Twelve tips for medical school faculty to support students with disabilities.

As medical schools embrace diversity, it is increasingly acknowledged that medical students with disabilities must be welcome and supported in becoming physicians. Students should be able to ask for and receive reasonable accommodations to support their education. However, a practical shared approach to supporting medical students with disabilities is needed. The 12 tips in this article use sense-making theory as a framework to guide medical school faculty in supporting medical students with disabilities. The tips center on perceiving cues, creating interpretations, taking action, and communicating with students. The 12 tips can be utilized by faculty members across universities to take a proactive role in implementing support for medical students with disabilities and, in turn, nurturing an inclusive educational environment.

Association between tolerance for ambiguity specific to the clinical context and empathy in medical trainees: A multicenter cross-sectional study in Japan.

PURPOSE: Physicians' empathy and ambiguity tolerance have recently become a focus of medical education. However, the association between the two concepts remains unclear. This study examined the association between empathy and ambiguity tolerance in the clinical context among medical trainees. METHODS: We conducted a multicenter cross-sectional study in 12 institutions: 2 universities for medical students and 10 hospitals for residents. We assessed ambiguity tolerance using the Japanese version of the Tolerance of Ambiguity in Medical Students and Doctors scale. The outcome variable was empathy, measured using the Japanese translation of the Jefferson Scales of Empathy (JSE). RESULTS: Data from 100 medical students and 135 residents were analyzed. After adjustment for possible confounders, the factor scores of 'tolerance for things that are not black or white in medicine' showed a dose-dependent association with the JSE. There was no clear trend in the association between the total scores or other factor scores and empathy. CONCLUSION: This nationwide multicenter study showed that the factor scores of 'tolerance for things that are not black or white in medicine' were associated with empathy among medical trainees. Our findings may be helpful for developing interventions in the field of medical education to nurture empathy.

A qualitative study examining the critical differences in the experience of and response to formative feedback by undergraduate medical students in Japan and the UK.

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.

Translation, adaptation, and validation of the Tolerance of Ambiguity in Medical Students and Doctors (TAMSAD) scale for use in Japan.

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.

Identity conflicts of student affairs officers in a medical university.

INTRODUCTION: 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.

Current perception of social accountability of medical schools in Japan: A qualitative content analysis.

INTRODUCTION: The concept of social accountability in medical schools is globally accepted, but data regarding Japanese medical schools are lacking and unclear. This study aimed to elucidate the perception of social accountability of medical schools in Japan and compare this to global frameworks. METHODS: A document on Japanese medical accreditation standards (Basic Medical Education: Japanese Specifications WFME Global Standards for Quality Improvement) was used for this study. We included 45 medical schools in a qualitative content analysis done via inductive category formation. The documents were also assessed using the social obligation scale. RESULTS: Three main categories and 15 categories were identified. The three main categories were as follows: Issues in society, Quality assurance of medical school, and Improvement of individual quality. Most categories were common to those in global frameworks, but some were characteristic of the Japanese context. The distribution of schools on the social obligation scale in six elements varied mainly 'from responsibility to responsiveness' or equal unless the elements were promoted by national policy. CONCLUSIONS: The social accountability of Japanese medical schools is mostly common with the global frameworks. Our findings will help the social accountability of medical schools to become better understood and developed beyond contextual borders.

Levosimendan Increases Survival in a D-Galactosamine and Lipopolysaccharide Rat Model.

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.

Sevoflurane Does Not Promote the Colony-Forming Ability of Human Mesenchymal Glioblastoma Stem Cells In Vitro.

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.

Theranostics Using Indocyanine Green Lactosomes.

Lactosomes™ are biocompatible nanoparticles that can be used for cancer tissue imaging and drug delivery. Lactosomes are polymeric micelles formed by the self-assembly of biodegradable amphiphilic block copolymers composed of hydrophilic polysarcosine and hydrophobic poly-L-lactic acid chains. The particle size can be controlled in the range of 20 to 100 nm. Lactosomes can also be loaded with hydrophobic imaging probes and photosensitizers, such as indocyanine green. Indocyanine green-loaded lactosomes are stable for long-term circulation in the blood, allowing for accumulation in cancer tissues. Such lactosomes function as a photosensitizer, which simultaneously enables fluorescence diagnosis and photodynamic therapy. This review provides an overview of lactosomes with respect to molecular design, accumulation in cancer tissue, and theranostics applications. The use of lactosomes can facilitate the treatment of cancers in unresectable tissues, such as glioblastoma and head and neck cancers, which can lead to improved quality of life for patients with recurrent and unresectable cancers. We conclude by describing some outstanding questions and future directions for cancer theranostics with respect to clinical applications.

Ambivalent professional identity of early remedial medical students from Generation Z: a qualitative study.

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.

Efficacy of a third-generation oncolytic herpes simplex virus in refractory soft tissue sarcoma xenograft models.

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 < 0.001). In the SK-LMS-1 xenotransplantation model, tumor growth was suppressed by T-01 administration (p = 0.02). In the CCRF S-180II subcutaneous tumor model, bilateral tumor growth was significantly suppressed in the T-01-treated group compared with the control group (p < 0.001). In the peritoneal dissemination model, T-01 treatment caused significant survival prolongation compared with the control (p < 0.01). In conclusion, third-generation genetically modified herpes simplex virus type 1 may be an effective novel therapy against refractory sarcomas.

Leaders' perspectives and actions to manage challenges in medical education presented by the COVID-19 pandemic: a nationwide survey of Japanese medical colleges.

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.

Transition from undergraduates to residents: A SWOT analysis of the expectations and concerns of Japanese medical graduates during the COVID-19 pandemic.

INTRODUCTION: Interruptions 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. METHODS: An 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. RESULTS: Graduates 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. CONCLUSIONS: The 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.

Person-centered dementia care during COVID-19: a qualitative case study of impact on and collaborations between caregivers.

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.

PC3-Secreted Microprotein Is Expressed in Glioblastoma Stem-Like Cells and Human Glioma Tissues.

Glioblastoma multiforme (GBM) is the most prevalent malignant primary brain tumor with a high recurrence rate. Despite multimodal therapy including surgical resection, chemotherapy, and radiotherapy, the median survival time after the initial diagnosis of GBM is approximately 14 months. Since cancer stem cells (CSCs) are considered the leading cause of cancer recurrence, glioblastoma stem cell-targeted therapy is a promising strategy for the treatment of GBM. However, because CSC heterogeneity has been implicated in the difficulties of CSC-target therapy, more in-depth knowledge of CSC biology is still required to develop novel therapies. In this study, we established single cell-derived tumorspheres from human glioblastoma U87MG cells. One of these tumorspheres, P4E8 clone, showed CSC-like phenotypes, such as self-renewal capacity, expression of CSC markers, resistance to anti-cancer agents, and in vivo tumorigenicity. Therefore, we used P4E8 cells as a cell-based model of glioblastoma stem cells (GSCs). Gene expression analysis using microarray indicated that the most highly expressed genes in P4E8 cells compared to the parental U87MG were PC3-secreted microprotein (MSMP). Furthermore, MSMP was expressed in patient-derived GSCs and human glioma tissues at the protein level, implying that MSMP might contribute to glioma development and progression.

Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation.

Thiazoline-related innate fear-eliciting compounds (tFOs) orchestrate hypothermia, hypometabolism, and anti-hypoxia, which enable survival in lethal hypoxic conditions. Here, we show that most of these effects are severely attenuated in transient receptor potential ankyrin 1 (Trpa1) knockout mice. TFO-induced hypothermia involves the Trpa1-mediated trigeminal/vagal pathways and non-Trpa1 olfactory pathway. TFOs activate Trpa1-positive sensory pathways projecting from trigeminal and vagal ganglia to the spinal trigeminal nucleus (Sp5) and nucleus of the solitary tract (NTS), and their artificial activation induces hypothermia. TFO presentation activates the NTS-Parabrachial nucleus pathway to induce hypothermia and hypometabolism; this activation was suppressed in Trpa1 knockout mice. TRPA1 activation is insufficient to trigger tFO-mediated anti-hypoxic effects; Sp5/NTS activation is also necessary. Accordingly, we find a novel molecule that enables mice to survive in a lethal hypoxic condition ten times longer than known tFOs. Combinations of appropriate tFOs and TRPA1 command intrinsic physiological responses relevant to survival fate.

Intestinal TMEM16A control luminal chloride secretion in a NHERF1 dependent manner.

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.

Pituitary adenylate cyclase-activating polypeptide promotes cutaneous dendritic cell functions in contact hypersensitivity.

BACKGROUND: Sensory nerves regulate cutaneous local inflammation indirectly through induction of pruritus and directly by acting on local immune cells. The underlying mechanisms for how sensory nerves influence cutaneous acquired immune responses remain to be clarified. OBJECTIVE: This study aimed to explore the effect of peripheral nerves on cutaneous immune cells in cutaneous acquired immune responses. METHODS: We analyzed contact hypersensitivity (CHS) responses as a murine model of delayed-type hypersensitivity in absence or presence of resiniferatoxin-induced sensory nerve denervation. We conducted ear thickness measurements, flow cytometric analyses, and mRNA expression analyses in CHS. RESULTS: CHS responses were attenuated in mice that were denervated during the sensitization phase of CHS. By screening neuropeptides, we found that pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA expression was decreased in the dorsal root ganglia after denervation. Administration of PACAP restored attenuated CHS response in resiniferatoxin-treated mice, and pharmacological inhibition of PACAP suppressed CHS. Flow cytometric analysis of skin-draining lymph nodes showed that cutaneous dendritic cell migration and maturation were reduced in both denervated mice and PACAP antagonist-treated mice. The expression of chemokine receptors CCR7 and CXCR4 of dendritic cell s was enhanced by addition of PACAP in vitro. CONCLUSION: These findings indicate that a neuropeptide PACAP promotes the development of CHS responses by inducing cutaneous dendritic cell functions during the sensitization phase.