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Objective The purpose of this study was to determine whether gender influences the likelihood of receiving a lower-third global assessment (GA) on the standardized letter of evaluation (SLOE) submitted as part of the emergency medicine (EM) application process as well as the impact of gender on ultimate match outcomes for applicants receiving a lower-third GA ranking. Our hypothesis was that female applicants with a lower-third GA ranking have a higher risk of not matching. Methods We conducted a retrospective cohort study evaluating U.S.-based allopathic applicants to a single EM residency program in the Mid-Atlantic region during the 2017-2018 and 2018-2019 match cycles. GA SLOE rankings and gender for all applicants were extracted and compared to the National Resident Matching Program (NRMP) data for each applicant on match outcome. Comparative analyses were conducted between gender and SLOE GA rankings in order to obtain an odds ratio (OR) of gender and match outcomes. Results A total of 2,017 SLOEs were reviewed from 798 applicants in the 2018 and 2019 EM match cycles. Overall, 716 (90%) applicants successfully matched in EM, with 82 (10%) applicants failing to match into EM; 277 students had at least one lower-third GA ranking. For all applicants, having at least one lower-third GA ranking was associated with a significant risk of not matching (OR: 0.20; 95% CI: 0.12-0.34). Of the 277 students with at least one lower-third GA ranking, 85 (31%) were female and 192 (69%) were male. Of the female applicants with a lower-third GA ranking, 15 (18%) failed to match in EM, and 39 (20%) of the males failed to match in EM. For applicants with a lower-third GA ranking, female gender alone was not associated with a significantly increased risk of not matching (OR: 1.18; 95% CI: 0.61-2.21). Conclusions Female applicants receive a lower-third GA ranking less frequently than their male counterparts. One or more lower-third rankings on the GA significantly reduced an applicant's chances of matching into an EM program. For those with a lower-third GA ranking, female gender alone does not significantly increase the risk of not matching into EM.
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INTRODUCTION: The blood-brain barrier (BBB) is damaged in tauopathies, including progressive supranuclear palsy (PSP) and Alzheimer's disease (AD), which is thought to contribute to pathogenesis later in the disease course. In AD, BBB dysfunction has been associated with amyloid beta (Aß) pathology, but the role of tau in this process is not well characterized. Since increased BBB permeability is found in tauopathies without Aß pathology, like PSP, we suspected that tau accumulation alone could not only be sufficient, but even more important than Aß for BBB damage. RESULTS: Longitudinal evaluation of brain tissue from the tetracycline-regulatable rTg4510 tau transgenic mouse model showed progressive IgG, T cell and red blood cell infiltration. The Evans blue (EB) dye that is excluded from the brain when the BBB is intact also permeated the brains of rTg4510 mice following peripheral administration, indicative of a bonafide BBB defect, but this was only evident later in life. Thus, despite the marked brain atrophy and inflammation that occurs earlier in this model, BBB integrity is maintained. Interestingly, BBB dysfunction emerged at the same time that perivascular tau emerged around major hippocampal blood vessels. However, when tau expression was suppressed using doxycycline, BBB integrity was preserved, suggesting that the BBB can be stabilized in a tauopathic brain by reducing tau levels. CONCLUSIONS: For the first time, these data demonstrate that tau alone can initiate breakdown of the BBB, but the BBB is remarkably resilient, maintaining its integrity in the face of marked brain atrophy, neuroinflammation and toxic tau accumulation. Moreover, the BBB can recover integrity when tau levels are reduced. Thus, late stage interventions targeting tau may slow the vascular contributions to cognitive impairment and dementia that occur in tauopathies.