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The bacterial SecYEG translocon functions as a conserved protein-conducting channel. Conformational transitions of SecYEG allow protein translocation across the membrane without perturbation of membrane permeability. Here, we report the crystal structures of intact SecYEG at 2.7-Å resolution and of peptide-bound SecYEG at 3.6-Å resolution. The higher-resolution structure revealed that the cytoplasmic loop of SecG covers the hourglass-shaped channel, which was confirmed to also occur in the membrane by disulfide bond formation analysis and molecular dynamics simulation. The cytoplasmic loop may be involved in protein translocation. In addition, the previously unknown peptide-bound crystal structure of SecYEG implies that interactions between the cytoplasmic side of SecY and signal peptides are related to lateral gate opening at the first step of protein translocation. These SecYEG structures therefore provide a number of structural insights into the Sec machinery for further study.

Abstract Background Most Japanese medical schools likely continue to rely on peer physical examination (PPE) as a tool to for teaching physical examination skills to students. However, the attitudes of medical students in Japan toward PPEs have not be identified. Therefore, we evaluated students’ attitudes toward PPE in a Japanese medical school as a preparation for developing a PPE policy tailored to the context of Japanese culture. Methods We conducted a mixed-methods study with an explanatory sequential approach, in which qualitative data were used to interpret the quantitative findings. Surveys and interviews were conducted with medical students and junior residents at a Japanese university. A total of 63 medical students and 50 junior residents responded to the questionnaire. We interviewed 16 participants to reach theoretical saturation and investigated the attitudes of medical students toward PPE and the themes emerging from the interview data, providing detailed descriptions of the quantitative findings. Results Female participants were significantly more likely than male participants to report varying degrees of resistance to being a model patient during PPE (male: 59.7%, female: 87%, p

ABSTRACTIntroduction The COVID-19 pandemic had an additional negative impact on the mental health of healthcare workers, including residents. Previous studies revealed that grit, which is an individual trait to achieve long-term goals unrelated to intelligence quotient, is not only positively associated with academic achievement and career success but also negatively correlated with depression. This study aimed to examine the association between grit and depressive symptoms among residents at the time of job start during the coronavirus disease 2019 (COVID-19) pandemic in Japan.Materials and methods This cross-sectional study used data from all post-graduate year 1 residents from March 2020 to April 2022 at Tokyo Medical and Dental University, Tokyo, Japan. Grit was measured by the Japanese version of Grit-S. The resident’s depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. The association of interest was examined using logistic regression analysis.Results Among 221 residents, 28 (12.7%) have depressive symptoms. One unit increase in Grit-S score after adjusting for age, sex, graduated university, and sleeping hours was associated with lower odds of having depressive symptoms by 63% (odds ratio [OR]: 0.37; 95% confidence interval [CI]: 0.19–0.74). Further, the perseverance of effort subscale score was associated with lower odds of having depressive symptoms after covariate adjustment (OR: 0.43; 95% CI: 0.22–0.84).Conclusions Higher grit scores were associated with lower odds of having depressive symptoms among residents at the timing of job start during the COVID-19 pandemic. Regular mental health assessment is particularly important for residents with low grit scores at entry.

Objective To clarify the reasons for consultation, advice sought by frontline physicians and relationship between the patient’s pathology and the type of advice provided to guide the future development of telecritical care services.Design Secondary analysis of transcripts of telephone calls originally recorded for quality control purposes was conducted using a thematic content analysis. The calls were conducted between December 2019 and April 2021 (total cases: 70; total time: ~15 hour).Settings Intensivists provided consultation services to frontline physicians at secondary care institutions in the Kansai and Chubu regions.Participants Non-intensive care frontline physicians working in five secondary care institutions in the Kansai and Chubu regions and intensivists providing a consultation service (n=26).Interventions Not applicable.Primary and secondary outcome measures The main outcome was the themes emerging from the language used during telephone and video consultations, indicating the gap filled by the telecritical care service.Findings We analysed 70 cases and approximately 15 hours of anonymised audio data. We identified the following reasons for consultation: ‘lack of competence in treatment and diagnostic testing’ and ‘lack of access to consultation in their own hospital’. Frontline physicians most often sought advice related to ‘treatment’, followed by ‘patient triage and transfer’, ‘diagnosis’ and ‘diagnostic testing and evaluation’. Regarding the relationship between the patient’s pathology and type of advice provided, the most commonly sought advice by frontline physicians varied based on the patient’s pathology.Conclusion This study explored the characteristics of 70 telecritical sessions and identified the reasons for and nature of the consultations. These findings can be used to guide the future provision and scale up of telecritical services.

IntroductionNR5A1 and NR5A2 belong to an orphan nuclear receptor group, and approximately 60% of their amino acid sequences are conserved. Transcriptional regulation of NR5A receptors depends on interactions with co-factors or unidentified ligands.Purpose and methodsWe employed in vitro and in silico analysis for elucidating the pathophysiology of a novel variant in the ligand-binding domain of NR5A1, p.R350W which was identified from a 46,XY patient with atypical genitalia.ResultsIn the study, [1] reporter assays demonstrated that R350 is essential for NR5A1; [2] 3D model analysis predicted that R350 interacted with endogenous ligands or unknown cofactors rather than stabilizing the structure; [3] R350 is not conserved in NR5A2 but is specifically required for NR5A1; and [4] none of the 22 known missense variants of the ligand binding domain satisfied all the previous conditions [1]-[3], suggesting the unique role of R350 in NR5A1.ConclusionOur data suggest that NR5A1 has unidentified endogenous ligands or co-activators that selectively potentiate the transcriptional function of NR5A1 in vivo.

Background The Japanese healthcare system currently faces numerous challenges, including a super-aging society and an excessive burden on medical workers; therefore, the need for innovative solutions from healthcare ventures to tackle these issues has increased. Meanwhile, as physicians play important roles in healthcare ventures, the need for Japanese physician entrepreneurs is more important than ever. Given the lack of research examining barriers to physicians starting ventures and what skills, knowledge, and surrounding environments act as facilitators, this study aimed to identify the facilitators and barriers faced by physicians to start ventures. Methods Between September and November 2019 and in May 2021, qualitative interviews were conducted with 33 participants, which included eight physician entrepreneurs; two administrative officers at the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry; three faculty members at Tokyo Medical and Dental University (in-depth interviews); and 20 medical students (focus group discussions). The interviews were deductively coded based on the social ecological model. The inductive approach was applied to coding any knowledge necessary to start a business. We conducted member checking with three physician entrepreneurs and seven medical students to improve our results’ credibility. Results The factors influencing a physician’s decision to launch a new business include their willingness to contribute to society, the unique environment in which an individual is placed while in medical school and afterward, negative aspects of the lack of diversity in physicians’ careers, the financial stability provided by a medical license, and self-efficacy. Conclusions Our study revealed facilitators and barriers to physicians’ entrepreneurial ventures. Knowledge about these factors might be useful in supporting physicians to launch or become involved in healthcare ventures.