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This study determined the level of implementation and the importance placed on various nursing activities at clinics in rural areas of Japan in order to explore the achievement and perceived importance of implementing certain nursing roles and activities at such clinics. To identify these items, a questionnaire was administered to 40 nurses working in rural clinics. The results showed that activities related to “Basic Nursing Practice” and “Community Understanding” were recognized as important and were performed by almost all nurses. Some activities related to “Administration and Operation” and “Cooperation with Local Government” were recognized as important, but were not implemented, thereby hampering the continuum of care across the health system. These activities, which are related to collaboration with hospitals and local governments that support the clinics, included adjustment of staff inside and outside the facilities to guarantee the use of paid holidays, as well as collaboration with acute care, remote medical systems, and local governments during emergencies and for disaster preparation. Additional support for nurses in collaboration between clinics in rural areas, hospitals, and regional administrations that support the clinics remains a challenge to be addressed.

Inflammation and oxidative stress contribute to the progression of nonalcoholic steatohepatitis (NASH). Hepatic fibrosis and activated hepatic stellate cells (Ac-HSCs) are attenuated by Angiotensin-II type 1 Receptor Blocker (ARB), and L-carnitine is effective for NASH by ameliorating oxidative stress, but neither agent is effective in a clinical setting. We evaluated the effect of the combination of L-carnitine and ARB on liver fibrosis using a rat NASH model. A Choline-Deficient/L-Amino Acid-defined (CDAA) diet was fed to F344 rats for 8 weeks. The rats were then divided into a control group, group receiving L-carnitine or ARB alone, and group receiving L-carnitine plus ARB. Therapeutic efficacy was assessed by evaluating liver fibrosis, liver fatty acid metabolism, and oxidative stress. ARB inhibited liver-specific tumor necrotic factor-α and LPS-binding protein, which are involved in hepatic inflammation. L-Carnitine reduced hepatic oxidative stress by rescuing hepatic sterol-regulatory elementbinding protein 1 and thiobarbituric acid reactive substances induced by the CDAA diet. Combination of L-carnitine and ARB improved liver fibrosis, with concomitant HSC suppression. Therefore, we suggest that L-carnitine and ARB are effective in suppressing liver fibrosis. Currently both drugs are in clinical use, and a combination of the two could be an effective therapy for NASH fibrosis., 博士（医学）・甲第736号・令和2年3月16日, Copyright © 2019 Hideto Kawaratani, Biomed J Sci & Tech Res. This is an openaccess article distributed under the terms of the Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/).

Aim: Non-alcoholic steatohepatitis (NASH) has a broad clinicopathological spectrum (inflammation to severe fibrosis). The farnesoid X receptor agonist obeticholic acid (OCA) ameliorates the histological features of NASH; satisfactory antifibrotic effects have not yet been reported. Here, we investigated the combined effects of OCA + a dipeptidyl peptidase-4 inhibitor (sitagliptin) on hepatic fibrogenesis in a rat model of NASH. Methods: Fifty Fischer 344 rats were fed a choline-deficient L-amino-acid-defined (CDAA) diet for 12 weeks. The in vitro and in vivo effects of OCA + sitagliptin were assessed along with hepatic fibrogenesis, lipopolysaccharide-Toll-like receptor 4 (TLR4) regulatory cascade and intestinal barrier function. Direct inhibitory effects of OCA + sitagliptin on activated hepatic stellate cells (Ac-HSCs) were assessed in vitro. Results: Treatment with OCA + sitagliptin potentially inhibited hepatic fibrogenesis along with Ac-HSC proliferation and hepatic transforming growth factor (TGF)-β1, α1(I)-procollagen, and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression and hydroxyproline levels. Obeticholic acid inhibited hepatic TLR4 expression and increased hepatic matrix metalloproteinase-2 expression. Obeticholic acid decreased intestinal permeability by ameliorating CDAA diet-induced zonula occludens-1 disruption, whereas sitagliptin directly inhibited Ac-HSC proliferation. The in vitro suppressive effects of OCA + sitagliptin on TGF-β1 and α1(I)-procollagen mRNA expression and p38 phosphorylation in Ac-HSCs were almost consistent. Sitagliptin directly inhibited the regulation of Ac-HSC. Conclusions: Treatment with OCA + sitagliptin synergistically affected hepatic fibrogenesis by counteracting endotoxemia induced by intestinal barrier dysfunction and suppressing Ac-HSC proliferation. Thus, OCA + sitagliptin could be a promising therapeutic strategy for NASH., 博士（医学）・甲第737号・令和2年3月16日, © 2019 The Japan Society of Hepatology, This is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/hepr.13385], which has been published in final form at [https://doi.org/10.1111/hepr.13385]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Cholangiocarcinoma (CCA) is a destructive malignancy with limited responsiveness to conventional chemotherapy. Although angiotensin receptor blockers (ARBs) have gained attention for their potential anticancer activity, little is known about their effects on CCA. The transcriptional co-activator, Yes-associated protein (YAP) is a critical oncogene in several cancers, including CCA. Following recent evidence showing that YAP is regulated by angiotensin II (AT-II), we investigated the effects of an ARB, losartan, on two human CCA cell lines (KKU-M213 and HuCCT-1) with regards to YAP oncogenic regulation. Losartan suppressed AT-II-induced CCA cell proliferation in a dose-dependent manner, induced apoptosis, decreased YAP (Ser127), and downregulated the YAP target genes CTGF, CYR61, ANKRD1, and MFAP5. However, losartan did not affect epithelial-mesenchymal transition, differentiation, or stemness in the CCA cells. Xenograft tumor growth assay showed that oral administration of a low clinical dose of losartan considerably reduced subcutaneous tumor burden and attenuated intratumor vascularization in CCA cell-derived xenograft tumors in BALB/c nude mice. These results indicate that ARB therapy could serve as a potential novel strategy for CCA treatment., 博士（医学）・甲第728号・令和2年3月16日, Copyright © 2018 Elsevier B.V. All rights reserved.

2013年に採択された博士課程教育リーディングプログラム複合領域型（多文化共生社会）「ウェルビーイング in アジア」の実現のための女性リーダー育成プログラムにおいて，筆者らは2018年にはじめてミャンマーでの海外実地研修を展開した。本稿では今後ミャンマーでの海外研修を企画する方にむけたヒントの提供を目的として，研修とその構築過程を回顧的に記述した。ミャンマーを専門としない教員による海外実地研修を成立させる上では，特に大学内外のリソースや現地の縁故を最大限有効利用すること，ミャンマー人の文化的背景に精通した仲介者の支援を得て展開することが肝要であるとむすんだ。

Recent reports have revealed the impact of a western diet containing large amounts of fructose on the pathogenesis of non-alcoholic steatohepatitis (NASH). Fructose exacerbates hepatic inflammation in NASH by inducing increasing intestinal permeability. However, it is not clear whether fructose contributes to the progression of liver fibrosis and hepatocarcinogenesis in NASH. The aim of this study was to investigate the effect of fructose intake on NASH in a rat model. A choline-deficient/L-amino acid diet was fed to F344 rats to induce NASH. Fructose was administrated to one group in the drinking water. The development of liver fibrosis and hepatocarcinogenesis were evaluated histologically. Oral fructose administration exacerbated liver fibrosis and increased the number of preneoplastic lesions positive for glutathione S-transferase placental form. Fructose-treated rats had significantly higher expression of hepatic genes related to toll-like receptor-signaling, suggesting that fructose consumption increased signaling in this pathway, leading to the progression of NASH. We confirmed that intestinal permeability was significantly higher in fructose-treated rats, as evidenced by a loss of intestinal tight junction proteins. Fructose exacerbated both liver fibrosis and hepatocarcinogenesis by increasing intestinal permeability. This observation strongly supports the role of endotoxin in the progression of NASH., 博士（医学）・乙第1432号・令和元年9月27日, Copyright © 2018 Impact Journals, LLC, Copyright © Seki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0 https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.