Not taking sick leave for gynecologic cancer treatment is negatively associated with returning to the same workplace

Background: Gynecologic cancers are one of the most common types of malignancies in working-age women. We aimed to determine the factors that impede women from returning to the same workplace after treatment for such cancers. Methods: A questionnaire-based survey was conducted on 194 women who underwent treatment for gynecologic cancer at the Okayama University (≥1 year after cancer treatment and Results: The median age at diagnosis was 49.0 years, and the median time from cancer treatment to questionnaire completion was 3.8 years. Not returning to the same workplace was positively associated with not being regularly employed (P = 0.018), short work time per day (P = 0.023), low personal income (P = 0.004), not taking sick leave (P Conclusions: Not taking sick leave likely was negatively associated with returning to the same workplace after the treatment for gynecologic cancer. Therefore, we suggest that steps be taken to formally introduce a sick leave system over and above the paid leave system in Japan

Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling

Myocardial oxidative stress and inflammation are key mechanisms in cardiovascular remodeling. C-type natriuretic peptide (CNP) is an endothelium-derived cardioprotective factor, although its effect on cardiac superoxide generation has not been investigated in vivo. This study tested the hypothesis that suppression of superoxide production contributes to the cardioprotective action of CNP. Angiotensin II (Ang II) or saline was continuously infused subcutaneously into mice using an osmotic minipump. Simultaneously with the initiation of Ang II treatment, mice were infused with CNP (0.05 μg/kg/min) or vehicle for 2 weeks. The heart weight to tibial length ratio was significantly increased by Ang II in vehicle-treated mice. Treatment with CNP decreased Ang II-induced cardiac hypertrophy without affecting systolic blood pressure. Echocardiography showed that CNP attenuated Ang II-induced increase in wall thickness, left ventricular dilatation, and decrease in fractional shortening. CNP reduced Ang II-induced increases in cardiomyocyte size and interstitial fibrosis and suppressed hypertrophic- and fibrosis-related gene expression. Finally, CNP decreased Ang II-induced cardiac superoxide production. These changes were accompanied by suppression of NOX4 gene expression. Our data indicate that treatment with CNP attenuated Ang II-induced cardiac hypertrophy, fibrosis, and contractile dysfunction which were accompanied by reduced cardiac superoxide production

Newly Developed Fully Covered Metal Stent for Unresectable Malignant Biliary Stricture

We herein report two patients with unresectable malignant biliary stricture who underwent stenting with a newly developed fully-covered metal stent. In the first case of lower-middle bile duct cancer, a stent was placed through the stenosis. In the second case of middle bile duct stricture due to lymph node metastases from gallbladder cancer, a stent was placed in the bile duct across the stenosis. No procedure-related complications were observed. Unevenness of the outer surface and a low shortening ratio are expected to lessen the occurrence of complications characteristic of covered metal stents such as stent migration and bile duct kinking

Aortic Dissection in a Patient with Human Immunodeficiency Virus Infection That was Diagnosed at Autopsy : A Case Report.

A 43-year-old homosexual man was referred to our hospital for chest pain and loss of consciousness. He was hypertensive, and had an uncontrolled viral load. Serum creatinine revealed acute renal failure, and he died 3 days later. On autopsy, aortic dissection (TypeB) was found. No obvious inflammatory change, granulation, bacterial or fungal infection, or medionecrosis were seen at the dissection site. To our knowledge, this was the first case with HIV in whom aortic dissection was diagnosed at autopsy. Aortic dissection is a potential differential diagnosis even in young patients presenting with hypertension and chest pain

CCL2 as a potential therapeutic target for clear cell renal cell carcinoma

We previously reported that the pVHL-atypical PKC-JunB pathway contributed to promotion of cell invasiveness and angiogenesis in clear cell renal cell carcinoma (ccRCC), and we detected chemokine (C-C motif) ligand-2 (CCL2) as one of downstream effectors of JunB. CCL2 plays a critical role in tumorigenesis in other types of cancer, but its role in ccRCC remains unclear. In this study, we investigated the roles and therapeutic potential of CCL2 in ccRCC. Immunohistochemical analysis of CCL2 expression for ccRCC specimens showed that upregulation of CCL2 expression correlated with clinical stage, overall survival, and macrophage infiltration. For functional analysis of CCL2 in ccRCC cells, we generated subclones of WT8 cells that overexpressed CCL2 and subclones 786-O cells in which CCL2 expression was knocked down. Although CCL2 expression did not affect cell proliferation in vitro, CCL2 overexpression enhanced and CCL2 knockdown suppressed tumor growth, angiogenesis, and macrophage infiltration in vivo. We then depleted macrophages from tumor xenografts by administration of clodronate liposomes to confirm the role of macrophages in ccRCC. Depletion of macrophages suppressed tumor growth and angiogenesis. To examine the effect of inhibiting CCL2 activity in ccRCC, we administered CCL2 neutralizing antibody to primary RCC xenografts established from patient surgical specimens. Inhibition of CCL2 activity resulted in significant suppression of tumor growth, angiogenesis, and macrophage infiltration. These results suggest that CCL2 is involved in angiogenesis and macrophage infiltration in ccRCC, and that CCL2 could be a potential therapeutic target for ccRCC

Novel oestrogen receptor beta-selective ligand reduces obesity and depressive-like behaviour in ovariectomized mice

Hormonal changes due to menopause can cause various health problems including weight gain and depressive symptoms. Multiple lines of evidence indicate that oestrogen receptors (ERs) play a major role in postmenopausal obesity and depression. However, little is known regarding the ER subtype-specific effects on obesity and depressive symptoms. To delineate potential effects of ER beta activation in postmenopausal women, we investigated the effects of a novel oestrogen receptor beta-selective ligand (C-1) in ovariectomized mice. Uterine weight, depressive behaviour, and weight gain were examined in sham-operated control mice and ovariectomized mice administered placebo, C-1, or 17 beta-oestradiol (E2). Administration of C-1 or E2 reduced body weight gain and depressive-like behaviour in ovariectomized mice, as assessed by the forced swim test. In addition, administration of E2 to ovariectomized mice increased uterine weight, but administration of C-1 did not result in a significant increase in uterine weight. These results suggest that the selective activation of ERa in ovariectomized mice may have protective effects against obesity and depressive-like behaviour without causing an increase in uterine weight. The present findings raise the possibility of the application of ER beta-ligands such as C-1 as a novel treatment for obesity and depression in postmenopausal women.ArticleSCIENTIFIC REPORTS. 7:4663 (2017)journal articl

The Japan Monkey Centre Primates Brain Imaging Repository for comparative neuroscience: an archive of digital records including records for endangered species

Advances in magnetic resonance imaging (MRI) and computational analysis technology have enabled comparisons among various primate brains in a three-dimensional electronic format. Results from comparative studies provide information about common features across primates and species-specific features of neuroanatomy. Investigation of various species of non-human primates is important for understanding such features, but the majority of comparative MRI studies have been based on experimental primates, such as common marmoset, macaques, and chimpanzee. A major obstacle has been the lack of a database that includes non-experimental primates’ brain MRIs. To facilitate scientific discoveries in the field of comparative neuroanatomy and brain evolution, we launched a collaborative project to develop an open-resource repository of non-human primate brain images obtained using ex vivo MRI. As an initial open resource, here we release a collection of structural MRI and diffusion tensor images obtained from 12 species: pygmy marmoset, owl monkey, white-fronted capuchin, crab-eating macaque, Japanese macaque, bonnet macaque, toque macaque, Sykes’ monkey, red-tailed monkey, Schmidt’s guenon, de Brazza’s guenon, and lar gibbon. Sixteen postmortem brain samples from the 12 species, stored in the Japan Monkey Centre (JMC), were scanned using a 9.4-T MRI scanner and made available through the JMC collaborative research program (http://www.j-monkey.jp/BIR/index_e.html). The expected significant contributions of the JMC Primates Brain Imaging Repository include (1) resources for comparative neuroscience research, (2) preservation of various primate brains, including those of endangered species, in a permanent digital form, (3) resources with higher resolution for identifying neuroanatomical features, compared to previous MRI atlases, (4) resources for optimizing methods of scanning large fixed brains, and (5) references for veterinary neuroradiology. User-initiated research projects beyond these contributions are also anticipated

Comprehensive analysis of resistance-nodulation-cell division superfamily (RND) efflux pumps from Serratia marcescens, Db10

We investigated the role of the resistance-nodulation-cell division superfamily (RND) efflux system on intrinsic multidrug resistance in Serratia marcescens. We identified eight putative RND efflux system genes in the S. marcescens Db10 genome that included the previously characterized systems, sdeXY, sdeAB, and sdeCDE. Six out of the eight genes conferred multidrug resistance on KAM32, a drug hypersensitive strain of Escherichia coil. Five out of the eight genes conferred resistance to benzalkonium, suggesting the importance of RND efflux systems in biocide resistance in S. marcescens. The energy-dependent efflux activities of five of the pumps were examined using a rhodamine 6G efflux assay. When expressed in the toiC-deficient strain of E. coil, KAM43, none of the genes conferred resistance on E. coil. When hasF, encoding the S. marcescens ToIC ortholog, was expressed in KAM43, all of the genes conferred resistance on E. coil, suggesting that HasF is a major outer membrane protein that is used by all RND efflux systems in this organism. We constructed a sdeXY deletion mutant from a derivative strain of the clinically isolated multidrug-resistant S. marcescens strain and found that the sdeXY deletion mutant was sensitive to a broad spectrum of antimicrobial agents

本邦で分離されたカルバペネマーゼ産生肺炎桿菌の分子遺伝学的解析

Carbapenemase-producing Enterobacteriaceae represent a serious public health threat worldwide. Carbapenemase genes, harbored on a transferable plasmid, have been isolated globally with distinct geographical features. Klebsiella pneumoniae, included in Enterobacteriaceae, also produces carbapenemase and often shows hypervirulence. Overlapping carbapenem resistance and hypervirulence in K. pneumoniae have been reported, but such strains have not yet been found in Japan. Here, we screened 104 carbapenemase-producing K. pneumoniae isolates collected from 37 hospitals and outpatient clinics in Japan between September 2014 and July 2015. PCR and DNA sequencing demonstrated IMP-1 in 21 isolates and IMP-6 in 83 isolates, 77 of which coharbored CTX-M-2. Most of the isolates showed low MICs toward imipenem and meropenem but high MICs toward penicillin and cephalosporins. Conjugation experiments with an Escherichia coli J53 recipient showed that most of the plasmids in IMP-6 producers were transferable, whereas only one-half of the plasmids in IMP-1 producers were transferable. PCR-based replicon typing and multiplex PCR identified five isolates belonging to the CG258 non-tonB79 cluster and no isolate belonging to the CG258-tonB79 cluster or sequence type 307 (ST307). Four K1-ST23 isolates, 10 K2-ST65 isolates, and 7 K2-ST86 isolates were detected that harbored virulence genes. The resistance genes in 85 isolates were transferable, but the virulence genes were not transferred. These results demonstrate the acquisition of IMP-type carbapenemase genes and CTX-M-type genes among hypervirulence isolates in Japan, warranting further attention and countermeasures. In this study, we have determined the molecular characteristics and epidemiology of IMP-6 producers that coharbored various CTX-M genes in Japan.IMPORTANCE Carbapenems serve as a last resort for the clinical treatment of multidrug-resistant infections. Therefore, the rapid spread of carbapenemase-producing strains represents a serious public health threat, further limiting antibiotic choices. The current findings of hypervirulent carbapenemase-producing Klebsiella pneumoniae clinical isolates in Japan demonstrate the potential broad spread and transfer of these genes, necessitating close surveillance.博士（医学）・乙第1509号・令和3年3月15日Copyright © 2020 Yonekawa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license(https://creativecommons.org/licenses/by/4.0/)