RESUMEN
PURPOSE: Student-run clinics (SRCs) are prevalent in medical schools. Although these are popular among students and provide ample learning opportunities, these opportunities are not well-characterized. SRCs are poised to support medical schools' ability to meet accreditation standards and student growth and learning, particularly in areas missing from traditional curricula, such as social determinants of health, interprofessional education and inequities. MATERIALS AND METHODS: At the Crimson Care Collaborative (CCC), a network of 7 Harvard Medical School affiliated student-faculty practices in the greater Boston area, we sought to understand what learning opportunities and challenges exist and if a standardized curriculum could improve learning and result in less duplication of teaching efforts. We conducted semi-structured individual interviews of student and faculty leaders and conducted a thematic analysis of the data. RESULTS: Four key themes emerged: (1) Standardization provides opportunities and challenges, (2) Embrace the unique learning opportunities of each clinic, (3) Educational coaches enhance learning opportunities and increase efficiency, (4) Reflection is a useful tool for improvement & learning. DISCUSSION: Our results demonstrate a benefit to both a standardized curriculum for all SRC sites focused on broad clinical, skill-based training and site-specific teaching focusing on the unique clinical needs of each student-run clinic.
Asunto(s)
Educación de Pregrado en Medicina , Educación Médica , Estudiantes de Medicina , Humanos , Curriculum , Aprendizaje , Red Social , Facultades de Medicina , Educación de Pregrado en Medicina/métodosRESUMEN
Inhibitors of the enzyme xanthine oxidase (XO) with radical scavenging properties hold promise as novel agents against reperfusion injuries after ischemic events. By suppressing the formation of damaging reactive oxygen species (ROS) by XO or scavenging ROS from other sources, these compounds may prevent a buildup of ROS in the aftermath of a heart attack or stroke. To combine these two properties in a single molecule, we synthesized and characterized the non-purine XO inhibitor caffeic acid phenethylester (CAPE) and 19 derivatives using a convenient microwave-assisted Knoevenagel condensation protocol. Varying systematically the number and positions of the hydroxyl groups at the two phenyl rings, we derived structure-activity relationships based on experimentally determined XO inhibition data. Molecular docking suggested that critical enzyme/inhibitor interactions involved π-π interactions between the phenolic inhibitor ring and Tyr914, hydrogen bonds between inhibitor hydroxyl groups and Glu802, and hydrophobic interactions between the CAPE phenyl ring and non-polar residues located at the entrance of the binding site. To effectively scavenge the stable radical DPPH, two hydroxyl groups in 1,2- or 1,4-position at the phenyl ring were required. Among all compounds tested, E-phenyl 3-(3,4-dihydroxyphenyl)acrylate, a CAPE analog without the ethyl tether, showed the most promising properties.
Asunto(s)
Ácidos Cafeicos/farmacología , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/farmacología , Alcohol Feniletílico/análogos & derivados , Xantina Oxidasa/antagonistas & inhibidores , Animales , Compuestos de Bifenilo/antagonistas & inhibidores , Ácidos Cafeicos/síntesis química , Ácidos Cafeicos/química , Bovinos , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Modelos Moleculares , Estructura Molecular , Alcohol Feniletílico/síntesis química , Alcohol Feniletílico/química , Alcohol Feniletílico/farmacología , Picratos/antagonistas & inhibidores , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Xantina Oxidasa/metabolismoRESUMEN
Fluorinated isoflavanones and bifunctionalized isoflavanones were synthesized through a one-step gold(I)-catalyzed annulation reaction. These compounds were evaluated for their in vitro inhibitory activities against aromatase in a fluorescence-based enzymatic assay. Selected compounds were tested for their anti-proliferative effects on human breast cancer cell line MCF-7. Compounds 6-methoxy-3-(pyridin-3-yl)chroman-4-one (3c) and 6-fluoro-3-(pyridin-3-yl)chroman-4-one (3e) were identified as the most potent aromatase inhibitors with IC50 values of 2.5 µM and 0.8 µM. Therefore, these compounds have great potential for the development of pharmaceutical agents against breast cancer.