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1.
J Gen Intern Med ; 36(8): 2230-2236, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33575907

RESUMO

INTRODUCTION: In 2020, roughly 25% of applicants who matched into internal medicine (IM) residencies were international medical graduates (IMGs). We examine 12-year trends in distribution of IMGs among IM training programs and explore differences in program perceptions towards IMG recruitment. METHODS: Since 2007, Association of Program Directors in Internal Medicine Annual Surveys have collected data about trainees by medical school graduate type. Sixteen additional questions regarding perceptions of IMGs were included in the 2017 spring survey. RESULTS: The 2017 survey response rate was 63.3% (236/373) and ranged from 61.9 to 70.2% for the 2007-2019 Annual Surveys. During that 12-year period, 55-70% of community programs' and 22-30% of university programs' PGY1 positions were filled by IMGs. In 2017, 45% of community programs' and 15% of university programs' interview and ranking positions were allocated to IMGs. Departmental pressure (university 45.6% [95% CI 43.7-47.5]; community 28.2% [95% CI 26.6-29.7]; p = 0.007), institutional priority (university 64.0% [95% CI 62.1-66.0]; community 41% [95% CI 36.9-44.6]; p = 0.001), and reputational concerns (university 52.8% [95% CI 50.0-55.6]; community 38.5% [95% CI 36.0-40.9]; p = 0.045) were cited as factors influencing recruitment of IMGs. CONCLUSION: Our study was limited to exploring program factors in residency recruitment and did not assess applicant preferences. There is a large, longstanding difference in the recruitment of IMGs to US community-based and university residencies, beginning during the interview and ranking process. Further research in disparities in IMG recruitment is needed, including exploring pressures, preferences, and potential biases associated with the recruitment of IMGs.


Assuntos
Médicos Graduados Estrangeiros , Internato e Residência , Educação de Pós-Graduação em Medicina , Humanos , Medicina Interna/educação , Estudos Longitudinais , Estados Unidos
2.
Biophys J ; 118(12): 2879-2893, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32407684

RESUMO

The natural peptide-major histocompatibility complex (pMHC) ligand for T cell receptors (TCRs) is inactive from solution yet capable of activating T cells at single-molecule levels when membrane-associated. This distinctive feature stems from the mechanism of TCR activation, which is thought to involve steric phosphatase exclusion as well as direct mechanical forces. It is possible to defeat this mechanism and activate T cells with solution ligands by cross-linking pMHC or using multivalent antibodies to TCR. However, these widely used strategies activate TCRs through a nonphysiological mechanism and can produce different activation profiles than natural, monovalent, membrane-associated pMHC. Here, we introduce a strictly monovalent anti-TCRß H57 Fab' ligand that, when coupled to a supported lipid bilayer via DNA complementation, triggers TCRs and activates nuclear translocation of the transcription factor nuclear factor of activated T cells (NFAT) with a similar potency to pMHC in primary murine T cells. Importantly, like monovalent pMHC and unlike bivalent antibodies, monovalent Fab'-DNA triggers TCRs only when physically coupled to the membrane, and only around 100 individual Fab':TCR interactions are necessary to stimulate early T cell activation.


Assuntos
Ativação Linfocitária , Receptores de Antígenos de Linfócitos T , Animais , Ligantes , Complexo Principal de Histocompatibilidade , Camundongos , Linfócitos T
3.
J Gen Intern Med ; 35(5): 1458-1464, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31823308

RESUMO

BACKGROUND: The US internal medicine workforce relies on international and osteopathic medical graduates to fill gaps in residency. Little is known about the distribution and impact of IMGs, DOs, and USMDs concentrating in different types of IM programs. OBJECTIVE: Determining the extent to which USMDs, DOs, and IMGs concentrate in different types of IM programs and comparing Board pass rates by program concentration. DESIGN, SETTINGS, AND PARTICIPANTS: This survey study used data from the AMA's FREIDA database for 476 non-military IM programs in 2017-2018, and 2016-2018 ABIM exam pass rates for 388 accredited programs. MEASUREMENTS: Outcomes were (1) program concentration based on percentage of residents who were USMDs, IMGs, and DOs in 2017-2018 and (2) 2016-2018 program ABIM pass rates as proxies for program quality. Key independent variables were hospital type (community-based, community-based university-affiliated, or university-based) when program concentration was the outcome, and program concentration when Board pass rates were the outcome. RESULTS: Twenty-five percent of programs were "USMD-dominated," 17% were "DO-dominated," 42% were "IMG dominated," and 16% were "integrated." The chances that a university hospital was USMD-dominated were 32 percentage points higher than that for a community hospital (AME = 0.32, baseline probability = 0.11, 95% CI, 0.17-0.46, P < .001). USMD-dominated programs also had significantly higher pass rates by 4.0 percentage points (AME = 0.04, baseline proportion = 0.90, 95% CI, 0.02-0.06, P < .001) than integrated programs, while DO-dominated programs had significantly lower pass rates (AME = - 0.1, baseline proportion = 0.90, 95% CI, - 0.15 to - 0.04, P < .001). CONCLUSION: USMDs and non-USMDs systematically cluster in certain types of residency programs and their training may not be equal, as measured by board pass rates.


Assuntos
Internato e Residência , Educação de Pós-Graduação em Medicina , Humanos , Medicina Interna/educação , Estados Unidos
4.
Proc Natl Acad Sci U S A ; 114(46): 12190-12195, 2017 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-29087297

RESUMO

Antigen discrimination by T cells occurs at the junction between a T cell and an antigen-presenting cell. Juxtacrine binding between numerous adhesion, signaling, and costimulatory molecules defines both the topographical and lateral geometry of this cell-cell interface, within which T cell receptor (TCR) and peptide major histocompatibility complex (pMHC) interact. These physical constraints on receptor and ligand movement have significant potential to modulate their molecular binding properties. Here, we monitor individual ligand:receptor binding and unbinding events in space and time by single-molecule imaging in live primary T cells for a range of different pMHC ligands and surface densities. Direct observations of pMHC:TCR and CD80:CD28 binding events reveal that the in situ affinity of both pMHC and CD80 ligands for their respective receptors is modulated by the steady-state number of agonist pMHC:TCR interactions experienced by the cell. By resolving every single pMHC:TCR interaction it is evident that this cooperativity is accomplished by increasing the kinetic on-rate without altering the off-rate and has a component that is not spatially localized. Furthermore, positive cooperativity is observed under conditions where the T cell activation probability is low. This TCR-mediated feedback is a global effect on the intercellular junction. It is triggered by the first few individual pMHC:TCR binding events and effectively increases the efficiency of TCR scanning for antigen before the T cell is committed to activation.


Assuntos
Antígenos/imunologia , Antígeno B7-1/imunologia , Antígenos CD28/imunologia , Complexo Principal de Histocompatibilidade , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Animais , Antígenos/metabolismo , Antígeno B7-1/genética , Antígenos CD28/genética , Expressão Gênica , Ligantes , Bicamadas Lipídicas/química , Ativação Linfocitária , Camundongos , Cultura Primária de Células , Ligação Proteica , Receptores de Antígenos de Linfócitos T/genética , Transdução de Sinais/imunologia , Análise de Célula Única , Linfócitos T/citologia
5.
Biophys J ; 123(15): E1-E3, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39002539
6.
J Cell Sci ; 127(Pt 24): 5228-39, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25335894

RESUMO

Activation of the macrophage colony stimulating factor-1 receptor (CSF-1R) by CSF-1 stimulates pronounced macropinocytosis and drives proliferation of macrophages. Although the role of macropinocytosis in CSF-1R signaling remains unknown, we show here that, despite internalizing large quantities of plasma membrane, macropinosomes contribute little to the internalization of the CSF-1-CSF-1R complex. Rather, internalization of the CSF-1R in small endocytic vesicles that are sensitive to clathrin disruption, outcompetes macropinosomes for CSF-1R endocytosis. Following internalization, small vesicles carrying the CSF-1R underwent homotypic fusion and then trafficked to newly formed macropinosomes bearing Rab5. As these macropinosomes matured, acquiring Rab7, the CSF-1R was transported into their lumen and degraded. Inhibition of macropinocytosis delayed receptor degradation despite no disruption to CSF-1R endocytosis. These data indicate that CSF-1-stimulated macropinosomes are sites of multivesicular body formation and accelerate CSF-1R degradation. Furthermore, we demonstrate that macropinocytosis and cell growth have a matching dose dependence on CSF-1, suggesting that macropinosomes might be a central mechanism coupling CSF-1R signaling and macrophage growth.


Assuntos
Macrófagos/metabolismo , Pinocitose , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Clatrina/metabolismo , Endocitose/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Endossomos/metabolismo , Humanos , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Mitógenos/farmacologia , Modelos Biológicos , Pinocitose/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo , proteínas de unión al GTP Rab7
7.
Ann Nutr Metab ; 68(2): 94-102, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26667891

RESUMO

BACKGROUND: Deficiency of vitamin B12 (B12) and folate (FA) leads to a wide spectrum of disorders that affect all age groups. However, reports on B12 and FA status in healthy adults in India are limited. Hence, we determined the plasma levels and dietary intake of B12 and FA in the adult population. METHODS: We conducted a community-based cross-sectional study in an urban setup among 630 apparently healthy adults distributed into 3 age groups: 21-40, 41-60 and >60 years. Plasma concentrations of B12 and FA were analyzed by radio immunoassay and dietary intake by 24-hour recall method. RESULTS: The overall prevalence of FA deficiency was 12%, but there was no significant difference in plasma FA concentrations among the groups. While the overall prevalence of B12 deficiency was 35%, it was significantly higher in the 21-40 (44%) and 41-60 age groups (40%) when compared with the >60 group (30%). B12 deficiency was higher in vegetarians (54%) compared to those consuming mixed diet (31%), and the reverse was the case with FA. However, the dietary intakes of FA and B12 were not significantly different among the groups. CONCLUSIONS: These results indicate a higher prevalence of B12 deficiency in apparently healthy adults in an urban setup.


Assuntos
Ácido Fólico/metabolismo , Estado Nutricional , Vitamina B 12/metabolismo , Vitaminas/metabolismo , Adulto , Fatores Etários , Idoso , Antropometria , Estudos Transversais , Dieta , Dieta Vegetariana , Feminino , Deficiência de Ácido Fólico/epidemiologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Prevalência , População Urbana , Deficiência de Vitamina B 12/epidemiologia , Adulto Jovem
8.
Teach Learn Med ; 26(3): 296-303, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25010243

RESUMO

BACKGROUND: To address the country's most pressing healthcare needs, medical students must choose careers in primary care and commit to working with underserved populations. Involvement in student service organizations has been shown to strengthen leadership, empathy, and commitment to underserved health and may lead students to pursue careers in primary care. DESCRIPTION: In 2010, the University of Chicago Pritzker School of Medicine developed a novel 1-year longitudinal service-learning elective called SERVE (Service, Education, Reflection, Volunteerism Elective). Students earned elective credit for completing three course requirements: 10 service sessions, monthly reflections, and a service-learning project. EVALUATION: One third of the class enrolled in the course (33/99), 25 students completed the course, and 20 completed the final evaluation. Both quantitative and qualitative analyses of the final evaluations demonstrated high satisfaction with the course, and appreciation of the opportunity to volunteer, teach, and develop service projects. SERVE students reported a strong commitment to continuing community service after graduation, with 100% planning to continue volunteering and 70% strongly agreeing with the statement that they would practice in an underserved community in the future. This commitment was higher than that expressed by the graduating class of 2012 (34%) and higher compared to a national average (30.9%). CONCLUSIONS: SERVE is a unique 1-year course that reengages 4th-year medical students in service to their communities in a structured educational environment. SERVE students report that the course has increased their involvement in the community, supported their growth into a teaching role, and enhanced continuity within student-run free clinics. Future directions include assessing the impact of SERVE students on the experience of preclinical medical students in student-run free clinics; community response to SERVE projects; and the impact of SERVE on volunteerism, primary care specialty choice, and future practice in underserved communities for class participants during their medical careers.


Assuntos
Serviços de Saúde Comunitária , Currículo , Educação de Graduação em Medicina/organização & administração , Área Carente de Assistência Médica , Saúde Pública/educação , Adulto , Chicago , Avaliação Educacional , Feminino , Humanos , Estudos Longitudinais , Masculino , Avaliação de Programas e Projetos de Saúde
9.
Teach Learn Med ; 26(4): 420-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25318040

RESUMO

BACKGROUND: Although medical school typically lasts 4 years, little attention has been devoted to the structure of the educational experience that takes place during the final year of medical school. SUMMARY: In this perspectives paper, we outline goals for the 4th year of medical school to facilitate a transition from undergraduate to graduate medical education. We provide recommendations for capstone courses, subinternship rotations, and specialty-specific schedules, and we conclude with recommendations to medical students and medical schools for how to use the recommendations contained in this document. CONCLUSIONS: We provide an overview of general competencies and specialty specific recommendations to serve as a foundation for medical schools to develop robust 4th-year curricula and for medical students to plan their 4th-year schedules.


Assuntos
Currículo/tendências , Educação de Graduação em Medicina/tendências , Faculdades de Medicina/organização & administração , Humanos , Inovação Organizacional , Objetivos Organizacionais , Estados Unidos
10.
Mol Biol Cell ; 35(3): ar38, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38170572

RESUMO

The ubiquitination of transmembrane receptors regulates endocytosis, intracellular traffic, and signal transduction. Bone marrow-derived macrophages from myeloid Cbl-/- and Cbl-b-/- double knockout (DKO) mice display sustained proliferation mirroring the myeloproliferative disease that these mice succumb to. Here, we found that the ubiquitin ligases Cbl and Cbl-b have overlapping functions for controlling the endocytosis and intracellular traffic of the CSF-1R. DKO macrophages displayed complete loss of ubiquitination of the CSF-1R whereas partial ubiquitination was observed for either single Cbl-/- or Cbl-b-/- macrophages. Unlike wild type, DKO macrophages were immortal and displayed slower CSF-1R internalization, elevated AKT signaling, and a failure to transport the CSF-1R into the lumen of nascent macropinosomes, leaving its cytoplasmic region available for signaling. CSF-1R degradation depended upon lysosomal vATPase activity in both WT and DKO macrophages, with this degradation confined to macropinosomes in WT but occurring in distributed/tubular lysosomes in DKO cells. RNA-sequencing comparison of Cbl-/-, Cbl-b-/- and DKO macrophages indicated that while the overall macrophage transcriptional program remained intact, DKO macrophages had alterations in gene expression associated with growth factor signaling, cell cycle, inflammation and senescence. Cbl-b-/- had minimal effect on the transcriptional program whereas Cbl-/- led to more alternations but only DKO macrophages demonstrated substantial changes in the transcriptome, suggesting overlapping but unique functions for the two Cbl-family members. Thus, Cbl/Cbl-b-mediated ubiquitination of CSF-1R regulates its endocytic fate, constrains inflammatory gene expression, and regulates signaling for macrophage proliferation.


Assuntos
Receptor de Fator Estimulador de Colônias de Macrófagos , Ubiquitina , Camundongos , Animais , Ubiquitina/metabolismo , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/metabolismo , Fator Estimulador de Colônias de Macrófagos/farmacologia , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Macrófagos/metabolismo
11.
Biophys J ; 105(6): 1533-43, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-24048005

RESUMO

ErbB1 overexpression is strongly linked to carcinogenesis, motivating better understanding of erbB1 dimerization and activation. Recent single-particle-tracking data have provided improved measures of dimer lifetimes and strong evidence that transient receptor coconfinement promotes repeated interactions between erbB1 monomers. Here, spatial stochastic simulations explore the potential impact of these parameters on erbB1 phosphorylation kinetics. This rule-based mathematical model incorporates structural evidence for conformational flux of the erbB1 extracellular domains, as well as asymmetrical orientation of erbB1 cytoplasmic kinase domains during dimerization. The asymmetric dimer model considers the theoretical consequences of restricted transactivation of erbB1 receptors within a dimer, where the N-lobe of one monomer docks with the C-lobe of the second monomer and triggers its catalytic activity. The dynamic nature of the erbB1 phosphorylation state is shown by monitoring activation states of individual monomers as they diffuse, bind, and rebind after ligand addition. The model reveals the complex interplay between interacting liganded and nonliganded species and the influence of their distribution and abundance within features of the membrane landscape.


Assuntos
Receptores ErbB/metabolismo , Modelos Biológicos , Membrana Celular/metabolismo , Receptores ErbB/química , Ligantes , Fosforilação , Estrutura Terciária de Proteína , Análise Espacial , Processos Estocásticos
12.
ACS Biomater Sci Eng ; 8(5): 1860-1866, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35377599

RESUMO

The use of biomaterials for the inclusion and stabilization of biopolymers is an ongoing challenge. Herein, we disclose three-dimensional (3D) coiled-coil peptide crystals with metal ions that include and overgrow His-tagged fluorescent proteins within the crystal. The protein guests are found within two symmetry-related growth sectors of the crystalline host that are associated with faces of the growing crystal that display ligands for metal ions. The fluorescent proteins are included within this "hourglass" region of the crystals at a notably high level, display order within the crystal hosts, and demonstrate sufficiently tight packing to enable energy transfer between a donor-acceptor pair. His-tagged fluorescent proteins display remarkable thermal stability to denaturation over extended periods of time (days) at high temperatures when within the crystals. Ultimately, this strategy may prove useful for the prolonged storage of thermally sensitive biopolymer guests within a 3D crystalline matrix.


Assuntos
Peptídeos , Proteínas , Sequência de Aminoácidos , Peptídeos/química
13.
Nat Commun ; 13(1): 7446, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460640

RESUMO

LAT assembly into a two-dimensional protein condensate is a prominent feature of antigen discrimination by T cells. Here, we use single-molecule imaging techniques to resolve the spatial position and temporal duration of each pMHC:TCR molecular binding event while simultaneously monitoring LAT condensation at the membrane. An individual binding event is sufficient to trigger a LAT condensate, which is self-limiting, and neither its size nor lifetime is correlated with the duration of the originating pMHC:TCR binding event. Only the probability of the LAT condensate forming is related to the pMHC:TCR binding dwell time. LAT condenses abruptly, but after an extended delay from the originating binding event. A LAT mutation that facilitates phosphorylation at the PLC-γ1 recruitment site shortens the delay time to LAT condensation and alters T cell antigen specificity. These results identify a function for the LAT protein condensation phase transition in setting antigen discrimination thresholds in T cells.


Assuntos
Imagem de Difusão por Ressonância Magnética , Receptores de Antígenos de Linfócitos T , Especificidade do Receptor de Antígeno de Linfócitos T , Fosforilação , Contagem de Linfócitos
14.
Food Funct ; 12(10): 4402-4410, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33928954

RESUMO

Diabetic retinopathy (DR) is one of the leading causes of blindness. Carotenoids are plant-derived pigments required for general health and particularly for vision. In this study, we evaluated the dietary intake and blood carotenoid levels of type 2 diabetes (T2D) patients with and without DR. A cross-sectional case-control study was conducted among 151 age-matched controls and 344 T2D patients, of which 194 had DR and 150 had no DR (NDR). After a complete ophthalmic examination, the demographic, anthropometric and clinical profiles were obtained. Carotenoids in the plasma were measured by HPLC and dietary intakes were obtained using a food frequency questionnaire. The mean plasma levels of carotenoids (except γ-carotene) were significantly lower in the DR group compared to the Control and NDR groups. The dietary intakes of zeaxanthin, lycopene, α-carotene and ß-carotene were significantly lower in the NDR group compared to the Control group, and were further lower in the DR group compared to the NDR group. Plasma carotenoid levels were significantly inversely associated with the duration of diabetes, RBS and HbA1c but positively associated with HDL. This study demonstrated decreased plasma levels and lower dietary intakes of carotenoids in DR subjects.


Assuntos
Carotenoides/administração & dosagem , Carotenoides/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Doenças Retinianas/sangue , Doenças Retinianas/complicações , Estudos de Casos e Controles , Estudos Transversais , Ingestão de Alimentos , Feminino , Hemoglobinas Glicadas , Humanos , Licopeno/administração & dosagem , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e Questionários , Zeaxantinas/administração & dosagem , beta Caroteno/administração & dosagem
15.
J Aging Res ; 2020: 8763413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695510

RESUMO

The purpose of this study was to assess the prevalence of frailty and nutritional status among older adults. This population-based cross-sectional study was conducted in 163 subjects aged 60-88 years, from Hyderabad City, South India. Data were obtained on sociodemographic details and anthropometry and biochemical parameters. Dietary intake was assessed by a three-day 24 h dietary recall, and the probability of adequacy (PA) was calculated using the estimated average requirements. Frailty indicators were as follows: handgrip strength was measured by using a Jamar dynamometer, gait speed was measured by a ten-meter length walk test, and low physical activity level, weight loss, and exhaustion were assessed using a questionnaire. Among the study population, 20% of the participants were frail and 80% were nonfrail. The prevalence of frailty is higher in older (30.1%) than the younger (12.2%) age groups, and it is more so in women (32.4%) than in men (10.1%). The lower educational status and income were associated with frailty. The PA of most of the nutrients was low in the frail group. Noticeably, the mean PA (MPA) across the fourteen micronutrients was significantly higher in nonfrail (38%) compared to the frail group (25%). The prevalence of frailty was higher in the lowest tertile of most of the food groups and nutrient intake compared to the highest tertile. The study revealed a 20% prevalence of frailty among urban older adults and provided evidence that inadequate intake of nutrients is independently associated with frailty.

16.
Nutrition ; 63-64: 106-113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30954757

RESUMO

OBJECTIVES: Studies in children and pregnant women consistently showed pandemic proportions of micronutrient deficiencies in the Indian subcontinent. However, vitamin deficiencies in apparently healthy adults are seldom recognized, hence the aim of this exploratory study was to assess their subclinical vitamin status and dietary intakes. METHODS: In all, 270 apparently healthy urban adults 30 to 70 y of age, from Hyderabad city, India participated in this study. Blood levels of vitamins (A, B1, B2, B6, total and active B12, D, and folate) and homocysteine were assessed. Anthropometric parameters were measured; dietary intake was obtained by food frequency questionnaire, and probability of adequacy (PA) was calculated by the estimated average requirement. RESULTS: Among the study population, the overall prevalence of deficiency of vitamin B2 was strikingly high (50%) followed by the vitamins B6 (46%), active B12 (46%), total B12 (37%), folate (32%), D (29%), B1 (11%), and A (6%). Hyperhomocysteinemia (HHcys) was widely prevalent (52%) in the study participants. In case of dietary intakes, PA was lowest for vitamin B12 (4%) and folate (9%) followed by vitamins A (22%), B2 (33%), B6 (30%), and B1 (59%). The mean PA of these vitamins was noticeably low (28%). The unadjusted logistic regression analysis found men and those with a deficiency of folate and total and active B12 to be at higher risk for HHcys. In the adjusted model, the risk for active B12 deficiency almost doubled. CONCLUSION: The study demonstrated a high prevalence of multiple subclinical vitamin deficiencies, dietary inadequacies, and HHcys, which are possible risk factors for disease burden among apparently healthy adults.


Assuntos
Deficiência de Vitaminas/epidemiologia , Dieta/efeitos adversos , População Urbana/estatística & dados numéricos , Adulto , Idoso , Deficiência de Vitaminas/etiologia , Dieta/estatística & dados numéricos , Inquéritos sobre Dietas , Ingestão de Alimentos , Feminino , Homocisteína/sangue , Humanos , Índia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prevalência , Fatores de Risco , Vitaminas/sangue
17.
Sci Signal ; 12(564)2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30647147

RESUMO

T cell receptor (TCR) binding to agonist peptide major histocompatibility complex (pMHC) triggers signaling events that initiate T cell responses. This system is remarkably sensitive, requiring only a few binding events to successfully activate a cellular response. On average, activating pMHC ligands exhibit mean dwell times of at least a few seconds when bound to the TCR. However, a T cell accumulates pMHC-TCR interactions as a stochastic series of discrete, single-molecule binding events whose individual dwell times are broadly distributed. With activation occurring in response to only a handful of such binding events, individual cells are unlikely to experience the average binding time. Here, we mapped the ensemble of pMHC-TCR binding events in space and time while simultaneously monitoring cellular activation. Our findings revealed that T cell activation hinges on rare, long-dwell time binding events that are an order of magnitude longer than the average agonist pMHC-TCR dwell time. Furthermore, we observed that short pMHC-TCR binding events that were spatially correlated and temporally sequential led to cellular activation. These observations indicate that T cell antigen discrimination likely occurs by sensing the tail end of the pMHC-TCR binding dwell time distribution rather than its average properties.


Assuntos
Ativação Linfocitária/imunologia , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Algoritmos , Sequência de Aminoácidos , Animais , Células Cultivadas , Cinética , Ligantes , Complexo Principal de Histocompatibilidade/imunologia , Camundongos Transgênicos , Microscopia de Fluorescência , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/citologia , Linfócitos T/metabolismo
18.
J Grad Med Educ ; 10(2): 149-154, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29686752

RESUMO

BACKGROUND: Role models in medical school may influence students' residency specialty choice. OBJECTIVE: We examined whether medical students who reported clinical exposure to a role model during medical school would have an increased likelihood of selecting the role model's specialty for their residencies. METHODS: We conducted a 5-year prospective, national longitudinal study (2011-2016) of medical students from 24 US allopathic medical schools, starting from the middle of their third year. The primary outcome measure was type of residency specialty choice 4 years after graduation. Main predictors were the clinical specialty of a student's most admired physician and the relative importance of 7 potentially influential factors for specialty choice in the fourth year of medical school. RESULTS: From 919 eligible participants, 564 (61%) responded to the first survey; 474 of the respondents (84%) completed the follow-up survey. We excluded 29 participants who were not in their fourth year by the time of the follow-up survey. Of the follow-up respondents, 427 (96%) had specialty data 4 years after graduation. In our multivariate models, exposure to an admired generalist physician prior to medical school (odds ratio [OR] = 2.21, 95% confidence interval [CI] 1.03-4.73) and during medical school (OR = 2.62, 95% CI 1.69-4.05) had the strongest odds with respect to training in a generalist residency 4 years after graduation. Role model exposure also predicted specialty choice among those training in surgical and radiology, ophthalmology, anesthesiology, and dermatology (ROAD) specialties. CONCLUSIONS: Personal exposure to role models in medical school is an important predictor of residency training in that role model's specialty.


Assuntos
Escolha da Profissão , Educação de Pós-Graduação em Medicina , Internato e Residência , Mentores , Especialização , Estudantes de Medicina/psicologia , Adulto , Comportamento de Escolha , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Estados Unidos
19.
J Grad Med Educ ; 10(6): 657-664, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30619523

RESUMO

BACKGROUND: Geriatric patients account for a growing proportion of dermatology clinic visits. Although their biopsychosocial needs differ from those of younger adults, there are no geriatrics training requirements for dermatology residency programs. OBJECTIVE: This study explored the state of geriatrics education in dermatology programs in 2016. METHODS: This constructivist study employed cross-sectional, mixed-methods analysis with triangulation of semistructured interviews, surveys, and commonly used curricular materials. We used purposive sampling of 5 US academic allopathic dermatology programs of different sizes, geographic locations, and institutional resources. Participants were interviewed about informal curricula, barriers, and suggestions for improving geriatrics education, and they also completed a survey about the geriatrics topics that should be taught. The constant comparative method with grounded theory was used for qualitative analysis. We identified formal geriatrics curricular content by electronically searching and counting relevant key texts. RESULTS: Fourteen of 17 participants (82%) agreed to be interviewed, and 10 of 14 (71%) responded to the survey. Themes of what should be taught included diagnosing and managing skin diseases common in older adults, holistic treatment, cosmetic dermatology, benign skin aging, and the basic science of aging. Topics currently covered that could be expanded included communication, systems-based challenges, ethical issues, safe prescribing, quality improvement, and elder abuse. Cosmetic dermatology was the most commonly taught formal geriatrics curricular topic. CONCLUSIONS: There were discrepancies among topics participants felt were important to teach about geriatric dermatology and curricular coverage of these areas. We identified challenges for expanding geriatrics curricula and potential solutions.


Assuntos
Currículo/normas , Dermatologia/educação , Geriatria/educação , Internato e Residência/normas , Estudos Transversais , Educação de Pós-Graduação em Medicina/métodos , Humanos , Avaliação das Necessidades , Inquéritos e Questionários , Estados Unidos
20.
J Grad Med Educ ; 10(2): 209-213, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29686762

RESUMO

BACKGROUND: Bullying of medical trainees is believed to occur more frequently in medical education than once thought. OBJECTIVE: We conducted a survey to understand internal medicine program director (PD) perspectives and awareness about bullying in their residency programs. METHODS: The 2015 Association of Program Directors in Internal Medicine (APDIM) annual survey was e-mailed to 368 of 396 PDs with APDIM membership, representing 93% of internal medicine residency programs. Questions about bullying were embedded within the survey. Bivariate analyses were performed on PD and program characteristics. RESULTS: Of a total of 368 PD APDIM members, 227 PDs (62%) responded to the survey. Less than one-third of respondents (71 of 227, 31%) reported being aware of bullying in their residency programs during the previous year. There were no significant differences in program or PD characteristics between respondents who reported bullying in their programs and those who did not (gender, tenure as PD, geographic location, or specialty, all P > .05). Those who acknowledged bullying in their program were more likely to agree it was a problem in graduate medical education (P < .0001), and it had a significant negative impact on the learning environment (P < .0001). The majority of reported events entailed verbal disparagements, directed toward interns and women, and involved attending physicians, other residents, and nurses. CONCLUSIONS: This national survey of internal medicine PDs reveals that a minority of PDs acknowledged recent bullying in their training programs, and reportedly saw it as a problem in the learning environment.


Assuntos
Conscientização , Bullying , Educação de Pós-Graduação em Medicina , Medicina Interna/educação , Internato e Residência , Adulto , Feminino , Humanos , Masculino , Inquéritos e Questionários , Estados Unidos
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