Both HIV-1 virions and infected cells use their surface regulators of complement activation (RCA) to resist antibody-dependent complement-mediated lysis (ADCML). Blockage of the biological function of RCA members, particularly CD59 (a key RCA member that controls formation of the membrane attack complex at the terminal stage of the complement activation cascades via all three activation pathways), has rendered both HIV-1 virions and infected cells sensitive to ADCML mediated by anti-Env antibodies (Abs) or sera/plasma from patients at different stages of viral infection. In the current study, we used the well-characterized anti-HIV-1 neutralizing Abs (nAbs), including 2G12, 2F5, and 4E10, and non-nAbs, including 2.2C, A32, N5-i5, and N12-i15, to investigate whether the enhancement of ADCML by blockage of CD59 function is mediated by nAbs, non-nAbs, or both. We found that all nAbs and two non-nAbs (N5-i5 and A32) strongly reacted to three HIV-1 laboratory strains (R5, X4, and R5/ X4), six primary isolates, and provirus-activated ACH-2 cells examined. In contrast, two non-nAbs, 2.2C and N12-i15, reacted weakly and did not react to these targets, respectively. After blockage of CD59 function, the reactive Abs, regardless of their neutralizing activities, significantly enhanced specific ADCML of HIV-1 virions (both laboratory strains and primary isolates) and provirus-activated latently infected cells. The ADMCL efficacy positively correlated with the enzyme-linked immunosorbent assay-reactive intensity of those Abs with their targets. Thus, blockage of RCA function represents a novel approach to restore activities of both nAbs and non-nAbs in triggering ADCML of HIV-1 virions and provirus-activated latently infected cells. IMPORTANCEThere is a renewed interest in the potential role of non-nAbs in the control of HIV-1 infection. Our data, for the first time, demonstrated that blockage of the biological function of RCA members rendered both HIV-1 virions and infected cells sensitive to ADCML mediated by not only nAbs but also non-nAbs. Our results are significant in developing novel immune-based approaches to restore the functions of nAbs and non-nAbs in the circulation of HIV-1-infected individuals to specifically target and clear HIV-1 virions and infected cells. Our data also provide new insights into the mechanisms by which HIV-1 virions and infected cells escape Ab-mediated immunity and could aid in the design and/or development of therapeutic HIV-1 vaccines. In addition, a combination of antiretroviral therapy with RCA blockage, provirus activators, and therapeutic vaccines may represent a novel approach to eliminate HIV-1 reservoirs, i.e., the infected cells harboring replication-competent proviruses and residual viremia.
Introduction: The National Residency Matching Program (NRMP) allows post-interview contact between residency applicants and residency programs. Thank-you communications represent one of the most common forms, but data on their value to applicants and program directors (PD) are limited. The objective of this study was to assess the effect of thank-you communications on applicant- and residency-program rank lists. Methods: Two anonymous, voluntary surveys were sent after the 2018 NRMP Match, one to applicants who were offered an interview at a single academic site in the 2017-2018 Match cycle, and one to EM PDs nationwide. The surveys were designed in conjunction with a nationally-recognized survey center and piloted and revised based on feedback from residents and faculty. Results: Of 196 residency applicants, 97 (49.5%) responded to the survey. Of these, 73/95 (76.8%) reported sending thank-you communications. Twenty-two of 73 (30%) stated that they sent thank-you communications to improve their spot on a program’s rank list; and 16 of 73 (21.9%) reported that they changed their rank list based upon the responses they received to their thank-you communications. Of 163 PDs, 99 (60.7%) responded to the survey. Of those PDs surveyed, 22.6% reported that an applicant could be moved up their program’s rank list and 10.8% reported that an applicant could move down a program’s rank list based on their thank-you communications (or lack thereof). Conclusion: The majority of applicants to EM are sending thank-you communications. A significant minority of applicants and PDs changed their rank list due to post-interview thank-you communications.
Introduction: Emergency medicine (EM) residents take the American Board of Emergency Medicine (ABEM) In-Training Examination (ITE) every year. This examination is based on the ABEM Model of Clinical Practice (Model). The purpose of this study was to determine whether a relationship exists between the number of patient encounters a resident sees within a specific clinical domain and their ITE performance on questions that are related to that domain. Methods: Chief complaint data for each patient encounter was taken from the electronic health record for EM residents graduating in three consecutive years between 2016-2021. We excluded patient encounters without an assigned resident or a listed chief complaint. Chief complaints were then categorized into one of 20 domains based on the 2016 Model. We calculated correlations between the total number of encounters seen by a resident for all clinical years and their ITE performance for the corresponding clinical domain from their third year of training. Results: Available for analysis were a total of 232,625 patient encounters and 69 eligible residents who treated the patients. We found no statistically significant correlations following Bonferroni correction for multiple analyses. Conclusion: There was no correlation between the number of patient encounters a resident has within a clinical domain and their ITE performance on questions corresponding to that domain. This suggests the need for separate but parallel educational missions to achieve success in both the clinical environment and standardized testing.
Each year, residency programs face the daunting task of screening hundreds of applications and choosing which students to invite for an interview and how to rank them. The average number of applications received by an emergency medicine (EM) program in 2019, for example, was 909; 1 however, a programs have needed to only rank between 5.9 and 6.8 applicants per position to fill. 2 To help narrow down the field of candidates into a final list, programs may resort to easily accessible means of screening, such as medical school attended, standardized test scores, medical school grades, letters of evaluation, and impressions during interviews. It
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