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男女医学生のメンタルヘルスの状態 予備研究
No full textThe educational process brings a considerable amount of stress to medical students; this can influence mental health status and contribute to furthering professional burnout. This study assessed mental health status with the intention of identifying different patterns in female and male medical students. This applied cross-sectional study was conducted using two questionnaires. That is, it explored demographic data and mental health status through the 30-item General Health Questionnaire (GHQ-30) of 816 medical students who attended Nara Medical University, Japan, between 2011 and 2019. The valid response rate was 94.1 %. During the study period, female medical students assessed their physical health status as being worse compared to male medical students overall. For medical students, especially female ones, it is necessary to establish a system for early awareness and management of their mental health, and to consider appropriate support methods.博士（医学）・乙第1501号・令和3年3月15
経動脈的化学塞栓術における予防的抗菌薬と肝膿瘍発症の関連 : 後方視的コホート研究
Get PDFObjectives: Clinical evidence on prophylactic antibiotics for transarterial chemoembolization (TACE) to prevent liver abscess is limited because liver abscess is a rare event. This study aimed to analyse the association between prophylactic antibiotic use for TACE and the occurrence of liver abscess after TACE. Methods: Using the nationwide Diagnosis Procedure Combination database in Japan, we retrospectively identified patients who underwent TACE for hepatic cancer between July 2010 and March 2017. The primary outcome was liver abscess requiring procedural intervention within 30 days of TACE. Secondary outcomes included 30-day in-hospital mortality and length of stay. Propensity score matching was performed to adjust for potential confounding factors and compare outcomes between patients with and without prophylactic antibiotics. Results: Among 167 544 eligible patients, 134 712 received antibiotics and 32 832 did not. In the matched cohort of 29 211 pairs, the proportion of patients with liver abscess requiring procedural intervention was significantly lower in the antibiotics group than in the no-antibiotics group (0.08% vs. 0.22%, p 0.001; relative risk (95% confidence interval), 0.35 (0.22-0.57); absolute risk reduction, 0.0014 (0.0008-0.0021); and number needed to treat, 696 (476-1223)). There was no significant difference in 30-day in-hospital mortality between the groups. The length of stay was longer in the antibiotics group than in the no-antibiotics group (median, 10 vs. 9 days, p < 0.001). Conclusions: Prophylactic antibiotic use in patients undergoing TACE was associated with a reduced occurrence of liver abscess requiring procedural intervention.博士（医学）・甲第794号・令和3年6月25日Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved
TGR5活性化はアナグリプチンによる糖尿病ラットに対する肝線維化抑制効果を増強する
Get PDFHyperglycemia and hyperinsulinemia activate the proliferative potential of hepatic stellate cells (HSCs) and promote hepatic fibrosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, antidiabetic agents, reportedly inhibit the HSC proliferation. Additionally, Takeda G protein-coupled receptor 5 (TGR5) agonists induce the systemic release of glucagon-like peptides from intestinal L cells, which maintains glycemic homeostasis. This study assessed the combined effect of TGR5 agonist and DPP-4 inhibitor on diabetes-based liver fibrosis development. Male diabetic rats received intraperitoneal injection of porcine serum (PS) to induce liver fibrosis, and they were orally administered the following agents: oleanolic acid (OA) as a TGR5 agonist, anagliptin (ANA) as a DPP-4 inhibitor, and a combination of both agents. Treatment with OA or ANA significantly improved glycemic status and attenuated intrahepatic steatosis and lipid peroxidation in diabetic rats. PS-induced liver fibrosis development was also drastically suppressed by treatment with either agent, and the combination of both reciprocally enhanced the antifibrotic effect. Fecal microbiome demonstrated that both agents inhibited the increase in the Firmicutes/Bacteroidetes ratio, an indicator of dysbiosis related to metabolic syndromes. Furthermore, ANA directly inhibited in vitro HSC proliferative and profibrogenic activities. Collectively, TGR5 agonist and DPP-4 inhibitor appears to be a novel strategy against liver fibrosis under diabetic conditions.博士（医学）・甲第766号・令和3年3月15日© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
27ヒドロキシコレステロールはエストロゲン受容体を介してヒトSLC22A12の発現を制御する
Get PDFThe excretion and reabsorption of uric acid both to and from urine are tightly regulated by uric acid transporters. Metabolic syndrome conditions, such as obesity, hypercholesterolemia, and insulin resistance, are believed to regulate the expression of uric acid transporters and decrease the excretion of uric acid. However, the mechanisms driving cholesterol impacts on uric acid transporters have been unknown. Here, we show that cholesterol metabolite 27-hydroxycholesterol (27HC) upregulates the uric acid reabsorption transporter URAT1 encoded by SLC22A12 via estrogen receptors (ER). Transcriptional motif analysis showed that the SLC22A12 gene promoter has more estrogen response elements (EREs) than other uric acid reabsorption transporters such as SLC22A11 and SLC22A13, and 27HC-activated SLC22A12 gene promoter via ER through EREs. Furthermore, 27HC increased SLC22A12 gene expression in human kidney organoids. Our results suggest that in hypercholesterolemic conditions, elevated levels of 27HC derived from cholesterol induce URAT1/SLC22A12 expression to increase uric acid reabsorption, and thereby, could increase serum uric acid levels.博士（医学）・甲第772号・令和3年3月15日© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes
胆汁酸吸着薬であるセベラマーは、内因性のリポポリサッカライドの過負荷を軽減して、非アルコール性脂肪性肝炎の肝線維化を改善する。
Get PDFDespite the use of various pharmacotherapeutic strategies, fibrosis due to nonalcoholic steatohepatitis (NASH) remains an unsatisfied clinical issue. We investigated the effect of sevelamer, a hydrophilic bile acid sequestrant, on hepatic fibrosis in a murine NASH model. Male C57BL/6J mice were fed a choline-deficient, L-amino acid-defined, high-fat (CDHF) diet for 12 weeks with or without orally administered sevelamer hydrochloride (2% per diet weight). Histological and biochemical analyses revealed that sevelamer prevented hepatic steatosis, macrophage infiltration, and pericellular fibrosis in CDHF-fed mice. Sevelamer reduced the portal levels of total bile acid and inhibited both hepatic and intestinal farnesoid X receptor activation. Gut microbiome analysis demonstrated that sevelamer improved a lower α-diversity and prevented decreases in Lactobacillaceae and Clostridiaceae as well as increases in Desulfovibrionaceae and Enterobacteriaceae in the CDHF-fed mice. Additionally, sevelamer bound to lipopolysaccharide (LPS) in the intestinal lumen and promoted its fecal excretion. Consequently, the sevelamer treatment restored the tight intestinal junction proteins and reduced the portal LPS levels, leading to the suppression of hepatic toll-like receptor 4 signaling pathway. Furthermore, sevelamer inhibited the LPS-mediated induction of fibrogenic activity in human hepatic stellate cells in vitro. Collectively, sevelamer inhibited the development of murine steatohepatitis by reducing hepatic LPS overload.博士（医学）・甲第779号・令和3年3月15日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
皮下埋没縫合および皮下閉鎖式陰圧ドレーン挿入による、回腸人工肛門閉鎖術後創部感染の減少効果について
Get PDFPurpose: The purpose of this study was to evaluate the effectiveness of a wound closure method using a combination of subcuticular sutures and subcutaneous closed-suction drainage (SS closure) for preventing incisional surgical site infection (SSI) in loop ileostomy closure. Methods: A total of 178 consecutive patients who underwent loop ileostomy closure at Nara Medical University Hospital between 2004 and 2018 were retrospectively assessed. The patients were divided into 2 groups: the conventional skin closure (CC) group from 2004 to 2009 (75 patients) and the SS closure (SS) group from 2010 to 2018 (103 patients). The incidence of incisional SSI was compared between the two groups, and the factors associated with incisional SSI were examined by univariate and multivariate analyses. Results: Incisional SSI occurred in 7 cases (9.3%) in the CC group but was significantly reduced to only 1 case (0.9%) in the SS group (p = 0.034). In the univariate analysis, the hemoglobin levels, serum creatinine levels, and SS closure were associated with incisional SSI. SS closure was the only independent preventive factor for incisional SSI according to the multivariate analysis (hazard ratio = 0.24, p = 0.011). Conclusion: The combination of subcuticular sutures and subcutaneous closed-suction drainage may be a promising way of preventing incisional SSI in loop ileostomy closure.博士（医学）・乙第1496号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Surgery today. The final authenticated version is available online at: https://doi.org/10.1007/s00595-020-02128-x
加速度と接触力センサーを用いた手指運動の可視化と評価 : POC試験
Get PDFThe 10-s grip and release is a method to evaluate hand dexterity. Current evaluations only visually determine the presence or absence of a disability, but experienced physicians may also make other diagnoses. In this study, we investigated a method for evaluating hand movement function by acquiring and analyzing fingertip data during a 10-s grip and release using a wearable sensor that can measure triaxial acceleration and strain. The subjects were two healthy females. The analysis was performed on the x-, y-, and z-axis data, and absolute acceleration and contact force of all fingertips. We calculated the variability of the data, the number of grip and release, the frequency response, and each finger's correlation. Experiments with some grip-and-release patterns have resulted in different characteristics for each. It was suggested that this could be expressed in radar charts to intuitively know the state of grip and release. Contact-force data of each finger were found to be useful for understanding the characteristics of grip and release and improving the accuracy of calculating the number of times to grip and release. Frequency analysis suggests that knowing the periodicity of grip and release can detect unnatural grip and release and tremor states. The correlations between the fingers allow us to consider the finger's grip-and-release characteristics, considering the hand's anatomy. By taking these factors into account, it is thought that the 10-s grip-and-release test could give us a new value by objectively assessing the motor functions of the hands other than the number of times of grip and release.博士（医学）・甲第795号・令和3年6月25日© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
成人発症の微小変化型ネフローゼ症候群に対するプレドニゾロン初期投与量と，寛解，再発，及び感染症との関連
Get PDFBackground: A dose of 0.5-1 mg/kg/day of prednisolone (PSL) is administered for the initial treatment of minimal change disease (MCD). However, little is known about the optimal PSL dose for the initial treatment of MCD. Methods: We conducted a retrospective multicenter cohort study of treatment-naive adult patients with MCD diagnosed by renal biopsy from 1981 to 2015 in whom PSL monotherapy was performed as the initial treatment. The exposure of interest was an initial median PSL dose of < 0.63 mg/kg/day (Group L) compared to ≥ 0.63 mg/kg/day (Group H). Cumulative remission and relapse after remission were compared between these groups using Cox regression adjusted for baseline characteristics. Results: Ninety-one patients met the inclusion criteria. During a median follow-up of 2.98 years, 87 (95.6%) patients achieved complete remission, and 47.1% relapsed after remission. There was no significant difference in the remission rate between the groups at 4 weeks of follow-up (66.7 vs. 82.6%). The median time to remission in Group L was comparable to that in Group H (17.0 vs. 14.0 days). A multivariable Cox hazard model revealed that the initial PSL dose was not a significant predictor of remission. The cumulative steroid doses at 6 months, 1 year, and 2 years after treatment initiation were significantly lower in Group L than in Group H. Conclusion: The initial PSL dose was not associated with time to remission, remission rate, time to relapse, or relapse rate. Therefore, a low initial steroid dose may be sufficient to achieve remission.博士（医学）・甲第803号・令和3年12月21日© 2021. The Author(s).
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/