSugiuraProteo-Science Research Center, Ehime UniversityMichihiroSugaResearch Institute for Interdisciplinary Science, Okayama UniversityShenJian-RenResearch Institute for Interdisciplinary Science, Okayama UniversityThree psbA genes (psbA1, psbA2, and psbA3) encoding the D1 subunit of photosystem II (PSII) are present in the ther-mophilic cyanobacterium Thermosynechococcus elongatus and are expressed differently in response to changes in the growth environment. To clarify the functional differences of the D1 protein expressed from these psbA genes, PSII dimers from two strains, each expressing only one psbA gene (psbA2 or psbA3), were crystallized, and we analyzed their structures at resolu-tions comparable to previously studied PsbA1-PSII. Our results showed that the hydrogen bond between pheophytin/D1 (PheoD1) and D1-130 became stronger in PsbA2-and PsbA3-PSII due to change of Gln to Glu, which partially explains the increase in the redox potential of PheoD1 observed in PsbA3. In PsbA2, one hydrogen bond was lost in PheoD1 due to the change of D1-Y147F, which may explain the decrease in stability of PheoD1 in PsbA2. Two water molecules in the Cl-1 channel were lost in PsbA2 due to the change of D1-P173M, leading to the narrowing of the channel, which may explain the lower efficiency of the S-state transition beyond S2 in PsbA2-PSII. In PsbA3-PSII, a hydrogen bond between D1-Ser270 and a sulfoquinovosyl-diacylglycerol molecule near QB dis-appeared due to the change of D1-Ser270 in PsbA1 and PsbA2 to D1-Ala270. This may result in an easier exchange of bound QB with free plastoquinone, hence an enhancement of oxygen evolution in PsbA3-PSII due to its high QB exchange efficiency. These results provide a structural basis for further functional examination of the three PsbA variants.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0042-68225542021Cryphonectria nitschkei chrysovirus 1 with unique molecular features and a very narrow host range5562ENSabitreeShahiInstitute of Plant Science and Resources, Okayama UniversitySotaroChibaGraduate School of Bioagricultural Sciences, Nagoya UniversityHidekiKondoInstitute of Plant Science and Resources, Okayama UniversityNobuhiroSuzukiInstitute of Plant Science and Resources, Okayama UniversityCryphonectria nitschkei chrysovirus 1 (CnCV1), was described earlier from an ascomycetous fungus, Cryphonectria nitschkei strain OB5/11, collected in Japan; its partial sequence was reported a decade ago. Complete sequencing of the four genomic dsRNA segments revealed molecular features similar to but distinct from previously reported members of the family Chrysoviridae. Unique features include the presence of a mini-cistron preceding the major large open reading frame in each genomic segment. Common features include the presence of CAA repeats in the 5′-untranslated regions and conserved terminal sequences. CnCV1-OB5/11 could be laterally transferred to C. nitschkei and its relatives C. radicalis and C. naterciae via coculturing, virion transfection and protoplast fusion, but not to fungal species other than the three species mentioned above, even within the genus Cryphonectria, suggesting a very narrow host range. Phenotypic comparison of a few sets of CnCV1-infected and -free isogenic strains showed symptomless infection in new hosts.No potential conflict of interest relevant to this article was reported.