6. Perspectives on Researcher Development / 医学教育

In the new Model Core Curriculum, the objective stated is to "understand the importance of medical research for the advancement of medicine and medical care, and support innovation in medicine through involvement in academic and research activities, developing one's scientific thinking skills." Importantly, scientific background and researcher training education, such as laboratory assignments, are clearly positioned in the Model Core Curriculum and are available to all students. The curriculum consists of five components : Developing a research mindset, Understanding established theories, Conducting Research, Publishing Research, and Research Ethics. In addition, laboratory experience and practical training in basic medicine were also added to the description. Further policy and financial support for researchers will be necessary to increase the number of basic medical researchers in the future.

4. Alignment of the 2022 Revision of the Model Core Curriculum for Medical Education in Japan with the‘Standards of the National Medical Practitioners Qualifying Examination' / 医学教育

In this revision, we have attempted to align the Model Core Curriculum for Medical Education competency, "problem-solving ability based on specialized knowledge," with the "Standards of National Examination for Medical Practitioners." The major diseases and syndromes in "Essential Fundamentals" correspond to the basic diseases in Table 1 of the Core Curriculum, symptoms, physical and laboratory examinations, and treatment in "General Medicine" correspond to the items in Table 2 of the Core Curriculum, and the diseases in "Medical Theory" correspond to the diseases in PS-02 of the Core Curriculum. The validity of the diseases in the Core Curriculum was verified using the evaluation results of the examination level classification of the "Research for Revision of National Examination Criteria." Approximately 690 diseases were conclusively selected. This revision mentions the number of diseases in the Core Curriculum for the first time. Hopefully, this will lead to a deeper examination of diseases that should be studied in medical schools in the future.

Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome

Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting in the production of a truncated protein product-progerin. WS is caused by mutations in WRN gene, encoding a loss-of-function RecQ DNA helicase. Here, by gene editing we created isogenic human embryonic stem cells (ESCs) with heterozygous (G608G/+) or homozygous (G608G/G608G) LMNA mutation and biallelic WRN knockout, for modeling HGPS and WS pathogenesis, respectively. While ESCs and endothelial cells (ECs) did not present any features of premature senescence, HGPS- and WS-mesenchymal stem cells (MSCs) showed aging-associated phenotypes with different kinetics. WS-MSCs had early-onset mild premature aging phenotypes while HGPS-MSCs exhibited late-onset acute premature aging characterisitcs. Taken together, our study compares and contrasts the distinct pathologies underpinning the two premature aging disorders, and provides reliable stem-cell based models to identify new therapeutic strategies for pathological and physiological aging.

CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts of familial ALS patients bearing SOD1 and FUS mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived from SOD1 and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.

A joint survey of medical students' self-assessment of competency after clinical clerkship and learning strategies among 9 universities in Japan / 医学教育

<p>Abstract:</p><p></p><p> This study examined the ability of medical students to self-assess basic clinical competence and learning strategies including simulation-based medical education for sixth-year medical students (n=903) at nine universities in Japan. About 40% of 27 procedures to achieve clinical skills in a model curriculum were taught using simulators with or without clinical training in hospitals. We noted that significant numbers of procedures were not practiced through any learning strategies. Higher self-assessment scores were observed among students in 4 schools who had more frequent learning opportunities through simulation-based education than among those with less frequent opportunities in 5 schools.</p>

1. How to use performance appraisal for faculty members / 医学教育

<p>Recently, performance appraisal became necessary for faculty members. According to the questionnaire survey by the Ministry of Education, Culture, Sports, Science and Technology, the number of questionnaire items on education is on the increase, and performance appraisal is widely used for decisions on allowance and employment. In our college, performance appraisal on education, research, and medical care is used to decide on the size of bonuses. Performance appraisal for faculty members has already come into force in many universities. However, services in medical schools include many different aspects, and precise quantification of performance appraisal is very difficult. Now, exact evaluation methods and appropriate utilization are necessary for performance appraisal for faculty members.</p>

4. Investigation of educational achievements of medical department faculties and healthcare providers using a rating form to evaluate medical education performance / 医学教育

<p>Introduction: Compared with faculties in clinical and medical research departments, those in medical departments are not appropriately evaluated in terms of their contributions to or achievements in medical education. Therefore, the aims of this study were to investigate the contributions of medical department faculties to medical education, and to examine differences in contributions according to duty positions and specialties.</p><p>Methods: Five-grade self-assessments in relation to 20 items on a rating form for performance in medical education, which was developed by the Japan Society for Medical Education's Committee for Performance Evaluation, were carried out by medical department faculties in Japanese universities. The data were then totalized and analyzed.</p><p>Results and Discussion: Although faculties belonging to departments other than medical education units did not actively participate in examinations or the education system, they still made contributions to lectures and practice. In addition, faculties with positions with more duties tended to show greater participation in the education system.</p><p></p><p>Conclusion: Based on these findings, we recommend the use of a rating form as a standard scale to evaluate performance in medical education.</p>

CRISPR/Cas9 and TALE: beyond cut and paste

Nuclease-based genome editing has proven to be a powerful and promising tool for disease modeling and gene therapy. Recent advances in CRISPR/Cas and TALE indicate that they could also be used as a targeted regulator of gene expression, as well as being utilized for illuminating specific chromosomal structures or genomic regions.

Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes

With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT(+)) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types.

Establishment of hepatic and neural differentiation platforms of Wilson's disease specific induced pluripotent stem cells

The combination of disease-specific human induced pluripotent stem cells (iPSC) and directed cell differentiation offers an ideal platform for modeling and studying many inherited human diseases. Wilson's disease (WD) is a monogenic disorder of toxic copper accumulation caused by pathologic mutations of the ATP7B gene. WD affects multiple organs with primary manifestations in the liver and central nervous system (CNS). In order to better investigate the cellular pathogenesis of WD and to develop novel therapies against various WD syndromes, we sought to establish a comprehensive platform to differentiate WD patient iPSC into both hepatic and neural lineages. Here we report the generation of patient iPSC bearing a Caucasian population hotspot mutation of ATP7B. Combining with directed cell differentiation strategies, we successfully differentiated WD iPSC into hepatocyte-like cells, neural stem cells and neurons. Gene expression analysis and cDNA sequencing confirmed the expression of the mutant ATP7B gene in all differentiated cells. Hence we established a platform for studying both hepatic and neural abnormalities of WD, which may provide a new tool for tissue-specific disease modeling and drug screening in the future.

Advanced Objective Structured Clinical Examination Trial at Hyogo College of Medicine / 医学教育

The objective structured clinical examination (OSCE) is expected to be used for the Japanese medical license exami-nation (Advanced OSCE). An Advanced OSCE trial was conducted at Hyogo College of Medicine. We examined 96 stu-dents in 11 areas in 1 day with 58 examiners, 5 simulated patients, 70 student volunteers, and 34 clerks. According to thequestionnaire filled out by the students and examiners, this trial was moderately or rather difficult. This trial suggeststhat the Advanced OSCE can be used for the license examination, although some aspects should be improved.

Significance of Instructors' Assessments in Medical Ethics Education / 医学教育

Our medical ethics course emphasizes problem-based-learning (PBL) via group discussion of clinical cases. The significanceof instructors' assessments of PBL in ethics education was studied with different assessment tools during thelast 2 years. In the first year, students' behavior and level of functioning in group discussion were assessed on a group basiswith an 8-item instrument. In the second year, students' level of functioning and flexibility in response to differentopinions in group discussion were assessed on an individual basis with a 2-item instrument. Instsments ofstudent's performance in group discussion were positively but weakly correlated with scores of their reports derivedfrom group discussions. Instructors could consistently assess student performance in PBL in terms of behavior and levelof functioning in group discussions. Furthermore, instructors rated flexibility in response to other opinions as an importantfactor in group dynamics, including interaction between students and instructors. These results suggest that instructors'assessments can be used to help evaluate students in a medical ethics course. Instructors' assessments of studentflexibility during PBL can be particularly useful in this regard.

Students' Evaluation of a Medical-ethics Course / 医学教育

A medical-ethics course was anonymously evaluated by first-year students over 2 years. The course emphasizes problem-based learning through group discussion of clinical cases and lectures on ethical issues. A tutorial system was added to the course in the second year. Students' evaluations indicated that most students had positive attitudes about the course and that both group discussion and lectures were helpful for achieving the general instructional objectives and specific behavioral objectives of the course. A comparison of the 2 years showed that a majority of evaluated items received higher evaluations from second-year students than from first-year students. We attribute the difference to the livelier discussion with the introduction of the tutorial system and the smaller discussion groups. These results indicate that students consider medical-ethics education to be useful.

Stress- and aging-associated modulation of macrophage functions

Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated that immune suppressive states seen in acute cold-stressed mice (8-10 weeks of age) is attributable to FcγRII(bright) suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of glucocorticoids (GC) receptor mRNA was observed in FcγRII(bright) cells from these mice. The increase of FcγRII(bright) cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly increased the proportion of FcγRII(bright) cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRII(bright) suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor. We likewise found that the proportion of FcγRII(bright) suppressor macrophages is increased in aged mice (22-24 months of age). Meanwhile, activated macrophages which function as antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is probably being responsible for immunosenescence.

Stress- and Aging-Associated Modulation of Macrophage Functions

Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated that immune suppressive states seen in acute cold-stressed mice (8-10 weeks of age) is attributable to FcγRIIbright suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of glucocorticoids (GC) receptor mRNA was observed in FcγRIIbright cells from these mice. The increase of FcγRIIbright cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly increased the proportion of FcγRIIbright cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRIIbright suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor. We likewise found that the proportion of FcγRIIbright suppressor macrophages is increased in aged mice (22-24 months of age). Meanwhile, activated macrophages which function as antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is probably being responsible for immunosenescence.