Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells

Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor. However, the effect of TBT toxicity on the developmental process of iPSCs was not clear. The present study examined the effect of TBT on the differentiation of iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the induction of iPSCs into the ectoderm, which is the first step in neurogenesis. We further assessed the effect of TBT on neural differentiation and found that it reduced the expression of several neural differentiation marker genes, which were also downregulated by Mfn1 knockdown in iPSCs. Taken together, these results indicate that TBT induces developmental neurotoxicity via Mfn1-mediated mitochondrial dysfunction in iPSCs

Locomotive syndrome is associated with body composition and cardiometabolic disorders in elderly Japanese women

The 25-question Geriatric Locomotive Function Scale [7]. (DOCX 154 kb

Maternal Body Mass Index and Breastfeeding Non-Initiation and Cessation: A Quantitative Review of the Literature

This study aims to investigate which maternal body mass index (BMI) categories are associated with the non-initiation or cessation of breastfeeding (BF) based on a quantitative review of the literature. We searched Ovid MEDLINE and EBSCO CINAHL for peer-reviewed articles published between 1946 (MEDLINE) or 1981 (CINAHL), and 2019. Selected studies were either cross-sectional or cohort studies, of healthy mothers and infants, that reported nutrition method (exclusive/full or any) and period (initiation/duration/cessation) of breastfeeding according to maternal BMI levels. Pairwise meta-analyses of 57 studies demonstrated that the pooled odds risks (OR) of not initiating BF among overweight and obese mothers compared to normal weight mothers were significant across 29 (OR 1.33, 95% confidence interval (CI), 1.15-1.54, I-2 = 98%) and 26 studies (OR 1.61, 95% CI, 1.33-1.95, I-2 = 99%), respectively; the pooled risks for BF cessation were inconsistent in overweight and obese mothers with substantial heterogeneity. However, we found that overweight mothers (n = 10, hazard ratio (HR) 1.16, 95% CI, 1.07-1.25; I-2 = 23%) and obese mothers (n = 7, HR 1.45, 95% CI: 1.27-1.65; I-2 = 44%) were both associated with an increased risk of not continuing any BF and exclusive BF, respectively. Overweight and obese mothers may be at increased risk of not initiating or the cessation of breastfeeding

The Relationship between Locomotive Syndrome and Depression in Community-Dwelling Elderly People

Locomotive syndrome (LS) is a concept that refers to the condition of people requiring healthcare services because of problems associated with locomotion. Depression is a major psychiatric disease among the elderly, in addition to dementia. The purpose of this study was to determine the association between LS and depression. The study participants were 224 healthy elderly volunteers living in a rural area in Japan. LS was defined as scores ≥ 16 on the 25-question Geriatric Locomotive Function Scale (GLFS-25). Depression was defined as scores ≥ 5 on the 15-item Geriatric Depression Scale (GDS-15). Height and body weight were measured. The prevalence of LS and depression was 13.9% and 24.2%, respectively. Compared with the non-LS group, the LS group was older, was shorter, had a higher BMI, and had higher GDS-15 scores. Logistic regression analysis showed that participants with GDS-15 scores ≥ 6 had higher odds for LS than those with GDS-15 scores < 6 (odds ratio [OR] = 4.22). Conversely, the depression group had higher GLFS-25 scores than the nondepression group. Participants with GLFS-25 scores ≥ 5 had higher odds for depression than those with GLFS-25 scores < 5 (OR = 4.53). These findings suggest that there is a close relationship between LS and depression

Theoretical Studies for Molecular Modeling of New Camptothecin Analogues

Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino carbonyloxycamptothecin: CPT-11) is a widely used potent antitumor drug that is developed based on camptothecin. However, overexpression of ABCG2 (BCRP/MXR/ABCP) confers cancer cells resistance to SN-38, that is, the active metabolite of irinotecan. In the present study to develop a platform for the molecular modeling to circumvent cancer drug resistance associated with ABCG2, we have characterized a total of fourteen new SN-38 analogues by some typical properties, which were evaluated by molecular orbital (MO) calculations and neural network (NN) QSAR technique

Gender Division of Labor, Burnout, and Intention to Leave Work Among Young Female Nurses in Japan: A Cross-Sectional Study

Women in Japan face difficulties balancing work and personal life due to the gender division of labor, and medical professions are no exception. The purpose of this study was to investigate if the gender division of labor affects the intention to leave the workplace among the nursing profession. Among 328 female nurses working for three university-affiliated hospitals in Tokyo, Japan, above 70% were in their 20s and 30s and single, and agreed with the gender division of labor that men should be the breadwinner and women should assume family responsibilities. Adjusting for three types of Copenhagen burnout inventory, stepwise multivariable logistic regression models identified that being younger (all p-values < 0.05), each domain of burnout score (each p < 0.001 for work-, personal-, and client-related burnout) increased a risk of intention to leave, and high support decreased the risk (all p < 0.001). Women who agreed with the gender division of labor were more likely to have intentions to leave (p = 0.003 but this association disappeared when adjusted. The findings of study demonstrate that perceptions toward gender division of labor are not a determinant of intention to leave the workplace but the young nurses and those who scored high on burnout were the most vulnerable population

Cross-sectional survey of depressive symptoms and suicide-related ideation at a Japanese national university during the COVID-19 stay-home order

Background We aimed to estimate the prevalence of depressive symptoms as well as suicide-related ideation among Japanese university students during the stay-home order necessitated by the coronavirus disease 2019 pandemic in Japan, and offer evidence in support of future intervention to depression and suicide prevention strategies among college and university students. Methods The data for this cross-sectional study were derived from the Student Mental Health Survey conducted from May 20 to June 16, 2020 at a national university in Akita prefecture. Among the 5111 students recruited, 2712 participated in this study (response rate, 53%; mean age ± standard deviation, 20.5 ±3.5 years; men, 53.8%). Depressive symptoms were identified by using the Patient Health Questionnaire-9 (PHQ-9). Results The prevalence of moderate depressive symptoms based on a PHQ-9 score ≥10 and suicide-related ideation based on question 9 of PHQ-9 ≥1, which encompasses thoughts of both suicide and self-harm, was 11.7% and 6.7%, respectively. Multivariable logistic regression analyses showed that risk factors for depression included being a woman, smoking, alcohol consumption, and social network communication using either video or voice. For suicide-related ideation, alcohol consumption was the only risk factor. Exercise and having someone to consult about worries were associated with decreased risk of both depressive symptoms and suicide-related ideation. Conclusions Negative lifestyles of smoking and drinking, and being a woman, may be important risk factors for depressive symptoms, whereas exercise and having someone to consult about worries may be protective factors

Comprehensive genomic profiling for patients with chemotherapy‐naïve advanced cancer

Comprehensive genomic profiling (CGP) testing by next-generation sequencing has been introduced into clinical practice as part of precision cancer medicine to select effective targeted therapies. However, whether CGP testing at the time of first-line chemotherapy could be clinically useful is not clear. We conducted this single-center, prospective, observational study to investigate the feasibility of CGP testing for chemotherapy-naïve patients with stage III/IV gastrointestinal cancer, rare cancer, and cancer of unknown primary, using the FoundationOne® companion diagnostic (F1CDx) assay. The primary outcome was the detection rate of at least one actionable/druggable cancer genomic alteration. Actionable/druggable cancer genomic alterations were determined by the F1CDx report. An institutional molecular tumor board determined the molecular-based recommended therapies. A total of 197 patients were enrolled from October 2018 to June 2019. CGP success rate was 76.6% (151 of 197 patients), and median turnaround time was 19 days (range: 10-329 days). Actionable and druggable cancer genomic alterations were reported in 145 (73.6%) and 124 (62.9%) patients, respectively. The highest detection rate of druggable genomic alterations in gastrointestinal cancers was 80% in colorectal cancer (48 of 60 patients). Molecular-based recommended therapies were determined in 46 patients (23.4%). CGP testing would be a useful tool for the identification of a potentially effective first-line chemotherapy

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