RESUMO
BACKGROUND: Less than 6% of U.S. medical school applicants are African-American. The lack of diversity among physicians, by race as well as other measures, confers a negative impact on the American healthcare system because underrepresented minority (URM) physicians are more likely to practice in underserved communities and deliver more equitable, culturally competent care. METHODS: MERIT (Medical Education Resources Initiative for Teens) is a nonprofit organization based in Baltimore, Maryland, USA. MERIT prepares URM high school students for health careers by providing a holistic support system for seven consecutive years. The program model, which utilizes weekly Saturday sessions, summer internships, and longitudinal mentoring, is built on four foundational pillars: (1) Ignite the Fire, (2) Illuminate the Path, (3) Create the Toolkit, and (4) Sustain the Desire. RESULTS: Since 2011, MERIT has supported 51 students in the Baltimore City Public School System. For the past two years, 100% (n = 14) of MERIT seniors enrolled in universities, compared to only 20.2% of Baltimore City students overall. While it is too early to know whether MERIT alumni will realize their goals of becoming healthcare professionals, they are currently excelling in universities and over 75% (n = 17) are still planning to pursue graduate degrees in health-related fields. DISCUSSION: After piloting an effective program model, MERIT now has three key priorities moving forward: (1) Creating a sustainable and thriving organization, (2) increasing the number of scholars the program supports in Baltimore, and (3) expanding MERIT to other cities.
Assuntos
Diversidade Cultural , Educação Médica/normas , Grupos Minoritários/educação , Critérios de Admissão Escolar , Apoio Social , Estudantes de Medicina/estatística & dados numéricos , Adolescente , Baltimore , Escolha da Profissão , Educação Médica/economia , Educação Médica/estatística & dados numéricos , Feminino , Humanos , Masculino , Mentores , Grupos Minoritários/estatística & dados numéricosRESUMO
Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase responsible for the degradation of fatty acid amide signaling molecules such as endocannabinoid anandamide (AEA), which has been shown to possess cannabinoid-like analgesic properties. Herein we report the optimization of spirocyclic 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane urea covalent inhibitors of FAAH. Using an iterative design and optimization strategy, lead compounds were identified with a remarkable reduction in molecular weight and favorable CNS drug like properties. 3,4-Dimethylisoxazole and 1-methyltetrazole were identified as superior urea moieties for this inhibitor class. A dual purpose in vivo efficacy and pharmacokinetic screen was designed to be the key decision enabling experiment affording the ability to move quickly from compound synthesis to selection of preclinical candidates. On the basis of the remarkable potency, selectivity, pharmacokinetic properties and in vivo efficacy, PF-04862853 (15p) was advanced as a clinical candidate.
Assuntos
Amidoidrolases/antagonistas & inibidores , Analgésicos/farmacologia , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Dor/tratamento farmacológico , Compostos de Espiro/farmacologia , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Compostos Aza/administração & dosagem , Compostos Aza/química , Compostos Aza/farmacologia , Compostos Aza/uso terapêutico , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Ratos , Compostos de Espiro/administração & dosagem , Compostos de Espiro/química , Compostos de Espiro/uso terapêuticoRESUMO
BACKGROUND: Patient-centred care is an important aspect of quality health care. The learning environment may impact medical students' adoption of patient-centred behaviours. METHODS: All medical students at a single institution received an anonymous, modified version of the Communication, Curriculum, and Culture instrument that measures patient-centredness in the training environment along three domains: role modelling, students' experience, and support for patient-centred behaviours. We compared domain scores and individual items by class year and gender, and qualitatively analyzed responses to two additional items that asked students to describe experiences that demonstrated varying degrees of patient-centredness. RESULTS: Year 1 and 2 students reported greater patient-centredness than year 3 and 4 students in each domain: role modelling (p = 0.03), students' experience (p = <0.001), and support for patient-centred behaviours (p < 0.001). Female students reported less support for patient-centred behaviours compared with male students (p = 0.03). Qualitative analysis revealed that explicit patient-centred curricula and positive role modelling fostered patient-centredness. Themes relating to low degrees of patient-centredness included negative role modelling and students being discouraged from being patient-centred. CONCLUSIONS: Students' perceptions of the patient-centredness of the learning environment decreased as students progressed through medical school, despite increasing exposure to patients. Qualitative analysis found that explicit patient-centred curricula cultivated patient-centred attitudes. Role modelling impacted student perceptions of patient-centredness within the learning environment.
RESUMO
Repeated cycles of binge alcohol drinking and abstinence are key components in the development of dependence. However, the precise behavioral mechanisms underlying binge-like drinking and its consequences on striatal synaptic physiology remain unclear. In the present study, ethanol and water drinking patterns were recorded with high temporal resolution over 6 weeks of binge-like ethanol drinking using the 'drinking in the dark' (DID) protocol. The bottle exchange occurring at the beginning of each session prompted a transient increase in the drinking rate that might facilitate the acquisition of ethanol binge-like drinking. Ethanol drinking mice also displayed a 'front-loading' behavior, in which the highest rate of drinking was recorded during the first 15 min. This rate increased over weeks and paralleled the mild escalation of blood ethanol concentrations. GABAergic and glutamatergic transmission in the dorsal striatum were examined following DID. Spontaneous glutamatergic transmission and the density of dendritic spines were unchanged after ethanol drinking. However, the frequency of GABAA receptor-mediated inhibitory postsynaptic currents was depressed in medium spiny neurons of ethanol drinking mice. A history of ethanol drinking also increased ethanol preference and altered the acute ethanol effects on GABAergic transmission differentially in dorsolateral and dorsomedial striatum. Together, the study shows that the bottle exchange during DID promotes fast, voluntary ethanol drinking and that this intermittent pattern of ethanol drinking causes a depression of GABAergic transmission in the dorsal striatum.
Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Depressores do Sistema Nervoso Central/administração & dosagem , Corpo Estriado/citologia , Etanol/administração & dosagem , Neurônios GABAérgicos/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Análise de Variância , Animais , Comportamento de Escolha/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Corpo Estriado/efeitos dos fármacos , Etanol/metabolismo , Antagonistas GABAérgicos/farmacologia , Ácido Glutâmico/metabolismo , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Neurônios/ultraestrutura , Picrotoxina/farmacologia , Fatores de TempoRESUMO
Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence.