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1.
2.
Nature ; 576(7785): 143-148, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31776512

RESUMEN

Bile acids are abundant in the mammalian gut, where they undergo bacteria-mediated transformation to generate a large pool of bioactive molecules. Although bile acids are known to affect host metabolism, cancer progression and innate immunity, it is unknown whether they affect adaptive immune cells such as T helper cells that express IL-17a (TH17 cells) or regulatory T cells (Treg cells). Here we screen a library of bile acid metabolites and identify two distinct derivatives of lithocholic acid (LCA), 3-oxoLCA and isoalloLCA, as T cell regulators in mice. 3-OxoLCA inhibited the differentiation of TH17 cells by directly binding to the key transcription factor retinoid-related orphan receptor-γt (RORγt) and isoalloLCA increased the differentiation of Treg cells through the production of mitochondrial reactive oxygen species (mitoROS), which led to increased expression of FOXP3. The isoalloLCA-mediated enhancement of Treg cell differentiation required an intronic Foxp3 enhancer, the conserved noncoding sequence (CNS) 3; this represents a mode of action distinct from that of previously identified metabolites that increase Treg cell differentiation, which require CNS1. The administration of 3-oxoLCA and isoalloLCA to mice reduced TH17 cell differentiation and increased Treg cell differentiation, respectively, in the intestinal lamina propria. Our data suggest mechanisms through which bile acid metabolites control host immune responses, by directly modulating the balance of TH17 and Treg cells.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Ácido Litocólico/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacos , Animales , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Ácido Litocólico/química , Ratones , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células Th17/citología , Células Th17/inmunología , Células Th17/metabolismo
3.
Int J Geriatr Psychiatry ; 38(3): e5895, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36840547

RESUMEN

BACKGROUND: Older adults have a high risk of suicide following self-harm. Contemporary information on self-harm in this population is needed to inform care provision. OBJECTIVES: To examine subgroup differences in the incidence of self-harm, sociodemographic and clinical characteristics, preceding life problems and outcomes in individuals aged 60 years and over presenting to hospital following self-harm. METHOD: Data on Emergency Department (ED) presentations for self-harm from 2003 to 2016 from three centres in the Multicentre Study of Self-Harm in England were analysed. Changes in self-harm rates were examined using Poisson regression. Univariable logistic regression was used to investigate factors associated with 12-month self-harm repetition. RESULTS: There were 3850 presentations for self-harm by 2684 individuals aged 60 years and over. Self-harm rates increased over time for 60-74-year-old men (Incident Rate Ratio = 1.04, 95% Confidence Interval 1.02-1.06, p < 0.0001). Problems most frequently reported to have preceded self-harm were mental health (40.5%) and physical health (38.3%) concerns. Problems with alcohol, finances, employment and relationship with partner were found more frequently in 60-74-year-olds compared with those aged over 74 years. Physical health problems were common with increasing age, as were problems with alcohol for men. One in ten (10.8%) individuals presented to hospital with self-harm within 12 months of their index presentation. CONCLUSIONS: Self-harm-related ED attendances in older men have increased, particularly for men aged 60-74 years. Prevention and clinical management should involve a comprehensive psychosocial assessment to target common precipitants for the wide range of problems preceding self-harm and may include support with physical and mental wellbeing and advice on safer alcohol use.


Asunto(s)
Conducta Autodestructiva , Suicidio , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Conducta Autodestructiva/epidemiología , Suicidio/psicología , Consumo de Bebidas Alcohólicas , Empleo , Inglaterra/epidemiología , Etanol , Servicio de Urgencia en Hospital
4.
Prev Sci ; 24(5): 985-998, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37358751

RESUMEN

The goal of the current study is to examine the degree to which measures of quality of implementation and student engagement moderate pretest-posttest changes in mediating variables that are targeted by DARE "keepin' it REAL." DARE officers (10 elementary school, five middle school) taught DARE "keepin' it REAL lessons to 1,017 elementary students (480 boys and 534 girls) and 435 middle school students (217 boys and 215 girls). We examined teachers' and students' ratings of elementary and middle schools in response to DARE officers' delivery of the program. HLM analyses revealed that students' engagement was a significant and meaningful predictor of changes in targeted mediators. Teachers' ratings of student responsiveness added little in terms of understanding these outcomes with main effects observed only for students' ability to respond to bulling and students' estimates of peer drug use. Teachers' ratings of the quality of officer implementation, on the other hand, did add to understanding students' outcomes. Effects were seen for three (peer norms about drug use, decision-making (DM) skills, intentions to avoid drug use) out of six outcome variables and suggest a stronger positive effect for elementary versus middle school students. At least for these three outcomes, understanding quality of implementation added to our ability to interpret results. Specifically, in addition to students' engagement, quality of implementation (which varied by grade) contributed to achieving positive changes in students' outcomes.


Asunto(s)
Personal Docente , Trastornos Relacionados con Sustancias , Masculino , Femenino , Humanos , Niño , Curriculum , Instituciones Académicas , Estudiantes , Intención , Maestros
5.
J Am Chem Soc ; 144(42): 19326-19336, 2022 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-36223664

RESUMEN

Prenyltransfer is an early-stage carbon-hydrogen bond (C-H) functionalization prevalent in the biosynthesis of a diverse array of biologically active bacterial, fungal, plant, and metazoan diketopiperazine (DKP) alkaloids. Toward the development of a unified strategy for biocatalytic construction of prenylated DKP indole alkaloids, we sought to identify and characterize a substrate-permissive C2 reverse prenyltransferase (PT). As the first tailoring event within the biosynthesis of cytotoxic notoamide metabolites, PT NotF catalyzes C2 reverse prenyltransfer of brevianamide F. Solving a crystal structure of NotF (in complex with native substrate and prenyl donor mimic dimethylallyl S-thiolodiphosphate (DMSPP)) revealed a large, solvent-exposed active site, intimating NotF may possess a significantly broad substrate scope. To assess the substrate selectivity of NotF, we synthesized a panel of 30 sterically and electronically differentiated tryptophanyl DKPs, the majority of which were selectively prenylated by NotF in synthetically useful conversions (2 to >99%). Quantitative representation of this substrate library and development of a descriptive statistical model provided insight into the molecular origins of NotF's substrate promiscuity. This approach enabled the identification of key substrate descriptors (electrophilicity, size, and flexibility) that govern the rate of NotF-catalyzed prenyltransfer, and the development of an "induced fit docking (IFD)-guided" engineering strategy for improved turnover of our largest substrates. We further demonstrated the utility of NotF in tandem with oxidative cyclization using flavin monooxygenase, BvnB. This one-pot, in vitro biocatalytic cascade enabled the first chemoenzymatic synthesis of the marine fungal natural product, (-)-eurotiumin A, in three steps and 60% overall yield.


Asunto(s)
Productos Biológicos , Dimetilaliltranstransferasa , Animales , Dimetilaliltranstransferasa/química , Dicetopiperazinas , Ciencia de los Datos , Alcaloides Indólicos/química , Ingeniería de Proteínas , Flavinas/metabolismo , Oxigenasas de Función Mixta/metabolismo , Solventes , Carbono , Especificidad por Sustrato
6.
BMC Med Educ ; 21(1): 481, 2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-34496820

RESUMEN

BACKGROUND: The COVID-19 pandemic fundamentally changed every aspect of healthcare delivery and training. Few studies have reported on the impact of these changes on the experiences, skill development, and career expectations of medical students. METHOD: Using 59 responses to a short reflection essay prompt, 3rd year medical students in Philadelphia described how the COVID-19 pandemic affected their education in mid-2020. Using conventional content analysis, six main themes were identified across 14 codes. RESULTS: Students reported concerns regarding their decreased clinical skill training and specialty exposure on their career development due to the loss of in-person experience during their family medicine clerkship. A small number felt very let down and exploited by the continued high cost of tuition while missing clinical interactions. However, many students also expressed professional pride and derived meaning from limited patient and mentorship opportunities. Many students developed a new sense of purpose and a call to become stronger public health and patient advocates. CONCLUSIONS: The medical field will need to adapt to support medical students adversely impacted by the COVID-19 pandemic, from an educational and mental health standpoint. However, there are encouraging signs that this may also galvanize many students to engage in leadership roles in their communities, to become more empathetic and thoughtful physicians, and to redesign healthcare in the future to better meet the needs of their most vulnerable patients.


Asunto(s)
COVID-19 , Educación de Pregrado en Medicina , Estudiantes de Medicina , Humanos , Pandemias , SARS-CoV-2
7.
J Am Chem Soc ; 142(5): 2244-2252, 2020 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-31904957

RESUMEN

The paraherquamides are potent anthelmintic natural products with complex heptacyclic scaffolds. One key feature of these molecules is the spiro-oxindole moiety that lends a strained three-dimensional architecture to these structures. The flavin monooxygenase PhqK was found to catalyze spirocycle formation through two parallel pathways in the biosynthesis of paraherquamides A and G. Two new paraherquamides (K and L) were isolated from a ΔphqK strain of Penicillium simplicissimum, and subsequent enzymatic reactions with these compounds generated two additional metabolites, paraherquamides M and N. Crystal structures of PhqK in complex with various substrates provided a foundation for mechanistic analyses and computational studies. While it is evident that PhqK can react with various substrates, reaction kinetics and molecular dynamics simulations indicated that the dioxepin-containing paraherquamide L is the favored substrate. Through this effort, we have elucidated a key step in the biosynthesis of the paraherquamides and provided a rationale for the selective spirocyclization of these powerful anthelmintic agents.

8.
Chembiochem ; 21(17): 2449-2454, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32246875

RESUMEN

The fungal indole alkaloids are a unique class of complex molecules that have a characteristic bicyclo[2.2.2]diazaoctane ring and frequently contain a spiro-oxindole moiety. While various strains produce these compounds, an intriguing case involves the formation of individual antipodes by two unique species of fungi in the generation of the potent anticancer agents (+)- and (-)-notoamide A. NotI and NotI' have been characterized as flavin-dependent monooxygenases that catalyze epoxidation and semi-pinacol rearrangement to form the spiro-oxindole center within these molecules. This work elucidates a key step in the biosynthesis of the notoamides and provides an evolutionary hypothesis regarding a common ancestor for production of enantiopure notoamides.


Asunto(s)
Flavinas/metabolismo , Alcaloides Indólicos/metabolismo , Oxigenasas de Función Mixta/metabolismo , Oxindoles/metabolismo , Compuestos de Espiro/metabolismo , Flavinas/química , Alcaloides Indólicos/química , Oxigenasas de Función Mixta/química , Conformación Molecular , Oxindoles/química , Compuestos de Espiro/química , Estereoisomerismo
9.
JMIR Form Res ; 8: e58322, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39018090

RESUMEN

BACKGROUND: Extremism continues to raise concerns about conflict and violent attacks that can lead to deaths, injuries, trauma, and stress. Adolescents are especially vulnerable to radicalization by extremists. Given its location in a region that often experiences extremism, Bahrain developed 4 peaceful coexistence lessons and 4 antiextremism lessons to be implemented as part of their Drug Abuse Resistance Education (D.A.R.E.) program. OBJECTIVE: The aim of this study is to report the results of the preparation phase of the multiphase optimization strategy (MOST) to develop a peaceful coexistence program and an antiextremism program implemented by D.A.R.E. officers in Bahrain. METHODS: We developed conceptual models for the peaceful coexistence and antiextremism programs, indicating which mediators each lesson should target, the proximal outcomes that should be shaped by these mediators, and the distal and ultimate outcomes that the intervention should change. We recruited 20 middle schools to pilot test our research protocol, survey measures, and the existing intervention lessons. A total of 854 seventh and ninth grade students completed a pretest survey, 4 peaceful coexistence intervention lessons, and an immediate posttest survey; and a total of 495 ninth grade students completed the pretest survey, 4 antiextremism lessons, and an immediate posttest survey. A series of 3-level models, nesting students within classrooms within schools, tested mean differences from pretest to posttest. RESULTS: Pilot test results indicated that most measures had adequate reliability and provided promising evidence that the existing lessons could change some of the targeted mediators and proximal outcomes. Specifically, students who completed the peaceful coexistence lessons reported significant changes in 5 targeted mediating variables (eg, injunctive norms about intolerance, P<.001) and 3 proximal outcomes [eg, social skills empathy (P=.008); tolerance beliefs (P=.041)]. Students who completed the antiextremism lessons reported significant changes in 3 targeted mediators [eg, self-efficacy to use resistance skills themselves (P<.001)], and 1 proximal outcome (ie, social skills empathy, P<.001). CONCLUSIONS: An effective antiextremism program has the potential to protect youth from radicalization and increase peaceful coexistence. We used the preparation phase of MOST to (1) develop a conceptual model, (2) identify the 4 lessons in each program as the components we will evaluate in the optimization phase of MOST, (3) pilot test the existing lessons, our newly developed measures, and research protocol, and (4) determine that our optimization objective will be all effective components. We will use these results to revise the existing lessons and conduct optimization trials to evaluate the efficacy of the individual lessons.

10.
J Eukaryot Microbiol ; 60(4): 342-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23594128

RESUMEN

Cochliopodium pentatrifurcatum n. sp. (ATCC(©) 30935(TM) ) is described based on light microscopic morphology, fine structure, and molecular genetic evidence. Cochliopodium pentatrifurcatum n. sp. (length ~ 25 µm) is characterized by surface microscales (0.3 µm tall) containing a circular porous base (~ 0.6 µm diam.) with a thin peripheral rim. Five radially arranged feet, emanating from the base, support a short central column terminating apically as a funnel-shaped collar (~ 0.5 µm diam.) composed of five radial, trifurcate rays extending from the center toward a thin peripheral rim. The central spine is 0.5-0.6 µm long. The comparative morphologies and combined molecular genetic evidence, SSU-rDNA and COI, indicate that the new species falls in a clade sufficiently different from other species to suggest that it is a valid new species.


Asunto(s)
Amoeba/genética , Amoeba/clasificación , Amoeba/ultraestructura , Amebozoos/clasificación , Amebozoos/genética , Amebozoos/ultraestructura , Animales , ADN Ribosómico/genética , Microscopía Electrónica de Transmisión , Filogenia , Reacción en Cadena de la Polimerasa
11.
Fam Med ; 55(2): 89-94, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36689454

RESUMEN

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic highlighted the shortcomings of our health care delivery system for vulnerable populations and created a need to rethink health disparity education in medical training. We examined how the early COVID-19 pandemic impacted third-year medical students' attitudes, perceptions, and sense of responsibility regarding health care delivery for vulnerable populations. METHODS: Third-year family medicine clerkship students at a large, private medical school in Philadelphia, Pennsylvania responded to a reflection assignment prompt asking how the COVID-19 pandemic impacted their thoughts about health care delivery for vulnerable populations in mid-2020 (N=59). Using conventional content analysis, we identified three main themes across 24 codes. RESULTS: Students recognized homeless individuals and Black, indigenous, and persons of color (BIPOC) as vulnerable populations impacted by the pandemic. Students reported causes of vulnerability that focused heavily on social determinants of health, increased risk for contracting COVID-19 infections, and difficulty adhering to COVID-19 prevention guidelines. Notable action-oriented approaches to addressing these disparities included health care reform and community health intervention. CONCLUSIONS: Our findings describe an educational approach to care for vulnerable populations based on awareness, attitudes, and social action. Medical education must continue to teach students how to identify ways to mitigate disparities in order to achieve health equity.


Asunto(s)
COVID-19 , Estudiantes de Medicina , Humanos , Pandemias , Poblaciones Vulnerables , Actitud del Personal de Salud
12.
PLoS One ; 18(4): e0284457, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37115774

RESUMEN

In response to a need to implement an evidence-based prevention program, D.A.R.E. America adopted keepin' it REAL. The program was previously developed and tested in middle school settings. As part of its adoption, an elementary version of the program was developed. This study tests the effectiveness of keepin' it REAL when delivered to fifth graders. The intervention was delivered to two cohorts of students, the first in the 2019-2020 school year, the second in the 2020-2021 school year. Pretest surveys were completed by 6,122 students. The COVID-19 pandemic interfered with posttest and follow-up data collection. At immediate posttest, 2,049 students (33.5%) completed analyzable posttest surveys. One year after the pretest, 1,486 (24.3%) students completed usable follow-up surveys. We used algorithmically generated cases (virtual controls) that use treatment cases' pretest psychosocial scores to assess program effectiveness. When compared to virtual control cases, the program had identifiable improvements in both a key psychosocial measure and in terms of deterring the onset of 30-day alcohol use, drunkenness, and vaping. Outcomes suggest that the delivery of elementary school keepin' it REAL by D.A.R.E. officers is having a positive effect in terms of deterring the onset of alcohol use and vaping.


Asunto(s)
COVID-19 , Trastornos Relacionados con Sustancias , Humanos , Pandemias/prevención & control , COVID-19/epidemiología , COVID-19/prevención & control , Curriculum , Evaluación de Programas y Proyectos de Salud , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/prevención & control , Trastornos Relacionados con Sustancias/psicología , Servicios de Salud Escolar
13.
J Affect Disord ; 335: 67-74, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37149057

RESUMEN

BACKGROUND: Increases in poor mental health and suicide have been identified among university students in the UK. However, little is known about self-harm in this group. AIMS: To describe and identify care needs of university aged-students who self-harm via comparisons with an age-equivalent non-student group who self-harm. METHODS: Observational cohort data from The Multicentre Study of Self-harm in England were used to investigate students aged 18 to 24 years who presented to emergency departments for self-harm, 2003 to 2016. Data were collected via clinician reports and medical records from five hospitals in three English regions. Characteristics, rates, repetition, and mortality outcomes were investigated. RESULTS: The student sample included 3491 individuals (983, 28.2 % men; 2507, 71.8 % women; 1 unknown) compared to 7807 (3342, 42.8 % men; 4465, 57.2 % women) non-students. Self-harm increased over time in students (IRR 1.08, 95%CI 1.06-1.10, p < 0.01) but not in non-students (IRR 1.01, 95%CI 1.00-1.02, p = 0.15). There were differences in monthly distribution of self-harm with more presentations by students in October, November, and February. Characteristics were broadly similar, but students reported more problems with studying and mental health. Repetition (HR 0.78, 95%CI 0.71-0.86, p < 0.01) and mortality (HR 0.51, 95%CI 0.33-0.80, p < 0.01) were lower in students than non-students. CONCLUSIONS: Self-harm in students may be directly related the student experience, such as academic pressure, relocation, and the transition to independent living. Wellbeing initiatives targeting these factors, alongside mental health awareness training for academic and non-academic staff may help to support students at risk.


Asunto(s)
Conducta Autodestructiva , Suicidio , Femenino , Humanos , Masculino , Inglaterra/epidemiología , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/psicología , Estudiantes/psicología , Suicidio/psicología , Universidades , Adolescente , Adulto Joven
14.
Sci Transl Med ; 15(702): eadd1175, 2023 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-37379368

RESUMEN

Notch signaling promotes T cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like Notch ligand DLL4. To assess whether Notch's effects are evolutionarily conserved and to identify the mechanisms of Notch signaling inhibition, we studied antibody-mediated DLL4 blockade in a nonhuman primate (NHP) model similar to human allo-HCT. Short-term DLL4 blockade improved posttransplant survival with durable protection from gastrointestinal GVHD in particular. Unlike prior immunosuppressive strategies tested in the NHP GVHD model, anti-DLL4 interfered with a T cell transcriptional program associated with intestinal infiltration. In cross-species investigations, Notch inhibition decreased surface abundance of the gut-homing integrin α4ß7 in conventional T cells while preserving α4ß7 in regulatory T cells, with findings suggesting increased ß1 competition for α4 binding in conventional T cells. Secondary lymphoid organ fibroblastic reticular cells emerged as the critical cellular source of Delta-like Notch ligands for Notch-mediated up-regulation of α4ß7 integrin in T cells after allo-HCT. Together, DLL4-Notch blockade decreased effector T cell infiltration into the gut, with increased regulatory to conventional T cell ratios early after allo-HCT. Our results identify a conserved, biologically unique, and targetable role of DLL4-Notch signaling in intestinal GVHD.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Ratones , Humanos , Animales , Trasplante Homólogo , Receptores Notch/metabolismo , Transducción de Señal , Enfermedad Injerto contra Huésped/metabolismo , Primates
15.
J Contin Educ Health Prof ; 42(2): 144-147, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35604663

RESUMEN

INTRODUCTION: Formal training in practice transformation, leadership, clinical education, and/or the time to gain these skills are limited postresidency for primary care physicians and physician assistants. Therefore, we created a novel Primary Care Champions fellowship program that provides practical experiences in education, practice transformation, and leadership for primary care physicians and physician assistants in community practice. The purpose of this study is to describe the fellowship and evaluate feedback from the first cohort. METHODS: In the Jefferson Primary Care Champions Fellowship, fellows are provided protected time from clinical obligations to engage in didactic, informal, and experiential learning. They meet monthly and participate in student precepting training and receive mentorship from senior clinician administrators, scientists, educators, and population health researchers to hone skills for leadership and practice transformation endeavors. Cohort one began in September 2018. All fellows were family physicians from community-based practices in Philadelphia, PA (N = 4) and selected in collaboration with their practice leadership. Mixed-methods postprogram evaluations included Organizational Readiness Assessment and qualitative feedback. RESULTS: Fellows denoted individual time, small-group mentorship, protected project time, and open-robust discussions about primary care most useful. Three fellows reported that they plan to continue their practice-improvement projects postfellowship and one published her initial project findings and reflections. DISCUSSION: Overall feedback from the first cohort was positive. Fellows greatly appreciated structured time to explore primary care interests, contemplated long-term career prospects, and considered leadership opportunities. Cohort two is currently underway and cohort three is in recruitment.


Asunto(s)
Asistentes Médicos , Médicos , Becas , Femenino , Humanos , Liderazgo , Mentores
16.
PRiMER ; 6: 512327, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36632489

RESUMEN

Background and Objectives: Medical schools must integrate educational curricula that teach how to apply quality improvement principles to improve care for vulnerable populations. In this report, we describe the development, implementation, and evaluation of a combined quality improvement (QI) and health disparities curriculum for third-year family medicine clerkship students. Methods: After conducting an educational needs assessment, we developed a health disparities curriculum focused on QI principles for the family medicine clerkship. From November 2019 through August 2021, third-year medical students (N=395) completed the curriculum. The curriculum was delivered in an asynchronous online format, followed by a small group collaboration project to design and present a QI intervention through process mapping. Students also completed an individual reflection assignment that focused on care for vulnerable populations. Pre- and post assessment questions were administered on Qualtrics, after review by the clerkship director, research faculty and staff, and content experts for content and item validity. We analyzed quantitative data using SPSS version 27 software and used paired t tests for pre/post comparisons. Results: In total, 392 students completed the preassessment survey, 395 students completed the postassessment surveys, and 341 had matching study identifiers. Pre-to-post assessment survey evaluations showed statistically significant changes for nine out of nine QI knowledge questions (P<.001), knowledge regarding a community health needs assessment (P<.001), and knowledge about caring for vulnerable populations (homeless, veterans, immigrants/refugees; P<.001). Conclusions: Preliminary evaluation of a combined QI and health disparities curriculum shows improvement in students' self-reported knowledge of use of a community health needs assessment, QI principles, and care for vulnerable populations.

17.
J Clin Invest ; 132(13)2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35579963

RESUMEN

In lymphopenic environments, secondary lymphoid organs regulate the size of B and T cell compartments by supporting the homeostatic proliferation of mature lymphocytes. The molecular mechanisms underlying these responses and their functional consequences remain incompletely understood. To evaluate homeostasis of the mature B cell pool during lymphopenia, we turned to an adoptive transfer model of purified follicular B cells into Rag2-/- mouse recipients. Highly purified follicular B cells transdifferentiated into marginal zone-like B cells when transferred into Rag2-/- lymphopenic hosts but not into wild-type hosts. In lymphopenic spleens, transferred B cells gradually lost their follicular phenotype and acquired characteristics of marginal zone B cells, as judged by cell surface phenotype, expression of integrins and chemokine receptors, positioning close to the marginal sinus, and an ability to rapidly generate functional plasma cells. Initiation of follicular to marginal zone B cell transdifferentiation preceded proliferation. Furthermore, the transdifferentiation process was dependent on Notch2 receptors in B cells and expression of Delta-like 1 Notch ligands by splenic Ccl19-Cre+ fibroblastic stromal cells. Gene expression analysis showed rapid induction of Notch-regulated transcripts followed by upregulated Myc expression and acquisition of broad transcriptional features of marginal zone B cells. Thus, naive mature B cells are endowed with plastic transdifferentiation potential in response to increased stromal Notch ligand availability during lymphopenia.


Asunto(s)
Linfopenia , Animales , Linfocitos B/metabolismo , Proliferación Celular , Homeostasis , Linfopenia/genética , Ratones , Ratones Endogámicos C57BL
18.
Fam Med ; 53(10): 882-885, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34780656

RESUMEN

BACKGROUND AND OBJECTIVES: There is emphasis on systems-based practice competencies and quality improvement (QI) training in postgraduate medical education. However, we lack effective approaches to provide experiences in these areas during undergraduate medical education. To address this, we developed a novel approach to providing didactic and experiential learning experiences in QI during a third-year family medicine clerkship. METHODS: We implemented and evaluated a QI curriculum combining self-directed learning with real-world experience to increase knowledge and confidence in the plan-do-study-act (PDSA) process for family medicine clerkship students. Students collaborated and presented their change ideas in a "Shark Tank" format for practice leaders at the end of their rotation. We used pre- and postcurriculum surveys to assess knowledge of and comfort with completing QI projects. RESULTS: Three hundred eighty-nine students completed precurriculum surveys and 242 completed postcurriculum surveys. Pre- and postlearning evaluations revealed an increase in agreement or strong agreement with self-reported understanding of specific QI topic areas of 50%. Almost all (91.3%) reported feeling confident or reasonably confident in their ability to create change in health care after exposure to the curriculum, compared with 66.3% in the precurriculum survey. One-third of students (34%) reported intent to complete the Institute for Healthcare Improvement Open School curriculum in QI. CONCLUSIONS: Self-directed learning about QI, combined with practice observation, small-group discussion and presentation in a Shark Tank format was effective and engaging for learners. Students had limited preexisting knowledge of QI principles, suggesting a need for preclinical exposure to this topic. The family medicine clerkship provides an ideal environment for teaching QI.


Asunto(s)
Prácticas Clínicas , Educación de Pregrado en Medicina , Curriculum , Medicina Familiar y Comunitaria , Humanos , Mejoramiento de la Calidad , Estudiantes
19.
J Natl Med Assoc ; 113(3): 297-300, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33342549

RESUMEN

INTRODUCTION: Clinical inertia remains a persistent problem in the treatment of diabetes in clinical care. Primary care provider behavior is thought to be a significant contributor to diabetes clinical inertia. This study used the lens of Critical Race Theory to examine whether provider's diabetes management activities differ by patient race and frame implications for future research. METHODS: Chart abstractors retrospectively reviewed a random sample of charts from primary care patients with persistently-elevated HbA1c to assess providers' diabetes management activities in the subsequent year. Provider activities aligned with the American Diabetes Association's standards of medical care and included HbA1c test ordering, documentation of patient medication adherence, counseling on lifestyle modification, lifestyle modification referral, endocrinologist participation in care, and medication titration. Differences in provider actions by patient race (Black, white, or other) were examined using chi-square tests. RESULTS: A total of 188 patient charts were reviewed. For all provider actions, there were statistically-significant differences by patient race. Black patients were least likely to be counseled on dietary changes (72.0%) or physical activity (57.7%) by their primary care provider, but most likely to be referred to an outside specialist for this counseling (46.2%). Black patients were also least likely to have medication adjustments made (72%). DISCUSSION: Study findings showed an association between provider diabetes management behaviors and patient race, Future studies showed explore providers' racial beliefs, attitudes and clinical decision-making, and patients' experiences with historical exclusion from medical care and racism in healthcare encounters In addition, more research is needed to explore the role of structural racism in clinical inertia.


Asunto(s)
Hemoglobina Glucada , Disparidades en Atención de Salud , Atención Primaria de Salud , Racismo , Negro o Afroamericano , Humanos , Estudios Retrospectivos , Población Blanca
20.
J Affect Disord ; 282: 991-995, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33601744

RESUMEN

BACKGROUND: The COVID-19 pandemic and public health measures necessary to address it may have major effects on mental health, including on self-harm. We have used well-established monitoring systems in two hospitals in England to investigate trends in self-harm presentations to hospitals during the early period of the pandemic. METHOD: Data collected in Oxford and Derby on patients aged 18 years and over who received a psychosocial assessment after presenting to the emergency departments following self-harm were used to compare trends during the three-month period following lockdown in the UK (23rd March 2020) to the period preceding lockdown and the equivalent period in 2019. RESULTS: During the 12 weeks following introduction of lockdown restrictions there was a large reduction in the number of self-harm presentations to hospitals by individuals aged 18 years and over compared to the pre-lockdown weeks in 2020 (mean weekly reduction of 13.5 (95% CI 5.6 - 21.4) and the equivalent period in 2019 (mean weekly reduction of 18.0 (95% CI 13.9 - 22.1). The reduction was greater in females than males, occurred in all age groups, with a larger reduction in presentations following self-poisoning than self-injury. CONCLUSIONS: A substantial decline in hospital presentations for self-harm occurred during the three months following the introduction of lockdown restrictions. Reasons could include a reduction in self-harm at the community level and individuals avoiding presenting to hospital following self-harm. Longer-term monitoring of self-harm behaviour during the pandemic is essential, together with efforts to encourage help-seeking and the modification of care provision.


Asunto(s)
COVID-19 , Conducta Autodestructiva , Adolescente , Adulto , Control de Enfermedades Transmisibles , Servicio de Urgencia en Hospital , Inglaterra/epidemiología , Femenino , Hospitales , Humanos , Masculino , Pandemias , SARS-CoV-2 , Conducta Autodestructiva/epidemiología
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