The Role of Gender-Concordant Mentorship in Women Premedical Students' Perception and Pursuit of Surgical Careers.

OBJECTIVE: Evaluate the impact of a 6-month structured mentorship program between women premedical student mentees paired with women medical students and surgical residents on mentees' interests and perceptions of surgical careers. DESIGN: Prospective qualitative and quantitative study. SETTING: This study took place at the Boston University School of Medicine, a single institution tertiary care hospital. PARTICIPANTS: Self-identified women premedical students at Boston University were eligible for inclusion in this program (n=90). Participants were recruited and grouped with self-identified women medical student (n=52) and resident (n=19) mentors. Participants were provided with a monthly curriculum to guide discussions. Mentees completed pre- and postprogram surveys with 5-point Likert scale questions regarding interest and exposure to surgery, role models and mentorship, and effect of COVID-19 on their career interests. Pre- and postprogram responses were compared using a Wilcoxon rank sum test. RESULTS: Of the 90 mentees, 63 (70%) completed preprogram surveys, and 53 (59%) completed postprogram surveys. Survey respondents indicated statistically significant increased exposure to positive role models (preprogram mean 3.15, postprogram mean 4.06, p=0.0003), increased exposure to women role models (preprogram 2.30, postprogram 3.79, p<0.0001), increased access to dedicated mentors (preprogram 2.11, postprogram 3.75, p<0.0001), and increased availability of support persons to answer their questions and concerns about careers in surgery (preprogram 3.03, postprogram 3.85, p=0.001). There was also a statistically significant increase in the reported effect that exposure to gender-concordant role models in surgery had on participants' decisions to consider a surgical career (preprogram 3.58, postprogram 4.23, p=0.001). CONCLUSION: This 6-month structured mentorship program for undergraduate premedical students increased mentees' exposure to positive women role models and mentors, and increased mentee's interest in pursuing a surgical career. This emphasizes the need for structured gender-concordant mentorship programs early in women's careers to encourage pursuit of surgical careers in an otherwise men-dominated field.

Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?

The novel coronavirus severe acute respiratory syndrome coronavirus 2 causing the Coronavirus disease (COVID-19) pandemic has ravaged the world with over 72 million total cases and over 1.6 million deaths worldwide as of early December 2020. An overwhelming preponderance of cases and deaths is observed within the elderly population, and especially in those with pre-existing conditions and comorbidities. Aging causes numerous biological changes in the immune system, which are linked to age-related illnesses and susceptibility to infectious diseases. Age-related changes influence the host immune response and therefore not only weaken the ability to fight respiratory infections but also to mount effective responses to vaccines. Immunosenescence and inflamm-aging are considered key features of the aging immune system wherein accumulation of senescent immune cells contribute to its decline and simultaneously increased inflammatory phenotypes cause immune dysfunction. Age-related quantitative and qualitative changes in the immune system affect cells and soluble mediators of both the innate and adaptive immune responses within lymphoid and non-lymphoid peripheral tissues. These changes determine not only the susceptibility to infections, but also disease progression and clinical outcomes thereafter. Furthermore, the response to therapeutics and the immune response to vaccines are influenced by age-related changes within the immune system. Therefore, better understanding of the pathophysiology of aging and the immune response will not only help understand age-related diseases but also guide targeted management strategies for deadly infectious diseases like COVID-19.

Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N-cadherin balance in mural cell-endothelial cell-regulated barrier function.

The integrity of the endothelial barrier between circulating blood and tissue is important for blood vessel function and, ultimately, for organ homeostasis. Here, we developed a vessel-on-a-chip with perfused endothelialized channels lined with human bone marrow stromal cells, which adopt a mural cell-like phenotype that recapitulates barrier function of the vasculature. In this model, barrier function is compromised upon exposure to inflammatory factors such as LPS, thrombin, and TNFα, as has been observed in vivo. Interestingly, we observed a rapid physical withdrawal of mural cells from the endothelium that was accompanied by an inhibition of endogenous Rac1 activity and increase in RhoA activity in the mural cells themselves upon inflammation. Using a system to chemically induce activity in exogenously expressed Rac1 or RhoA within minutes of stimulation, we demonstrated RhoA activation induced loss of mural cell coverage on the endothelium and reduced endothelial barrier function, and this effect was abrogated when Rac1 was simultaneously activated. We further showed that N-cadherin expression in mural cells plays a key role in barrier function, as CRISPR-mediated knockout of N-cadherin in the mural cells led to loss of barrier function, and overexpression of N-cadherin in CHO cells promoted barrier function. In summary, this bicellular model demonstrates the continuous and rapid modulation of adhesive interactions between endothelial and mural cells and its impact on vascular barrier function and highlights an in vitro platform to study the biology of perivascular-endothelial interactions.