start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=11 article-no= start-page=e0295078 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between oral condition and subjective psychological well-being among older adults attending a university hospital dental clinic: A cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Positive psychological well-being has a favorable impact on survival rates in both healthy and unhealthy populations. Oral health is also associated with psychological well-being, is multidimensional in nature, and includes physical, psychological, emotional, and social domains that are integral to overall health and well-being. This study aimed to identify the associations between individual and environmental characteristics, oral condition and nutritional status in relation to subjective well-being among older adults using the Wilson and Cleary conceptual model. The participants were older adults (age >= 60 years) attending a university hospital. Subjective well-being was assessed using the World Health Organization-5 Well-Being Index, oral condition was assessed based on the number of bacteria in the tongue coating, oral wettability, tongue pressure, occlusal force, oral diadochokinesis, and masticatory ability, and subjective swallowing function was assessed using the Eating Assessment Tool, number of remaining teeth, and number of functional teeth. In addition, factors related to well-being, including social networks, life-space mobility, nutritional status, smoking history, drinking history, and medical history were assessed. In the analysis, structural equation modeling was used to investigate the association between oral condition and subjective well-being. Confirmatory factor analysis revealed oral condition as a latent variable, including tongue pressure, oral diadochokinesis /pa/, /ta/, /ka/, occlusal force, masticatory ability, subjective swallowing function, and number of functional teeth. Structural Equation Modeling revealed that oral condition was positively correlated with nutritional status, and nutritional status was positively correlated with the World Health Organization-5 Well-Being Index. These findings suggest that oral condition may influence subjective well-being via nutritional status or social environmental factors. en-copyright= kn-copyright= en-aut-name=TakeuchiNoriko en-aut-sei=Takeuchi en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawadaNanami en-aut-sei=Sawada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Health, Takarazuka University of Medical and Health Care kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=e0296408 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Aromatic oil from lavender as an atopic dermatitis suppressant en-subtitle= kn-subtitle= en-abstract= kn-abstract=In atopic dermatitis (AD), nerves are abnormally stretched near the surface of the skin, making it sensitive to itching. Expression of neurotrophic factor Artemin (ARTN) involved in such nerve stretching is induced by the xenobiotic response (XRE) to air pollutants and UV radiation products. Therefore, AD can be monitored by the XRE response. Previously, we established a human keratinocyte cell line stably expressing a NanoLuc reporter gene downstream of XRE. We found that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan metabolite and known inducer of the XRE, increased reporter and Artemin mRNA expression, indicating that FICZ-treated cells could be a model for AD. Lavender essential oil has been used in folk medicine to treat AD, but the scientific basis for its use is unclear. In the present study, we investigated the efficacy of lavender essential oil and its major components, linalyl acetate and linalool, to suppress AD and sensitize skin using the established AD model cell line, and keratinocyte and dendritic cell activation assays. Our results indicated that lavender essential oil from L. angustifolia and linalyl acetate exerted a strong AD inhibitory effect and almost no skin sensitization. Our model is useful in that it can circumvent the practice of using animal studies to evaluate AD medicines. en-copyright= kn-copyright= en-aut-name=SatoHaruna en-aut-sei=Sato en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoKosuke en-aut-sei=Kato en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoreishiMayuko en-aut-sei=Koreishi en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujinoYoshio en-aut-sei=Tsujino en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Science, Technology, and Innovation, Kobe University kn-affil= affil-num=6 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=11 article-no= start-page=e0294491 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis. en-copyright= kn-copyright= en-aut-name=TamuraShuta en-aut-sei=Tamura en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HoriNaoto en-aut-sei=Hori en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiYuncheng en-aut-sei=Li en-aut-mei=Yuncheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=e0291677 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231020 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Shortage and unequal distribution of infectious disease specialists in Japan: How can we refine the current situation? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
This study aimed to assess the distribution of board-certified infectious disease (ID) specialists at medical schools and Designated Medical Institutions (DMIs) in Japan.
Methods
Data on the number of board-certified ID specialists was extracted by gender, prefecture, and hospital from the Japanese Association for Infectious Diseases database. The numbers and types of Japanese university hospitals that have a Faculty of Medicine, as well as the DMIs legally determined by the Infectious Diseases Control Law, were collected from the database of the Ministry of Health, Labour, and Welfare of Japan.
Results
As of November 2022, there were 1,688 board-certified ID specialists in Japan, with 510 employed at 82 university hospitals. Two medical schools had no ID specialists, and six had only one ID specialist. There was no ID specialists in 14.3% of Class I DMIs and 66.7% of Class II DMIs. Additionally, 14.9% of prefectures had no ID specialists at all in their Class II DMIs. The percentage of female doctors among ID specialists was 12.7%, approximately half of the overall male-to-female ratio of medical doctors in Japan.
Conclusion
The allocation of Japanese ID specialists to medical schools and legally designated healthcare institutes is inadequate and skewed. Female physicians are expected to play a more active role in this increasing demand. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=e0287501 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A randomized controlled trial of teprenone in terms of preventing worsening of COVID-19 infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections.
Methods
This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or noteprenone groups in a 1:1 ratio. We stratified patients by sex, age < and >= 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate.
Results
One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/ 49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325).
Conclusion
Teprenone afforded no clinical benefit. en-copyright= kn-copyright= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaKou en-aut-sei=Hasegawa en-aut-mei=Kou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanimotoYasushi en-aut-sei=Tanimoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsumuneSho en-aut-sei=Mitsumune en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamadaHaruto en-aut-sei=Yamada en-aut-mei=Haruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakataIchiro en-aut-sei=Takata en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=8 en-affil=Department of Infectious Disease, Okayama City Hospital kn-affil= affil-num=9 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=5 article-no= start-page=e0285273 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC.

Methods
Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more.

Results
We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11).

Conclusion
Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. en-copyright= kn-copyright= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHiroyuki en-aut-sei=Suzuki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoIsao en-aut-sei=Sano en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujinagaTakuji en-aut-sei=Fujinaga en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaMasafumi en-aut-sei=Kataoka en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerazakiYasuhiro en-aut-sei=Terazaki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakaShinji en-aut-sei=Kosaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaYoshinori en-aut-sei=Yamashita en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MatsuoKeitaro en-aut-sei=Matsuo en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SakamotoJunichi en-aut-sei=Sakamoto en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Chest Surgery, Fukushima Medical University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center kn-affil= affil-num=10 en-affil=Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory S0urgery, Saga-Ken Medical Centre Koseikan kn-affil= affil-num=12 en-affil=Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Thoracic Surgery, Shimane Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical Center kn-affil= affil-num=17 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=18 en-affil=Division of General Thoracic Surgery, Tottori University Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=20 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=22 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=23 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=24 en-affil=Tokai Central Hospital kn-affil= affil-num=25 en-affil=Department of Thoracic Surgery, Kyoto University Hospital kn-affil= affil-num=26 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=8 article-no= start-page=e0289599 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230804 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Selective DNA-binding of SP120 (rat ortholog of human hnRNP U) is mediated by arginine-glycine rich domain and modulated by RNA en-subtitle= kn-subtitle= en-abstract= kn-abstract=A human protein heterogeneous ribonucleoprotein U (hnRNP U) also known as Scaffold attachment factor A (SAF-A) and its orthologous rat protein SP120 are abundant and multifunctional nuclear protein that directly binds to both DNA and RNA. The C-terminal region of hnRNP U enriched with arginine and glycine is essential for the interaction with RNA and the N-terminal region of SAF-A termed SAP domain has been ascribed to the DNA binding. We have reported that rat hnRNP U specifically and cooperatively binds to AT-rich DNA called nuclear scaffold/matrix-associated region (S/MAR) although its detailed mechanism remained unclear. In the present study analysis of hnRNP U deletion mutants revealed for the first time that a C-terminal domain enriched with Arg-Gly (defined here as 'RG domain') is predominantly important for the S/MAR-selective DNA binding activities. RG domain alone directly bound to S/MAR and coexistence with the SAP domain exerted a synergistic effect. The binding was inhibited by netropsin, a minor groove binder with preference to AT pairs that are enriched in S/MAR, suggesting that RG domain interacts with minor groove of S/MAR DNA. Interestingly, excess amounts of RNA attenuated the RG domain-dependent S/MAR-binding of hnRNP U. Taken together, hnRNP U may be the key element for the RNA-regulated recognition of S/MAR DNA and thus contributing to the dynamic structural changes of chromatin compartments. en-copyright= kn-copyright= en-aut-name=MiyajiMary en-aut-sei=Miyaji en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawanoShinji en-aut-sei=Kawano en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurutaRyohei en-aut-sei=Furuta en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiEmi en-aut-sei=Murakami en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaShogo en-aut-sei=Ikeda en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsutsuiKimiko M. en-aut-sei=Tsutsui en-aut-mei=Kimiko M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsutsuiKen en-aut-sei=Tsutsui en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Science, Department of Biochemistry, Okayama University of Science kn-affil= affil-num=3 en-affil=Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Science, Department of Biochemistry, Okayama University of Science kn-affil= affil-num=5 en-affil=Faculty of Science, Department of Biochemistry, Okayama University of Science kn-affil= affil-num=6 en-affil=Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=7 article-no= start-page=e0288175 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Augmented reality-based affective training for improving care communication skill and empathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=It is important for caregivers of people with dementia (PwD) to have good patient communication skills as it has been known to reduce the behavioral and psychological symptoms of dementia (BPSD) of PwD as well as caregiver burnout. However, acquiring such skills often requires one-on-one affective training, which can be costly. In this study, we propose affective training using augmented reality (AR) for supporting the acquisition of such skills. The system uses see-through AR glasses and a nursing training doll to train the user in both practical nursing skills and affective skills such as eye contact and patient communication. The experiment was conducted with 38 nursing students. The participants were assigned to either the Doll group, which only used a doll for training, or the AR group, which used both a doll and the AR system. The results showed that eye contact significantly increased and the face-to-face distance and angle decreased in the AR group, while the Doll group had no significant difference. In addition, the empathy score of the AR group significantly increased after the training. Upon analyzing the correlation between personality and changes of physical skills, we found a significant positive correlation between the improvement rate of eye contact and extraversion in the AR group. These results demonstrated that affective training using AR is effective for improving caregivers' physical skills and their empathy for their patients. We believe that this system will be beneficial not only for dementia caregivers but for anyone looking to improve their general communication skills. en-copyright= kn-copyright= en-aut-name=NakazawaAtsushi en-aut-sei=Nakazawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamotoMiyuki en-aut-sei=Iwamoto en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurazumeRyo en-aut-sei=Kurazume en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NunoiMasato en-aut-sei=Nunoi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiMasaki en-aut-sei=Kobayashi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HondaMiwako en-aut-sei=Honda en-aut-mei=Miwako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Advanced Fibro-Science, Kyoto Institute of Technology kn-affil= affil-num=3 en-affil=Faculty of Information Science and Electrical Engineering, Kyushu University kn-affil= affil-num=4 en-affil=School of Human Sciences, Sugiyama Jogakuen University kn-affil= affil-num=5 en-affil=Division of geriatric medicine, Rochester Regional Health System kn-affil= affil-num=6 en-affil=Division of Geriatric Research, National Hospital Organization Tokyo Medical Center kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=2 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of calculation processes of apparent diffusion coefficient subtraction method (ASM) imaging en-subtitle= kn-subtitle= en-abstract= kn-abstract=A number of restricted diffusion (RD) imaging techniques, such as diffusion kurtosis (DK) imaging and Q space imaging, have been developed and proven to be useful for the diagnosis of diseases, including cerebral gliomas and cerebrovascular infarction. In particular, apparent diffusion coefficient (ADC) subtraction method (ASM) imaging has become available recently as a novel RD imaging technique. ASM is based on the difference between the ADC values in an image pair of two ADC maps, ADC basic (ADCb) and ADC modify (ADCm), which are created from diffusion-weighted images taken using short and long effective diffusion times, respectively. The present study aimed to assess the potential of different types of ASM imaging by comparing them with DK imaging which is the gold-standard RD imaging technique. In the present basic study using both polyethylene glycol phantom and cell-containing bio-phantom, three different types of ASM images were created using different calculation processes. ASM/A is an image calculated by dividing the absolute difference between ADCb and ADCm by ADCb several times. By contrast, ASM/S is an image created by dividing the absolute difference between ADCb and ADCm by the standard deviation of ADCb several times. As for positive ASM/A image (PASM/A), the positive image, which was resultant after subtracting ADCb from ADCm, was divided by ADCb several times. A comparison was made between the types of ASM and DK images. The results showed the same tendency between ASM/A in addition to both ASM/S and PASM/A. By increasing the number of divisions by ADCb from three to five times, ASM/A images transformed from DK-mimicking to more RD-sensitive images compared with DK images. These observations suggest that ASM/A images may prove useful for future clinical applications in RD imaging protocols for the diagnosis of diseases. en-copyright= kn-copyright= en-aut-name=BarhamMajd en-aut-sei=Barham en-aut-mei=Majd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshimuraYuuki en-aut-sei=Yoshimura en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamadaKentaro en-aut-sei=Hamada en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KhasawnehAbdullah en-aut-sei=Khasawneh en-aut-mei=Abdullah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KonishiKohei en-aut-sei=Konishi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TekikiNouha en-aut-sei=Tekiki en-aut-mei=Nouha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugiantoIrfan en-aut-sei=Sugianto en-aut-mei=Irfan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BamgboseBabatunde O. en-aut-sei=Bamgbose en-aut-mei=Babatunde O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshizakaHinata en-aut-sei=Ishizaka en-aut-mei=Hinata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimizuYudai en-aut-sei=Shimizu en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamitsuYuki en-aut-sei=Nakamitsu en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Al-HammadWlla E. en-aut-sei=Al-Hammad en-aut-mei=Wlla E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KamizakiRyo en-aut-sei=Kamizaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KurozumiAkira en-aut-sei=Kurozumi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsushitaToshi en-aut-sei=Matsushita en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OhnoSeiichiro en-aut-sei=Ohno en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=16 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=17 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=18 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page=e0283701 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of illness representational patterns and examining differences of self-care behavior in the patterns in chronic kidney disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Self-care behavior is considered important for preventing the progression of chronic kidney disease (CKD). Although lifestyle interventions are popular, they have not been sufficiently effective. According to studies on other chronic diseases, illness representation has been found to formulate a pattern, and self-care behavior could differ depending on the pattern, which suggests difference in self-care behavior based on illness representation. This study examined what kind of illness representational patterns exist among CKD patients and whether there is a difference in self-care behavior depending on the pattern. A survey was conducted from the beginning of June to the end of October 2019 on 274 CKD patients who were either outpatients or hospitalized at general hospitals in Western Japan. The Illness Perception Questionnaire-Revised was used to assess illness representation and the Japanese Chronic Kidney Disease Self-Care scale was used to assess self-care behavior. Two-stage cluster analysis was used to identify clusters. Cluster features were examined using analysis of variance and Tukey HSD tests. Differences in self-care behavior scores among identified clusters were investigated. Two hundred and forty-four questionnaires were received, and 212 were analyzed. Participants were aged 64.9 +/- 12.9, and the estimated glomerular filtration rate was 33.7 +/- 15.8. Three clusters were identified: Cluster 1 represented the difficulty of making sense of the changed condition caused by the disease and easily falling into misunderstanding; Cluster 2 represented patients with disease conditions that impacted their daily life and emotional responses; Cluster 3 represented the controllability and understandability of the disease. Total self-care behavior scores indicated a significant difference between Cluster 1 (52.1 +/- 9.7) and Cluster 3 (57.7 +/- 8.2). In conclusion, we showed that three representational patterns exist among CKD patients. In addition, a difference was found in self-care behavior depending on the illness representational pattern, suggesting the need to focus on illness representation. en-copyright= kn-copyright= en-aut-name=KajiwaraYuki en-aut-sei=Kajiwara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorimotoMichiko en-aut-sei=Morimoto en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Health Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page=e0283426 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230329 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Consistently low levels of histidine-rich glycoprotein as a new prognostic biomarker for sepsis: A multicenter prospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Few sepsis biomarkers accurately predict severity and mortality. Previously, we had reported that first-day histidine-rich glycoprotein (HRG) levels were significantly lower in patients with sepsis and were associated with mortality. Since the time trends of HRG are unknown, this study focused on the time course of HRG in patients with sepsis and evaluated the differences between survivors and non-survivors.
Methods
A multicenter prospective observational study was conducted involving 200 patients with sepsis in 16 Japanese hospitals. Blood samples were collected on days 1, 3, 5, and 7, and 28-day mortality was used for survival analysis. Plasma HRG levels were determined using a modified quantitative sandwich enzyme-linked immunosorbent assay.
Results
First-day HRG levels in non-survivors were significantly lower than those in survivors (mean, 15.7 [95% confidence interval (CI), 13.4-18.1] vs 20.7 [19.5-21.9] mu g/mL; P = 0.006). Although there was no time x survivors/non-survivors interaction in the time courses of HRG (P = 0.34), the main effect of generalized linear mixed models was significant (P < 0.001). In a univariate Cox proportional hazards model with each variable as a time-dependent covariate, higher HRG levels were significantly associated with a lower risk of mortality (hazard ratio, 0.85 [95% CI, 0.78-0.92]; P < 0.001). Furthermore, presepsin levels (P = 0.02) and Sequential Organ Function Assessment scores (P < 0.001) were significantly associated with mortality. Harrell's C-index values for the 28-day mortality effect of HRG, presepsin, procalcitonin, and C-reactive protein were 0.72, 0.70, 0.63, and 0.59, respectively.
Conclusions
HRG levels in non-survivors were consistently lower than those in survivors during the first seven days of sepsis. Repeatedly measured HRG levels were significantly associated with mortality. Furthermore, the predictive power of HRG for mortality may be superior to that of other singular biomarkers, including presepsin, procalcitonin, and C-reactive protein. en-copyright= kn-copyright= en-aut-name=KawanoueNaoya en-aut-sei=Kawanoue en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaKosuke en-aut-sei=Kuroda en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasudaHiroko en-aut-sei=Yasuda en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OiwaMasahiko en-aut-sei=Oiwa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiSatoshi en-aut-sei=Suzuki en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HosoiHiroki en-aut-sei=Hosoi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Data Science Division, Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=2 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diarrhea and related personal characteristics among Japanese university students studying abroad in intermediate- and low-risk countries en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite an increasing number of students studying abroad worldwide, evidence about health risks while they are abroad is limited. Diarrhea is considered the most common travelers' illness, which would also apply to students studying abroad. We examined diarrhea and related personal characteristics among Japanese students studying abroad. Japanese university students who participated in short-term study abroad programs between summer 2016 and spring 2018 were targeted (n = 825, 6-38 travel days). Based on a 2-week-risk of diarrhea (passing three or more loose or liquid stools per day) among travelers by country, the destination was separated into intermediate- and low-risk countries. After this stratification, the associations between personal characteristics and diarrhea during the first two weeks of their stay were evaluated using logistic regression models. Among participants in intermediate-risk countries, teenagers, males and those with overseas travel experience were associated with an elevated risk of diarrhea; the odds ratios (95% confidence intervals) were 2.42 (1.08-5.43) for teenagers (vs. twenties), 1.93 (1.08-3.45) for males (vs. females) and 2.37 (1.29-4.33) for those with overseas experience (vs. none). Even restricting an outcome to diarrhea during the first week did not change the results substantially. The same tendency was not observed for those in the low-risk countries. Teenage students, males and those with overseas travel experience should be cautious about diarrhea while studying abroad, specifically in intermediate-risk countries. en-copyright= kn-copyright= en-aut-name=YamakawaMichiyo en-aut-sei=Yamakawa en-aut-mei=Michiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsudaToshihide en-aut-sei=Tsuda en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaKeiko en-aut-sei=Wada en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagataChisato en-aut-sei=Nagata en-aut-mei=Chisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Human Ecology, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Epidemiology and Preventive Medicine, Graduate School of Medicine, Gifu University kn-affil= affil-num=4 en-affil=Department of Epidemiology and Preventive Medicine, Graduate School of Medicine, Gifu University kn-affil= affil-num=5 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=4 article-no= start-page=e1010732 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overexpression profiling reveals cellular requirements in the context of genetic backgrounds and environments en-subtitle= kn-subtitle= en-abstract= kn-abstract=Overexpression can help life adapt to stressful environments, making an examination of overexpressed genes valuable for understanding stress tolerance mechanisms. However, a systematic study of genes whose overexpression is functionally adaptive (GOFAs) under stress has yet to be conducted. We developed a new overexpression profiling method and systematically identified GOFAs in Saccharomyces cerevisiae under stress (heat, salt, and oxidative). Our results show that adaptive overexpression compensates for deficiencies and increases fitness under stress, like calcium under salt stress. We also investigated the impact of different genetic backgrounds on GOFAs, which varied among three S. cerevisiae strains reflecting differing calcium and potassium requirements for salt stress tolerance. Our study of a knockout collection also suggested that calcium prevents mitochondrial outbursts under salt stress. Mitochondria-enhancing GOFAs were only adaptive when adequate calcium was available and non-adaptive when calcium was deficient, supporting this idea. Our findings indicate that adaptive overexpression meets the cell's needs for maximizing the organism's adaptive capacity in the given environment and genetic context. Author summaryThe study aimed to investigate how overexpression of genes can aid organisms in adapting to stress. The researchers utilized a new method to identify genes in yeast that demonstrated functional adaptability when overexpressed under stress such as heat, salt, and oxidative stress. The results indicated that overexpressing specific genes, like calcium, during salt stress could counteract deficiencies and improve the organism's ability to withstand stress. The study also examined the effect of different genetic backgrounds on these genes and discovered that the impact differed among various yeast strains. Additionally, the study revealed that calcium could play a key role in adapting to salt stress by preventing mitochondrial outbursts. These findings suggest that overexpressing certain genes can help the organism maximize its adaptability to stress in a given environment and genetic context. en-copyright= kn-copyright= en-aut-name=SaekiNozomu en-aut-sei=Saeki en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoChie en-aut-sei=Yamamoto en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EguchiYuichi en-aut-sei=Eguchi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekitoTakayuki en-aut-sei=Sekito en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigenobuShuji en-aut-sei=Shigenobu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimuraMami en-aut-sei=Yoshimura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YashirodaYoko en-aut-sei=Yashiroda en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BooneCharles en-aut-sei=Boone en-aut-mei=Charles kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriyaHisao en-aut-sei=Moriya en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Biomedical Business Center, RICOH Futures BU kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Ehime University kn-affil= affil-num=5 en-affil=National Institute for Basic Biology kn-affil= affil-num=6 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=7 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=8 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=9 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Knockout of ribosomal protein RpmJ leads to zinc resistance in Escherichia coli en-subtitle= kn-subtitle= en-abstract= kn-abstract=Zinc is an essential metal for cells, but excess amounts are toxic. Other than by regulating the intracellular zinc concentration by zinc uptake or efflux, the mechanisms underlying bacterial resistance to excess zinc are unknown. In the present study, we searched for zinc-resistant mutant strains from the Keio collection, a gene knockout library of Escherichia coli, a model gram-negative bacteria. We found that knockout mutant of RpmJ (L36), a 50S ribosomal protein, exhibited zinc resistance. The rpmJ mutant was sensitive to protein synthesis inhibitors and had altered translation fidelity, indicating ribosomal dysfunction. In the rpmJ mutant, the intracellular zinc concentration was decreased under excess zinc conditions. Knockout of ZntA, a zinc efflux pump, abolished the zinc-resistant phenotype of the rpmJ mutant. RNA sequence analysis revealed that the rpmJ mutant exhibited altered gene expression of diverse functional categories, including translation, energy metabolism, and stress response. These findings suggest that knocking out RpmJ alters gene expression patterns and causes zinc resistance by lowering the intracellular zinc concentration. Knockouts of other ribosomal proteins, including RplA, RpmE, RpmI, and RpsT, also led to a zinc-resistant phenotype, suggesting that deletion of ribosomal proteins is closely related to zinc resistance. en-copyright= kn-copyright= en-aut-name=ShirakawaRiko en-aut-sei=Shirakawa en-aut-mei=Riko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=2 article-no= start-page=e0281516 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fucosyltransferase 8 (FUT8) and core fucose expression in oxidative stress response en-subtitle= kn-subtitle= en-abstract= kn-abstract=GlycoMaple is a new tool to predict glycan structures based on the expression levels of 950 genes encoding glycan biosynthesis-related enzymes and proteins using RNA-seq data. The antioxidant response, protecting cells from oxidative stress, has been focused on because its activation may relieve pathological conditions, such as neurodegenerative diseases. Genes involved in the antioxidant response are defined within the GO:0006979 category, including 441 human genes. Fifteen genes overlap between the glycan biosynthesis-related genes defined by GlycoMaple and the antioxidant response genes defined by GO:0006979, one of which is FUT8. 5-Hydroxy-4-phenyl-butenolide (5H4PB) extracted from Chinese aromatic vinegar induces the expression of a series of antioxidant response genes that protect cells from oxidative stress via activation of the nuclear factor erythroid 2-related factor 2-antioxidant response element pathway. Here, we show that FUT8 is upregulated in both our RNA-seq data set of 5H4PB-treated cells and publicly available RNA-seq data set of cells treated with another antioxidant, sulforaphane. Applying our RNA-seq data set to GlycoMaple led to a prediction of an increase in the core fucose of N-glycan that was confirmed by flow cytometry using a fucose-binding lectin. These results suggest that FUT8 and core fucose expression may increase upon the antioxidant response. en-copyright= kn-copyright= en-aut-name=KyunaiYuki en-aut-sei=Kyunai en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakamotoMika en-aut-sei=Sakamoto en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoreishiMayuko en-aut-sei=Koreishi en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujinoYoshio en-aut-sei=Tsujino en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=2 en-affil=National Institute of Genetics, ROIS kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Science, Technology, and Innovation, Kobe University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collaborative support for child abuse prevention: Perspectives of public health nurses and midwives regarding pregnant and postpartum women of concern en-subtitle= kn-subtitle= en-abstract= kn-abstract=Child abuse is a globally prevalent problem, and its numbers have continuously increased in Japan over the past 30 years. Prevention of child abuse depends on the support available to pregnant and postpartum women from the time of pregnancy. Public health nurses and midwives are expected to provide preventive support in cooperation, as they can support pregnant and postpartum women from close proximity and recognize their health problems and potential signs of child abuse. This study aimed to deduce the characteristics of pregnant and postpartum women of concern, as observed by public health nurses and midwives, from the perspective of child abuse prevention. The participants comprised ten public health nurses and ten midwives with five or more years of experience working at the Okayama Prefecture municipal health centers and obstetric medical institutions. Data were collected through a semi-structured interview survey and analyzed qualitatively and descriptively using an inductive approach. The characteristics of pregnant and postpartum women, as confirmed by public health nurses, included four main categories: having "difficulties in daily life;" "a sense of discomfort of not feeling like a normal pregnant woman;" "difficulty in child-rearing behavior;" and "multiple risk factors checked by objective indicators using an assessment tool." The characteristics observed by midwives were grouped into four main categories: "mental and physical safety of the mother is in jeopardy;" have "difficulty in child-rearing behavior;" "difficulties in maintaining relationships with the surrounding people;" and "multiple risk factors recognized by an assessment tool." Public health nurses evaluated pregnant and postpartum women's daily life factors, while midwives evaluated the mothers' health conditions, their feelings toward the fetus, and stable child-rearing skills. To prevent child abuse, they utilized their respective specialties to observe those pregnant and postpartum women of concern with multiple risk factors. en-copyright= kn-copyright= en-aut-name=YokomizoAkemi en-aut-sei=Yokomizo en-aut-mei=Akemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaeHiroko en-aut-sei=Nagae en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AthurupanaRukmali en-aut-sei=Athurupana en-aut-mei=Rukmali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakatsukaMikiya en-aut-sei=Nakatsuka en-aut-mei=Mikiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Kameda University of Health Science, Kamogawa City kn-affil= affil-num=3 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=e1011162 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Capsid structure of a fungal dsRNA megabirnavirus reveals its previously unidentified surface architecture en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a non-enveloped icosahedral double-stranded (ds)RNA virus that infects the ascomycete fungus Rosellinia necatrix, a causative agent that induces a lethal plant disease white root rot. Herein, we have first resolved the atomic structure of the RnMBV1 capsid at 3.2 angstrom resolution using cryo-electron microscopy (cryo-EM) single-particle analysis. Compared with other non-enveloped icosahedral dsRNA viruses, the RnMBV1 capsid protein structure exhibits an extra-long C-terminal arm and a surface protrusion domain. In addition, the previously unrecognized crown proteins are identified in a symmetry-expanded cryo-EM model and are present over the 3-fold axes. These exclusive structural features of the RnMBV1 capsid could have been acquired for playing essential roles in transmission and/or particle assembly of the megabirnaviruses. Our findings, therefore, will reinforce the understanding of how the structural and molecular machineries of the megabirnaviruses influence the virulence of the disease-related ascomycete fungus. Author summaryA fungal plant soil-borne pathogen, Rosellinia necatrix, which can cause devastating disease white root rot in many highly valued fruit trees, is difficult to be controlled with conventional approaches such as fungicide applications. Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a dsRNA virus isolated from the R. necatrix field strain, W779, and this virus can be a viro-control candidate to confer hypovirulence in its host R. necatrix. To make use of RnMBV1 in the white root rot disease control, more molecular and structural investigations will offer us more insights. Here, we have performed cryo-electron microscopy (cryo-EM) single-particle analysis, to obtain the first atomic models of RnMBV1 particles. Based on the atomic structures, we found unique both surface and interior features. In addition, we found a previously unidentified protein on the viral surface. These aforementioned structural features might play important roles in the viral life cycles, and will enable us to apply this fungal virus as a viro-control approach. en-copyright= kn-copyright= en-aut-name=WangHan en-aut-sei=Wang en-aut-mei=Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SalaipethLakha en-aut-sei=Salaipeth en-aut-mei=Lakha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyazakiNaoyuki en-aut-sei=Miyazaki en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkamotoKenta en-aut-sei=Okamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=The Laboratory of Molecular Biophysics, Department of Cell and Molecular Biology, Uppsala University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Life Science Center of Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=The Laboratory of Molecular Biophysics, Department of Cell and Molecular Biology, Uppsala University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enzymatic measurement of short-chain fatty acids and application in periodontal disease diagnosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontal disease is a chronic inflammatory condition caused by periodontal pathogens in the gingival sulcus. Short-chain fatty acids (SCFAs) produced by causal bacteria are closely related to the onset and progression of periodontal disease and have been reported to proliferate in the periodontal sulcus of patients experiencing this pathology. In such patients, propionic acid (C3), butyric acid (C4), isobutyric acid (IC4), valeric acid (C5), isovaleric acid (IC5), and caproic acid (C6), henceforth referred to as [C3-C6], has been reported to have a detrimental effect, while acetic acid (C2) exhibits no detrimental effect. In this study, we established an inexpensive and simple enzymatic assay that can fractionate and measure these acids. The possibility of applying this technique to determine the severity of periodontal disease by adapting it to specimens collected from humans has been explored. We established an enzyme system using acetate kinase and butyrate kinase capable of measuring SCFAs in two fractions, C2 and [C3-C6]. The gingival crevicular fluid (GCF) and saliva of 10 healthy participants and 10 participants with mild and severe periodontal disease were measured using the established enzymatic method and conventional gas chromatography-mass spectrometry (GC-MS). The quantification of C2 and [C3-C6] in human GCF and saliva was well correlated when using the GC-MS method. Furthermore, both C2 and [C3-C6] in the GCF increased with disease severity. However, while no significant difference was observed between healthy participants and periodontal patients when using saliva, [C3-C6] significantly differed between mild and severe periodontal disease. The enzymatic method was able to measure C2 and [C3-C6] separately as well as using the GC-MS method. Furthermore, the C2 and [C3-C6] fractions of GCF correlated with disease severity, suggesting that this method can be applied clinically. In contrast, the quantification of C2 and [C3-C6] in saliva did not differ significantly between healthy participants and patients with periodontal disease. Future studies should focus on inflammation rather than on tissue destruction. en-copyright= kn-copyright= en-aut-name=HatanakaKazu en-aut-sei=Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirahaseYasushi en-aut-sei=Shirahase en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaToshiyuki en-aut-sei=Yoshida en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KonoMari en-aut-sei=Kono en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyaNaoki en-aut-sei=Toya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakasegawaShin-Ichi en-aut-sei=Sakasegawa en-aut-mei=Shin-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KonishiKenji en-aut-sei=Konishi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OchiaiKuniyasu en-aut-sei=Ochiai en-aut-mei=Kuniyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Sysmex Corporation kn-affil= affil-num=3 en-affil=Sysmex Corporation kn-affil= affil-num=4 en-affil=Sysmex Corporation kn-affil= affil-num=5 en-affil=Sysmex Corporation kn-affil= affil-num=6 en-affil=Asahi Kasei Pharma Corporation kn-affil= affil-num=7 en-affil=Asahi Kasei Pharma Corporation kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Pathophysiology-Periodontal Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=3 article-no= start-page=e0245502 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Usefulness of right ventriculography compared with computed tomography for ruling out the possibility of lead perforation before lead extraction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose High-risk patients can be identified by preprocedural computed tomography (CT) before lead extraction. However, CT evaluation may be difficult especially for lead tip identification due to artifacts in the leads. Selective right ventriculography (RVG) may enable preprocedural evaluation of lead perforation. We investigated the efficacy of RVG for identifying right ventricular (RV) lead perforation compared with CT in patients who underwent lead extraction. Methods Ninety-five consecutive patients who were examined by thin-section non-ECG-gated multi-detector CT and RVG before lead extraction were investigated retrospectively. Newly recognized pericardial effusion after lead extraction was used as a reference standard for lead perforation. We analyzed the prevalence of RV lead perforation diagnosed by each method. The difference in the detection rates of lead perforation by RVG and CT was evaluated. Results Of the 115 RV leads in the 95 patients, lead perforation was diagnosed for 35 leads using CT, but the leads for 29 (83%) of those 35 leads diagnosed as lead perforation by CT were shown to be within the right ventricle by RVG. Three patients with 5 leads could not be evaluated by CT due to motion artifacts. The diagnostic accuracies of RVG and CT were significantly different (p < 0.001). There was no complication of pericardial effusion caused by RV lead extraction. Conclusion RVG for identification of RV lead perforation leads to fewer false-positives compared to non-ECG-gated CT. However, even in cases in which lead perforation is diagnosed, most leads may be safely extracted by transvenous lead extraction. en-copyright= kn-copyright= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinyaTakayoshi en-aut-sei=Shinya en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyoshiAkihito en-aut-sei=Miyoshi en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorimotoYoshimasa en-aut-sei=Morimoto en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatric Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=10 article-no= start-page=e0241120 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Local perspectives on Ebola during its tenth outbreak in DR Congo: A nationwide qualitative study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
The Democratic Republic of Congo (DR Congo) struggled to end the tenth outbreak of Ebola virus disease (Ebola), which appeared in North Kivu in 2018. It was reported that rumors were hampering the response effort. We sought to identify any rumors that could have influenced outbreak containment and affected prevention in unaffected areas of DR Congo.
Methods
We conducted a qualitative study in DR Congo over a period of 2 months (from August 1 to September 30, 2019) using in-depth interviews (IDIs) and focus group discussions (FGDs). The participants were recruited from five regional blocks using purposeful sampling. Both areas currently undergoing outbreaks and presently unaffected areas were included. We collected participants’ opinions, views, and beliefs about the Ebola virus. The IDIs (n = 60) were performed with key influencers (schoolteachers, religious and political leaders/analysts, and Ebola-frontline workers), following a semi-structured interview guide. FGDs (n = 10) were conducted with community members. Interviews were recorded with a digital voice recorder and simultaneous note-taking. Participant responses were categorized in terms of their themes and subthemes.
Results
We identified 3 high-level themes and 15 subthemes (given here in parentheses): (1) inadequate knowledge of the origin or cause of Ebola (belief in a metaphysical origin, insufficient awareness of Ebola transmission via an infected corpse, interpretation of disease as God’s punishment, belief in nosocomial Ebola, poor hygiene, and bathing in the Congo River). Ebola was interpreted as (2) a plot by multinational corporations (fears of genocide, Ebola understood as a biological weapon, concerns over organ trafficking, and Ebola was taken to be the result of business actions). Finally Ebola was rumored to be subject to (3) politicization (political authorities seen as ambivalent, exclusion of some community leaders from response efforts, distrust of political authorities, and distrust in the healthcare system).
Conclusions
Due to the skepticism against Ebola countermeasures, it is critical to understand widespread beliefs about the disease to implement actions that will be effective, including integrating response with the unmet needs of the population. en-copyright= kn-copyright= en-aut-name=MuzemboBasilua Andre en-aut-sei=Muzembo en-aut-mei=Basilua Andre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NtontoloNgangu Patrick en-aut-sei=Ntontolo en-aut-mei=Ngangu Patrick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NgatuNlandu Roger en-aut-sei=Ngatu en-aut-mei=Nlandu Roger kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KhatiwadaJanuka en-aut-sei=Khatiwada en-aut-mei=Januka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NgombeKabamba Leon en-aut-sei=Ngombe en-aut-mei=Kabamba Leon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NumbiOscar Luboya en-aut-sei=Numbi en-aut-mei=Oscar Luboya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NzajiKabamba Michel en-aut-sei=Nzaji en-aut-mei=Kabamba Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaotelaKabinda Jeff en-aut-sei=Maotela en-aut-mei=Kabinda Jeff kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NgoyiMukonkole Jean en-aut-sei=Ngoyi en-aut-mei=Mukonkole Jean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuzukiTomoko en-aut-sei=Suzuki en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WadaKoji en-aut-sei=Wada en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaShunya en-aut-sei=Ikeda en-aut-mei=Shunya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Family Medicine and Primary health, Protestant University of Congo kn-affil= affil-num=3 en-affil=Department of Public Health, Kagawa University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Public Health, School of Medicine, International University of Health and Welfare kn-affil= affil-num=5 en-affil=Department of Public Health, University of Kamina kn-affil= affil-num=6 en-affil=School of Public Health, University of Lubumbashi kn-affil= affil-num=7 en-affil=School of Public Health, University of Lubumbashi kn-affil= affil-num=8 en-affil=Centre National de Transfusion Sanguine kn-affil= affil-num=9 en-affil=Research Unit, ISTM-Lubumbashi kn-affil= affil-num=10 en-affil=Department of Public Health, School of Medicine, International University of Health and Welfare kn-affil= affil-num=11 en-affil=Department of Public Health, School of Medicine, International University of Health and Welfare kn-affil= affil-num=12 en-affil=Department of Public Health, School of Medicine, International University of Health and Welfare kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=e0245115 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amplitude of circadian rhythms becomes weaken in the north, but there is no cline in the period of rhythm in a beetle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Many species show rhythmicity in activity, from the timing of flowering in plants to that of foraging behavior in animals. The free-running periods and amplitude (sometimes called strength or power) of circadian rhythms are often used as indicators of biological clocks. Many reports have shown that these traits are highly geographically variable, and interestingly, they often show latitudinal or longitudinal clines. In many cases, the higher the latitude is, the longer the free-running circadian period (i.e., period of rhythm) in insects and plants. However, reports of positive correlations between latitude or longitude and circadian rhythm traits, including free-running periods, the power of the rhythm and locomotor activity, are limited to certain taxonomic groups. Therefore, we collected a cosmopolitan stored-product pest species, the red flour beetle Tribolium castaneum, in various parts of Japan and examined its rhythm traits, including the power and period of the rhythm, which were calculated from locomotor activity. The analysis revealed that the power was significantly lower for beetles collected in northern areas than southern areas in Japan. However, it is worth noting that the period of circadian rhythm did not show any clines; specifically, it did not vary among the sampling sites, despite the very large sample size (n = 1585). We discuss why these cline trends were observed in T. castaneum. en-copyright= kn-copyright= en-aut-name=AbeMasato S. en-aut-sei=Abe en-aut-mei=Masato S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumuraKentarou en-aut-sei=Matsumura en-aut-mei=Kentarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Center for Advanced Intelligence Project, RIKEN kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil= Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=12 article-no= start-page=e0243382 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Shape analysis of rectus extraocular muscles with age and axial length using anterior segment optical coherence tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose
This study aimed to evaluate the shape of the extraocular muscles (EOMs) in normal subjects using the en-face images of anterior segment optical coherence tomography (AS-OCT). The EOM insertion and the direction of the muscle fibers were investigated.
Subjects and methods
A total of 97 healthy normal subjects (194 eyes) at Okayama University Hospital (age, 47.1±21.5 years; range, 8–79 years) participated in the study. A series of 256 tomographic images of the rectus EOMs were captured using the C-scan function of the AS-OCT (CASIA2, TOMEY Co., Japan), and the images were converted to en-face images in multi-TIFF format. The anterior chamber angle to EOM insertion distance (AID) and the angle of the muscle fibers from the insertion site (angle of muscles) were measured from the images. The correlations of AID and angle of muscles with age and axial length were investigated and evaluated.
Results
AID and angle of muscles were significantly correlated with age or axial length in some EOMs. The AIDs of medial rectus (MR) (P = 0.000) and superior rectus (SR) (P = 0.005) shortened with age. The AIDs of MR (P = 0.001) and inferior rectus (IR) (P = 0.035) elongated with axial length, whereas lateral rectus (LR) (P = 0.013) shortened. The angles of MR (P = 0.001) and LR (P = 0.000) were found to have a more downward direction toward the posterior in older subjects.
Conclusion
En-face images can be created by AS-OCT, and the shape of the EOMs in normal subjects using these image measurements was available. With the ability to assess the EOMs, AID and angle of muscles are expected give useful information for treating and diagnosing strabismus-related diseases. en-copyright= kn-copyright= en-aut-name=ShibataKiyo en-aut-sei=Shibata en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraAtsushi en-aut-sei=Fujiwara en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamasakiIchiro en-aut-sei=Hamasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimizuTakehiro en-aut-sei=Shimizu en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KonoReika en-aut-sei=Kono en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanenagaKeisuke en-aut-sei=Kanenaga en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakazawaMasanori en-aut-sei=Nakazawa en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthoptics, Faculty of Rehabilitation, Kawasaki University of Medical Welfare kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=11 article-no= start-page=e0242223 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Short-term and long-term comparisons of laparoscopy-assisted proximal gastrectomy with esophagogastrostomy by the double-flap technique and laparoscopy-assisted total gastrectomy for proximal gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Although proximal gastrectomy (PG) is a recognized surgical procedure for early proximal gastric cancer, total gastrectomy (TG) is sometimes selected due to concern about severe gastroesophageal reflux. Esophagogastrostomy by the double-flap technique (DFT) is an anti-reflux reconstruction after PG, and its short-term effectiveness has been reported. However, little is known about the long-term effects on nutritional status and quality of life (QOL).
Methods
Gastric cancer patients who underwent laparoscopy-assisted PG (LAPG) with DFT or laparoscopy-assisted TG (LATG) between April 2011 and March 2014 were retrospectively analyzed. Body weight (BW), body mass index (BMI), and prognostic nutritional index (PNI) were reviewed to assess nutritional status, and the Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 was used to assess QOL.
Results
A total of 36 patients (LATG: 17, LAPG: 19) were enrolled. Four of 17 LATG patients (24%) were diagnosed with Stage ≥II after surgery, and half received S-1 adjuvant chemotherapy. BW and PNI were better maintained in LAPG than in LATG patients until 1-year follow-up. Seven of 16 LATG patients (44%) were categorized as “underweight (BMI<18.5 kg/m2)” at 1-year follow-up, compared to three of 18 LAPG patients (17%; p = 0.0836). The PGSAS-45 showed no significant difference in all QOL categories except for decreased BW (p = 0.0132). Multivariate analysis showed that LATG was the only potential risk factor for severe BW loss (odds ratio: 3.03, p = 0.0722).
Conclusions
LAPG with DFT was superior to LATG in postoperative nutritional maintenance, and can be the first option for early proximal gastric cancer. en-copyright= kn-copyright= en-aut-name=TsumuraTomoko en-aut-sei=Tsumura en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishizakiMasahiko en-aut-sei=Nishizaki en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakataNobuo en-aut-sei=Takata en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoAtene en-aut-sei=Ito en-aut-mei=Atene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeMegumi en-aut-sei=Watanabe en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuwadaKazuya en-aut-sei=Kuwada en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=10 article-no= start-page=e0240936 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201019 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The inclusion of blastomeres into the inner cell mass in early-stage human embryos depends on the sequence of cell cleavages during the fourth division en-subtitle= kn-subtitle= en-abstract= kn-abstract=The fate of the ICM in humans is still unknown, due to the ethical difficulties surrounding experimentation in this field. In this study we have explored the existing time-lapse recording data of embryos in the early stages of development, taking advantage of the large refractile bodies (RBs) within blastomeres as cellular markers. Our study found that the cellular composition of the ICM in humans is largely determined at the time of the fourth division and blastomeres which cleave first to fourth, during the fourth division from 8 cells to 16 cells, have the potential to be incorporated in the ICM. en-copyright= kn-copyright= en-aut-name=OtsukiJunko en-aut-sei=Otsuki en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwasakiToshiroh en-aut-sei=Iwasaki en-aut-mei=Toshiroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EnatsuNoritoshi en-aut-sei=Enatsu en-aut-mei=Noritoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatadaYuya en-aut-sei=Katada en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuruhashiKohyu en-aut-sei=Furuhashi en-aut-mei=Kohyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiotaniMasahide en-aut-sei=Shiotani en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Assisted Reproductive Technology Center, Okayama University kn-affil= affil-num=2 en-affil=Hanabusa Women’s Clinic kn-affil= affil-num=3 en-affil=Hanabusa Women’s Clinic kn-affil= affil-num=4 en-affil=Hanabusa Women’s Clinic kn-affil= affil-num=5 en-affil=Hanabusa Women’s Clinic kn-affil= affil-num=6 en-affil=Hanabusa Women’s Clinic kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=10 article-no= start-page=e0240333 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fgf10-CRISPR mosaic mutants demonstrate the gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung en-subtitle= kn-subtitle= en-abstract= kn-abstract=CRISPR/Cas9-mediated gene editing often generates founder generation (F0) mice that exhibit somatic mosaicism in the targeted gene(s). It has been known thatFibroblast growth factor 10(Fgf10)-null mice exhibit limbless and lungless phenotypes, while intermediate limb phenotypes (variable defective limbs) are observed in theFgf10-CRISPR F0 mice. However, how the lung phenotype in theFgf10-mosaic mutants is related to the limb phenotype and genotype has not been investigated. In this study, we examined variable lung phenotypes in theFgf10-targeted F0 mice to determine if the lung phenotype was correlated with percentage of functionalFgf10genotypes. Firstly, according to a previous report,Fgf10-CRISPR F0 embryos on embryonic day 16.5 (E16.5) were classified into three types: type I, no limb; type II, limb defect; and type III, normal limbs. Cartilage and bone staining showed that limb truncations were observed in the girdle, (type I), stylopodial, or zeugopodial region (type II). Deep sequencing of theFgf10-mutant genomes revealed that the mean proportion of codons that encode putative functional FGF10 was 8.3 +/- 6.2% in type I, 25.3 +/- 2.7% in type II, and 54.3 +/- 9.5% in type III (mean +/- standard error of the mean) mutants at E16.5. Histological studies showed that almost all lung lobes were absent in type I embryos. The accessory lung lobe was often absent in type II embryos with other lobes dysplastic. All lung lobes formed in type III embryos. The number of terminal tubules was significantly lower in type I and II embryos, but unchanged in type III embryos. To identify alveolar type 2 epithelial (AECII) cells, known to be reduced in theFgf10-heterozygous mutant, immunostaining using anti-surfactant protein C (SPC) antibody was performed: In the E18.5 lungs, the number of AECII was correlated to the percentage of functionalFgf10genotypes. These data suggest theFgf10gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung. Since dysfunction of AECII cells has been implicated in the pathogenesis of parenchymal lung diseases, theFgf10-CRISPR F0 mouse would present an ideal experimental system to explore it. en-copyright= kn-copyright= en-aut-name=HabutaMunenori en-aut-sei=Habuta en-aut-mei=Munenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasueAkihiro en-aut-sei=Yasue en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuzukiKen-Ichi T. en-aut-sei=Suzuki en-aut-mei=Ken-Ichi T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaHirofumi en-aut-sei=Fujita en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonoHitomi en-aut-sei=Kono en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakayamaAyuko en-aut-sei=Takayama en-aut-mei=Ayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BandoTetsuya en-aut-sei=Bando en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyaishiSatoru en-aut-sei=Miyaishi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OyadomariSeiichi en-aut-sei=Oyadomari en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanakaEiji en-aut-sei=Tanaka en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School kn-affil= affil-num=3 en-affil=Department of Mathematical and Life Sciences, Hiroshima University kn-affil= affil-num=4 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Center for the Development of New Model Organisms, National Institute for Basic Biology kn-affil= affil-num=8 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Molecular Biology, Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=11 en-affil=Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School kn-affil= affil-num=12 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=10 article-no= start-page=e1009091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Proper control of gene expression levels upon various perturbations is a fundamental aspect of cellular robustness. Protein-level dosage compensation is one mechanism buffering perturbations to stoichiometry of multiprotein complexes through accelerated proteolysis of unassembled subunits. Although N-terminal acetylation- and ubiquitin-mediated proteasomal degradation by the Ac/N-end rule pathway enables selective compensation of excess subunits, it is unclear how widespread this pathway contributes to stoichiometry control. Here we report that dosage compensation depends only partially on the Ac/N-end rule pathway. Our analysis of genetic interactions between 18 subunits and 12 quality control factors in budding yeast demonstrated that multiple E3 ubiquitin ligases and N-acetyltransferases are involved in dosage compensation. We find that N-acetyltransferases-mediated compensation is not simply predictable from N-terminal sequence despite their sequence specificity for N-acetylation. We also find that the compensation of Pop3 and Bet4 is due in large part to a minor N-acetyltransferase NatD. Furthermore, canonical NatD substrates histone H2A/H4 were compensated even in its absence, suggesting N-acetylation-independent stoichiometry control. Our study reveals the complexity and robustness of the stoichiometry control system. Author summary Quality control of multiprotein complexes is important for maintaining homeostasis in cellular systems that are based on functional complexes. Proper stoichiometry of multiprotein complexes is achieved by the balance between protein synthesis and degradation. Recent studies showed that translation efficiency tends to scale with stoichiometry of their subunits. On the other hand, although protein N-terminal acetylation- and ubiquitin-mediated proteolysis pathway is involved in selective degradation of excess subunits, it is unclear how widespread this pathway contributes to stoichiometry control due to the lack of a systematic investigation using endogenous proteins. To better understand the landscape of the stoichiometry control system, we examined genetic interactions between 18 subunits and 12 quality control factors (E3 ubiquitin ligases and N-acetyltransferases), in total 114 combinations. Our data suggest that N-acetyltransferases are partially responsible for stoichiometry control and that N-acetylation-independent pathway is also involved in selective degradation of excess subunits. Therefore, this study reveals the complexity and robustness of the stoichiometry control system. Further dissection of this complexity will help to understand the mechanisms buffering gene expression perturbations and shaping proteome stoichiometry. en-copyright= kn-copyright= en-aut-name=IshikawaKoji en-aut-sei=Ishikawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiharaAkari en-aut-sei=Ishihara en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyaHisao en-aut-sei=Moriya en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= affil-num=2 en-affil=Course of Agrochemical Bioscience, Faculty of Agriculture, Okayama University kn-affil= affil-num=3 en-affil= Research Core for Interdisciplinary Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=7 article-no= start-page=e0235790 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Triple-negative pleomorphic lobular carcinoma and expression of androgen receptor: Personal case series and review of the literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pleomorphic lobular carcinoma (PLC) is a histological variant of invasive lobular carcinoma (ILC) and is associated with worse prognosis than classical ILC. It exhibits a greater degree of cellular atypia and pleomorphism and is occasionally accompanied with apocrine morphology. We investigated the immunohistochemical characteristics of samples from 31 Japanese patients with PLC to elucidate the clinicopathological characteristics of PLC including androgen receptor (AR) immunoreactivity. The surrogate molecular subtypes were luminal A-like, luminal B-like, luminal B-like/HER2, HER2-type, and triple-negative in 5, 4, 3, 5, and 14 cases, respectively. AR was positive in 92.8% (13/14) of the triple-negative PLC cases and 100% (10/10) of the non-triple-negative PLC cases. Disease-specific survival was worse in patients with histological grade 3 PLCs than in those with histological grade 2 PLCs (p = 0.007). However, there was no significant difference in the progression-free survival between the two groups (p = 0.152). No other clinicopathological characteristics were associated with prognosis. These results reveal that PLC exhibits various surrogate molecular subtypes and that the triple-negative subtype frequently expresses AR. The observed molecular apocrine differentiation implicates that triple-negative PLC can be categorized into the luminal AR subtype. Furthermore, AR-targeted therapy might be useful for patients with triple-negative PLC. en-copyright= kn-copyright= en-aut-name=TaniguchiKohei en-aut-sei=Taniguchi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakadaShinichi en-aut-sei=Takada en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoriMasako en-aut-sei=Omori en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IgawaTakuro en-aut-sei=Igawa en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritoToshiaki en-aut-sei=Morito en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchimuraKouichi en-aut-sei=Ichimura en-aut-mei=Kouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pathology, Yuai Memorial Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, Kurashiki Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=7 en-affil=Department of Pathology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=8 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=7 article-no= start-page=e0236259 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200723 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship between oral hygiene knowledge, source of oral hygiene knowledge and oral hygiene behavior in Japanese university students: A prospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this prospective cohort study was to examine whether oral hygiene knowledge, and the source of that knowledge, affect oral hygiene behavior in university students in Japan. An oral exam and questionnaire survey developed to evaluate oral hygiene knowledge, the source of that knowledge, and oral hygiene behavior, such as the frequency of tooth brushing and regular dental checkups and the use of dental floss, was conducted on university student volunteers. In total, 310 students with poor tooth brushing behavior (frequency of tooth brushing per day [<= once]), 1,963 who did not use dental floss, and 1,882 who did not receive regular dental checkup during the past year were selected. Among these students, 50, 364, and 343 in each respective category were analyzed in over the 3-year study period (follow-up rates: 16.1%, 18.5%, and 18.2%, respectively). The odds ratios (ORs) and 95% confidence intervals (CIs) for oral hygiene behavior were calculated based on oral hygiene knowledge and the source of that knowledge using logistic regression models. The results showed that dental clinics were the most common (> 50%) source of oral hygiene knowledge, and that a more frequent use of dental floss was significantly associated with dental clinics being a source of oral hygiene knowledge (OR, 4.11; 95%CI, 1.871-9.029; p < 0.001). In addition, a significant association was seen between dental clinics being a source of oral hygiene knowledge and more frequent regular dental checkups (OR, 13.626; 95%CI, 5.971-31.095; p < 0.001). These findings suggest the existence of a relationship between dental clinics being the most common source of oral hygiene knowledge and improved oral hygiene behavior in Japanese university students. en-copyright= kn-copyright= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KataokaKota en-aut-sei=Kataoka en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Taniguchi-TabataAyano en-aut-sei=Taniguchi-Tabata en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Uchida-FukuharaYoko en-aut-sei=Uchida-Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YonedaToshiki en-aut-sei=Yoneda en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiuraYoshio en-aut-sei=Sugiura en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IslamMonirul en-aut-sei=Islam en-aut-mei=Monirul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SahoHikari en-aut-sei=Saho en-aut-mei=Hikari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Health Service Center, Okayama University kn-affil= affil-num=12 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=8 article-no= start-page=e0236935 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200827 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nintedanib can be used safely and effectively for idiopathic pulmonary fibrosis with predicted forced vital capacity <= 50%: A multi-center retrospective analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Nintedanib is a multi-kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF); however, its efficacy and safety for patients with IPF and restricted pulmonary function remain unclear. Therefore, the objective of this study was to determine the efficacy and safety of nintedanib for patients with IPF and forced vital capacity (FVC) ≤ 50%.
Methods
This was a multi-center retrospective study performed by the Okayama Respiratory Disease Study Group. Patients were allocated into FVC ≤ 50% and FVC > 50% groups based on their predicted FVC. The primary endpoints were FVC changes from baseline after 6 and 12 months.
Results
45 patients were eligible for the study. 18 patients had FVC ≤ 50%, and 27 patients had FVC > 50%. Overall, 31 and 19 patients underwent pulmonary function tests at 6 and 12 months after initiating nintedanib, respectively. FVC changes from baseline at 6 and 12 months after initiating nintedanib were comparable between the two groups. Adverse events were seen in all patients, and the rates of patients who discontinued nintedanib were also comparable (38.9% vs. 37.0%, p = 1.000). Multiple regression analysis showed that age and forced expiratory volume in 1 second (FEV1)/FVC were negatively correlated with changes in FVC at 6 months after initiating nintedanib.
Conclusions
Our data suggest that nintedanib can be a useful agent for IPF patients, including those with a low FVC, and that age and FEV1/FVC are predictive markers for changes in FVC following nintedanib treatment. en-copyright= kn-copyright= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItanoJunko en-aut-sei=Itano en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuwakiToshimitsu en-aut-sei=Suwaki en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FuchimotoYasuko en-aut-sei=Fuchimoto en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KajimotoKazuhiro en-aut-sei=Kajimoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShibayamaTakuo en-aut-sei=Shibayama en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanimotoYasushi en-aut-sei=Tanimoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KanehiroArihiko en-aut-sei=Kanehiro en-aut-mei=Arihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=Okayama Respiratory Disease Study Group (ORDSG) en-aut-sei=Okayama Respiratory Disease Study Group (ORDSG) en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama City Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Japan Organization of Occupational Health and Safety Okayama Rosai Hospita kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospita kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=18 en-affil=Department of Respiratory Medicine, Japan Organization of Occupational Health and Safety Okayama Rosai Hospital kn-affil= affil-num=19 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Autophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of human glomerular diseases is largely unknown. The current study aimed to demonstrate morphological evidence of autophagy and its association with the ultrastructural changes of podocytes and clinical data in patients with idiopathic nephrotic syndrome, a disease in which patients exhibit podocyte injury. The study population included 95 patients, including patients with glomerular disease (minimal change nephrotic syndrome [MCNS], n = 41; idiopathic membranous nephropathy [IMN], n = 37) and 17 control subjects who underwent percutaneous renal biopsy. The number of autophagic vacuoles and the grade of foot process effacement (FPE) in podocytes were examined by electron microscopy (EM). The relationships among the expression of autophagic vacuoles, the grade of FPE, and the clinical data were determined. Autophagic vacuoles were mainly detected in podocytes by EM. The microtubule-associated protein 1 light chain 3 (LC3)-positive area was co-localized with the Wilms tumor 1 (WT1)-positive area on immunofluorescence microscopy, which suggested that autophagy occurred in the podocytes of patients with MCNS. The number of autophagic vacuoles in the podocytes was significantly correlated with the podocyte FPE score (r = -0.443, p = 0.004), the amount of proteinuria (r = 0.334, p = 0.033), and the level of serum albumin (r = -0.317, p = 0.043) in patients with MCNS. The FPE score was a significant determinant for autophagy after adjusting for the age in a multiple regression analysis in MCNS patients (p = 0.0456). However, such correlations were not observed in patients with IMN or in control subjects. In conclusion, the results indicated that the autophagy of podocytes is associated with FPE and severe proteinuria in patients with MCNS. The mechanisms underlying the activation of autophagy in association with FPE in podocytes should be further investigated in order to elucidate the pathophysiology of MCNS. en-copyright= kn-copyright= en-aut-name=Ogawa-AkiyamaAyu en-aut-sei=Ogawa-Akiyama en-aut-mei=Ayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitagawaMasashi en-aut-sei=Kitagawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanoYuzuki en-aut-sei=Kano en-aut-mei=Yuzuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiseKoki en-aut-sei=Mise en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtakaNozomu en-aut-sei=Otaka en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KinomuraMasaru en-aut-sei=Kinomura en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Medical Informatics,Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=4 article-no= start-page=e1008469 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200423 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Non-pathogenic Escherichia coli acquires virulence by mutating a growth-essential LPS transporter en-subtitle= kn-subtitle= en-abstract= kn-abstract=The molecular mechanisms that allow pathogenic bacteria to infect animals have been intensively studied. On the other hand, the molecular mechanisms by which bacteria acquire virulence functions are not fully understood. In the present study, we experimentally evaluated the evolution of a non-pathogenic strain of Escherichia coli in a silkworm infection model and obtained pathogenic mutant strains. As one cause of the high virulence properties of E. coli mutants, we identified amino acid substitutions in LptD (G580S) and LptE (T95I) constituting the lipopolysaccharide (LPS) transporter, which translocates LPS from the inner to the outer membrane and is essential for E. coli growth. The growth of the LptD and LptE mutants obtained in this study was indistinguishable from that of the parent strain. The LptD and LptE mutants exhibited increased secretion of outer membrane vesicles containing LPS and resistance against various antibiotics, antimicrobial peptides, and host complement. In vivo cross-linking studies revealed that the conformation of the LptD-LptE complex was altered in the LptD and LptE mutants. Furthermore, several clinical isolates of E. coli carried amino acid substitutions of LptD and LptE that conferred resistance against antimicrobial substances. This study demonstrated an experimental evolution of bacterial virulence properties in an animal infection model and identified functional alterations of the growth-essential LPS transporter that led to high bacterial virulence by conferring resistance against antimicrobial substances. These findings suggest that non-pathogenic bacteria can gain virulence traits by changing the functions of essential genes, and provide new insight to bacterial evolution in a host environment. Author summary Pathogenic bacteria developed their virulence properties by changing the functions of various genes after the emergence of the host animals on earth. The types of gene function alterations that confer bacterial virulence properties, however, have remained unclear. We utilized a silkworm infection model to perform an experimental evolution of bacterial virulence activity. From a non-pathogenic strain of Escherichia coli, we obtained a mutant strain that exhibited 500-fold higher virulence than the original strain and identified mutations of the lipopolysaccharide (LPS) transporter, which translocates LPS onto the bacterial surface, as one cause of the high virulence. The mutations changed the structure of the LPS transporter, increased the secretion of outer membrane vesicles, and enabled bacterial survival in the presence of host antimicrobial substances. This mechanism to gain high virulence occurs naturally, as several E. coli clinical isolates carried mutations of the LPS transporter that confer resistance against antimicrobial substances. Our study unveiled a novel mechanism by which bacteria increase their virulence through modifying their gene function. en-copyright= kn-copyright= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshikaiHirono en-aut-sei=Yoshikai en-aut-mei=Hirono kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakamatsuAi en-aut-sei=Wakamatsu en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyashitaAtsushi en-aut-sei=Miyashita en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoYasuhiko en-aut-sei=Matsumoto en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiyukiTomoko en-aut-sei=Fujiyuki en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoMasaru en-aut-sei=Kato en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OguraYoshitoshi en-aut-sei=Ogura en-aut-mei=Yoshitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HayashiTetsuya en-aut-sei=Hayashi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IsogaiTakao en-aut-sei=Isogai en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SekimizuKazuhisa en-aut-sei=Sekimizu en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Pharmaceutical Sciences, The University of Tokyo kn-affil= affil-num=3 en-affil=Japan Biological Informatics Consortium (JBIC) kn-affil= affil-num=4 en-affil=Graduate School of Pharmaceutical Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Microbiology, Meiji Pharmaceutical University kn-affil= affil-num=6 en-affil=The Institute of Medical Science, The University of Tokyo kn-affil= affil-num=7 en-affil=Devision of Bioanalytical Chemistry, School of Pharmacy,Showa University kn-affil= affil-num=8 en-affil=Department of Bacteriology, Faculty of Medical Sciences,Kyushu University kn-affil= affil-num=9 en-affil=Department of Bacteriology, Faculty of Medical Sciences,Kyushu University kn-affil= affil-num=10 en-affil=Translational Research Center, Fukushima Medical University kn-affil= affil-num=11 en-affil=Institute of Medical Mycology, Teikyo University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=10 article-no= start-page=e0218909 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191004 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differential scanning fluorimetric analysis of the amino-acid binding to taste receptor using a model receptor protein, the ligand-binding domain of fish T1r2a/T1r3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Taste receptor type 1 (T1r) is responsible for the perception of essential nutrients, such as sugars and amino acids, and evoking sweet and umami (savory) taste sensations. T1r receptors recognize many of the taste substances at their extracellular ligand-binding domains (LBDs). In order to detect a wide array of taste substances in the environment, T1r receptors often possess broad ligand specificities. However, the entire ranges of chemical spaces and their binding characteristics to any T1rLBDs have not been extensively analyzed. In this study, we exploited the differential scanning fluorimetry (DSF) to medaka T1r2a/T1r3LBD, a current sole T1rLBD heterodimer amenable for recombinant preparation, and analyzed their thermal stabilization by adding various amino acids. The assay showed that the agonist amino acids induced thermal stabilization and shifted the melting temperatures (T-m) of the protein. An agreement between the DSF results and the previous biophysical assay was observed, suggesting that DSF can detect ligand binding at the orthostericbinding site in T1r2a/T1r3LBD. The assay further demonstrated that most of the tested Lamino acids, but no D-amino acid, induced T-m shifts of T1r2a/T1r3LBD, indicating the broad L-amino acid specificities of the proteins probably with several different manners of recognition. The T-m shifts by each amino acid also showed a fair correlation with the responses exhibited by the full-length receptor, verifying the broad amino-acid binding profiles at the orthosteric site in LBD observed by DSF. en-copyright= kn-copyright= en-aut-name=YoshidaTakashi en-aut-sei=Yoshida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasuiNorihisa en-aut-sei=Yasui en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KusakabeYuko en-aut-sei=Kusakabe en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoChiaki en-aut-sei=Ito en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkamatsuMiki en-aut-sei=Akamatsu en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaAtsuko en-aut-sei=Yamashita en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Food Research Institute, National Agriculture and Food Research Organization kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=2 article-no= start-page=e1008566 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200218 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The persimmon genome reveals clues to the evolution of a lineage-specific sex determination system in plants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Most angiosperms bear hermaphroditic flowers, but a few species have evolved outcrossing strategies, such as dioecy, the presence of separate male and female individuals. We previously investigated the mechanisms underlying dioecy in diploid persimmon (D. lotus) and found that male flowers are specified by repression of the autosomal gene MeGI by its paralog, the Y-encoded pseudo-gene OGI. This mechanism is thought to be lineage-specific, but its evolutionary path remains unknown. Here, we developed a full draft of the diploid persimmon genome (D. lotus), which revealed a lineage-specific whole-genome duplication event and provided information on the architecture of the Y chromosome. We also identified three paralogs, MeGI, OGI and newly identified Sister of MeGI (SiMeGI). Evolutionary analysis suggested that MeGI underwent adaptive evolution after the whole-genome duplication event. Transformation of tobacco plants with MeGI and SiMeGI revealed that MeGI specifically acquired a new function as a repressor of male organ development, while SiMeGI presumably maintained the original function. Later, a segmental duplication event spawned MeGI's regulator OGI on the Y-chromosome, completing the path leading to dioecy, and probably initiating the formation of the Y-chromosome. These findings exemplify how duplication events can provide flexible genetic material available to help respond to varying environments and provide interesting parallels for our understanding of the mechanisms underlying the transition into dieocy in plants. Author summary Plant sexuality has fascinated scientists for decades. Most plants can self-reproduce but not all. For example, a small subset of species have evolved a system called dioecy, with separate male and female individuals. Dioecy has evolved multiple times independently and, while we do not understand the molecular mechanisms underlying dioecy in many of these species yet, a picture is starting to emerge with recent progress in several dioecious species. Here, we focused on the evolutionary events leading to dioecy in persimmon. Our previous work had identified a pair of genes regulating sex in this species, called OGI and MeGI. We drafted the whole genome sequence of diploid persimmon to investigate their evolutionary history. We discovered a lineage-specific whole-genome duplication event, and observed that MeGI underwent adaptive evolution after this event. Transgenic analyses validated that MeGI newly acquired a male-suppressor function, while the other copy of this gene, SiMeGI, did not. The regulator of MeGI, OGI, resulted from a second smaller-scale segmental duplication event, finalizing the system. This study sheds light on the role of duplication as a mechanism that promote flexible genes functions, and how it can affect important biological functions, such as the establishment of a new sexual system. en-copyright= kn-copyright= en-aut-name=AkagiTakashi en-aut-sei=Akagi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirasawaKenta en-aut-sei=Shirasawa en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagasakiHideki en-aut-sei=Nagasaki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirakawaHideki en-aut-sei=Hirakawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaoRyutaro en-aut-sei=Tao en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ComaiLuca en-aut-sei=Comai en-aut-mei=Luca kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HenryIsabelle M. en-aut-sei=Henry en-aut-mei=Isabelle M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Kazusa DNA Research Institute kn-affil= affil-num=3 en-affil=Kazusa DNA Research Institute kn-affil= affil-num=4 en-affil=Kazusa DNA Research Institute kn-affil= affil-num=5 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=6 en-affil=Genome Center and Department of Plant Biology, University of California Davis kn-affil= affil-num=7 en-affil=Genome Center and Department of Plant Biology, University of California Davis kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=e0207049 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mortality in trauma patients admitted during, before, and after national academic emergency medicine and trauma surgery meeting dates in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Annually, many physicians attend national academic meetings. While participating in these meetings can have a positive impact on daily medical practice, attendance may result in reduced medical staffing during the meeting dates. We sought to examine whether there were differences in mortality after trauma among patients admitted to the hospital during, before, and after meeting dates. Using the Japan Trauma Data Bank, we analyzed in-hospital mortality in patients with traumatic injury admitted to the hospital from 2004 to 2015 during the dates of two national academic meetings-the Japanese Association for Acute Medicine (JAAM) and the Japanese Association for the Surgery of Trauma (JAST). We compared the data with that of patients admitted with trauma during identical weekdays in the weeks before and after the meetings, respectively. We used multiple logistic regression analysis to compare outcomes among the three groups. A total of 7,491 patients were included in our analyses, with 2,481, 2,492, and 2,518 patients in the during, before, and after meeting dates groups, respectively; their mortality rates were 7.3%, 8.0%, and 8.5%, respectively. After adjusting for covariates, no significant differences in in-hospital mortality were found among the three groups (adjusted odds ratio [95% CI] of the before meeting dates and after meeting dates groups; 1.18 [0.89-1.56] and 1.23 [0.93-1.63], respectively, with the during meeting dates group as the reference category). No significant differences in in-hospital mortality were found among trauma patients admitted during, before, and after the JAAM and JAST meeting dates. en-copyright= kn-copyright= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaitouHiromichi en-aut-sei=Naitou en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IhoriyaHiromi en-aut-sei=Ihoriya en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Human Ecology,Okayama University Graduate School of Environmental and Life Science kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=5 article-no= start-page=e0217517 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Staphylococcus aureus aggregation in the plasma fraction of silkworm hemolymph en-subtitle= kn-subtitle= en-abstract= kn-abstract= Staphylococcus aureus formed bacterial aggregates in the plasma fraction of the hemolymph of silkworm, the larva of Bombyx mori, in a growth-dependent manner. The addition of arabinose or galactose inhibited the formation of S. aureus aggregates in the silkworm plasma. Formation of the bacterial aggregates depended on S. aureus genes required for the synthesis of bacterial surface polysaccharides-ypfP and ltaA, which are involved in lipoteichoic acid synthesis, and the tagO gene, which is involved in wall teichoic acid synthesis. These findings suggest that S. aureus forms bacterial aggregates in the silkworm plasma via bacterial surface teichoic acids. en-copyright= kn-copyright= en-aut-name=RyunoHiroki en-aut-sei=Ryuno en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NigoFuki en-aut-sei=Nigo en-aut-mei=Fuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaguroIsao en-aut-sei=Naguro en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekimizuKazuhisa en-aut-sei=Sekimizu en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Pharmaceutical Sciences, The University of Tokyo kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Pharmaceutical Sciences, The University of Tokyo kn-affil= affil-num=4 en-affil=Institute of Medical Mycology, Teikyo University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=11 article-no= start-page=e50082 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20121126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial localization of ABC transporter ABCG2 and its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol. en-copyright= kn-copyright= en-aut-name=KobuchiHirotsugu en-aut-sei=Kobuchi en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriyaKoko en-aut-sei=Moriya en-aut-mei=Koko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OginoTetsuya en-aut-sei=Ogino en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaHirofumi en-aut-sei=Fujita en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueKeiji en-aut-sei=Inoue en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShuinTaro en-aut-sei=Shuin en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaTatsuji en-aut-sei=Yasuda en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UtsumiToshihiko en-aut-sei=Utsumi en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=1 Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University kn-affil= affil-num=3 en-affil=Department of Nursing Science, Faculty of Health and Welfare Science, Okayama Prefectural University kn-affil= affil-num=4 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Urology, Kochi Medical School kn-affil= affil-num=6 en-affil=Department of Urology, Kochi Medical School kn-affil= affil-num=7 en-affil=1 Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=2 article-no= start-page=e56068 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trends in the prevalence of diarrheagenic Escherichia coli among hospitalized diarrheal patients in Kolkata, India en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND:  To analyse the trends in the prevalence of different pathogroups of diarrheagenic Escherichia coli (DEC) among hospitalized acute diarrheal patients.  METHODOLOGY/PRINCIPAL FINDINGS:  From the active surveillance of diarrheal disease at the Infectious Diseases Hospital, Kolkata, 3826 stool specimens collected during 2008-2011 were screened for DEC and other enteric pathogens. PCR was used in the detection of enterotoxigenic, enteropathogenic and enteroaggregative E. coli and 10 major colonization factor antigens (CFs) of enterotoxigenic E. coli. The relationship between DEC infected patient's age group and clinical symptoms were also investigated. Multiplex PCR assay showed that the prevalence of EAEC was most common (5.7%) followed by ETEC (4.2%) and EPEC (1.8%). In diarrheal children >2 year of age, EAEC and EPEC were detected significantly (p = 0.000 and 0.007, respectively). In children >2 to 5 and >5 to 14 years, ETEC was significantly associated with diarrhea (p = 0.000 each). EAEC was significantly associated with diarrheal patients with age groups >14 to 30 and >30 to 50 years (p = 0.001, and p = 0.009, respectively). Clinical symptoms such as vomiting, abdominal pain, watery diarrhea, were recorded in patients infected with ETEC. Dehydration status was severe among patients infected by ST-ETEC (19%) and EPEC (15%). CS6 was frequently detected (37%) among ETEC.  CONCLUSIONS/SIGNIFICANCE:  Hospital based surveillance reviled that specific pathogroups of DEC are important to certain age groups and among ETEC, CS6 was predominant. en-copyright= kn-copyright= en-aut-name=DuttaSanjucta en-aut-sei=Dutta en-aut-mei=Sanjucta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GuinSucharita en-aut-sei=Guin en-aut-mei=Sucharita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GhoshSantanu en-aut-sei=Ghosh en-aut-mei=Santanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PazhaniGururaja P. en-aut-sei=Pazhani en-aut-mei=Gururaja P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RajendranKrishnan en-aut-sei=Rajendran en-aut-mei=Krishnan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BhattacharyaMihir K. en-aut-sei=Bhattacharya en-aut-mei=Mihir K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakedaYoshifumi en-aut-sei=Takeda en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NairG. Balakrish en-aut-sei=Nair en-aut-mei=G. Balakrish kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=RamamurthyThandavarayan en-aut-sei=Ramamurthy en-aut-mei=Thandavarayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Division of Bacteriology, National, Collaborative Research Centre of Okayama University for Infectious Diseases in India kn-affil= affil-num=2 en-affil=Clinical Division, Institute of Cholera and Enteric Diseases, Collaborative Research Centre of Okayama University for Infectious Diseases in India kn-affil= affil-num=3 en-affil=Division of Bacteriology, National, Collaborative Research Centre of Okayama University for Infectious Diseases in India kn-affil= affil-num=4 en-affil=Division of Bacteriology, National, Collaborative Research Centre of Okayama University for Infectious Diseases in India kn-affil= affil-num=5 en-affil=Division of Bacteriology, National, Collaborative Research Centre of Okayama University for Infectious Diseases in India kn-affil= affil-num=6 en-affil=Clinical Division, Institute of Cholera and Enteric Diseases, Collaborative Research Centre of Okayama University for Infectious Diseases in India kn-affil= affil-num=7 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=8 en-affil=Translational Health Science and Technology Institute kn-affil= affil-num=9 en-affil=Division of Bacteriology, National, Collaborative Research Centre of Okayama University for Infectious Diseases in India kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=9 article-no= start-page=e0162394 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel High-Throughput 3D Screening System for EMT Inhibitors: A Pilot Screening Discovered the EMT Inhibitory Activity of CDK2 Inhibitor SU9516 en-subtitle= kn-subtitle= en-abstract= kn-abstract= Epithelial-mesenchymal transition (EMT) is a crucial pathological event in cancer, particularly in tumor cell budding and metastasis. Therefore, control of EMT can represent a novel therapeutic strategy in cancer. Here, we introduce an innovative three-dimensional (3D) high-throughput screening (HTS) system that leads to an identification of EMT inhibitors. For the establishment of the novel 3D-HTS system, we chose NanoCulture Plates (NCP) that provided a gel-free micro-patterned scaffold for cells and were independent of other spheroid formation systems using soft-agar. In the NCP-based 3D cell culture system, A549 lung cancer cells migrated, gathered, and then formed multiple spheroids within 7 days. Live cell imaging experiments showed that an established EMT-inducer TGF-β promoted peripheral cells around the core of spheroids to acquire mesenchymal spindle shapes, loss of intercellular adhesion, and migration from the spheroids. Along with such morphological change, EMT-related gene expression signatures were altered, particularly alteration of mRNA levels of ECAD/CDH1, NCAD/CDH2, VIM and ZEB1/TCF8. These EMT-related phenotypic changes were blocked by SB431542, a TGF-βreceptor I (TGFβR1) inhibitor. Inside of the spheroids were highly hypoxic; in contrast, spheroid-derived peripheral migrating cells were normoxic, revealed by visualization and quantification using Hypoxia Probe. Thus, TGF-β-triggered EMT caused spheroid hypoplasia and loss of hypoxia. Spheroid EMT inhibitory (SEMTIN) activity of SB431542 was calculated from fluorescence intensities of the Hypoxia Probe, and then was utilized in a drug screening of EMT-inhibitory small molecule compounds. In a pilot screening, 9 of 1,330 compounds were above the thresholds of the SEMTIN activity and cell viability. Finally, two compounds SB-525334 and SU9516 showed SEMTIN activities in a dose dependent manner. SB-525334 was a known TGFβR1 inhibitor. SU9516 was a cyclin-dependent kinase 2 (CDK2) inhibitor, which we showed also had an EMT-inhibitory activity. The half maximal inhibitory concentration (IC50) of SB-525334 and SU9516 were 0.31 μM and 1.21 μM, respectively, while IC50 of SB431542 was 2.38 μM. Taken together, it was shown that this 3D NCP-based HTS system was useful for screening of EMT-regulatory drugs. en-copyright= kn-copyright= en-aut-name=AraiKazuya en-aut-sei=Arai en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RahmanM. Mamunur en-aut-sei=Rahman en-aut-mei=M. Mamunur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoRuriko en-aut-sei=Sakamoto en-aut-mei=Ruriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaNorio en-aut-sei=Masuda en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakatsuraTetsuya en-aut-sei=Nakatsura en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KozakiKen-ichi en-aut-sei=Kozaki en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItohManabu en-aut-sei=Itoh en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=SCIVAX Life Sciences, Inc. kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=SCIVAX USA, Inc. kn-affil= affil-num=4 en-affil=SCIVAX Life Sciences, Inc. kn-affil= affil-num=5 en-affil=SCIVAX Life Sciences, Inc. kn-affil= affil-num=6 en-affil=Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center kn-affil= affil-num=7 en-affil=Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=8 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=SCIVAX Life Sciences, Inc. kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=2 article-no= start-page=e0171356 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20170203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Yes1 signaling mediates the resistance to Trastuzumab/Lap atinib in breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND: Overexpression of human epidermal growth factor receptor 2 (HER2) is observed in approximately 15-23% of breast cancers and these cancers are classified as HER2-positive breast cancer. Trastuzumab is the first-line targeted therapeutic drug for HER2-positive breast cancer and has improved patient overall survival. However, acquired resistance to trastuzumab is still a critical issue in breast cancer treatment. We previously established a trastuzumab-resistant breast cancer cell line (named as BT-474-R) from a trastuzumab-sensitive HER2-amplified cell line BT-474. Lapatinib is also a molecular-targeted drug for HER2-positive breast cancer, which acquired the resistance to trastuzumab. Acquired resistance to lapatinib is also an issue to be conquered. METHODS: We established trastuzumab/lapatinib-dual resistant cell line (named as BT-474-RL2) by additionally treating BT-474-R with lapatinib. We analyzed the mechanisms of resistance to trastuzumab and lapatinib. Besides, we analyzed the effect of the detected resistance mechanism in HER2-positive breast cancer patients. RESULTS: Proto-oncogene tyrosine-protein kinase Yes1, which is one of the Src family members, was amplified, overexpressed and activated in BT-474-R and BT-474-RL2. Silencing of Yes1 by siRNA induced both BT-474-R and BT-474-RL2 to restore the sensitivity to trastuzumab and lapatinib. Pharmaceutical inhibition of Yes1 by the Src inhibitor dasatinib was also effective to restore the sensitivity to trastuzumab and lapatinib in the two resistant cell lines. Combination treatment with dasatinib and trastuzumab induced down-regulation of signaling molecules such as HER2 and Akt. Moreover, the combination treatments induced G1-phase cell-cycle arrest and apoptosis. Consistent with cell line data, high expression of Yes1 mRNA was correlated with worse prognosis in patients with HER2-positive breast cancer. CONCLUSION: Yes1 plays an important role in acquired resistance to trastuzumab and lapatinib in HER2-positive breast cancer. Our data suggest that pharmacological inhibition of Yes1 may be an effective strategy to overcome resistance to trastuzumab and lapatinib. en-copyright= kn-copyright= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanzakiHirotaka en-aut-sei=Kanzaki en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiokaTakahiro en-aut-sei=Yoshioka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=CuiXiaojiang en-aut-sei=Cui en-aut-mei=Xiaojiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MuraliRamachandran en-aut-sei=Murali en-aut-mei=Ramachandran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NambaKei en-aut-sei=Namba en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoHiroki en-aut-sei=Sato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AsanoHiroaki en-aut-sei=Asano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Surgery, Cedars-Sinai Medical Center kn-affil= affil-num=8 en-affil=Department of Biomedical Sciences, Cedars-Sinai Medical Center kn-affil= affil-num=9 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=9 article-no= start-page=e107934 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exacerbation of diabetic renal alterations in mice lacking vasohibin-1 en-subtitle= kn-subtitle= en-abstract= kn-abstract= Vasohibin-1 (VASH1) is a unique endogenous inhibitor of angiogenesis that is induced in endothelial cells by pro-angiogenic factors. We previously reported renoprotective effect of adenoviral delivery of VASH1 in diabetic nephropathy model, and herein investigated the potential protective role of endogenous VASH1 by using VASH1-deficient mice. Streptozotocin-induced type 1 diabetic VASH1 heterozygous knockout mice (VASH1(+/-)) or wild-type diabetic mice were sacrificed 16 weeks after inducing diabetes. In the diabetic VASH1(+/-) mice, albuminuria were significantly exacerbated compared with the diabetic wild-type littermates, in association with the dysregulated distribution of glomerular slit diaphragm related proteins, nephrin and ZO-1, glomerular basement membrane thickening and reduction of slit diaphragm density. Glomerular monocyte/macrophage infiltration and glomerular nuclear translocation of phosphorylated NF-κB p65 were significantly exacerbated in the diabetic VASH1(+/-) mice compared with the diabetic wild-type littermates, accompanied by the augmentation of VEGF-A, M1 macrophage-derived MCP-1 and phosphorylation of IκBα, and the decrease of angiopoietin-1/2 ratio and M2 macrophage-derived Arginase-1. The glomerular CD31(+) endothelial area was also increased in the diabetic VASH1(+/-) mice compared with the diabetic-wild type littermates. Furthermore, the renal and glomerular hypertrophy, glomerular accumulation of mesangial matrix and type IV collagen and activation of renal TGF-β1/Smad3 signaling, a key mediator of renal fibrosis, were exacerbated in the diabetic VASH1(+/-) mice compared with the diabetic wild-type littermates. In conditionally immortalized mouse podocytes cultured under high glucose condition, transfection of VASH1 small interfering RNA (siRNA) resulted in the reduction of nephrin, angiopoietin-1 and ZO-1, and the augmentation of VEGF-A compared with control siRNA. These results suggest that endogenous VASH1 may regulate the development of diabetic renal alterations, partly via direct effects on podocytes, and thus, a strategy to recover VASH1 might potentially lead to the development of a novel therapeutic approach for diabetic nephropathy. en-copyright= kn-copyright= en-aut-name=HinamotoNorikazu en-aut-sei=Hinamoto en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaeshimaYohei en-aut-sei=Maeshima en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamasakiHiroko en-aut-sei=Yamasaki en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NasuTatsuyo en-aut-sei=Nasu en-aut-mei=Tatsuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoDaisuke en-aut-sei=Saito en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WatataniHiroyuki en-aut-sei=Watatani en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UjikeHaruyo en-aut-sei=Ujike en-aut-mei=Haruyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MasudaKana en-aut-sei=Masuda en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ArataYuka en-aut-sei=Arata en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatoYasufumi en-aut-sei=Sato en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil= kn-affil= affil-num=12 en-affil=Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University kn-affil= affil-num=13 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=11 article-no= start-page=e50082 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20121126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial localization of ABC transporter ABCG2 and its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation en-subtitle= kn-subtitle= en-abstract= kn-abstract= Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol. en-copyright= kn-copyright= en-aut-name=KobuchiHirotsugu en-aut-sei=Kobuchi en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriyaKoko en-aut-sei=Moriya en-aut-mei=Koko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OginoTetsuya en-aut-sei=Ogino en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaHirofumi en-aut-sei=Fujita en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueKeiji en-aut-sei=Inoue en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShuinTaro en-aut-sei=Shuin en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaTatsuji en-aut-sei=Yasuda en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UtsumiToshihiko en-aut-sei=Utsumi en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END