Suicidal ideation and burnout among psychiatric trainees in Japan

AIM: Burnout is a psychological condition that may occur in all workers after being exposed to excessive work-related stresses. We investigated suicidal ideation and burnout among Japanese psychiatric trainees as a part of the Burnout Syndrome Study (BoSS) International.  METHODS: In the Japanese branch, 91 trainees fully completed suicide ideation and behaviour questionnaire (SIBQ) and Maslach Burnout Inventory-General Survey (MBI-GS).  RESULTS: Passive suicidal ideation was reported by 38.5% of Japanese trainees and 22.0% of them had experienced active suicidal ideation. The burnout rate among Japanese subjects was 40.0%. These results were worse compared to the all 1980 trainees who fully completed the main outcome measure in BoSS International, 25.9%, 20.4% and 36.7%, respectively.  CONCLUSIONS: Our results suggest a higher risk of suicide among Japanese residents. Japan has a higher suicide rate than other countries. Early detection of, and appropriate intervention for, suicidal ideation is important in preventing suicide in psychiatry residents

The practice of child and adolescent psychiatry: a survey of early-career psychiatrists in Japan

<p>Abstract</p> <p>Background</p> <p>Child and adolescent psychiatry (CAP), a subspecialty of psychiatry in Japan, is facing a serious workforce shortage. To resolve this situation, the Japanese government has organized a task force and has been working to increase psychiatrists' clinical skills to improve care for children and adolescents with mental health problems. Using an online questionnaire system, the authors have conducted a survey to investigate the perceptions, experiences, and interests of early-career psychiatrists in CAP.</p> <p>Methods</p> <p>The subjects of this study were 182 psychiatrists in Japan whose individual clinical experiences did not exceed 15 years. The authors of this study created an online questionnaire system and e-mailed the URL and login password to all subjects. Respondents anonymously answered the questions. Most questions required an answer indicating a level of agreement scored on a nine-point scale. Responding to the questionnaire was considered to constitute consent, and all respondents' privacy was carefully protected.</p> <p>Results</p> <p>The mean age and clinical psychiatric experience of the subjects were found to be 33.1 ± 4.5 years and 5.43 ± 3.5 years, respectively. On a nine-point scale (with nine being the highest), experience and interest in CAP measured 3.05 ± 1.9 and 5.34 ± 2.5, respectively; further, these two factors showed significant correlation (r = 0.437, p < 0.0001). The mean score for the early-career psychiatrists' confidence in their ability to diagnose and appropriately treat was notably low, at 3.13 ± 1.9.</p> <p>Conclusion</p> <p>Our results demonstrated that early-career psychiatrists self-evaluated their CAP clinical experience as insufficient, and these clinicians' CAP experiences and interests correlated significantly. Therefore, in order to improve child and adolescent medical care, we need to expose young psychiatrists to sufficient CAP cases and explore the factors that could attract them to this field.</p

Anti-Tumor Effect against Human Cancer Xenografts by a Fully Human Monoclonal Antibody to a Variant 8-Epitope of CD44R1 Expressed on Cancer Stem Cells

BACKGROUND: CD44 is a major cellular receptor for hyaluronic acids. The stem structure of CD44 encoded by ten normal exons can be enlarged by ten variant exons (v1-v10) by alternative splicing. We have succeeded in preparing MV5 fully human IgM and its class-switched GV5 IgG monoclonal antibody (mAb) recognizing the extracellular domain of a CD44R1 isoform that contains the inserted region coded by variant (v8, v9 and v10) exons and is expressed on the surface of various human epithelial cancer cells. METHODS AND PRINCIPAL FINDINGS: We demonstrated the growth inhibition of human cancer xenografts by a GV5 IgG mAb reshaped from an MV5 IgM. The epitope recognized by MV5 and GV5 was identified to a v8-coding region by the analysis of mAb binding to various recombinant CD44 proteins by enzyme-linked immunosorbent assay. GV5 showed preferential reactivity against various malignant human cells versus normal human cells assessed by flow cytometry and immunohistological analysis. When ME180 human uterine cervix carcinoma cells were subcutaneously inoculated to athymic mice with GV5, significant inhibition of tumor formation was observed. Furthermore, intraperitoneal injections of GV5markedly inhibited the growth of visible established tumors from HSC-3 human larynx carcinoma cells that had been subcutaneously transplanted one week before the first treatment with GV5. From in vitro experiments, antibody-dependent cellular cytotoxicity and internalization of CD44R1 seemed to be possible mechanisms for in vivo anti-tumor activity by GV5. CONCLUSIONS: CD44R1 is an excellent molecular target for mAb therapy of cancer, possibly superior to molecules targeted by existing therapeutic mAb, such as Trastuzumab and Cetuximab recognizing human epidermal growth factor receptor family

RNA-Binding Protein Musashi1 Modulates Glioma Cell Growth through the Post-Transcriptional Regulation of Notch and PI3 Kinase/Akt Signaling Pathways

Musashi1 (MSI1) is an RNA-binding protein that plays critical roles in nervous-system development and stem-cell self-renewal. Here, we examined its role in the progression of glioma. Short hairpin RNA (shRNA)-based MSI1-knock down (KD) in glioblastoma and medulloblastoma cells resulted in a significantly lower number of self renewing colony on day 30 (a 65% reduction), compared with non-silencing shRNA-treated control cells, indicative of an inhibitory effect of MSI1-KD on tumor cell growth and survival. Immunocytochemical staining of the MSI1-KD glioblastoma cells indicated that they ectopically expressed metaphase markers. In addition, a 2.2-fold increase in the number of MSI1-KD cells in the G2/M phase was observed. Thus, MSI1-KD caused the prolongation of mitosis and reduced the cell survival, although the expression of activated Caspase-3 was unaltered. We further showed that MSI1-KD glioblastoma cells xenografted into the brains of NOD/SCID mice formed tumors that were 96.6% smaller, as measured by a bioluminescence imaging system (BLI), than non-KD cells, and the host survival was longer (49.3±6.1 days vs. 33.6±3.6 days; P<0.01). These findings and other cell biological analyses suggested that the reduction of MSI1 in glioma cells prolonged the cell cycle by inducing the accumulation of Cyclin B1. Furthermore, MSI1-KD reduced the activities of the Notch and PI3 kinase-Akt signaling pathways, through the up-regulation of Numb and PTEN, respectively. Exposure of glioma cells to chemical inhibitors of these pathways reduced the number of spheres and living cells, as did MSI1-KD. These results suggest that MSI1 increases the growth and/or survival of certain types of glioma cells by promoting the activation of both Notch and PI3 kinase/Akt signaling

Nationwide survey of work environment, work-life balance and burnout among psychiatrists in Japan.

BACKGROUND: Psychiatry has been consistently shown to be a profession characterised by 'high-burnout'; however, no nationwide surveys on this topic have been conducted in Japan. AIMS: The objective of this study was to estimate the prevalence of burnout and to ascertain the relationship between work environment satisfaction, work-life balance satisfaction and burnout among psychiatrists working in medical schools in Japan. METHOD: We mailed anonymous questionnaires to all 80 psychiatry departments in medical schools throughout Japan. Work-life satisfaction, work-environment satisfaction and social support assessments, as well as the Maslach Burnout Inventory (MBI), were used. RESULTS: Sixty psychiatric departments (75.0%) responded, and 704 psychiatrists provided answers to the assessments and MBI. Half of the respondents (n = 311, 46.0%) experienced difficulty with their work-life balance. Based on the responses to the MBI, 21.0% of the respondents had a high level of emotional exhaustion, 12.0% had a high level of depersonalisation, and 72.0% had a low level of personal accomplishment. Receiving little support, experiencing difficulty with work-life balance, and having less work-environment satisfaction were significantly associated with higher emotional exhaustion. A higher number of nights worked per month was significantly associated with higher depersonalisation. CONCLUSIONS: A low level of personal accomplishment was quite prevalent among Japanese psychiatrists compared with the results of previous studies. Poor work-life balance was related to burnout, and social support was noted to mitigate the impact of burnout

In vitro and in silico characterization of adiponectin-receptor agonist dipeptides

Abstract The aim of this study is to develop a dipeptide showing an adiponectin receptor 1 (AdipoR1) agonistic effect in skeletal muscle L6 myotubes. Based on the structure of the AdipoR1 agonist, AdipoRon, 15 synthetic dipeptides were targeted to promote glucose uptake in L6 myotubes. Tyr-Pro showed a significant increase in glucose uptake among the dipeptides, while other dipeptides, including Pro-Tyr, failed to exert this effect. Tyr-Pro induces glucose transporter 4 (Glut4) expression in the plasma membrane, along with adenosine monophosphate-activated protein kinase (AMPK) activation. In AdipoR1-knocked down cells, the promotion by Tyr-Pro was ameliorated, indicating that Tyr-Pro may directly interact with AdipoR1 as an agonist, followed by the activation of AMPK/Glut4 translocation in L6 myotubes. Molecular dynamics simulations revealed that a Tyr-Pro molecule was stably positioned in the two potential binding pockets (sites 1 and 2) of the seven-transmembrane receptor, AdipoR1, anchored in a virtual 1-palmitoyl-2-oleoyl-phosphatidylcholine membrane. In conclusion, we demonstrated the antidiabetic function of the Tyr-Pro dipeptide as a possible AdipoR1 agonist

RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients

Means MBI scores and burnout rates.

<p>a Chi-squared test; the results of three burnout subsets were compared.</p