Impact of Faculty Mentorship in the Orthopedic Surgery Interest Group at a New Medical School: A Blueprint for Future Initiatives.

OBJECTIVES: Orthopedic surgery is a highly competitive field. The residency applicant pool is expected to grow with the increasing number of new medical schools in the United States, posing significant challenges for applicants. This study explored the impact of an engaged faculty mentor in an orthopedic surgery interest group (OSIG) at a new medical school and the impact it has on students. The study aimed to uncover the most valuable features of an OSIG at a new medical school to create a blueprint for other student-leaders and/or faculty in future initiatives. METHODS: An observational study was conducted via survey responses from active OSIG members at a new medical school in Texas. Questions were mostly in a "before and after" format asking about students' perspectives of the group before and after the addition of an engaged faculty advisor. Descriptive and inferential statistics were used to analyze the data. RESULTS: Twenty of 21 (95.2%) eligible OSIG members participated in the study. The survey results revealed that faculty engagement significantly enhanced the OSIG and its members' medical school experience. Following faculty involvement, average OSIG event attendance more than tripled, there was a statistically significant increase in medical student well-being, and confidence in their ability to be a competitive orthopedic surgery applicant nearly doubled. OSIG participation influenced their career interests significantly more after faculty engagement. A total of 93.3% of participants voted that they felt having an engaged faculty advisor is critical for the OSIG. CONCLUSIONS: Mentorship was identified as the most crucial activity for career development, followed by clinical exposure and research. The study provides valuable insights for new medical schools in establishing and optimizing OSIGs and potentially other interest groups, particularly in competitive specialties.

Enhanced Hyaluronan Signaling and Autophagy Dysfunction by VPS35 D620N.

The motor features of Parkinson's disease (PD) result from the loss of dopaminergic (DA) neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. A PD-causing familial mutation in VPS35 (D620N) has been reported to inhibit autophagy. In order to identify signaling pathways responsible for this autophagy defect, we performed an unbiased screen using RNA sequencing (RNA-Seq) of wild-type or VPS35 D620N-expressing retinoic acid-differentiated SH-SY5Y cells. We report that VPS35 D620N-expressing cells exhibit transcriptome changes indicative of alterations in extracellular matrix (ECM)-receptor interaction as well as PI3K-AKT signaling, a pathway known to regulate autophagy. Hyaluronan (HA) is a major component of brain ECM and signals via the ECM receptors CD44, a top RNA-Seq hit, and HA-mediated motility receptor (HMMR) to the autophagy-regulating PI3K-AKT pathway. We find that high (>950 kDa), but not low (15-40 kDa), molecular weight HA treatment inhibits autophagy. In addition, VPS35 D620N facilitated enhanced HA-AKT signaling. Transcriptomic assessment and validation of protein levels identified the differential expression of CD44 and HMMR isoforms in VPS35 D620N mutant cells. We report that knockdown of HMMR or CD44 results in upregulated autophagy in cells expressing wild-type VPS35. However, only HMMR knockdown resulted in rescue of autophagy dysfunction by VPS35 D620N indicating a potential pathogenic role for this receptor and HA signaling in Parkinson's disease.