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 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 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 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 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 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 -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 Okayama0368-20481812-32010Angle-resolved photoemission spectroscopy for VO<sub>2</sub> thin films grown on TiO<sub>2</sub> (0 0 1) substrates249251ENYMuraokaKSaekiYYaoTWakitaMHiraiTYokoyaREguchiSShinWe present the results of angle-resolved photoemission spectroscopy (ARPES) measurements of metallic VO<sub>2</sub> thin films. The VO<sub>2</sub> thin films have been grown on TiO<sub>2</sub> (0 0 1) single crystal substrates using pulsed laser deposition. The films exhibit a first-order metal–insulator transition (MIT) at 305 K. In the ARPES spectra of the metallic phase for the films, the O 2p band shows highly dispersive feature in the binding energy range of 3–8 eV along the C–Z direction. The periodicity of the dispersive band is found to be 2.2 Å<sup>-1</sup> which is almost identical with the periodicity expected from the c-axis length of the VO<sub>2</sub> thin films. The overall feature of the experimental band structure is similar to the band structure calculations, supporting that we have succeeded in observing the dispersive band of the O 2p state in the metallic VO<sub>2</sub> thin film. The present work indicates that the ARPES measurements using epitaxial thin films are promising for determining the band structure of VO<sub>2</sub>.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0921-4534470S12010Angle-resolved photoemission study of Si electronic structure: Boron concentration dependenceS641S643ENTakanoriWakitaHiroyukiOkazakiYoshihikoTakanoMasaakiHiraiYujiMuraokaTakayoshiYokoyaThe boron concentration dependence of the Si electronic structure of Si(100)2 ~ 1 surfaces were investigated
by angle-resolved photoemission spectroscopy (ARPES). The ARPES spectra exhibit rigid shifts
toward lower binding energy as the boron concentration increases. The band dispersion was obtained
from fitting procedure, and it is found that the top of the valence band does not exceed the Fermi level
even with a boron concentration 35 times larger than the critical concentration of the metal-insulator
transition.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0921-4534470S12010Analysis on photoemission spectrum of superconducting FeSeS389S390ENRikiyaYoshidaTakanoriWakitaHiroyukiOkazakiYoshikazuMizuguchiShunsukeTsudaYoshihikoTakanoHiroyukiTakeyaKazutoHirataYukakoKatoTakayukiMuroMarioOkawaKyokoIshizakaShikShinHisatomoHarimaMasaakiHiraiYujiMuraokaTakayoshiYokoyaIn this paper, we present the result of soft X-ray photoemission spectroscopy and its comparison with the density functional calculation. Although local density approximation seems to be a good starting point for describing the electronic structure of FeSe, the simulated spectrum poorly reproduced the structure around E(B) = 2 eV. This result suggests the necessity of theoretical treatment beyond local density approximation.No 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 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 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 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 Okayama0093-691X7452010Application of a microfluidic sperm sorter to the in-vitro fertilization of porcine oocytes reduced the incidence of polyspermic penetration863870ENHikaruSanoKojiMatsuuraKeijiNaruseHiroakiFunahashiThe objective of this study was to use a microfluidic sperm sorter (MFSS), designed to isolate motile human spermatozoa with laminar flows (no centrifugation), for porcine IVF. Boar spermatozoa were diluted at 1 x 10(8) with a diluent containing 20% seminal fluid and flowed with modified TCM-199 (mM199, with 5 mM caffeine) to introduce motile sperm into the exit chamber for IVF. In Experiment 1, after flowing for 5 min, sperm concentration varied significantly among specific sites within the MFSS collecting chamber (range, 0.8 +/- 0.5 x 10(4) to 575.0 +/- 56.3 x 10(4) cells/mL; mean +/- SEM). In Experiment 2, when porcine IVM oocytes were placed at three locations in the MFSS exit chamber (where only motile spermatozoa accumulated) and subsequently cultured in caffeine-free mM199 for 8 h, sperm penetration rate was not significantly different among places (86.1 +/- 10.5 to 100%), but the monospermic penetration rate was lower (P < 0.05) in oocytes 3.5 mm from the exit position (12.5 +/- 4.8%) than those at 7.5 mm (53.1 +/- 6.0%) or further (41.9 +/- 2.8%) from the exit. In Experiment 3, the normal fertilization index (ratio of monospermic oocytes to number of oocytes examined) 8 h after insemination was higher (P < 0.05) in the MFSS-IVF system (0.375 +/- 0.040) than both standard IVF and transient IVF (0.222 +/- 0.028 and 0.189 +/- 0.027, respectively, with co-culture for 8 h and for 5 min). Developmental competence of fertilized oocytes (blastocyst formation) was higher (P < 0.05) in the MFSS-IVF system (40.9 +/- 2.3%) than in either standard or transient IVF (22.6 +/- 1.4 and 33.7 +/- 3.5%). In conclusion, brief co-culture of porcine oocytes with spermatozoa gradually accumulated in the MFSS chamber improved the efficiency of producing monospermic fertilized embryos and blastocysts. Furthermore, efficiencies were significantly affected by oocyte location within the chamber.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0015-02829432010Blastocyst quality scoring based on morphologic grading correlates with cell number11351137ENKojiMatsuuraNobuyoshiHayashiChisatoTakiueReiHirataToshihiroHabaraKeijiNaruseBlastocyst quality score (BQS), first reported by Rehman et al., is a numerical blastocyst-morphology grading system based on the criteria established by Gardner and Schoolcraft. We demonstrate a positive correlation between the calculated BQS score and cell number by staining thawed human embryos and suggest that BQS can be applied to evaluate culture systems clinically.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 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 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 Okayama1323-89306512016Regulatory effect of TLR3 signaling on staphylococcal enterotoxin-induced IL-5, IL-13, IL-17A and IFN- 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)- 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- by DNPCs. Pretreatment with Poly(IC) dose-dependently inhibited SEB-induced IL-5, IL-13 and IL-17A, but not IFN- 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 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 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 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 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 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 Okayama2405-89634982016A State-Space Modeling via the Galerkin Approximation for a Boundary Control System712ENJunImaiOkayama UniversityKatsuyukiNosoOkayama UniversityAkikoTakahashiOkayama UniversityShigeyukiFunabikiOkayama University For linear distributed parameter systems with a finite number of boundary inputs, we propose a framework to implement the method of weighted residuals using candidate trial functions without boundary homogenization. Proposed scheme utilizes inner product matrix, or Grammian, of the trial functions to separate appropriate homogenized basis functions and the other trial functions matching inhomogeneous boundary conditions. The finite-dimensional approximate model by using the proposed scheme is represented in descriptor form and it is proved to be straightforwardly transformed into state space form. Feasibility of the method is illustrated by a brief controller design example using the approximate model of a heat conduction rod with Dirichlet boundary input.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 1(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 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-1 mRNAs could not be detected. However, VEGF and HIF-1 mRNAs were found in cultured meniscal cells (VEGF: outer > inner; HIF-1: outer = inner). Injury increased mRNA levels of both VEGF and HIF-1, 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-1 expression and VEGF deposition were high in injured meniscal tissue. Our results suggest that injury stimulates the expression of HIF-1 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 Okayama0949-26582242017A giraffe neck sign of the medial meniscus: A characteristic finding of the medial meniscus posterior root tear on magnetic resonance imaging731736ENTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasatakaFujiiDepartment 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 SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBACKGROUND:
The posterior root ligament of the medial meniscus (MM) has a critical role in regulating the MM movement. An accurate diagnosis of the MM posterior root tear (MMPRT) using magnetic resonance imaging (MRI) is important for preventing sequential osteoarthritis following the MMPRT. However, diagnosis of the MMPRT is relatively difficult even after using several characteristic MRI findings. The aim of this study was to identify a useful meniscal body sign of the MMPRT for improving diagnostic MRI reading.
METHODS:
Eighty-five patients who underwent surgical treatments for the MMPRT (39 knees) and other types of MM tears (49 knees) were included. The presence of characteristic MRI findings such as cleft sign, ghost sign, radial tear sign, medial extrusion sign, and new meniscal body shape-oriented "giraffe neck sign" was evaluated in 120 MRI examinations.
RESULTS:
Giraffe neck signs were observed in 81.7% of the MMPRTs and in 3.3% of other MM tears. Cleft, ghost, and radial tear signs were highly positive in the MMPRTs compared with other MM tears. Medial extrusion signs were frequently observed in both groups. Coexistence rates of any 2 MRI signs, except for medial extrusion sign, were 91.7% in the MMPRT group and 5% in other MM tears.
CONCLUSIONS:
This study demonstrated that a new characteristic MRI finding "giraffe neck sign" was observed in 81.7% of the MMPRT. Our results suggest that the combination of giraffe neck, cleft, ghost, and radial tear signs may be important for an accurate diagnostic MRI reading of the MMPRT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0006291X2018Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transitionENToshifumiFujiwaraDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakanoriEguchiDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChiharuSogawaDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKishoOnoDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunMurakamiDepartment of Oral Diagnosis and Dent-maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroIbaragiAdvanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJun-ichiAsaumiDepartment of Oral Diagnosis and Dent-maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKuniakiOkamotoDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityStuart K.CalderwoodDepartment of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolKen-ichiKozakiDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.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--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 g/ml final concentration. The most effective compounds, ralhibitins A, C, and E completely inhibited the growth of Rs1002 at 1.25 g/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 g/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 g/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 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 11B 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 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 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 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 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 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 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 Okayama029414493672019Axially asymmetric traveling fronts in balanced bistable reaction-diffusion equations17911816ENMasaharuTaniguchiResearch Institute for Interdisciplinary Science, Okayama University For a balanced bistable reaction-diffusion equation, an axisymmetric traveling front has been well known. This paper proves that an axially asymmetric traveling front with any positive speed does exist in a balanced bistable reaction-diffusion equation. Our method is as follows. We use a pyramidal traveling front for an unbalanced reaction-diffusion equation whose cross section has a major axis and a minor axis. Preserving the ratio of the major axis and a minor axis to be a constant and taking the balanced limit, we obtain a traveling front in a balanced bistable reaction-diffusion equation. This traveling front is monotone decreasing with respect to the traveling axis, and its cross section is a compact set with a major axis and a minor axis when the constant ratio is not 1.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0022510X4002019A unique Japanese CPEO family with a novel homozygous m.14819 T > G (p. S25A) substitution145147ENEmiNomuraDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasuyukiOhtaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKohTadokoroDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKotaSatoDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyoSasakiDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshiakiTakahashiDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruYamashitaDepartment 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 UniversityYu-ichiGotoMedical Genome Center (MGC), Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience (NIN), National Center of Neurology and PsychiatryKojiAbeDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo 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 -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 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 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 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 Okayama0045-78253502019An iterative Bayesian filtering framework for fast and automated calibration of DEM models268294ENHongyangChengMulti-Scale Mechanics (MSM), Faculty of Engineering Technology, MESA+, University of TwenteTakayukiShukuGraduate School of Environmental and Life Science, Okayama UniversityKlausThoeniCentre for Geotechnical Science and Engineering, The University of NewcastlePamelaTemponeDivision of Exploration and ProductionStefanLudingMulti-Scale Mechanics (MSM), Faculty of Engineering Technology, MESA+, University of TwenteVanessaMagnanimoMulti-Scale Mechanics (MSM), Faculty of Engineering Technology, MESA+, University of TwenteThe nonlinear, history-dependent macroscopic behavior of a granular material is rooted in the micromechanics between constituent particles and irreversible, plastic deformations reflected by changes in the microstructure. The discrete element method (DEM) can predict the evolution of the microstructure resulting from interparticle interactions. However, micromechanical parameters at contact and particle levels are generally unknown because of the diversity of granular materials with respect to their surfaces, shapes, disorder and anisotropy.
The proposed iterative Bayesian filter consists in recursively updating the posterior distribution of model parameters and iterating the process with new samples drawn from a proposal density in highly probable parameter spaces. Over iterations the proposal density is progressively localized near the posterior modes, which allows automated zooming towards optimal solutions. The Dirichlet process Gaussian mixture is trained with sparse and high dimensional data from the previous iteration to update the proposal density.
As an example, the probability distribution of the micromechanical parameters is estimated, conditioning on the experimentally measured stress–strain behavior of a granular assembly. Four micromechanical parameters, i.e., contact-level Youngfs modulus, interparticle friction, rolling stiffness and rolling friction, are chosen as strongly relevant for the macroscopic behavior. The a priori particle configuration is obtained from 3D X-ray computed tomography images. The a posteriori expectation of each micromechanical parameter converges within four iterations, leading to an excellent agreement between the experimental data and the numerical predictions. As new result, the proposed framework provides a deeper understanding of the correlations among micromechanical parameters and between the micro- and macro-parameters/quantities of interest, including their uncertainties. Therefore, the iterative Bayesian filtering framework has a great potential for quantifying parameter uncertainties and their propagation across various scales in granular materials.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0753-33221152019Comprehensive behavioral study of the effects of vanillin inhalation in mice108879ENHiroshiUenoDepartment of Medical Technology, Kawasaki University of Medical WelfareAtsumiShimadaDivision of Food and Nutrition, Nakamura Gakuen University Junior CollegeShunsukeSuemitsuDepartment of Psychiatry, Kawasaki Medical SchoolShinjiMurakamiDepartment of Psychiatry, Kawasaki Medical SchoolNaoyaKitamuraDepartment of Psychiatry, Kawasaki Medical SchoolKentaWaniDepartment of Psychiatry, Kawasaki Medical SchoolYuTakahashiDepartment 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 UniversityYukoFujiwaraDepartment of Health and Sports Science, Kawasaki University of Medical WelfareTakeshiIshiharaDepartment of Psychiatry, Kawasaki Medical SchoolVanillin is widely used in food and cosmetics, among other substances, for its sweet smell. However, the neuropsychological effects of vanillin inhalation have not been elucidated. In this study, we investigated the effect of vanillin inhalation on mouse behavior. First, we investigated whether the aroma of vanillin was attractive or repulsive for mice. Thereafter, the mice inhaled vanillin for 20 min before each test in a series of behavioral tests (elevated plus maze, open field, Y-maze, tail suspension, cotton bud biting, and Porsolt forced swim tests). In these tests, the mice showed a neutral response to vanillin. Mice that inhaled vanillin had a suppressed pain response in the hot plate test. In addition, the grip strength of the forelimbs of mice that inhaled vanillin was decreased. No significant differences were found between the mice inhaling vanillin and control mice in the open field, Y-maze, tail suspension, forced swimming, and aggression tests. These results show that vanillin inhalation has anti-nociceptive effects, similar to other routes of administration. The results also show that vanillin inhalation does not cause significant behavioral effects.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama105230572872019Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion19932002ENXiaLiuDepartment 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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMamiTakemotoDepartment 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/>
Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid- accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood.<br/>
METHODS:<br/>
APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry.<br/>
RESULTS:<br/>
In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid- plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid- pathology and neuronal loss, alleviated neuroinflammation and oxidative stress.<br/>
CONCLUSIONS:<br/>
The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24055808182019Convenient methodology for extraction and subsequent selective propagation of mouse melanocytes in culture from adult mouse skin tissue100619ENNahokoTomonobuDepartment 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 SciencesI. WayanSumardikaDepartment 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 SciencesYusukeInoueFaculty of Science and Technology, Division of Molecular Science, Gunma University, KiryuAkiraYamauchiDepartment of Biochemistry, Kawasaki Medical SchoolKen-ichiYamamotoDepartment 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 SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMouse melanoma B16-BL6 cells are useful cells for cancer metastatic studies. To understand the metastatic principle at molecular levels, it is necessary to carry out experiments in which cancer cells and their normal counterparts are compared. However, unlike normal human melanocytes, preparation of normal mouse melanocytes is quite difficult due to the lack of marketing and insufficient information on an established protocol for primary culture of mouse melanocytes. In this study, we aimed to establish a convenient method for primary culture of mouse melanocytes on the basis of the protocol for human melanocytes. The main obstacles to preparing pure mouse melanocytes are how to digest mouse skin tissue and how to reduce the contamination of keratinocytes and fibroblasts. The obstacles were overcome by collagenase digestion for skin specimens, short time trypsinization for separating melanocytes and keratinocytes, and use of 12-O-Tetradecanoylphorbol 13-acetate (TPA) and cholera toxin in the culture medium. These supplements act to prevent the proliferation of keratinocytes and fibroblasts, respectively. The convenient procedure enabled us to prepare a pure culture of normal mouse melanocytes. Using enriched normal mouse melanocytes and cancerous B16-BL6 cells, we compared the expression levels of melanoma cell adhesion molecule (MCAM), an important membrane protein for melanoma metastasis, in the cells. The results showed markedly higher expression of MCAM in B16-BL6 cells than in normal mouse melanocytes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama138824811042019Bipolar anodic electrochemical exfoliation of graphite powders106475ENHidekiHashimotoDepartment of Applied Chemistry, School of Advanced Engineering, Kogakuin UniversityYusukeMuramatsuDepartment of Applied Chemistry, School of Advanced Engineering, Kogakuin UniversityYutaNishinaResearch Core for Interdisciplinary Sciences, Okayama UniversityHidetakaAsohDepartment of Applied Chemistry, School of Advanced Engineering, Kogakuin UniversityThe electrochemical exfoliation of graphite has attracted considerable attention as a method for large-scale, rapid production of graphene and graphene oxide (GO). As exfoliation typically requires direct electrical contact, and is limited by the shape and/or size of the starting graphite, treatment of small graphite particles and powders, the typical form available commercially, is extremely difficult. In this study, GO nanosheets were successfully prepared from small graphite particles and powders by a bipolar electrochemical process. Graphite samples were placed between two platinum feeder electrodes, and a constant current was applied between the feeder electrodes using dilute sulfuric acid as the electrolyte. Optical microscopy, atomic force microscopy, X-ray diffractometry, Raman spectroscopy, and X-ray photoelectron spectroscopy were employed to examine the samples obtained after electrolysis. The results obtained from these analyses confirmed that anodic electrochemical exfoliation occurs in the graphite samples, and the exfoliated samples are basically highly crystalline GO nanosheets with a low degree of oxidation (C/O = 3.6–5.3). This simple electrochemical method is extremely useful for preparing large amounts of graphene and GO from small particles of graphite.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 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 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 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 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 Okayama092318119612019TNF- 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- 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- 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 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 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 Okayama153847211852019Biochemical outcomes and predictive factors by risk group after permanent iodine-125 seed implantation: Prospective cohort study in 2,316 patients574582EN NorihisaKatayamaDepartment of Radiology, Okayama University Medical School KatsumasaNakamuraDepartment of Radiation Oncology, Hamamatsu University School of Medicine AtsunoriYorozuDepartment of Radiation Oncology, National Hospital Organization Tokyo Medical Center TakashiKikuchiTranslational Research Informatics Center MasanoriFukushimaTranslational Research Informatics Center ShiroSaitoDepartment of Urology, National Hospital Organization Tokyo Medical Center TakushiDokiyaDepartment of Radiology, Kyoundo HospitalPurpose: To evaluate the biochemical freedom from failure (bFFF) by risk group and treatment modality and the predictive factors of bFFF by risk group in patients with prostate cancer undergoing permanent seed implantation (PI) with or without external beam radiation therapy (EBRT) in a nationwide prospective cohort study (Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 [I-125] Seed Implantation) in Japan during the first 2 years.<br/>
Methods and materials: The analyses included 2,316 participants in 42 institutions; bFFF was evaluated using the Phoenix definition and calculated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify the factors associated with bFFF.<br/>
Results: Median followup period was 60.0 months. The 5-year bFFF rates in all patients, 1,028 low-risk patients, 1,114 intermediate-risk patients, and 133 high-risk patients were 93.6%, 94.9%, 92.7%, and 91.1%, respectively. The 5-year bFFF rates in the PI group and EBRT combination therapy group were 93.7% and 93.3%, respectively. In a multivariate analysis, younger age, higher Gleason score (GS), higher percent positive biopsies (%PB), and lower prostate V100 (p = 0.0012, 0.0030, 0.0026, and 0.0368) in all patients; younger age, higher pretreatment prostate-specific antigen, and lower prostate V100 (p = 0.0002, 0.0048, and 0.0012) in low-risk patients; higher GS, higher %PB, and no hormonal treatment (p = 0.0005, 0.0120, and 0.0022) in intermediate-risk patients; and higher GS and higher %PB (p = 0.0329 and 0.0120) in high-risk patients were significantly associated with bFFF.<br/>
Conclusions: PI with or without EBRT resulted in excellent short-term biochemical outcomes in all risk groups, especially in high-risk patients. Age, pretreatment prostate-specific antigen, and prostate V100 in low-risk patients; GS, %PB, and hormonal treatment in intermediate-risk patients; and GS and %PB in high-risk patients were independently affected bFFF.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama075333221172019Behavioural effects of inhalation exposure to dizocilpine (MK-801) in mice109038EN HiroshiUenoDepartment of Medical Technology, Kawasaki University of Medical Welfare ShunsukeSuemitsuDepartment of Psychiatry, Kawasaki Medical School ShinjiMurakamiDepartment of Psychiatry, Kawasaki Medical School NaoyaKitamuraDepartment of Psychiatry, Kawasaki Medical School KentaWaniDepartment of Psychiatry, Kawasaki Medical School YuTakahashiDepartment of Psychiatry, Kawasaki Medical School YosukeMatsumotoDepartment of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University MotoiOkamotoDepartment of Medical Technology, Graduate School of Health Sciences, Okayama University TakeshiIshiharaDepartment of Psychiatry, Kawasaki Medical SchoolThe complex pathophysiology of brain disorders and the difficulty of delivering therapeutic agents to the brain remain major obstacles in the research and development of new therapeutic methods for brain disorders. Therefore, delivering existing therapeutic agents to the central nervous system is expected to provide benefits in various diseases. In this study, we investigated whether inhaled central nervous system drugs reached the brain and affected mouse behaviour. Dizocilpine (MK-801), which increases locomotor activity in mice, was mainly used to study this hypothesis. First, we administered MK-801, an N-methyl-d-aspartate receptor antagonist, to mice via inhalation and examined whether it induced excessive activity similar to that observed after intraperitoneal administration. We also examined the time- and dose-dependency of drug induced changes in mouse behaviour after MK-801 inhalation. Next, we investigated whether inhalation of scopolamine, pentobarbital, and imipramine also affected mouse behaviour. Mice that inhaled MK-801 showed MK-801–induced hyperactivity similar to that observed following intraperitoneal administration. Furthermore, the extent of activity changed in a time- and dose-dependent manner after MK-801 inhalation. Inhalation of pentobarbital, scopolamine, and imipramine also changed mouse behaviour. These results demonstrate that inhalation of MK-801 exerts effects similar to those achieved with intraperitoneal and oral administration in mice. Thus, central nervous system agonists can reach the brain efficiently via inhalation. This finding may facilitate the development of improved therapies for brain disorders.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama132389302019Breastfeeding and risk of food allergy: A nationwide birth cohort in JapanEN NaomiMatsumotoDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University TakashiYorifujiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University KazueNakamuraDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University MasanoriIkedaDepartment of Pediatric Acute Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HirokazuTsukaharaDepartment of Pediatrics, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HiroyukiDoiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground<br/>
Although breastfeeding has been well-established as the preferred method for infant nutrition, its prophylactic effects on food allergy remain controversial. Infantile eczema has been linked to food allergy via percutaneous sensitization; however, this relationship has not been considered in previous studies. We aimed to uncover the prophylactic effects of breastfeeding on food allergy, focusing on eczema-mediated percutaneous sensitization. <br/>
Methods<br/>
This retrospective cohort study was based on 46,616 children from the Longitudinal Survey of Newborns in the 21st Century in Japan, begun in 2001. We classified participants into three groups based on infant feeding practices (exclusive breastfeeding, partial breastfeeding including only colostrum, and formula feeding only) and used information from at least one outpatient visit for food allergy during two observation periods (age 6–18 months and age 6–66 months) as health outcomes. We performed log-binomial regression analysis adjusted for potential confounders and stratified analysis according to infantile eczema status. <br/>Results<br/>
Compared with formula feeding, partial breastfeeding including only colostrum reduced the risk of food allergy only in children with infantile eczema, (RR = 0.66, 95% CI: 0.46, 0.96 for age 6–66 months), whereas exclusive breastfeeding increased this risk in those without infantile eczema (RR = 2.41, 95% CI: 1.40, 4.15, age 6–66 months). The prophylactic effects of breastfeeding on food allergy in the infantile eczema group increased with shorter breastfeeding duration. <br/>
Conclusions<br/>
Our results showed that breastfeeding, especially colostrum, had prophylactic effects on food allergy only among high-risk children with infantile eczema whereas prolonged breastfeeding increased the risk of food allergy.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 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 Okayama22147519182019Cavernous malformation of the optic chiasm with continuous hemorrhage in a pregnant woman: A case report100489ENYusukeTomitaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKentaroFujiiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhikoKurozumiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyojiImotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakashiMitsuiDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSakurakoMishimaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKenichiInagakiDepartment of Endocrine Center, Okayama University HospitalHisashiMasuyamaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesIsaoDateDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground Cavernous malformation of the anterior visual pathway is rare, especially in pregnant woman. Planning a treatment strategy with cross-disciplinary specialists is important. <br/>
Case description A 27-year-old pregnant woman presented with acute hemorrhage around the right optic nerve and chiasm, manifesting as poor vision in both eyes. Examination revealed right-eye deteriorated acuity and bilateral temporal hemianopsia. Computed tomography showed an oval high-density mass in the suprasellar region. Gradient echo-based T2-weighted magnetic resonance imaging showed the lesion to be hypointense (possibly a hematoma) and mainly in the optic chiasm. Fluid attenuated inversion recovery imaging showed a bilateral optic tract surrounding the lesion, which enlarged over 1 week, increasing the loss of visual function. Five days after admission, she delivered a healthy >2500-g baby by cesarean section (CS). Right frontotemporal craniotomy was performed 7 days after CS. Incision of the right optic nerve's lateral surface revealed clotted blood with abnormal vascular construction from the right side of the chiasm. We removed the hematoma and vascular lesion. Visual evoked potentials were detected only after optic chiasm decompression. Histological evaluation revealed a hematoma-like lesion with capsules and hemosiderin deposition, suggesting cavernous malformation. Her postoperative recovery was uneventful, with right visual acuity returning to normal, and her visual field not deteriorating any more. <br/>
Conclusion Devising a treatment strategy with the obstetrician was important in this case to manage the hematoma and cavernous malformation safely.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 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 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 Okayama22102612652019A case of spontaneous mesenteric hematoma successfully diagnosed and treated with aggressive imaging124126ENShunsukeNakamuraDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTaiheiYamadaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTsuyoshiNojimaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHiromichiNaitouDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHitoshiKogaDepartment of Emergency Medicine, St. Maryfs HospitalHisashiYamashitaDepartment of Emergency Medicine, St. Maryfs HospitalAkiraGochiDepartment of Surgery, Ibara City HospitalAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesIntroduction: Spontaneous mesenteric hematoma is an uncommon syndrome triggered by bleeding localized in the mesenteric vascular tree of a bowel segment for no apparent underlying reason. We herein report a surgical patient with an extremely rapidly growing spontaneous mesenteric hematoma that we successfully diagnosed using careful radiologic examination.<br/>
Presentation of case: A 56-year-old old male presenting sudden onset lower abdominal pain was referred to our emergency department. At the time of admission, his physical examination revealed stable vital signs without radiological abnormality. On the following day, the patient suddenly presented hypotension, tachycardia, and increased abdominal pain. Contrast-enhanced computed tomography examination showed a mass with both high- and low-density areas with a 130 mm maximum diameter bordering the transverse colon. Since interventional radiologists were not available, we decided to perform emergency exploratory laparotomy. On laparotomy, a 13 ~ 8 cm hematoma was found in the mesentery of the transverse colon. As bleeding was noted from the branches of the middle colic artery and gastrocolic artery, these responsible vessels were ligated. The patient was finally given the diagnosis of spontaneous mesenteric hematoma.<br/>
Discussion and conclusion: The present case, initially diagnosed as enterocolitis, suddenly manifested hypovolemic shock. Close monitoring for any signs of further deterioration, as well as aggressive imaging diagnosis, enabled us to avoid delays in treatment. Early diagnosis and treatment of mesenteric hematomas are essential to prevent them from rupturing and triggering life-threatening adverse events.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama22144269212019Clinical and genetic aspects of mild hypophosphatasia in Japanese patients100515ENKatsuyukiYokoiDepartment of Pediatrics, Fujita Health University School of MedicineYokoNakajimaDepartment of Pediatrics, Fujita Health University School of MedicineYasukoShinkaiDivision of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health UniversityYoshimiSanoDepartment of Plastic Surgery, Division of Pediatric Dentistry & Orthodontics, Fujita Health University of MedicineMototakaImamuraDepartment of Plastic Surgery, Division of Pediatric Dentistry & Orthodontics, Fujita Health University of MedicineTomoyukiAkiyamaDepartment of Child Neurology, Okayama University HospitalTetsushiYoshikawaDepartment of Pediatrics, Fujita Health University School of MedicineTetsuyaItoDepartment of Pediatrics, Fujita Health University School of MedicineHirokiKurahashiDivision of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health UniversityBackground: Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from a dysfunctional tissue non-specific alkaline phosphatase enzyme (TNSALP). Although genotype-phenotype correlations have been described in HPP patients, only sparse information is currently available on the genetics of mild type HPP.<br/>
Methods: We investigated 5 Japanese patients from 3 families with mild HPP (patients 1 and 2 are siblings; patient 4 is a daughter of patient 5) who were referred to Fujita Health University due to the premature loss of deciduous teeth. Physical and dental examinations, and blood, urine and bone density tests were conducted. Genetic analysis of the ALPL gene was performed in all patients with their informed consent.<br/>
Results: After a detailed interview and examination, we found characteristic symptoms of HPP in some of the study cases. Mobile teeth or the loss of permanent teeth were observed in 2 patients, and 3 out of 5 patients had a history of asthma. The serum ALP levels of all patients were 30% below the lower limit of the age equivalent normal range. ALPL gene analysis revealed compound heterozygous mutations, including Ile395Val and Leu520Argfs in family 1, Val95Met and Gly491Arg in family 2, and a dominant missense mutation (Gly456Arg) in family 3. The 3D-modeling of human TNSALP revealed three mutations (Val95Met, Ile395Val and Gly456Arg) at the homodimer interface. Severe collisions between the side chains were predicted for the Gly456Arg variant.<br/>
Discussion: One of the characteristic findings of this present study was a high prevalence of coexisting asthma and a high level serum IgE level. These characteristics may account for the fragility of tracheal tissues and a predisposition to asthma in patients with mild HPP. The genotypes of the five mild HPP patients in our present study series included 1) compound heterozygous for severe and hypomorphic mutations, and 2) dominant-negative mutations. All of these mutations were at the homodimer interface, but only the dominant-negative mutation was predicted to cause a severe collision effect between the side chains. This may account for varying mechanisms leading to different effects on TNSALP function.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 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 Okayama12019712912019Collagen adhesion gene is associated with blood stream infections caused by methicillin-resistant Staphylococcus aureus2231ENYasunoriIwataDivision of Infection Control, Kanazawa UniversityKenjiSatouFaculty of Electrical and Computer Engineering, Kanazawa UniversityKengoFuruichiDivision of Nephrology, Kanazawa Medical University School of MedicineIkukoYonedaDivision of Nephrology, Kanazawa UniversityTakuhiroMatsumuraDepartment of Bacteriology, Kanazawa UniversityMasahiroYutaniGraduate School of Environmental and Life Science, Okayama UniversityYukakoFujinagaGraduate School of Environmental and Life Science, Okayama UniversityAtsushiHaseFaculty of Electrical and Computer Engineering, Kanazawa UniversityHidetoshiMoritaGraduate School of Environmental and Life Science, Okayama UniversityToshikoOhtaUniversity of TsukubaYasukoSendaDivision of Infection Control, Kanazawa UniversityYukikoSakai-TakemoriDivision of Infection Control, Kanazawa UniversityTaizoWadaDivision of Infection Control, Kanazawa UniversityShinichiFujitaDivision of Infection Control, Kanazawa UniversityTaitoMiyakeDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa UniversityHarukaYasudaDepartment of Nephrology and Laboratory Medicine, Kanazawa UniversityNorihikoSakaiDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Division of Blood Purification, Kanazawa UniversityShinjiKitajimaDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa UniversityTadashiToyamaDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa UniversityYasuyukiShinozakiDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa UniversityAkihiroSagaraDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa UniversityTaroMiyagawaDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa UniversityAkinoriHaraDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa UniversityMihoShimizuDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa UniversityYasutakaKamikawaDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa UniversityKazuhoIkeoLaboratory of DNA Data Analysis, National Institute of GeneticsShigeyukiShichinoDepartment of Molecular Preventive Medicine, University of TokyoSatoshiUehaDepartment of Molecular Preventive Medicine, University of TokyoTakuyaNakajimaDepartment of Molecular Preventive Medicine, University of TokyoKoujiMatsushimaDepartment of Molecular Preventive Medicine, University of TokyoShuichiKanekoepartment of Disease Control and Homeostasis, Kanazawa UniversityTakashiWadaDivision of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Nephrology and Laboratory Medicine, Kanazawa UniversityObjectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. It is not clear whether genetic characteristics of the bacteria contribute to disease pathogenesis in MRSA infection. We hypothesized that whole genome analysis of MRSA strains could reveal the key gene loci and/or the gene mutations that affect clinical manifestations of MRSA infection.<br/>
Methods: Whole genome sequences (WGS) of MRSA of 154 strains were analyzed with respect to clinical manifestations and data. Further, we evaluated the association between clinical manifestations in MRSA infection and genomic information.<br/>
Results: WGS revealed gene mutations that correlated with clinical manifestations of MRSA infection. Moreover, 12 mutations were selected as important mutations by Random Forest analysis. Cluster analysis revealed strains associated with a high frequency of bloodstream infection (BSI). Twenty seven out of 34 strains in this cluster caused BSI. These strains were all positive for collagen adhesion gene (cna) and have mutations in the locus, those were selected by Random Forest analysis. Univariate and multivariate analysis revealed that these gene mutations were the predictor for the incidence of BSI. Interestingly, mutant CNA protein showed lower attachment ability to collagen, suggesting that the mutant protein might contribute to the dissemination of bacteria.<br/>
Conclusions: These findings suggest that the bacterial genotype affects the clinical characteristics of MRSA infection. (c) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. 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 Okayama01452134962019Association between mothersf problematic Internet use and maternal recognition of child abuse104086ENAyaSakakiharaCommunity Health Nursing, Faculty of Medicine, Shimane UniversityChiyoriHagaCommunity Health Nursing, Graduate School of Health Sciences, Okayama UniversityAyaKinjoDivision of Environmental and Preventive Medicine, Faculty of Medicine, Tottori UniversityYoneatsuOsakiDivision of Environmental and Preventive Medicine, Faculty of Medicine, Tottori UniversityBackground: There are few studies about mothers' problematic Internet use (PIU). Mothers' PIU may lead to inadequate parenting and child abuse.<br/>
Objective: This cross-sectional study aimed to clarify the association between mothers' PIU and their recognition of child abuse.<br/>
Participants and setting: We analyzed data collected of health examinations of children aged 4 months, 1.5 years, and 3 years which were carried out in Matsue City, Shimane Prefecture, Japan between April 2016 and March 2017. The number of the subjects were 1685, 1729, 1674, respectively.<br/>
Methods: We used logistic regression analysis to clarify the association between mothers' PIU (Young's Diagnostic Questionnaire for Internet Addiction score: ≥5) and their recognition of child abuse (selecting < True of me > for < I sometimes think that I am abusing my child > on a questionnaire survey), which was adjusted for covariates such as maternal age, number of children, daytime caretaker, social support, postpartum depression, and current smoking status of the parents.<br/>
Results: Based on the multivariate logistic regression analysis, the mothers' PIU was significantly correlated with their recognition of child abuse for children aged 4 months, 1.5 years, or 3 years [odds ratio (OR): 13.30, 95% confidence interval (CI): 1.26-139.98, OR: 7.02, 95% CI: 1.28-38.55, and OR: 28.06, 2.48-317.93, respectively].<br/>
Conclusion: This study revealed the possibility that mothers with PIU recognize child abuse more than mothers without PIU. However, further studies should be conducted to increase reliability and validity.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 Okayama1052305728102019Twendee X Ameliorates Phosphorylated Tau, -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 -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--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 -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 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)-1 and tumor necrosis factor (TNF)--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 B (NF-B) 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 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 17O 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 17O of their olivines range from |23.7 to |6.2. In group 1 olivines, as Fa content increases, variation of 7Li becomes smaller and 7Li 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 7Li 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 17O of ∼|25 to |20, 7Li ranges from |23 to |3; in olivine grains with 17O > |20, 7Li 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 7Li ∼ |11 is inferred.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 Okayama209044792019CO2 concentration measurements inside expansion-compression engine under high EGR conditions using an infrared absorption methodENFatma B.M.AhmedDepartment of Physics, Faculty of Science, Aswan UniversityMohamed F.C.EsmailDepartment Mechanical Power Engineering, Faculty of Energy Engineering, Aswan UniversityNobuyukiKawaharaDepartment of Mechanical Engineering, Okayama UniversityEijiTomitaDepartment of Mechanical Engineering, Okayama UniversityThe purpose of this study is to measure the high concentrations of CO2 near a spark plug inside an internal combustion engine, and an infrared absorption method is used for the measurement. The spark plug sensor was adapted to a compression-expansion machine, and the CO2 concentration near the spark plug was measured by adding a gas mixture, including CO2 to imitate EGR. Next, the EGR ratio was changed from 10 to 40%, and the CO2 concentration was measured. The effect of the CO2 on the flame propagation was investigated by visualizing the bottom view of the compression-expansion machine. The measurements of CO2 mass concentration are in agreement with those predicted by direct-absorption spectroscopy fundamental theory from the crank angle |60 to |15 deg ATDC. The error was less than 20%, and under the conditions with an EGR ratio of 20–40%.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 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 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 Okayama2213-0071282019A case of axillary lymphadenitis caused by Mycobacterium intracellulare in an immunocompetent patient100947ENJunkoItanoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalSatoruSenooDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaohiroOdaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaNishiiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihikoTaniguchiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Medical Technology, Okayama University Graduate School of Health SciencesYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University Hospital Axillary lymphadenitis caused by non-tuberculous mycobacteria is rare and has been reported in immunocompromised hosts. Herein, we report the case of a 67-year-old man without immunodeficiency who developed right axillary lymphadenitis caused by Mycobacterium intracellulare and showed a small nodular shadow in the left pulmonary apex. Biopsy of the right axillary lymph node revealed several epithelioid granulomas, and the culture of the lymph node aspirate yielded Mycobacterium intracellulare. The lymph node lesion and left lung apex shadow resolved spontaneously after careful outpatient monitoring. This case suggests that axillary lymphadenitis could be caused by Mycobacterium intracellulare in an immunocompetent patient.No 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 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 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 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 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 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 Okayama0360-30167342009Analysis of Factors Associated With Radiation-Induced Bronchiolitis Obliterans Organizing Pneumonia Syndrome After Breast-Conserving Therapy10491054ENNorihisaKatayamaDepartment of Radiology, Okayama University HospitalShuheiSatoDepartment of Radiology, Okayama University HospitalKuniakiKatsuiDepartment of Radiology, Okayama University HospitalMitsuhiroTakemotoDepartment of Radiology, Okayama University HospitalToshihideTsudaDepartment of Radiology, Okayama University HospitalAtsushiYoshidaDepartment of Radiology, Okayama University HospitalTsuneharuMoritoDepartment of Radiology, Okayama University HospitalTomioNakagawaDepartment of Radiology, Okayama University HospitalAkifumiMizutaniDepartment of Radiology, Okayama University HospitalTakahiroWakiDepartment of Radiology, Okayama University HospitalHarutakaNiiyaDepartment of Radiology, Okayama University HospitalSusumuKanazawaDepartment of Radiology, Okayama University HospitalPurpose: To evaluate factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome after breast-conserving therapy.<br/>
Methods and materials: A total of 702 women with breast cancer who received radiotherapy after breast-conserving surgery at seven institutions between July 1995 and December 2006 were analyzed. In all patients, the whole breast was irradiated with two tangential photon beams. The criteria used for the diagnosis of radiation-induced BOOP syndrome were as follows: (1) radiotherapy to the breast within 12 months, (2) general and/or respiratory symptoms lasting for >or=2 weeks, (3) radiographs showing lung infiltration outside the radiation port, and (4) no evidence of a specific cause.<br/>
Results: Radiation-induced BOOP syndrome was seen in 16 patients (2.3%). Eleven patients (68.8%) were administered steroids. The duration of steroid administration ranged from 1 week to 3.7 years (median, 1.1 years). Multivariate analysis revealed that age (>or=50 years; odds ratio [OR] 8.88; 95% confidence interval [CI] 1.16-67.76; p = 0.04) and concurrent endocrine therapy (OR 3.05; 95% CI 1.09-8.54; p = 0.03) were significantly associated with BOOP syndrome. Of the 161 patients whose age was >or=50 years and who received concurrent endocrine therapy, 10 (6.2%) developed BOOP syndrome.<br/>
Conclusions: Age (>or=50 years) and concurrent endocrine therapy can promote the development of radiation-induced BOOP syndrome after breast-conserving therapy. Physicians should carefully follow patients who received breast-conserving therapy, especially those who are older than 50 years and received concurrent endocrine therapy during radiotherapy.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 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 gacA 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 Okayama0304-39402020Effects 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 -aminobutyric acid (GABA) and N,N-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 Okayama0306-45223692018Bitter Taste Responses of Gustducin-positive Taste Cells in Mouse Fungiform and Circumvallate Papillae2939ENRyusukeYoshidaSection of Oral Neuroscience, Graduate School of Dental Science, Kyushu UniversityShingoTakaiSection of Oral Neuroscience, Graduate School of Dental Science, Kyushu UniversityKeisukeSanematsuSection of Oral Neuroscience, Graduate School of Dental Science, Kyushu UniversityRobert F.MargolskeeMonell Chemical Senses CenterNoriatsuShigemuraSection of Oral Neuroscience, Graduate School of Dental Science, Kyushu UniversityYuzoNinomiyaSection of Oral Neuroscience, Graduate School of Dental Science, Kyushu University Bitter taste serves as an important signal for potentially poisonous compounds in foods to avoid their ingestion. Thousands of compounds are estimated to taste bitter and presumed to activate taste receptor cells expressing bitter taste receptors (Tas2rs) and coupled transduction components including gustducin, phospholipase C2 (PLC2) and transient receptor potential channel M5 (TRPM5). Indeed, some gustducin-positive taste cells have been shown to respond to bitter compounds. However, there has been no systematic characterization of their response properties to multiple bitter compounds and the role of transduction molecules in these cells. In this study, we investigated bitter taste responses of gustducin-positive taste cells in situ in mouse fungiform (anterior tongue) and circumvallate (posterior tongue) papillae using transgenic mice expressing green fluorescent protein in gustducin-positive cells. The overall response profile of gustducin-positive taste cells to multiple bitter compounds (quinine, denatonium, cyclohexamide, caffeine, sucrose octaacetate, tetraethylammonium, phenylthiourea, L-phenylalanine, MgSO4, and high concentration of saccharin) was not significantly different between fungiform and circumvallate papillae. These bitter-sensitive taste cells were classified into several groups according to their responsiveness to multiple bitter compounds. Bitter responses of gustducin-positive taste cells were significantly suppressed by inhibitors of TRPM5 or PLC2. In contrast, several bitter inhibitors did not show any effect on bitter responses of taste cells. These results indicate that bitter-sensitive taste cells display heterogeneous responses and that TRPM5 and PLC2 are indispensable for eliciting bitter taste responses of gustducin-positive taste cells.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 Womenfs and Childrenfs 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 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 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 Okayama0968-08962812020Development and characterization of a 68Ga-labeled A20FMDV2 peptide probe for the PET imaging of v6 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 V6 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 V6 integrin-positive PDAC. We selected A20FMDV2 peptide, which binds specifically to v6 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 V6 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 V6 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 V6 integrin-positive xenografts were clearly visualized by PET imaging with [68Ga]Ac-CG6. The intratumoral distribution of [68Ga]Ac-CG6 coincided with the V6 integrin-positive regions detected by immunohistochemistry. Thus, [68Ga]Ac-CG6 is a useful peptide probe for the imaging of V6 integrin in PDAC.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama027753871792020A specific formation of an iridium(III) hydrido complex bearing 8-(diphenylphosphino)quinoline114401ENKeitaAriyoshiDepartment of Chemistry, Faculty of Science, Okayama UniversityMaiKoteraDepartment of Chemistry, Faculty of Science, Osaka UniversityAtsushiNamiokaDepartment of Chemistry, Faculty of Science, Okayama UniversityTakayoshiSuzukiDepartment of Chemistry, Faculty of Science, Okayama UniversityA reaction of [Cp*IrCl(Ph2Pqn)]PF6 {Cp* = 5-pentamethylcyclopentadienyl; Ph2Pqn = 8-(diphenylphosphino)quinoline} and Ag(CF3SO3) in methanol afforded orange crystals of the corresponding hydrido complex, [Cp*IrH(Ph2Pqn)]PF6, which was identified by 1H, 31P{1H} NMR and IR spectroscopy as well as X-ray structural analysis. The reactions in deuterated solvents indicated that formation of the hydrido complex proceeded via -hydrogen elimination of the coordinated methanol molecule. It was also revealed that the hydrido formation was specific for the complex bearing Ph2Pqn ancillary ligand; the analogous complex with 1,2-bis(diphenylphosphino)benzene (diphos) or 1,10-phenanthroline (phen) did not give the corresponding hydrido complex by a similar reaction with Ag+ in methanol. In order to elucidate the reason for the different reactivity among these complexes, the crystal structures of the precursor chlorido complexes, [Cp*IrCl(Ph2Pqn)]PF6, [Cp*IrCl(diphos)]PF6 and [Cp*IrCl(phen)]PF6, as well as an acetonitrile complex of [Cp*Ir(Ph2Pqn)(CH3CN)](PF6)2, were also determined by X-ray analysis. The resulting structural information suggested that a specific formation of the hydrido complex with Ph2Pqn could be originated from the facile formation of the corresponding methanol complex and the hemilabile nature of ancillary Ph2Pqn ligand, which induced the reactivity of the coordinated methanol toward -hydrogen elimination.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 Okayama0968-01602732020Comparison of the clinical outcomes of transtibial pull-out repair for medial meniscus posterior root tear: Two simple stitches versus modified Mason-Allen suture701708ENTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University HospitalTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University HospitalShinichiMiyazawaDepartment of Orthopaedic Surgery, Okayama University HospitalYoshikiOkazakiDepartment of Orthopaedic Surgery, Okayama University HospitalYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University HospitalShotaTakihiraDepartment of Orthopaedic Surgery, Okayama University HospitalYuyaKodamaDepartment of Orthopaedic Surgery, National Hospital Organization Iwakuni Clinical CenterYusukeKamatsukiDepartment of Orthopaedic Surgery, National Hospital Organization Iwakuni Clinical CenterShinMasudaDepartment of Orthopaedic Surgery, Chikamori HospitalTaichiSaitoDepartment of Orthopaedic Surgery, Okayama University HospitalToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University HospitalBackground</br>
Transtibial pullout repair of a medial meniscus posterior root tear (MMPRT) is a commonly used procedure, and several techniques have been reported. We hypothesised that pull-out repairs using two simple stitches (TSS) would have similar postoperative outcomes as those using the modified Mason-Allen suture with FasT-Fix (F-MMA). We aimed to investigate the clinical outcomes of these techniques, including the meniscal healing status and osteoarthritic change.</br>
Methods</br>
The data of 68 patients who underwent transtibial pull-out repair were retrospectively investigated. The patients were divided into two groups of 41 and 27 patients using F-MMA and TSS, respectively. The clinical outcomes were assessed preoperatively and at second-look arthroscopy (the mean period from surgery was one year) using the Knee injury and Osteoarthritis Outcome Score. The meniscal healing status, evaluated at second-look arthroscopy, was compared between the two groups. The cartilage damage was graded as per the classification of the International Cartilage Repair Society and compared at the primary surgery and second-look arthroscopy.</br>
Results</br>
Both groups showed significant improvement in each clinical score. No significant difference was seen in the clinical outcome scores and the meniscal healing status between the two groups at second-look arthroscopy. Moreover, no significant progression of cartilage damage was observed in both groups. Fourteen patients in the F-MMA group developed a complication of suture bar failures postoperatively; however, there were no complications in the TSS group.</br>
Conclusions</br>
The TSS and F-MMA techniques showed favourable clinical outcomes and would be established as clinically useful techniques for the MMPRT treatment.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)-B 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 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 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 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 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 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 -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 -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 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 Okayama016890029592020Evaluation of gadoliniumfs 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, Kingfs College LondonB.Richards Department of Physics, Kingfs 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 techniquefs 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 Okayama094926582622020An MRI-based suspension bridge sign can predict an arthroscopically favorable meniscal healing following the medial meniscus posterior root repair237242ENTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University HospitalYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University HospitalTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University HospitalYuyaKodamaDepartment of Orthopaedic Surgery, Okayama University HospitalYusukeKamatsukiDepartment of Orthopaedic Surgery, Okayama University HospitalYoshikiOkazakiDepartment of Orthopaedic Surgery, Okayama University HospitalXimingZhangDepartment of Orthopaedic Surgery, Okayama University HospitalToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University HospitalBackground</br>
Medial meniscus (MM) posterior root repairs show favorable clinical outcomes in patients with MM posterior root tears (MMPRTs). However, there is no useful magnetic resonance imaging (MRI) finding to determine a functionally good meniscal healing following MM posterior root repairs. We hypothesized that a characteristic postoperative MRI finding can predict a good meniscal healing following pullout repairs. The aim of this study was to investigate a clinical usefulness of several MRI findings for estimating an actual meniscal healing following MMPRT repairs.</br>
Methods</br>
Fifty eight patients who had a posteromedial painful popping of the injured knee and underwent an arthroscopic pullout repair for the MMPRT were included. Arthroscopic meniscal healing was assessed according to the Furumatsu scoring system at 1 year postoperatively. We evaluated postoperative MRI-based meniscal healing using signal intensity, continuity, suspension bridge-like sign of the MM posterior root, and MM medial extrusion on coronal images. Postoperative clinical outcome evaluations were performed at second-look arthroscopy.</br>
Results</br>
Twenty three patients showed good arthroscopic healing scores (≥7 points). Thirty five patients had moderate/poor arthroscopic healing scores (<7 points). At 1-year follow-up period, clinical outcome scores were significantly higher in the good healing group than in the moderate/poor healing group. A characteristic meniscal shape, termed gsuspension bridge signh, was highly observed in the good meniscal healing group (83%) compared with in the moderate/poor healing group (26%, P < 0.001). High signal intensity and continuity of the MM posterior root and MM medial extrusion showed no differences between both groups.</br>
Conclusions</br>
Our study demonstrated that the MRI-based suspension bridge sign can predict an arthroscopically favorable meniscal healing following the MM posterior root repair. The suspension bridge-like MRI finding of the MM would be a useful indicator to evaluate the actual meniscal healing in patients who underwent pullout repairs for MMPRTs.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 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 g∙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 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 1(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 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 MiyazakiTakeshiFujigLocomo Challenge!h Promotion CouncilKenichiHiranoHirano Orthopaedics ClinicShinichiIkedaDepartment of Orthopaedic Surgery, Oita University,HideakiIshibashigLocomo Challenge!h Promotion CouncilYasuyukiIshibashiDepartment of Orthopaedic Surgery, Hirosaki University Graduate School of MedicineMuneakiIshijimagLocomo Challenge!h Promotion CouncilEijiItoiDepartment of Orthopaedic Surgery, Tohoku University Graduate School of MedicineNorimasaIwasakigLocomo Challenge!h Promotion CouncilRyoichiIzumidagLocomo Challenge!h 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 MedicineArihikoKanajigLocomo Challenge!h Promotion CouncilHiroyukiKatoDepartment of Orthopaedic Surgery, Shinshu University School of MedicineShunjiKishidagLocomo Challenge!h 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 ClinicKimihitoSatogLocomo Challenge!h 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 SurgerySatoshiYamaguchigLocomo Challenge!h Promotion CouncilNoriakiYamamotoNigata Rehabilitation HospitalKozoNakamuragLocomo Challenge!h Promotion Council OheTakashigLocomo Challenge!h 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 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 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 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 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 182W in modern basalts with high 3He/4He originating from the core-mantle boundary region reveal two distinct features: positive 182W in Phanerozoic flood basalts indicating the presence of primordial reservoir, and negative 182W in modern OIBs. One possibility to produce large variations in 182W 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 182W 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 182W and likely originated from the modified isotope region just above the core-mantle boundary, whereas those with positive 182W 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 182W can be added to the silicate mantle. As a result, the source region of the OIB would be effectively modified to a negative 182W.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 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 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 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)-/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 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 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 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, -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 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, ELSTsf 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, ELSTsf 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 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 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 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 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 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 gbarkingh 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 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-p69) 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 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 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 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 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 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- 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 Okayama0003497511212020Anatomical Risk Factors for Reintervention after Arterial Switch Operation for Taussig–Bing Anomaly163169ENYasuyukiKobayashiCardiovascular Surgery, Okayama University HospitalYasuhiroKotaniCardiovascular Surgery, Okayama University HospitalYosukeKurokoCardiovascular Surgery, Okayama University HospitalAtsushiTateishiCardiovascular Surgery, Okayama University HospitalShunjiSanoPediatric Cardiothoracic Surgery, University of California, San FranciscoShingoKasaharaCardiovascular Surgery, Okayama University HospitalBackground: This study aimed to determine the factors related to reintervention, especially for pulmonary artery stenosis (PS), in patients with Taussig–Bing anomaly (TBA) after arterial switch operation (ASO).<br>
Methods:This retrospective study included 34 patients with TBA who underwent ASO between 1993 and 2018. Preoperative anatomical and physiological differences and long-term outcomes were determined using a case-matched control with transposition of the great arteries (TGA) with ventricular septal defect (VSD) and TBA with an anterior and rightward aorta. <br>
Results: The median age and body weight at ASO were 43 (16–102) days and 3.6 (2.8–3.8) kg, respectively. Aortic arch obstruction and coronary anomalies were present in 64% and 41% patients, respectively. The hospital mortality rate was 11%, including one cardiac death, and late mortality rate was 2.9%. Furthermore, 41% patients underwent 26 reinterventions for PS. Patients undergoing PS-related reintervention had a significantly larger native pulmonary artery: aortic annulus size ratio than those not receiving reintervention (1.69 vs. 1.41, P = 0.02). This ratio was the only predictor of PS-related reintervention; it was significantly higher in the TBA group than in the TGA/VSD group. PS-related reintervention was required more in the TBA group than in the TGA/VSD group. <br>
Conclusions: Regardless of complex coronary anatomy and associated anomalies, early and late survival were acceptable. Postoperative PS was strongly associated with having a larger native pulmonary valve, suggesting that an optimal surgical reconstruction was required for achieving an appropriate aortopulmonary anatomical relationship during ASO. (243 words)No 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 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 Okayama2049-0801582020Continuing surgical education of non-technical skills177186ENMasaomiYamaneDepartments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEtsujiSuzukiDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeijuAokageDepartment of Thoracic Surgery, National Cancer Center Hospital EastMikioOkazakiDepartments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunichiSohDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of MedicineMakioHayamaDepartment of Thoracic Surgery, Japanese Red Cross Okayama HospitalYujiHiramiDepartment of General Thoracic Surgery, National Hospital Organization Okayama Medical CenterTakashiYorifujiDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground</br>
The non-technical skills for surgeons (NOTSS) system was developed as a tool to assess surgical skills for patient safety during surgery. This study aimed to develop a NOTSS-based training system for surgical trainees to acquire non-technical skills using a chest surgery scenario in a wet lab.</br>
Materials and methods</br>
Trainees were categorized into three subgroups according to the years of experience as follows: Level A: 6 years or more; Level B: 3–5 years; and Level C: 1–2 years. Three stages of surgical procedure were designed: 1. chest wall resection and right upper lobe lobectomy, 2. right middle lobe sleeve lobectomy, and 3. right lower lobe lobectomy. One instructor was assigned to each operation table, who evaluated each participant's NOTSS scores consisting of 16 elements.</br>
Results</br>
When comparing average NOTSS score of all the three procedures, significant differences were observed between Level A, B, and C trainees. As an example of varying elements by procedure, Level A trainees demonstrated differences in Situation Awareness, and a significant difference was observed in Level C trainees regarding the elements of Decision Making. On the contrary, no significant difference was observed among Level B trainees. In the comparison between first-time and experienced participants, a significant improvement was observed in some elements in Level B and C trainees.</br>
Conclusion</br>
This study highlights the usefulness and feasibility of the NOTSS scoring system for surgeons with different experiences and the effectiveness of providing feedback to trainees during intraoperative handoffs in a wet lab.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24055808222020Neuroplastin-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) downstream signal in lung cancer dissemination in the lung. The molecular mechanism of the signal pathway downstream of NPTN 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 NPTN has not been answered. Here, we show that the NPTN-SPDEF-mediated induction of solute carrier family 22 member 18 antisense (SLC22A18AS) is definitely required for the epithelial-mesenchymal transition (EMT) through the NPTN 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 NPTN. Our findings contribute to a better understanding of NPTN-mediated lung cancer metastasis.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 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 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 Okayama2405-8440662020Rapid and specific detection of oxidized LDL/2GPI 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 Sciences2-Glycoprotein I (2GPI) forms indissociable complex with oxidized LDL (oxLDL) into proatherogenic oxLDL/2GPI 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/2GPI 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/2GPI 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/2GPI LFIA in comparison to an ELISA-based detection method were assessed accordingly. The established oxLDL/2GPI LFIA was capable of detecting oxLDL/2GPI specifically without interference from autoantibodies and solitary components of oxLDL/2GPI present in test samples. A significant correlation (R2 > 0.8) was also obtained with the oxLDL/2GPI LFIA when compared to the ELISA-based detection. On the whole, the oxLDL/2GPI LFIA remains advantageous over the oxLDL/2GPI ELISA. The unnecessary washing step, short developmental and analytical time support facile and rapid detection of oxLDL/2GPI as opposed to the laborious ELISA system.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 Okayama2666250732020Bilateral segmental lung transplantation for children: Transplantation using split adult living-donor lower lobe311314ENTakahiroOtoTransplant Center, Okayama University HospitalYukikoHikasaAnesthesiology and Resuscitology, Okayama University HospitalAkikazuHagiyamaPhysical Medicine and Rehabilitation, Okayama University HospitalMotomuKobayashiAnesthesiology and Resuscitology, Okayama University HospitalNo 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 Okayama1341-321X26102020Antibiotic literacy among Japanese medical students11071109ENHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideoInoCenter for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazukiTokumasuDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokoOgawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoMiyoshiDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKanakoOchiCenter for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAntimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship.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 Okayama1873-5061462020Adult kidney stem/progenitor cells contribute to regeneration through the secretion of trophic factors101865ENKenjiTsujiDepartment 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 SciencesYizhenSangDepartment 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 SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAdult kidney stem cells are known to have important roles in renal regeneration after acute kidney injury. Although trophic factors from tissue stem cells have been reported to promote the regeneration of other organs, there is limited number of evidence of this phenomenon in the kidneys. Here, we explored the effects of secreted factors from kidney stem cells. We intraperitoneally administered culture supernatant obtained from adult rat kidney stem/progenitor cells into rat kidney ischemia/reperfusion injury models, and the treatment significantly ameliorated renal tubulointerstitial injury, suppressed tubular cell apoptosis, diminished inflammation and promoted the proliferation of both residual renal cells and immature cells. In vitro, treatment with culture supernatant from kidney stem cells significantly promoted cell proliferation and suppressed cisplatin-induced cell apoptosis in both normal rat kidney cells and kidney stem cells. In addition, treatment with culture supernatant increased the expression of nestin in normal rat kidney cells, suggesting the dedifferentiation of tubular cells into stem-like cells. Analysis of the culture supernatant revealed that it contained a variety of growth factors. Taken together, the results suggest that these factors together lead to renal regeneration. In conclusion, adult kidney stem cells contribute to renal regeneration indirectly through the secretion of regenerative factors.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-g/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 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)CTG-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 = 400 m in the setting depth of cut at fiber angle = 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 Okayama0168-17022442018A neo-virus lifestyle exhibited by a (+)ssRNA virus hosted in an unrelated dsRNA virus: Taxonomic and evolutionary considerations7583ENSakaeHisanoInstitute of Plant Science and Resources (IPSR), Okayama UniversityRuiZhangInstitute of Plant Science and Resources (IPSR), Okayama UniversityMd. IqbalFarukInstitute of Plant Science and Resources (IPSR), Okayama UniversityHidekiKondoInstitute of Plant Science and Resources (IPSR), Okayama UniversityNobuhiroSuzukiInstitute of Plant Science and Resources (IPSR), Okayama UniversityRecent studies illustrate that fungi as virus hosts provides a unique platform for hunting viruses and exploring virus/virus and virus/host interactions. Such studies have revealed a number of as-yet-unreported viruses and virus/virus interactions. Among them is a unique intimate relationship between a (+)ssRNA virus, yado-kari virus (YkV1) and an unrelated dsRNA virus, yado-nushi virus (YnV1). YkV1 dsRNA, a replicated form of YkV1, and RNA-dependent RNA polymerase, are trans-encapsidated by the capsid protein of YnV1. While YnV1 can complete its replication cycle, YkV1 relies on YnV1 for its viability. We previously proposed a model in which YkV1 diverts YnV1 capsids as the replication sites. YkV1 is neither satellite virus nor satellite RNA, because YkV1 appears to encode functional RdRp and enhances YnV1 accumulation. This represents a unique mutualistic virus/virus interplay and similar relations in other virus/host fungus systems are detectable. We propose to establish the family Yadokariviridae that accommodates YkV1 and recently discovered viruses phylogenetically related to YkV1. This article overviews what is known and unknown about the YkV1/YnV1 interactions. Also discussed are the YnV1 Phytoreo_S7 and YkV1 2A-like domains that may have been captured via horizontal transfer during the course of evolution and are conserved across extant diverse RNA viruses. Lastly, evolutionary scenarios are envisioned for YkV1 and YnV1.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 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 Okayama1590-86585172019Adenomyomatosis hyperplasia arising in the bile duct1060ENKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironariKatoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiNishidaDepartment 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 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 gnon-Mayah 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 gnon-Mayah elites from Western/Central Honduras.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 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 Womenfs and Childrenfs HospitalKatsumiImaiDepartment of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological DisordersNaokoIshiharaDepartment of Pediatrics, Fujita Health University School of MedicineYuriDowaDepartment of Neurology, Gunma Childrenfs Medical CenterTakayoshiKoikeDepartment of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological DisordersToshiyukiYamamotoInstitute of Clinical Genomics, Tokyo Womenfs Medical UniversityJunShibasakiDepartment of Neonatology, Kanagawa Childrenfs Medical CenterHirokoShimboClinical Institute, Kanagawa Childrenfs 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 Childrenfs 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, -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 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 Okayama2352-3964622020A detection method for latent circadian rhythm sleep-wake disorder103080ENMakotoAkashiThe Research Institute for Time Studies, Yamaguchi UniversityReimiSogawaDepartment of Clinical Genetics and Genomic Medicine, Okayama University HospitalRitsukoMatsumuraThe Research Institute for Time Studies, Yamaguchi UniversityAtsuhiroNishidaThe Research Institute for Time Studies, Yamaguchi UniversityRinoNakamuraThe Research Institute for Time Studies, Yamaguchi UniversityIsao T.TokudaDepartment of Mechanical Engineering, Ritsumeikan UniversityKoichiNodeDepartment of Cardiovascular Medicine, Saga UniversityBackground</br>
Individuals with typical circadian rhythm sleep-wake disorders (CRSWDs) have a habitual sleep timing that is desynchronized from social time schedules. However, it is possible to willfully force synchronisation against circadian-driven sleepiness, which causes other sleep problems. This pathology is distinguishable from typical CRSWDs and is referred to here as latent CRSWD (LCRSWD). Conventional diagnostic methods for typical CRSWDs are insufficient for detecting LCRSWD because sufferers have an apparently normal habitual sleep timing.</br>
Methods</br>
We first evaluated the reliability of circadian phase estimation based on clock gene expression using hair follicles collected at three time points without sleep interruption. Next, to identify detection criteria for LCRSWD, we compared circadian and sleep parameters according to estimated circadian phases, at the group and individual level, between subjects with low and high Pittsburgh Sleep Quality Index (PSQI) scores. To validate the reliability of identified detection criteria, we investigated whether the same subjects could be reproducibly identified at a later date and whether circadian amelioration resulted in sleep improvement.</br>
Findings</br>
We successfully validated the reliability of circadian phase estimation at three time points and identified potential detection criteria for individuals with LCRSWD attributed to delayed circadian-driven sleepiness. In particular, a criterion based on the interval between the times of the estimated circadian phase of clock gene expression and getting out of bed on work or school days was promising. We also successfully confirmed the reproducibility of candidate screening and sleep improvement by circadian amelioration, supporting the reliability of the detection criteria.</br>
Interpretation</br>
Although several limitations remain, our present study demonstrates a promising prototype of a detection method for LCRSWD attributed to delayed circadian-driven sleepiness. More extensive trials are needed to further validate this method.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 Okayama2451-830192020Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy102114ENHiroshiUenoDepartment of Medical Technology, Kawasaki University of Medical WelfareAtsumiShimadaDivision of Food and Nutrition, Nakamura Gakuen University Junior CollegeShunsukeSuemitsuDepartment of Psychiatry, Kawasaki Medical SchoolShinjiMurakamiDepartment of Psychiatry, Kawasaki Medical SchoolNaoyaKitamuraDepartment of Psychiatry, Kawasaki Medical SchoolKentaWaniDepartment of Psychiatry, Kawasaki Medical SchoolYuTakahashiDepartment 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 SchoolUnderstanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear.</br>
Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of -pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while -pinene treatment prevented an increase in seizures incidences. Both MK-801 and -pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules.</br>
Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and -pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production.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 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 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 Okayama2405-6502212020A case of type 1 facioscapulohumeral muscular dystrophy (FSHD) with restrictive ventilatory defect and congestive heart failure100284ENNobutoshiMorimotoDepartment of Neurology, Kagawa Central Prefectural HospitalMizukiMorimotoDepartment of Neurology, Kagawa Central Prefectural HospitalYoshiakiTakahashiDepartment of Neurology, Kagawa Central Prefectural HospitalMotonoriTakamiyaDepartment of Neurology, Kagawa Central Prefectural HospitalIchizoNishinoDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP)KojiAbeDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University[Background] Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease characterized by asymmetric involvement of muscles in the face, upper extremity, trunk, and lower extremity regions, with variable severity. It was recently reported that restrictive respiratory involvement is more frequent and severe than previously recognized, while cardiac dysfunction other than arrhythmia is still considered extremely rare in FSHD. [Case report] A 59-year-old man presenting with marked muscle atrophy in the trunk and asymmetrical muscle atrophy in the legs was hospitalized because of dyspnea and edema in the face and limbs. Shortness of breath with body movement started from approximately 40 years of age. Muscle biopsy revealed myopathic change with mild to moderate variation in fiber size. The diagnosis of FSHD was made by D4Z4 contraction to three repeats on genetic testing. A pulmonary function test revealed a decline of forced vital capacity (FVC) and a preserved FEV1/FVC indicating restrictive ventilatory defect (RVD). Ultrasonic echocardiogram (UCG) showed diffuse left ventricular hypokinesis, ventricular septum thickening, pericardial effusion, and decreased ejection fraction (LVEF 30%). [Conclusion] Although restrictive ventilatory defect and congestive heart failure are uncommon in FSHD, respiratory and cardiac evaluation may be necessary in patients with FSHD.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 Okayama2211-7539302020A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery2225ENKensukeUraguchiDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenichiKozakuraDepartment of Otorhinolaryngology, Kochi Health Sciences CenterSatoshiOkaDepartment of Hematology and Blood Transfusion, Kochi Health Sciences CenterTakayaHigakiDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroMakiharaDepartment of Otorhinolaryngology, Head and Neck Surgery, Kagawa Rosai HospitalToshiImaiDepartment of Hematology and Blood Transfusion, Kochi Health Sciences CenterAkiraDoiDepartment of Otorhinolaryngology, Kochi Health Sciences CenterTsuyoshiOhtaDepartment of Neurosurgery, Kochi Health Sciences CenterShinKariyaDepartment 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 SciencesA 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1349-00796242020Construction and characterization of the PGN_0296 mutant of Porphyromonas gingivalis322326ENAbu Saleh MuhammadShahriarDepartment of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShintaroOnoDepartment of Periodontal Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaakiNakayamaDepartment of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaokoOharaDepartment of Operative Dentistry, Okayama University Hospital, Okayama UniversityNaoyaOharaDepartment of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe periodontal pathogen Porphyromonas gingivalis produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in the organism's virulence, and pigmentation. We previously showed that deletion of the PGN_0297 and PGN_0300 genes reduced the proteolytic activity of gingipains. The role of the PGN_0296 gene, consisting of an operon with the PGN_0297 and PGN_0300 genes, is unclear. Herein, we examined the effect of PGN_0296 gene deletion on the proteolytic activity. Although the proteolytic activity of the gingipains did not decrease in the culture supernatant of a PGN_0296 gene deletion mutant (PGN_0296), the growth was delayed.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-2612762020A novel modified hanging maneuver in laparoscopic left hemihepatectomy251253ENKoseiTakagiDepartment 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 SciencesTakashiKuiseDepartment 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 SciencesKazuhiroYoshidaDepartment 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 SciencesYumaTaniDepartment 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>
The liver hanging maneuver is an essential technique for controlling bleeding in hepatectomy, however it is often difficult in laparoscopic major hepatectomy. The present study describes a novel modified hanging maneuver in laparoscopic left hemihepatectomy.</br>
Presentation of case</br>
A 29-year-old female underwent laparoscopic left hemihepatectomy for mucinous cystic neoplasm. After mobilizing the left lobe, the liver parenchyma was dissected along the demarcation line. For the hanging technique, the upper edge of the hanging tape was placed on the lateral side of the left hepatic vein, and fixed with the Falciform ligament. The lower edge of the tape was extracted outside the abdomen. Accordingly the hanging tape can be controlled extraperitoneally during the liver parenchyma dissection.</br>
Discussion</br>
This technique includes several advantages including no need of assistance using forceps, easy control of the hanging tape extraperitoneally, outflow control, better exposure of surgical field, and helpful guide of the liver dissection line toward the root of the left hepatic vein.
Conclusion</br>
Our novel modified hanging maneuver is easy and reproducible to use in laparoscopic left hemihepatectomy. Moreover, this technique can be applied to other laparoscopic hepatectomy.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 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 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 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.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 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 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 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 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 Okayama0269-74912692020Cadmium transfer in contaminated soil-rice systems: Insights from solid-state speciation analysis and stable isotope fractionation115934ENMatthiasWiggenhauserUniv. Grenoble AlpesAnne-MarieAucourUniversité de LyonSarahBureauUniv. Grenoble AlpesSylvainCampilloUniv. Grenoble AlpesPhilippeTeloukUniversité de LyonMarcoRomaniCentro Ricerche sul Riso, Ente Nazionale Risi, Strada per CerettoJian FengManstitute of Plant Science and Resources, Okayama UniversityGautierLandrotSynchrotron SOLEIL, LfOrmes des MerisiersGéraldineSarretUniv. Grenoble AlpesInitial Cadmium (Cd) isotope fractionation studies in cereals ascribed the retention of Cd and its light isotopes to the binding of Cd to sulfur (S). To better understand the relation of Cd binding to S and Cd isotope fractionation in soils and plants, we combined isotope and XAS speciation analyses in soil-rice systems that were rich in Cd and S. The systems included distinct water management (flooded vs. non-flooded) and rice accessions with (excluder) and without (non-excluder) functional membrane transporter OsHMA3 that transports Cd into root vacuoles. Initially, 13% of Cd in the soil was bound to S. Through soil flooding, the proportion of Cd bound to S increased to 100%. Soil flooding enriched the rice plants towards heavy isotopes (114/110Cd = |0.37 to |0.39%) compared to the plants that grew on non-flooded soils (114/110Cd = |0.45 to |0.56%) suggesting that preferentially light Cd isotopes precipitated into Cd sulfides. Isotope compositions in CaCl2 root extracts indicated that the root surface contributed to the isotope shift between soil and plant during soil flooding. In rice roots, Cd was fully bound to S in all treatments. The roots in the excluder rice strongly retained Cd and its lights isotopes while heavy isotopes were transported to the shoots (114/110Cdshoot-root 0.16–0.19). The non-excluder rice accumulated Cd in shoots and the apparent difference in isotope composition between roots and shoots was smaller than that of the excluder rice (114/110Cdshoot-root |0.02 to 0.08). We ascribe the retention of light Cd isotopes in the roots of the excluder rice to the membrane transport of Cd by OsHMA3 and/or chelating Cd–S complexes in the vacuole. Cd–S was the major binding form in flooded soils and rice roots and partly contributed to the immobilization of Cd and its light isotopes in soil-rice systems.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X26102020Concomitant vancomycin and piperacillin/tazobactam treatment is associated with an increased risk of acute kidney injury in Japanese patients10261032ENYutoHarukiDepartment of Pharmacy, Tsuyama Chuo HospitalHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaiHarukiDepartment of Pharmacy, Tsuyama Chuo HospitalYutaInoueDepartment of Pharmacy, Tsuyama Chuo HospitalTetsuhiroSugiyamaDepartment of Pharmacy, Tsuyama Chuo HospitalIntroduction</br>
Recent studies have corroborated that the co-administration of vancomycin (VCM) and piperacillin/tazobactam (PT) is correlated with an increased incidence of acute kidney injury (AKI). However, evidence directed at the Japanese population is scarce. Therefore, we conducted a retrospective study to compare the occurrence of AKI among Japanese patients who received VCM with PT (VP therapy) and VCM with another -lactams (VA therapy).</br>
Methods</br>
The present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and -lactam antibiotics for ≥48 h. We defined the primary outcome as the incidence of AKI based on the risk, injury, failure, loss, and end-stage kidney disease criteria. Patients' clinical characteristics and outcomes were reviewed and compared between the two groups with univariate and multivariate logistic regression analyses. Subgroup analysis was conducted by stratifying the patientsf baseline hospital admittance status, as intensive care unit or general wards.</br>
Results</br>
We analyzed 272 patients (92 V P therapy and 180 VA therapy). Univariate analysis revealed a significant difference in AKI development between VP and VA therapy (25.0% vs 12.2%; p < 0.01). A multivariate analysis demonstrated that VP therapy and VCM initial trough levels ≥15 g/mL were associated with an incidence of AKI. Patients at general wards, rather than those admitted at an intensive care unit, developed AKI with VP therapy (p = 0.02).</br>
Conclusion</br>
VP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.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 gspinal ejaculation generator (SEG).h 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 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 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 m after 27 days, and to over 10 m 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 Okayama2405-84406122020Antioxidative attributes of rice bran extracts in ameliorative effects of atherosclerosis-associated risk factorse05743ENWen TanXianDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazukoKobayashiCollaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShenLianhuaDepartment of Pathophysiology, Zunyi Medical UniversityJunkoInagakiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasahiroIdeDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSiaw SanHwangSchool of Chemical Engineering and Science, Faculty of Engineering, Computing and Science, Swinburne University of Technology Sarawak CampusEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical effect) are risk factors associated with the pathogenesis of atherosclerosis. Rice bran, a by-product of rice milling process, is known to house polyphenols and vitamins which exhibit potent antioxidant and anti-inflammatory properties. Through recent emerging knowledge of rice bran in health and wellness, the present study was aimed to assess the ameliorative effects of rice bran extracts (RBE) derived from Japanese colored rice varieties in modulating risk factors of atherosclerosis via in vitro and in vivo study models. Pre-treatment of lipopolysaccharide (LPS)-stimulated murine J774A.1 macrophage-like cells with RBE alleviated nitric oxide (NO) overproduction and downregulated gene expressions of pro-inflammatory modulators: tumor necrosis factor- (TNF-), interleukin (IL)- (IL-1), IL-1, IL-6, and inducible nitric oxide synthase (iNOS). In addition, RBE also significantly attenuated LPS-stimulated protein expressions of iNOS, TNF-, IL-1, and IL-6 in J774A.1 macrophage-like cells as compared to non-treated LPS control group. In in vivo, 12 weeks of RBE dietary supplementations significantly reduced (p < 0.05) total cholesterol, triglycerides, and pro-atherogenic oxidized LDL/2-glycoprotein I (oxLDL/2GPI) complexes at plasma levels, in high fat diet (HFD) induced low density lipoprotein receptor knockout (Ldlr|/-) mice. En face pathological assessments of murine aortas also revealed significant reductions by 38% (p < 0.05) in plaque sizes of RBE-supplemented HFD mice groups as compared to non RBE-supplemented HFD control mice group. Moreover, gene expressions of aortic (iNOS, TNF-, IL-1) and hepatic (TNF-, IL-1, IL-1) pro-inflammatory modulators were also downregulated in RBE-supplemented mice groups. Present study has revealed the potent health attributes and application of RBE as a dietary supplement to attenuate risks of inadvertent oxidative damage and chronic inflammation underlying the pathogenesis of atherosclerosis. Intrinsically, present preliminary findings may provide global health prospects for future dietary implementation of RBE in management of atherosclerosis.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 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 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 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 -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 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 gextrapolate emotional expressionsh 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 Okayama1387-70031242021Effect of ultrasonic irradiation on -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 (-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. -ferric oxyhydroxide (-FeOOH) was partially formed in addition to -ferric oxyhydroxide (-FeOOH) and thermally dehydrated to -Fe2O3 and hematite (-Fe2O3) by ultrasonic-assisted co-precipitation of Fe3+ salt and the excess KOH solution, whereas only -FeOOH and -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 -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 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 ghigh-risk PFOh 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 Chiarifs 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 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 -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 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 Okayama0921-50938072021Effects of microstructural characteristics on the hydrogen embrittlement characteristics of austenitic, ferritic, and – duplex stainless steels140851ENMitsuhiroOkayasuGraduate School of Natural Science and Technology, Okayama UniversityTakafumiFujiwaraGraduate School of Natural Science and Technology, Okayama UniversityHydrogen embrittlement (HE) characteristics of (AS), (FS), and – 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 and 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 / 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 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 m) 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 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.