RESUMO
Infertility is one of the important problems in the modern world. Male infertility is characterized by several clinical manifestations, including low sperm production (oligozoospermia), reduced sperm motility (asthenozoospermia), and abnormal sperm morphology (teratozoospermia). WDR4, known as Wuho, controls fertility in Drosophila. However, it is unclear whether WDR4 is associated with clinical manifestations of male fertility in human. Here, we attempted to determine the physiological functions of WDR4 gene. Two cohorts were applied to address this question. The first cohort was the general population from Taiwan Biobank. Genomic profiles from 68,948 individuals and 87 common physiological traits were applied for phenome-wide association studies (PheWAS). The second cohort comprised patients with male infertility from Wan Fang Hospital, Taipei Medical University. In total, 81 male participants were recruited for the genetic association study. Clinical records including gender, age, total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total sperm number, sperm motility, and sperm morphology were collected. In the first cohort, results from PheWAS exhibited no associations between WDR4 genetic variants and 87 common physiological traits. In the second cohort, a total of four tagging single-nucleotide polymorphisms (tSNPs) from WDR4 gene (rs2298666, rs465663, rs2248490, and rs3746939) were selected for genotyping. We found that SNP rs465663 solely associated with asthenozoospermia. Functional annotations through the GTEx portal revealed the correlation between TT or TC genotype and low expression of WDR4. Furthermore, we used mouse embryonic fibroblasts cells from mwdr4 heterozygous (+/â) mice for functional validation by western blotting. Indeed, low expression of WDR4 contributed to ROS-induced DNA fragmentation. In conclusion, our results suggest a critical role of WDR4 gene variant as well as protein expression in asthenozoospermia.
RESUMO
BACKGROUND AND OBJECTIVE: Objective Structured Clinical Examination (OSCE) has been used in many areas of healthcare training over the years. However, it constantly needs to be upgraded and enhanced due to technological and teaching changes. We aim at implementing an integrative OSCE method which employs informatics via the virtual patient within the pharmacy education curriculum at Taipei Medical University to enhance the pharmacy students' competence for using and disseminating information and to also improve critical thinking and clinical reasoning. METHODS: We propose an integrated pharmacy OSCE which uses standardized patients and virtual patients (DxR Clinician). To evaluate this method, we designed four simulated stations and pilot tested with 19 students in the first year of the Master in Clinical Pharmacy program. Three stations were simulated as the inpatient pharmacy: 1) History and lab data collection; 2) Prescription review; 3) Calling physician to discuss potential prescription problems. The fourth was simulated as the patient ward station to provide patient education. A satisfaction questionnaire was administered at the end of the study. RESULTS: Students rated their ability of 2.84, 2.37, 2.37, and 3.63 of 5 for each of the four stations, with the second and third being the most difficult stations. The method obtained an average rating of 4.32 of 5 for relevance, 4.16 for improving clinical ability, 4.32 for practicality in future healthcare work, and 4.28 for willing to have another similar learning experience. CONCLUSION: The integration of Virtual Patient in this study reveals that this assessment method is efficient and practical in many aspects. Most importantly, it provides the test taker with a much closer real-life clinical encounter. Although it is in many ways more difficult, it also provides for better "learning from mistakes" opportunities for test-takers.