The First Generation of iPSC Line from a Korean Alzheimer's Disease Patient Carrying APP-V715M Mutation Exhibits a Distinct Mitochondrial Dysfunction

Alzheimer's Disease (AD) is a progressive neurodegenerative disease, which is pathologically defined by the accumulation of amyloid plaques and hyper-phosphorylated tau aggregates in the brain. Mitochondrial dysfunction is also a prominent feature in AD, and the extracellular Aβ and phosphorylated tau result in the impaired mitochondrial dynamics. In this study, we generated an induced pluripotent stem cell (iPSC) line from an AD patient with amyloid precursor protein (APP) mutation (Val715Met; APP-V715M) for the first time. We demonstrated that both extracellular and intracellular levels of Aβ were dramatically increased in the APP-V715M iPSC-derived neurons. Furthermore, the APP-V715M iPSC-derived neurons exhibited high expression levels of phosphorylated tau (AT8), which was also detected in the soma and neurites by immunocytochemistry. We next investigated mitochondrial dynamics in the iPSC-derived neurons using Mito-tracker, which showed a significant decrease of anterograde and retrograde velocity in the APP-V715M iPSC-derived neurons. We also found that as the Aβ and tau pathology accumulates, fusion-related protein Mfn1 was decreased, whereas fission-related protein DRP1 was increased in the APP-V715M iPSC-derived neurons, compared with the control group. Taken together, we established the first iPSC line derived from an AD patient carrying APP-V715M mutation and showed that this iPSC-derived neurons exhibited typical AD pathological features, including a distinct mitochondrial dysfunction.

Development and Validation of a Questionnaire to Evaluate Medical Students' Evidence-Based Medicine Competencies / 한국의학교육

PURPOSE: The purpose of the study was to develop and validate a questionnaire to evaluate medical students' knowledge of, attitude towards and practice of evidence-based medicine (EBM). METHODS: The participants of the study were 418 medical students enrolled in the Kyung Hee University School of Medicine in Seoul, Korea. To examine construct validity of the questionnaire, an exploratory factor analysis (EFA) was performed with 118 participants; a confirmatory factor analysis (CFA) was conducted with the remaining 281 participants. We developed 41 items with a 4-point Likert scale. An EFA was performed to verify the emergence of four dimensions of EBM competencies. The principal axis factoring method and the direct oblimin rotation method were used. To confirm construct validity, a CFA was conducted with the remaining 281 participants. To evaluate model fitness, root mean square error of approximation (RMSEA) and comparative fit index (CFI) were used as fit indices. We conducted ANOVA with Scheffe as discriminant validation, and calculated Cronbach's alpha of 4 subscales as reliability checkup. RESULTS: After refinement procedure, factor analysis of the 32 items in therevised questionnaire yielded 4 factors. The Scree plot supported a 4 factor solution explaining 53.5% of the variance. The 4 components derived were: factor 1_knowledge on EBM (11 items; Cronbach's alpha=0.92); factor 2_ pursuit towards EBM (10; 0.88); factor 3_reluctance on EBM (7; 0.78); factor 4_practice of EBM (4; 0.75). The questionnaire could discriminate competence differences among 1-3 yr students. Satisfactory Cronbach's alpha scores were noted for each factor as well. CONCLUSION: The EBM competency questionnaire was validated.

Development and Validation of a Questionnaire to Evaluate Medical Students' Evidence-Based Medicine Competencies / 한국의학교육

PURPOSE: The purpose of the study was to develop and validate a questionnaire to evaluate medical students' knowledge of, attitude towards and practice of evidence-based medicine (EBM). METHODS: The participants of the study were 418 medical students enrolled in the Kyung Hee University School of Medicine in Seoul, Korea. To examine construct validity of the questionnaire, an exploratory factor analysis (EFA) was performed with 118 participants; a confirmatory factor analysis (CFA) was conducted with the remaining 281 participants. We developed 41 items with a 4-point Likert scale. An EFA was performed to verify the emergence of four dimensions of EBM competencies. The principal axis factoring method and the direct oblimin rotation method were used. To confirm construct validity, a CFA was conducted with the remaining 281 participants. To evaluate model fitness, root mean square error of approximation (RMSEA) and comparative fit index (CFI) were used as fit indices. We conducted ANOVA with Scheffe as discriminant validation, and calculated Cronbach's alpha of 4 subscales as reliability checkup. RESULTS: After refinement procedure, factor analysis of the 32 items in therevised questionnaire yielded 4 factors. The Scree plot supported a 4 factor solution explaining 53.5% of the variance. The 4 components derived were: factor 1_knowledge on EBM (11 items; Cronbach's alpha=0.92); factor 2_ pursuit towards EBM (10; 0.88); factor 3_reluctance on EBM (7; 0.78); factor 4_practice of EBM (4; 0.75). The questionnaire could discriminate competence differences among 1-3 yr students. Satisfactory Cronbach's alpha scores were noted for each factor as well. CONCLUSION: The EBM competency questionnaire was validated.