17 research outputs found
Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis
Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor beta, with up to 20% being estrogen receptor alpha positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1-differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key rote for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder
Implementation of a Monitored Educational Curriculum and Impact on Pediatrics Resident In-Training Examination Scores
Action video game play and transfer of navigation and spatial cognition skills in adolescents who are blind
Validation of an Evidence-Based Medicine Critically Appraised Topic Presentation Evaluation Tool (EBM C-PET)
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Identifying therapeutic candidates for endometriosis through a transcriptomics-based drug repositioning approach
Existing medical treatments for endometriosis-related pain are often ineffective, underscoring the need for new therapeutic strategies. In this study, we applied a computational drug repurposing pipeline to stratified and unstratified disease signatures based on endometrial gene expression data to identify potential therapeutics from existing drugs, based on expression reversal. Of 3,131 unique genes differentially expressed by at least one of six endometriosis signatures, only 308 (9.8%) were in common; however, 221 out of 299 drugs identified, (73.9%) were shared. We selected fenoprofen, an uncommonly prescribed NSAID that was the top therapeutic candidate for further investigation. When testing fenoprofen in an established rat model of endometriosis, fenoprofen successfully alleviated endometriosis-associated vaginal hyperalgesia, a surrogate marker for endometriosis-related pain. These findings validate fenoprofen as a therapeutic that could be utilized more frequently for endometriosis and suggest the utility of the aforementioned computational drug repurposing approach for endometriosis
Virtual environments for the transfer of navigation skills in the blind: a comparison of directed instruction vs. video game based learning approaches
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73. ETIOLOGY OF UNABLE TO ASSESS ENTRUSTABLE PROFESSIONAL ACTIVITIES IN A NATIONAL STUDY
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Longitudinal Assessment of Resident Performance Using Entrustable Professional Activities
Question What is the progression of performance for entrustable professional activities (EPAs) throughout pediatric residency training and at graduation? Findings This multisite cohort study of 1987 pediatric residents found that developmental growth curves can be established for EPAs. When generated to reflect the results in this study, at least 90% of trainees achieved the level of unsupervised practice at the end of residency for only 8 of the 17 EPAs studied. Meaning This study suggests that gaps exist between observed practice readiness and standards needed to produce physicians able to meet the health needs of the patient populations they serve based on the general pediatrics EPAs.
Importance Entrustable professional activities (EPAs) are an emerging workplace-based, patient-oriented assessment approach with limited empirical evidence. Objective To measure the development of pediatric trainees' clinical skills over time using EPA-based assessment data. Design, Setting, and Participants Prospective cohort study of categorical pediatric residents over 3 academic years (2015-2016, 2016-2017, and 2017-2018) assessed on 17 American Board of Pediatrics EPAs. Residents in training at 23 pediatric residency programs in the Association of Pediatric Program Directors Longitudinal Educational Assessment Research Network were included. Assessment was conducted by clinical competency committee members, who made summative assessment decisions regarding levels of supervision required for each resident and each EPA. Data were collected from May 2016 to November 2018 and analyzed from November to December 2018. Interventions Longitudinal, prospective assessment using EPAs. Main Outcomes and Measures Trajectories of supervision levels by EPA during residency training and how often graduating residents were deemed ready for unsupervised practice in each EPA. Results Across the 5 data collection cycles, 1987 residents from all 3 postgraduate years in 23 residency programs were assigned 25503 supervision level reports for the 17 general pediatrics EPAs. The 4 EPAs that required the most supervision across training were EPA 14 (quality improvement) on the 5-level scale (estimated mean level at graduation, 3.7; 95% CI, 3.6-3.7) and EPAs 8 (transition to adult care; mean, 7.0; 95% CI, 7.0-7.1), 9 (behavioral and mental health; mean, 6.6; 95% CI, 6.5-6.6), and 10 (resuscitate and stabilize; mean, 6.9; 95% CI, 6.8-7.0) on the expanded 5-level scale. At the time of graduation (36 months), the percentage of trainees who were rated at a supervision level corresponding to "unsupervised practice" varied by EPA from 53% to 98%. If performance standards were set to align with 90% of trainees achieving the level of unsupervised practice, this standard would be met for only 8 of the 17 EPAs (although 89% met this standard for EPA 17, performing the common procedures of the general pediatrician). Conclusions and Relevance This study presents initial evidence for empirically derived practice readiness and sets the stage for identifying curricular gaps that contribute to discrepancy between observed practice readiness and standards needed to produce physicians able to meet the health needs of the patient populations they serve. Future work should compare these findings with postgraduation outcomes data as a means of seeking validity evidence.
This cohort study measures the development of pediatric resident clinical skills using assessments based on entrustable professional activities