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Abstract Background Patient care ownership (PCO) among medical students is a growing area in the field of medical education. While PCO has received increasing attention, there are no instruments to assess PCO in the context of Japanese undergraduate medical education. This study aimed to translate, culturally adapt, and validate the PCO Scale – Medical students (PCOS-S) in the Japanese context. Methods We collected survey data from fifth- and sixth-grade medical students from five different universities varying in location and type. Structural validity, convergent validity, and internal consistency reliability were examined. Results Data from 122 respondents were analyzed. Factor analysis of the Japanese PCOS-S revealed three factors with Cronbach’s alpha values exceeding the satisfactory criterion (0.70). A positive correlation was observed between the total Japanese PCOS-S scores and the global rating scores for the clinical department as a learning environment (Pearson’s correlation coefficient = 0.61). Conclusions We conducted the translation of the PCOS-S into Japanese and assessed its psychometric properties. The Japanese version has good reliability and validity. This instrument has potential value in assessing the development of medical students’ PCO.

Abstract Background Formative feedback plays a critical role in guiding learners to gain competence, serving as an opportunity for reflection and feedback on their learning progress and needs. Medical education in Japan has historically been dominated by a summative paradigm within assessment, as opposed to countries such as the UK where there are greater opportunities for formative feedback. How this difference affects students’ interaction with feedback has not been studied. We aim to explore the difference in students’ perception of feedback in Japan and the UK. Methods The study is designed and analysed with a constructivist grounded theory lens. Medical students in Japan and the UK were interviewed on the topic of formative assessment and feedback they received during clinical placements. We undertook purposeful sampling and concurrent data collection. Data analysis through open and axial coding with iterative discussion among research group members was conducted to develop a theoretical framework. Results Japanese students perceived feedback as a model answer provided by tutors which they should not critically question, which contrasted with the views of UK students. Japanese students viewed formative assessment as an opportunity to gauge whether they are achieving the pass mark, while UK students used the experience for reflective learning. Conclusions The Japanese student experience of formative assessment and feedback supports the view that medical education and examination systems in Japan are focused on summative assessment, which operates alongside culturally derived social pressures including the expectation to correct mistakes. These findings provide new insights in supporting students to learn from formative feedback in both Japanese and UK contexts.

Abstract Background Ambiguity is inherent to the medical field; hence, assessing and educating medical trainees regarding ambiguity tolerance is essential. The Tolerance of Ambiguity in Medical Students and Doctors (TAMSAD) scale—a novel instrument that assesses ambiguity tolerance in clinical settings—has been widely used for medical education research in Western countries. However, a version of this scale applicable to the intricate clinical contexts of Japan has not yet been developed. In this study, we developed the Japanese version of the TAMSAD (J-TAMSAD) scale and tested its psychometric properties. Methods In this multicenter study, we collected data through a cross-sectional survey in two universities (medical students) and ten hospitals (residents) across Japan, and evaluated the structural validity, criterion-related validity, and internal consistency reliability of the J-TAMSAD scale. Results We analyzed the data of 247 participants. The sample was randomly divided in half, with exploratory factor analysis (EFA) performed on one half and confirmatory factor analysis (CFA) on the other. EFA led to an 18-item J-TAMSAD scale comprising five factors. CFA showed acceptable fit for this five-factor model (comparative fit index = 0.900, root mean square error of approximation = 0.050, standardized root mean square residual = 0.069, goodness of fit index = 0.987). There was a positive correlation between the J-TAMSAD scale scores and total reverse scores on the Japanese version of the Short Intolerance of Uncertainty Scale (Pearson correlation coefficient 0.41). The internal consistency was found to be satisfactory (Cronbach’s alpha 0.70). Conclusions The J-TAMSAD scale was developed, and its psychometric properties were confirmed. The instrument can be useful for assessing tolerance of ambiguity among medical trainees in Japan. With further validation, it could be used to verify the educational effectiveness of curricula that foster ambiguity tolerance in medical trainees, or even in research assessing the relationship with other variables.

ABSTRACTIntroduction Collaboration between student affairs officers and the faculty is important in dealing with the recent rapid changes in medical education, and mutual understanding is essential to ensure that participants become a cohesive social group. This study explores the identity conflicts of student affairs officers in medical universities using the figured worlds theory.Methods An exploratory qualitative case study was conducted with 24 student affairs officers at a private medical university in Japan. Data were collected through face-to-face, semi-structured interviews and analysed using thematic analysis from the perspective of a social constructivism paradigm.Results Qualitative analysis revealed the following three themes regarding the identity conflicts of student affairs officers: differences in the perception of medical students, difficulties in building trusting relationships with the faculty, and resistance to the medical university’s traditional atmosphere. Student affairs officers tended to provide support from a student-centred perspective when interacting with medical students, while the faculty employed a teacher-centred perspective.Discussion To promote understanding between professions, it is necessary to set aside certain professional views and welcome dialogue with other professionals with different values, while also understanding the multi-layered context of medical education, so that conflicts can be handled optimally and relationships can be professionalised for social cohesion.

Abstract Background Supporting professional identity development in medical students undergoing remediation in the first few years of their studies is an important topic. However, there is a lack of research on developing an effective and individualised process for successful remediation that targets learner identities. This study examined the identities of Generation Z remedial medical students through the lens of professional identity formation, focusing on the difficulties they faced and the support they sought. Methods An exploratory qualitative case study was conducted within a constructivist paradigm. Twenty-two medical students (14 males and 8 females) who had experienced remediation in their first few years of medical university participated in this study. All participants were members of Generation Z. Qualitative data were collected through face-to-face, semi-structured interviews and analysed using thematic analysis. Results Medical students undergoing remediation in the first few years experienced resistance to the medical profession and conflict due to the gap between the ideal and the reality they experienced after entering medical university. Students’ professional identities were closely intertwined with their pre-university identities; this affected the process of professional identity formation after entering medical university. They preferred assurances of confidentiality as a prerequisite and immediately sought advice through social networks to support their professional identity development. Conclusions When planning professional identity development support for Generation Z medical students undergoing remediation in the first few years, it is necessary to carefully select integrative interaction methods, focus on the context of individual learners, and collaboratively discuss specific responses between students and faculty. The results of this study could be useful to faculty in developing support systems for future remedial medical students that focuses on professional identity development and mentoring of remedial medical students.

Malignant soft tissue tumors, particularly highly malignant leiomyosarcomas, are resistant to chemotherapy and associated with a poor prognosis. T-01, a third-generation genetically modified herpes simplex virus type 1, replicates in tumor cells alone and exerts a cell-killing effect. The current study aimed to investigate the antitumor effect of T-01, which is a novel treatment for leiomyosarcoma. In vitro, six human cell lines and one mouse sarcoma cell line were assessed for T-01 cytotoxicity. In vivo, the efficacy of T-01 was examined in subcutaneously transplanted leiomyosarcoma (SK-LMS-1) cells and subcutaneously or intraperitoneally transplanted mouse sarcoma (CCRF S-180II) cells. Cytokines were assessed using ELISpot assay with splenocytes from the allogeneic models for immunological evaluation. T-01 showed cytotoxicity in all seven cell lines (p

Abstract Background The COVID-19 pandemic has caused medical colleges worldwide to suspend in-person classes and clinical clerkships. This fluid situation urgently required educators and learners to make a paradigm shift from traditional medical education. However, descriptions of how leaders manage policy decisions, especially considering cultural contexts, are limited. This study explores how the deans of medical colleges in Japan addressed the situations in which face-to-face contact is difficult and interacted with various stakeholders during the COVID-19 pandemic. Methods The study employed a nationwide online survey by sending individual e-mails to the director of medical education at each of the 82 medical colleges in Japan. Responses were collected between May 26 and June 12, 2020 from the deans or directors of medical education. The survey questions were developed based on a literature review and consultations with international research collaborators. The survey asked what difficulties and opportunities were encountered through curriculum adjustments during the COVID-19 pandemic and what lessons could be shared with medical educators worldwide. Survey responses were analyzed using thematic analysis. The themes were categorized by stakeholder and then analyzed using the domains of sensemaking theory. Results A total of 48 medical colleges in Japan completed the survey, yielding a response rate of 58.5%. The levels of participation in the study were 42.9%, 77.8%, and 74.2% among national, public, and private medical colleges, respectively, with responses from public and private medical colleges tending to be higher than those from national medical colleges. Japanese deans’ decisions for actions in adapting to COVID-19 involve perceiving cues from multiple stakeholder groups, including medical students, parents of medical students, medical faculties, and government officials. Thematic analysis of survey data reveals that Japanese deans’ actions in adapting to COVID-19 reflect characteristics of Japanese culture, with Japanese deans tending to emphasize in-depth introspection and collaboration with diverse stakeholders. Conclusions Despite a lack of clear national guidelines for decision making, Japanese deans adapted to COVID-19 challenges by learning from one another and seeking the perspectives of a diverse group of stakeholders, aligned with local cultural context. Their approach offers important lessons for global medical educators.

Abstract Background Little is known about the actual impact of COVID-19 on caregivers of older people with dementia and resultant collaborations among them to provide continued person-centered care while undertaking infection control measures. In this study, we explored the impact of providing dementia care during COVID-19 on caregivers involved in dementia care. Methods This is an exploratory qualitative case study. The participants were family members living with older people with dementia, care managers, and the medical and long-term care facility staff. Data were collected from 46 caregivers via face-to-face and semi-structured interviews and analyzed using thematic analysis. Results The interviews identified 22 themes related to the impact of COVID-19 on different positions of the caregivers involved in dementia care and their collaboration, and we categorized them into six categories. The core themes were “re-acknowledgement of care priorities” and “rebuilding of relationships.” When caregivers’ perceptions were aligned in the decision-making processes regarding care priorities, “reaffirmation of trust” and “strengthening of intimate relationships” emerged as positive changes in their relationships. Furthermore, the differences in the ability of each caregiver to access and select correct and appropriate information about COVID-19, and the extent of infection spread in the region were related to “anxiety during COVID-19 pandemic” and caused a “gap in perception” regarding infection control. Conclusions The present study clarified that the process of aligning the perceptions of caregivers to the objectives and priorities of care for older people with dementia during COVID-19 pandemic strengthened the relationships among caregivers. The findings of this study are useful for caregivers involved in person-centered dementia care.

Matsuo et al. report that thiazoline-related innate fear-eliciting compounds activate the spinal trigeminal nucleus (Sp5) and the nucleus of the solitary tract (NTS) via vagal/trigeminal TRPA1 to induce robust physiological alterations, enabling long time survival in a lethal hypoxic environment.

IntroductionInterruptions in undergraduate clinical clerkship during the COVID-19 pandemic have reduced the confidence and preparedness of residents beginning their postgraduate training. We explore the thoughts of new residents about this transition and reflect on the support needed.MethodsAn exploratory qualitative case study was conducted with 51 residents. All had experienced interruptions in clinical training due to the pandemic and had just started their postgraduate training. Qualitative data were collected through 6 focus groups and 12 individual follow-up interviews. A thematic analysis was undertaken, and the data were categorised using a Strengths, Weaknesses, Opportunities, and Threats (SWOT) framework.ResultsGraduates beginning their residency were aware of their professionalism and independence during the transition. They also faced the predicament of needing close supervision while their supervisors managed pandemic conditions. Residents emphasised the importance of developing relationships with colleagues and supervisors during the transition to residency and wanted direct observation and detailed feedback from their supervisors during procedures.ConclusionsThe experiences of residents were not uniformly negative. In fact, some had developed a positive mindset when entering the clinical field. Medical faculty members reflecting on interactions with new residents and planning future clinical internships could benefit from placing a high value on building relationships among residents, who may expect direct observation and detailed feedback from their supervisors.

Levosimendan, a calcium sensitizer, has an organ protective profile through the inhibition of inflammatory mediators and cytokines in critical conditions, such as heart failure, ischemia-reperfusion injury, and sepsis. The survival effect of levosimendan for acute liver failure has not been examined yet. Male Sprague-Dawley rats were examined in the D-galactosamine hydrochloride and lipopolysaccharide (GalN/LPS) model. Levosimendan was injected intraperitoneally before GalN/LPS treatment. Survival was monitored for 7 days. For biochemical analyses, liver and blood samples were collected from the rats at 1 and 8 h after GaIN/LPS treatment. The pretreatment of levosimendan at 4 mg/kg significantly increased survival in GalN/LPS rats. In the liver specimen, levosimendan significantly inhibited the activation of nuclear factor-κB (NF-κB) at 1 h, and significantly decreased the mRNA expression of inflammatory mediators, including inducible nitric oxide synthase and tumor necrosis factor-α (TNF-α), at 8 h. In serum, levosimendan decreased the levels of nitrite, a metabolite of nitric oxide, and TNF-α protein, as well as aspartate aminotransferase and alanine aminotransferase. These results indicated that Levosimendan ameliorated liver dysfunction and survival in acute liver failure model rats through the suppression of NF-κB activation.

Background and Objectives: Clinically used concentrations of sevoflurane, an inhaled anesthetic, have been reported to significantly inhibit tumor growth. We investigated the effects of sevoflurane on sphere formation and the proliferation of human glioblastoma stem cells (GSCs) to determine whether sevoflurane exerts short- and long-term effects on human tumor cells. Materials and Methods: High-grade patient-derived GSCs (MD13 and Me83) were exposed to 2% sevoflurane. To evaluate the effect of sevoflurane on viability, proliferation, and stemness, we performed a caspase-3/7 essay, cell proliferation assay, and limiting dilution sphere formation assays. The expression of CD44, a cell surface marker of cancer stem-like cells in epithelial tumors, was evaluated using quantitative reverse transcription PCR. Differences between groups were evaluated with a one-way analysis of variance (ANOVA). Results: Sevoflurane exposure for 4 days did not significantly promote caspase 3/7 activity in MD13 and Me83, and cell proliferation was not observed after 5 days of exposure. Furthermore, prolonged exposure to sevoflurane for 6 days did not promote the sphere-forming and proliferative potential of MD13 and Me83 cells. These results suggest that sevoflurane does not promote either apoptosis, proliferative capacity, or the colony-forming ability of human mesenchymal glioblastoma stem cells in vitro. Conclusions: Sevoflurane at clinically used concentrations does not promote the colony-forming ability of human mesenchymal glioblastoma stem cells in vitro. It is very important for neurosurgeons and anesthesiologists to know that sevoflurane, a volatile anesthetic used in surgical anesthesia, would not exacerbate the disease course of GSCs.

TMEM16A (Transmembrane protein 16A or Anoctamin1) is a calcium-activated chloride channel.(CaCC),that exerts critical roles in epithelial secretion. However, its localization, function, and regulation in intestinal chloride (Cl−) secretion remain obscure. Here, we show that TMEM16A protein abundance correlates with Cl− secretion in different regions of native intestine activated by the Ca2+-elevating muscarinic agonist carbachol (CCH). Basal, as well as both cAMP- and CCH-stimulated Isc, was largely reduced in Ano1 ± mouse intestine. We found CCH was not able to increase Isc in the presence of apical to serosal Cl− gradient, strongly supporting TMEM16A as primarily a luminal Cl− channel. Immunostaining demonstrated apical localization of TMEM16A where it colocalized with NHERF1 in mouse colonic tissue. Cellular depletion of NHERF1 in human colonic T84 cells caused a significant reduction of both cAMP- and CCH-stimulated Isc. Immunoprecipitation experiments revealed that NHERF1 forms a complex with TMEM16A through a PDZ-based interaction. We conclude that TMEM16A is a luminal Cl− channel in the intestine that functionally interacts with CFTR via PDZ-based interaction of NHERF1 for efficient and specific cholinergic stimulation of intestinal Cl− secretion.

Objectives Globalisation has given medical university students the opportunity to pursue international electives in other countries, enhancing the long-term socialisation of medical professionals. This study identified the long-term effects of international electives on the professional identity formation of medical students.Design This is a qualitative study.Setting The authors interviewed Japanese medical professionals who had completed their international electives more than 10 years ago, and analysed and interpreted the data using a social constructivism paradigm.Participants A total of 23 medical professionals (mean age 36.4 years; range 33–42 years) participated in face-to-face, semistructured in-depth interviews.Results During the data analysis, 36 themes related to professional identity formation were identified, and the resulting themes had five primary factors (perspective transformation, career design, self-development, diversity of values and leadership). It was concluded that international electives for medical students could promote reflective self-relativisation and contribute to medical professional identity formation. Additionally, such electives can encourage pursuing a specialisation and academic or non-academic work abroad. International electives for medical students could contribute to medical professional identity formation on the basis of cross-cultural understanding.Conclusions This study addressed a number of issues regarding the long-term impact of international elective experiences in various countries on the professional identity formation of Japanese medical professionals. This study offers some guidance to mentors conducting international electives and provides useful information for professional identity formation development in medical professionals.

Summary: Gut epithelial organoids are routinely used to investigate intestinal biology; however, current culture methods are not amenable to genetic manipulation, and it is difficult to generate sufficient numbers for high-throughput studies. Here, we present an improved culture system of human induced pluripotent stem cell (iPSC)-derived intestinal organoids involving four methodological advances. (1) We adopted a lentiviral vector to readily establish and optimize conditioned medium for human intestinal organoid culture. (2) We obtained intestinal organoids from human iPSCs more efficiently by supplementing WNT3A and fibroblast growth factor 2 to induce differentiation into definitive endoderm. (3) Using 2D culture, followed by re-establishment of organoids, we achieved an efficient transduction of exogenous genes in organoids. (4) We investigated suspension organoid culture without scaffolds for easier harvesting and assays. These techniques enable us to develop, maintain, and expand intestinal organoids readily and quickly at low cost, facilitating high-throughput screening of pathogenic factors and candidate treatments for gastrointestinal diseases.

Visceral fat accumulation as observed in Crohn's disease and obesity is linked to chronic gut inflammation, suggesting that accumulation of gut adipocytes can trigger local inflammatory signaling. However, direct interactions between intestinal epithelial cells (IECs) and adipocytes have not been investigated, in part because IEC physiology is difficult to replicate in culture. In this study, we originally prepared intact, polarized, and cytokine responsive IEC monolayers from primary or induced pluripotent stem cell-derived intestinal organoids by simple and repeatable methods. When these physiological IECs were co-cultured with differentiated adipocytes in Transwell, pro-inflammatory genes were induced in both cell types, suggesting reciprocal inflammatory activation in the absence of immunocompetent cells. These inflammatory responses were blocked by nuclear factor-κB or signal transducer and activator of transcription 3 inhibition and by anti-tumor necrosis factor- or anti-interleukin-6-neutralizing antibodies. Our results highlight the utility of these monolayers for investigating IEC biology. Furthermore, this system recapitulates the intestinal epithelium–mesenteric fat signals that potentially trigger or worsen inflammatory disorders such as Crohn's disease and obesity-related enterocolitis.

I participated in an international fellowship exchange program at Thomas Jefferson University (TJU) in Pennsylvania, USA. Through this fellowship, I was able to obtain an overview of the undergraduate medical curriculum taught at this university. Although I have contemplated the differences between medical education at TJU and the syllabus taught in Japan, I caution that one cannot directly transfer the components of TJU program to universities in Japan because of the dissimilar cultural contexts of Western countries and Asian nations. I believe that the focus of undergraduate medical education requires careful consideration of specific socio-cultural backgrounds.

Background Proper glycemic control is an important goal of critical care medicine, including perioperative patient care that can influence patients’ prognosis. Insulin secretion from pancreatic β-cells is generally assumed to play a critical role in glycemic control in response to an elevated blood glucose concentration. Many animal and human studies have demonstrated that perioperative drugs, including volatile anesthetics, have an impact on glucose-stimulated insulin secretion (GSIS). However, the effects of the intravenous anesthetic propofol on glucose metabolism and insulin sensitivity are largely unknown at present. Methods The effect of propofol on insulin secretion under low glucose or high glucose was examined in mouse MIN6 cells, rat INS-1 cells, and mouse pancreatic β-cells/islets. Cellular oxygen or energy metabolism was measured by Extracellular Flux Analyzer. Expression of glucose transporter 2 (GLUT2), potassium channels, and insulin mRNA was assessed by qRT-PCR. Protein expression of voltage-dependent potassium channels (Kv2) was also assessed by immunoblot. Propofol’s effects on potassium channels including stromatoxin-1-sensitive Kv channels and cellular oxygen and energy metabolisms were also examined. Results We showed that propofol, at clinically relevant doses, facilitates insulin secretion under low glucose conditions and GSIS in MIN6, INS-1 cells, and pancreatic β-cells/islets. Propofol did not affect intracellular ATP or ADP concentrations and cellular oxygen or energy metabolism. The mRNA expression of GLUT2 and channels including the voltage-dependent calcium channels Cav1.2, Kir6.2, and SUR1 subunit of KATP, and Kv2 were not affected by glucose or propofol. Finally, we demonstrated that propofol specifically blocks Kv currents in β-cells, resulting in insulin secretion in the presence of glucose. Conclusions Our data support the hypothesis that glucose induces membrane depolarization at the distal site, leading to KATP channel closure, and that the closure of Kv channels by propofol depolarization in β-cells enhances Ca2+ entry, leading to insulin secretion. Because its activity is dependent on GSIS, propofol and its derivatives are potential compounds that enhance and initiate β-cell electrical activity.

Objectives Globalisation has increased the opportunities for health professionals working in developed countries to provide clinical and educational support in developing countries. However, how these experiences contribute to the leadership competency of health professionals is unclear; therefore, this study explored this with the objective of analysing the process of developing individual leadership competency.Design This is a qualitative descriptive study. Qualitative descriptive study is widely used in healthcare research, particularly to describe the nature of various healthcare phenomena. Qualitative descriptive data were collected in face-to-face, semistructured interviews.Setting The authors interviewed Japanese health professionals who participated in an international medical cooperation project as part of a multinational medical team between July 2017 and March 2018, and analysed and interpreted the data using a social constructivism paradigm.Participants The authors interviewed 20 research participants, including 5 nurses, 5 dentists and 10 physicians with an average of 15.3 years of clinical experience.Results The interviews identified 58 emergent themes related to their leadership competency, 23 of which affected the actual medical care in their own institutions. The authors categorised the 58 emergent themes into seven competency areas: leadership concepts, teambuilding, direction setting, communication, business skills, working with others and self-development. The authors identified the relationships among each competency and identified differences between professions: nurses particularly reflected on their empathic attitudes towards patient after global clinical health experience; dentists tended to reflect on their business skills; physicians tended to reflect on their leadership concepts and teambuilding.Conclusions This study clarified the leadership competency gained through short-term global clinical health experience and the process of individual leadership competency development. The findings provide expected learning competency for those considering medical practice in developing or other countries in the future.