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1.
Artigo em Inglês | MEDLINE | ID: mdl-38860847

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PAs). Central to the remodeling process is a switch of pulmonary vascular cells to a proliferative, apoptosis-resistant phenotype. Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of urokinase-type and tissue-type plasminogen activators (uPA and tPA), but its role in PAH is unsettled. Here, we report that: (1) PAI-1 is deficient in remodeled small PAs and in early-passage PA smooth muscle and endothelial cells (PASMCs and PAECs) from subjects with PAH compared to controls; (2) PAI-1-/- mice spontaneously develop pulmonary vascular remodeling associated with up-regulation of mTORC1 signaling, pulmonary hypertension (PH), and right ventricle (RV) hypertrophy; and (3) pharmacological inhibition of uPA in human PAH PASMCs suppresses pro-proliferative mTORC1 and SMAD3 signaling, restores PAI-1 levels, reduces proliferation and induces apoptosis in vitro, and prevents the development of SU5416/hypoxia-induced PH and RV hypertrophy in vivo in mice. These data strongly suggest that down-regulation of PAI-1 in small PAs promotes vascular remodeling and PH due to unopposed activation of uPA and consequent up-regulation of mTOR and TGF-b signaling in PASMCs, and call for further studies to determine the potential benefits of targeting the PAI-1/uPA imbalance to attenuate and/or reverse pulmonary vascular remodeling and PH.

2.
JCO Oncol Pract ; 20(5): 717-724, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38285966

RESUMO

PURPOSE: There is a paucity of research on the supply of the hematology and oncology workforce despite projected shortages in the United States Over the past 15 years of the hematology and oncology match (HOM), we hypothesized that there would be more growth in the number of training positions relative to applicants, higher match rates for US allopathic graduates relative to non-US allopathic graduates, and fewer applicants matching at their top fellowship choices. METHODS: This was a national, retrospective cohort study of all applicants in the HOM (2009-2023). Match rates and applicant-to-training position ratios were calculated and compared over time with Pearson tests. RESULTS: Growth in the number of annual training positions (426-708; 66% increase) exceeded growth in the number of interested applicants (706-945; 34% increase; P < .001). Annual applicant-to-training position ratios decreased from 1.7 to 1.3 (r = -0.813; P < .001). Match rates increased over the study period for both US allopathic graduates (79%-88%; r = 0.761; P = .001) and non-US allopathic graduates (45%-63%; r = 0.801; P < .001). During each year, match rates for US allopathic graduates exceeded those for non-US allopathic graduates (P < .001). From 2018 to 2023, US allopathic graduates (83%) had higher match rates than US osteopathic graduates (60%) and international medical graduates (50%; P < .001). The percentage of applicants that matched at one of their top three fellowship choices increased from 53% to 60% (r = 0.480; P = .070). Fewer available annual training positions went unfilled over the study period (3%-0.3%; r = - 0.870; P < .001). CONCLUSION: Match rates have increased in the HOM but remain competitive especially for non-US allopathic graduates. Future investigation is needed to understand disparities in match outcomes by additional applicant and fellowship program characteristics. Ongoing surveillance of HOM outcomes remains critical given the projected shortages in the US hematology and oncology workforce.


Assuntos
Hematologia , Oncologia , Humanos , Estados Unidos/epidemiologia , Hematologia/educação , Hematologia/tendências , Oncologia/educação , Estudos Retrospectivos , Masculino , Feminino
3.
J Natl Med Assoc ; 116(1): 24-32, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142142

RESUMO

BACKGROUND: There are growing number of pathway programs, with an early assurance of admission, that target undergraduate students from groups underrepresented in medicine (URiM) to enable their competitiveness for and matriculation to medical school, including the Penn Access Summer Scholars (PASS) program. The psychological and emotional experiences of students in these programs, however, have not been previously described. METHODS: Students from the summer 2021 cohort of the PASS program were interviewed using a structured set of questions that explored four specific areas: (i) the application process; (ii) the benefits and value of being in the PASS program; (iii) the emotional and psychological challenges and stresses of being in the PASS program; (iv) feelings and emotions about not taking the MCAT or having to interview at multiple schools. The transcribed, de-identified interviews were then subjected to a qualitative analysis. RESULTS: Students in PASS reported that the program was valuable to them in that it reduced the stress of the pre-medical process; relieved worry and anxiety surrounding the MCAT; enabled development of supportive relationships and provided meaningful exposures to the medical profession and biomedical research. Despite this, students reported feelings of imposterism, guilt, and fear of disappointing, along with varying degrees of regret over not taking the MCAT and not interviewing at more than one medical school. CONCLUSIONS: URiM and other marginalized students participating in early assurance admissions programs likely enter medical school with a range of positive and negative emotions as a result of their participation in these programs. These data can be used to inform the development of programing and other initiatives that further support the transition and success of these students in medical school.


Assuntos
Grupos Minoritários , Estudantes de Medicina , Humanos , Grupos Minoritários/educação , Faculdades de Medicina , Estudantes , Emoções
4.
bioRxiv ; 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37790328

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive and potentially a rapidly fatal disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PA) leading to increased pulmonary vascular resistance and right heart failure. Central to the remodeling process is a switch of the smooth muscle cells in small PAs (PASMC) to a proliferative, apoptosis-resistant phenotype. There is reason to suspect that the plasminogen activator system may play an important role in the remodeling program in PAH based on its roles in vascular post-injury restenosis, fibrosis, angiogenesis and tumorigenesis. Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of the plasminogen activators - urokinase-type and tissue-type (uPA and tPA, respectively). Immunohisto- chemical and immunoblot analyses revealed that PAI-1 was deficient in smooth muscle areas of small remodeled PAs and early-passage PASMC from subjects with PAH compared to non-PAH controls. PAI1-/- male and female mice developed spontaneous pulmonary vascular remodeling and pulmonary hypertension (PH) as evidenced by significant increase in PA medial thickness, systolic right ventricular pressure, and right ventricular hypertrophy. Lastly, the uPA inhibitors upamostat (WX-671) and amiloride analog BB2-30F down-regulated mTORC1 and SMAD3, restored PAI-1 levels, reduced proliferation, and induced apoptosis in human PAH PASMC. We examined the effect of inhibition of uPA catalytic activity by BB2-30F on the development of SU5416/Hypoxia (SuHx)-induced PH in mice. Vehicletreated SuHx-exposed mice had up-regulated mTORC1 in small PAs, developed pulmonary vascular remodeling and PH, as evidenced by significant increase of PA MT, sRVP, RV hypertrophy, and a significant decrease in the pulmonary artery acceleration time/pulmonary ejection time (PAAT/PET) ratio compared to age- and sex-matched normoxia controls, whereas BB2-30F-treated group was protected from all these pathological changes. Taken together, our data strongly suggest that PAI-1 down- regulation in PASMC from human PAH lungs promotes PASMC hyper-proliferation, remodeling, and spontaneous PH due to unopposed uPA activation. Further studies are needed to determine the potential benefits of targeting the PAI-1/uPA imbalance to attenuate the progression and/or reverse pulmonary vascular remodeling and PH.

5.
BMC Med Educ ; 23(1): 620, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658394

RESUMO

INTRODUCTION: There have been increasing efforts to integrate the arts and humanities into medical education, particularly during undergraduate medical education (UME). Previous studies, however, have focused on courses and curricular programming without rigorous characterization of the associated paracurricular environment or infrastructure enabling or facilitating these offerings. METHODS: To assess opportunities for students to engage the arts and humanities during their medical education as well as the institutional resources to support those opportunities, we developed the Humanities and Arts Programming Scale (HARPS): an 18-point scale involving eight sub-domains (Infrastructure, Curricular Opportunities, Extracurricular Engagement, Opportunities for Immersion, Faculty Engagement, Staff Support, Student Groups, and Scholarship). This scale was used to evaluate the top-31 ranked United States medical schools as determined by US News and World Report's (USWNR) Medical School Research Rankings using information derived from public-facing, online information. RESULTS: Mean cumulative HARPS score was 11.26, with a median score of 12, a standard deviation of 4.32 and a score range of 3-17. Neither USWNR ranking nor private/public institution status were associated with the cumulative score (p = 0.121, p = 0.739). 52% of institutions surveyed had a humanities-focused center/division with more than 70% of the schools having significant (> 5) faculty engaged in the medical humanities. 65% of schools offered 10 or more paracurricular medical humanities events annually, while 68% of the institutions had more than 5 medical humanities student organizations. While elective, non-credit courses are available, only 3 schools required instruction in the arts and humanities, and comprehensive immersive experiences in the medical humanities were present in only 29% of the schools. CONCLUSIONS: Although there is a significant presence of the medical humanities in UME, there is a need for integration of the arts and humanities into required UME curricula and into immersive pathways for engaging the medical humanities.


Assuntos
Pesquisa Biomédica , Estudantes de Medicina , Humanos , Faculdades de Medicina , Ciências Humanas , Currículo
6.
J Gen Intern Med ; 38(14): 3252-3256, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37407762

RESUMO

BACKGROUND: Arts-and-humanities-based interventions are commonly implemented in medical education to promote well-being and mitigate the risk of burnout. However, mechanisms for achieving these effects remain uncertain within graduate medical education. The emerging field of the positive humanities offers a lens to examine whether and how arts-based interventions support well-being in internal medicine interns. AIM: Through program evaluation of this visual art workshop, we used a positive humanities framework to elucidate potential mechanisms by which arts-based curricula support well-being in internal medicine interns. SETTING: We launched the re-FRAME workshop at the Philadelphia Museum of Art in winter 2020. PARTICIPANTS: Fifty-six PGY-1 trainees from one internal medicine residency program. PROGRAM DESCRIPTION: The 3-h re-FRAME workshop consisted of an introductory session on emotional processing followed by two previously described arts-based interventions. PROGRAM EVALUATION: Participants completed an immediate post-workshop survey (91% response rate) assessing attitudes towards the session. Analysis of open-ended survey data demonstrated 4 categories for supporting well-being among participants: becoming emotionally aware/expressive through art, pausing for reflection, practicing nonjudgmental observation, and normalizing experiences through socialization. DISCUSSION: Our project substantiated proposed mechanisms from the positive humanities for supporting well-being-including reflectiveness, skill acquisition, socialization, and expressiveness-among medical interns.


Assuntos
Educação Médica , Ciências Humanas , Humanos , Ciências Humanas/educação , Currículo , Educação de Pós-Graduação em Medicina , Esgotamento Psicológico
8.
Sci Rep ; 13(1): 6593, 2023 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-37087509

RESUMO

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and often death. Here we report that deficiency of transcription factor GATA6 is a shared pathological feature of PA endothelial (PAEC) and smooth muscle cells (PASMC) in human PAH and experimental PH, which is responsible for maintenance of hyper-proliferative cellular phenotypes, pulmonary vascular remodeling and pulmonary hypertension. We further show that GATA6 acts as a transcription factor and direct positive regulator of anti-oxidant enzymes, and its deficiency in PAH/PH pulmonary vascular cells induces oxidative stress and mitochondrial dysfunction. We demonstrate that GATA6 is regulated by the BMP10/BMP receptors axis and its loss in PAECs and PASMC in PAH supports BMPR deficiency. In addition, we have established that GATA6-deficient PAEC, acting in a paracrine manner, increase proliferation and induce other pathological changes in PASMC, supporting the importance of GATA6 in pulmonary vascular cell communication. Treatment with dimethyl fumarate resolved oxidative stress and BMPR deficiency, reversed hemodynamic changes caused by endothelial Gata6 loss in mice, and inhibited proliferation and induced apoptosis in human PAH PASMC, strongly suggesting that targeting GATA6 deficiency may provide a therapeutic advance for patients with PAH.


Assuntos
Proteínas Morfogenéticas Ósseas , Fator de Transcrição GATA6 , Estresse Oxidativo , Hipertensão Arterial Pulmonar , Animais , Camundongos , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Proliferação de Células , Células Cultivadas , Hipertensão Pulmonar Primária Familiar/patologia , Fator de Transcrição GATA6/genética , Fator de Transcrição GATA6/metabolismo , Miócitos de Músculo Liso/metabolismo , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/patologia , Remodelação Vascular
9.
Am J Hosp Palliat Care ; 40(10): 1124-1131, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36592479

RESUMO

The importance of spirituality in patient care is well recognized and efforts to develop educational opportunities to improve medical students' competency in spirituality and health are ongoing. In this regard, shadowing of healthcare chaplains has emerged as an experiential approach for providing exposure to and instruction in issues of spirituality in the patient experience and in patient care. Recently published data suggest that a 6-8 hour experience of shadowing a trauma chaplain is effective at introducing first-year medical students to healthcare chaplaincy, difficult spiritual conversations with patients and families, and interprofessional collaboration. As a follow-up to these data, this study provides a qualitative analysis of student reflections written immediately after their shadowing experience with the goal of further characterizing the educational impact of trauma chaplain shadowing. Qualitative analysis of 90 anonymous, student reflections indicated that trauma chaplain shadowing was an experience that provided insights about nature of chaplaincy, enabled opportunities to closely observe the relational skills of chaplains, allowed students to bear witness to suffering, fostered growth toward a professional identity, and facilitated recognition of shortcomings in medical education and clinical medicine. These data therefore provide further evidence of the value of chaplain shadowing in not only enhancing students' understanding of various dimensions of spirituality and medicine but also in promoting their development of a strong physician identity.


Assuntos
Educação Médica , Assistência Religiosa , Estudantes de Medicina , Humanos , Clero , Espiritualidade
10.
JAMA ; 329(2): 119-120, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36477254

RESUMO

This Viewpoint argues that reversing or restricting the use of race and ethnicity in academic admission policies could also threaten the diversity of medical schools, both directly by restricting race consciousness in medical school admission practices and indirectly by reducing the overall number of minoritized undergraduate students attending US colleges and universities who could apply to medical school.


Assuntos
Diversidade, Equidade, Inclusão , Educação Médica , Critérios de Admissão Escolar , Faculdades de Medicina , Humanos , Grupos Raciais , Estudantes , Estudantes de Medicina , Etnicidade , Universidades , Diversidade Cultural
11.
Sci Signal ; 15(763): eabn2743, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36473049

RESUMO

Increased proliferation and survival of cells in small pulmonary arteries (PAs) drive pulmonary arterial hypertension (PAH). Because cell growth mediated by the mTOR-containing mTORC1 complex is inhibited by tuberous sclerosis complex 2 (TSC2), we investigated the role of this GTPase-activating protein in PAH pathology. TSC2 abundance was decreased in remodeled small PAs and PA vascular smooth muscle cells (PAVSMCs) from patients with PAH or from rodent pulmonary hypertension (PH) models, as well as PAVSMCs maintained on substrates that reproduced pathology-induced stiffness. Accordingly, mice with smooth muscle-specific reduction in TSC2 developed PH. At the molecular level, decreased TSC2 abundance led to stiffness-induced PAVSMC proliferation, increased abundance of the mechanosensitive transcriptional coactivators YAP/TAZ, and enhanced mTOR kinase activity. Moreover, extracellular matrix (ECM) produced by TSC2-deficient PAVSMCs stimulated the proliferation of nondiseased PA adventitial fibroblasts and PAVSMCs through fibronectin and its receptor, the α5ß1 integrin. Reconstituting TSC2 in PAVSMCs from patients with PAH through overexpression or treatment with the SIRT1 activator SRT2104 decreased YAP/TAZ abundance, mTOR activity, and ECM production, as well as inhibited proliferation and induced apoptosis. In two rodent models of PH, SRT2104 treatment restored TSC2 abundance, attenuated pulmonary vascular remodeling, and ameliorated PH. Thus, TSC2 in PAVSMCs integrates ECM composition and stiffness with pro-proliferative and survival signaling, and restoring TSC2 abundance could be an attractive therapeutic option to treat PH.


Assuntos
Hipertensão Pulmonar , Esclerose Tuberosa , Animais , Camundongos , Proliferação de Células , Matriz Extracelular , Hipertensão Pulmonar/genética , Humanos
12.
J Am Heart Assoc ; 11(24): e028237, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36533616

RESUMO

Background This study elucidates recent trends in application and match rates in the Cardiovascular Disease Fellowship Match. We hypothesized that (1) match rates have increased with time; (2) match rates are highest for US allopathic graduates; and (3) most candidates match at 1 of their top 3 ranked fellowship choices. Methods and Results This was a retrospective cohort study of all applicants in the Cardiovascular Disease Fellowship Match from 2010 to 2021 (n=14 674). Chi-square tests were used to compare trends over time and match rates by applicant archetype (US allopathic graduates and non-US allopathic graduates). The annual number of applicants increased from 1184 to 1575 (33% increase) while training positions increased 718 to 1045 (46% increase) over the study period. The percentage of applicants that matched increased from 61% in 2010 to 66% in 2021 (P=0.090). The average match rate was 70% over the study period. During each year, US allopathic graduates had higher match rates than non-US allopathic graduates (P<0.001), but this disparity narrowed with time (83% versus 41% in 2010 and 83% versus 54% in 2021). Most applicants matched at 1 of their top 3 choices (first, 37%; second, 12%; third, 7%). Applicants matching at 1 of their top 3 choices decreased from 51% in 2010 to 48% in 2021 (P=0.704). Conclusions The Cardiovascular Disease Fellowship Match has remained equally competitive over the past decade. US allopathic graduates have an advantage over non-US allopathic graduates. Most applicants match at 1 of their top 3 ranked fellowship choices.


Assuntos
Doenças Cardiovasculares , Internato e Residência , Humanos , Estados Unidos , Estudos Retrospectivos , Bolsas de Estudo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Educação de Pós-Graduação em Medicina
13.
J Am Board Fam Med ; 35(4): 656-667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35896471

RESUMO

PURPOSE: There is considerable interest in the association between food insecurity (FIS) and various cardiovascular risk factors such as dyslipidemia. Although the association between FIS and dyslipidemia has been studied across various methodologies and populations, there is no comprehensive systematic review and meta-analysis of these data. METHODS: A systematic literature search was conducted. Cross-sectional peer-review studies assessing the association between FIS and dyslipidemia were identified. Data extracted included population characteristics, study sizes, covariates explored, and laboratory assessments of dyslipidemia. Effect sizes were extracted or calculated, then synthesized across studies using a random effect model, and the heterogeneity, publication bias, and subgroup dependence for each meta-analysis were assessed. RESULTS: For adults, meta-analysis demonstrated no significantly elevated odds for FIS individuals to have a concomitant abnormal lipid measurement. Covariate-unadjusted analysis of standardized mean differences showed no significant differences in lipid measurements between food-insecure and food-secure individuals. In contrast to quantitative laboratory results, food-insecure patients were more likely to self-report previous diagnoses of dyslipidemia. CONCLUSIONS: Although current data do not suggest an association between FIS and dyslipidemia, more longitudinal studies and studies targeting women, children, the elderly, and patients with chronic diseases such as diabetes are needed to further address this issue.


Assuntos
Diabetes Mellitus , Dislipidemias , Adulto , Idoso , Criança , Estudos Transversais , Dislipidemias/epidemiologia , Dislipidemias/etiologia , Feminino , Insegurança Alimentar , Humanos , Lipídeos
14.
Front Med (Lausanne) ; 9: 886868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836951

RESUMO

Hyper-proliferation of pulmonary arterial vascular smooth muscle cells (PAVSMC) is an important pathological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Lipogenesis is linked to numerous proliferative diseases, but its role in PAVSMC proliferation in PAH remains to be elucidated. We found that early-passage human PAH PAVSMC had significant up-regulation of key fatty acids synthesis enzymes ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN), and increased unstimulated proliferation compared to control human PAVSMC. Treatment with an allosteric ACC inhibitor 5-tetradecyloxy-2-furoic acid (TOFA) significantly decreased proliferation and induced apoptosis of human PAH PAVSMC. Intracellular lipid content and proliferation of PAH PAVSMC were not reduced by incubation in lipid-depleted media but suppressed by a non-metabolizable analog of glucose 2-Deoxy-D-glucose (2-DG) and partially restored by addition of pyruvate. Protein kinase Akt was upregulated in human PAH PAVSMC in a sirtuin 7 (SIRT7)- and c-Jun N-terminal kinase (JNK)-dependent manner. Pharmacological inhibition of Akt down-regulated ACLY and ACC, significantly reduced intracellular lipid content, inhibited proliferation and induced apoptosis of human PAH PAVSMC. Taken together, these data demonstrate that human PAH PAVSMC have up-regulated lipogenesis, which is supported in an Akt- and glycolysis-dependent manner and is required for increased proliferation and survival. Our data suggest that there is a mechanistic link between glycolysis, lipogenesis, and the proliferation of human PAH PAVSMC and call for further studies to determine the potential attractiveness of a SIRT7/JNK-Akt-lipogenesis axis as a target pathway to inhibit PAVSMC hyper-proliferation in PAH.

15.
Circ Res ; 130(5): 760-778, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35124974

RESUMO

RATIONALE: The MSTs (mammalian Ste20-like kinases) 1/2 are members of the HIPPO pathway that act as growth suppressors in adult proliferative diseases. Pulmonary arterial hypertension (PAH) manifests by increased proliferation and survival of pulmonary vascular cells in small PAs, pulmonary vascular remodeling, and the rise of pulmonary arterial pressure. The role of MST1/2 in PAH is currently unknown. OBJECTIVE: To investigate the roles and mechanisms of the action of MST1 and MST2 in PAH. METHODS AND RESULTS: Using early-passage pulmonary vascular cells from PAH and nondiseased lungs and mice with smooth muscle-specific tamoxifen-inducible Mst1/2 knockdown, we found that, in contrast to canonical antiproliferative/proapoptotic roles, MST1/2 act as proproliferative/prosurvival molecules in human PAH pulmonary arterial vascular smooth muscle cells and pulmonary arterial adventitial fibroblasts and support established pulmonary vascular remodeling and pulmonary hypertension in mice with SU5416/hypoxia-induced pulmonary hypertension. By using unbiased proteomic analysis, gain- and loss-of function approaches, and pharmacological inhibition of MST1/2 kinase activity by XMU-MP-1, we next evaluated mechanisms of regulation and function of MST1/2 in PAH pulmonary vascular cells. We found that, in PAH pulmonary arterial adventitial fibroblasts, the proproliferative function of MST1/2 is caused by IL-6-dependent MST1/2 overexpression, which induces PSMC6-dependent downregulation of forkhead homeobox type O 3 and hyperproliferation. In PAH pulmonary arterial vascular smooth muscle cells, MST1/2 acted via forming a disease-specific interaction with BUB3 and supported ECM (extracellular matrix)- and USP10-dependent BUB3 accumulation, upregulation of Akt-mTORC1, cell proliferation, and survival. Supporting our in vitro observations, smooth muscle-specific Mst1/2 knockdown halted upregulation of Akt-mTORC1 in small muscular PAs of mice with SU5416/hypoxia-induced pulmonary hypertension. CONCLUSIONS: Together, this study describes a novel proproliferative/prosurvival role of MST1/2 in PAH pulmonary vasculature, provides a novel mechanistic link from MST1/2 via BUB3 and forkhead homeobox type O to the abnormal proliferation and survival of pulmonary arterial vascular smooth muscle cells and pulmonary arterial adventitial fibroblasts, remodeling and pulmonary hypertension, and suggests new target pathways for therapeutic intervention.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Hipertensão Pulmonar , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Hipertensão Arterial Pulmonar , Animais , Proliferação de Células , Células Cultivadas , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Mamíferos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Miócitos de Músculo Liso/metabolismo , Proteômica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Hipertensão Arterial Pulmonar/genética , Artéria Pulmonar/metabolismo , Remodelação Vascular/fisiologia
16.
J Gen Intern Med ; 37(4): 944-946, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34993859

RESUMO

Effective engagement on issues of diversity, equity, and inclusion (DEI) requires activities that promote deep introspection and group conversations that serve to complement and build upon formal DEI presentations. The arts and humanities by their nature allow for intentional and sustained reflection and have the potential to be transformative of thinking. We therefore propose that the next phase of institutional pro-equity/anti-racism efforts includes arts- and humanities-based initiatives to facilitate reflection and that serve to complement and build upon formal DEI didactic presentations, implicit bias workshops, and anti-racism training.


Assuntos
Ciências Humanas , Racismo , Comunicação , Humanos
17.
Mol Ther ; 30(4): 1536-1552, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35031433

RESUMO

Extravasation of circulating tumor cells (CTCs) is critical for metastasis and is initiated by adhesive interactions between glycoligands on CTCs and E-selectin on endothelia. Here, we show that the clinically approved proteasome inhibitor bortezomib (BZM; Velcade) counteracts the cytokine-dependent induction of E-selectin in the lung mediated by the primary tumor, thereby impairing endothelial adhesion and thus spontaneous lung metastasis in vivo. However, the efficacy of BZM crucially depends on the tumor cells' E-selectin ligands, which determine distinct adhesion patterns. The canonical ligands sialyl-Lewis A (sLeA) and sLeX mediate particularly high-affinity E-selectin binding so that the incomplete E-selectin-reducing effect of BZM is not sufficient to disrupt adhesion or metastasis. In contrast, tumor cells lacking sLeA/X nevertheless bind E-selectin, but with low affinity, so that adhesion and lung metastasis are significantly diminished. Such low-affinity E-selectin ligands apparently consist of sialylated MGAT5 products on CD44. BZM no longer has anti-metastatic activity after CD44 knockdown in sLeA/X-negative tumor cells or E-selectin knockout in mice. sLeA/X can be determined by immunohistochemistry in cancer samples, which might aid patient stratification. These data suggest that BZM might act as a drug for inhibiting extravasation and thus distant metastasis formation in malignancies expressing low-affinity E-selectin ligands.


Assuntos
Selectina E , Neoplasias Pulmonares , Animais , Bortezomib/farmacologia , Antígeno CA-19-9/farmacologia , Adesão Celular , Selectina E/genética , Selectina E/metabolismo , Humanos , Ligantes , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Metástase Neoplásica , Oligossacarídeos , Antígeno Sialil Lewis X
18.
J Surg Educ ; 79(2): 389-396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34674979

RESUMO

OBJECTIVE: Visual aids such as drawings have been reported to improve patient comprehension, retention, and adherence. We sought to determine the feasibility of teaching live drawing for clinical communication to medical students. DESIGN: We designed a course to teach basic drawing skills and visual communication of health information to senior medical students. Data was gathered from both an intervention and control group via written pre- and post-course surveys. The intervention group also completed a survey six months after the course. SETTING: The course was offered as an elective at the University of Pennsylvania Perelman School of Medicine during February 2020. PARTICIPANTS: The intervention group consisted of 17 enrolled students, while 17 students not taking the course served as a control group. Third year, fourth year, and research year medical students were invited to enroll in the course. RESULTS: The intervention group had significantly greater comfort with visual communication for patient care and increased objective drawing and visual communication scores compared to the control group. Visual abilities not targeted by the curriculum did not change between the intervention and control groups. At 6-months follow-up, course participants reported persistently elevated comfort in visual communication, as well as utilization of visual communication skills in their clinical practice. CONCLUSIONS: These data provide initial evidence of the efficacy of an elective course aimed at developing the skill and confidence to draw for visual communication in medicine as well as support for continued efforts to further develop and disseminate this type of curriculum.


Assuntos
Educação de Graduação em Medicina , Medicina , Estudantes de Medicina , Competência Clínica , Comunicação , Currículo , Humanos
19.
Endocrinol Diabetes Metab ; 5(1): e00315, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34726354

RESUMO

AIMS: Food insecurity (FIS) is a major public health issue with possible implications for type 2 diabetes mellitus (T2DM) risk. We conducted a systematic review and meta-analysis to explore the association between FIS and T2DM. METHODS: We performed a systematic search in PubMed, Embase, Scopus, and Web of Science. All cross-sectional, peer-reviewed studies investigating the link between FIS and T2DM were included. Population characteristics, study sizes, covariates, T2DM diagnoses, and diabetes-related clinical measures such as fasting blood glucose (FBG) and HbA1c were extracted from each study. Outcomes were compared between food insecure and food secure individuals. Effect sizes were combined across studies using the random effect model. RESULTS: Forty-nine peer-reviewed studies investigating the link between FIS and T2DM were identified (n = 258,250). Results of meta-analyses showed no association between FIS and clinically determined T2DM either through FBG or HbA1c: OR = 1.22 [95%CI: 0.96, 1.55], Q(df = 5) = 12.5, I2  = 60% and OR = 1.21 [95%CI: 0.95, 1.54], Q(df = 5) = 14; I2  = 71% respectively. Standardized mean difference (SMD) meta-analyses yielded no association between FIS and FBG or HbA1c: g = 0.06 [95%CI: -0.06, 0.17], Q(df = 5) = 15.8, I2  = 68%; g = 0.11 [95% CI: -0.02, 0.25], Q(df = 7) = 26.8, I2  = 74% respectively. For children, no association was found between FIS and HbA1c: g = 0.06 [95%CI: 0.00, 0.17], Q(df = 2) = 5.7, I2  = 65%. CONCLUSIONS: Despite multiple proposed mechanisms linking FIS to T2DM, integration of the available literature suggests FIS is not associated with clinically determined T2DM or increases in FBG or HbA1c among adult patients.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Adulto , Criança , Estudos Transversais , Insegurança Alimentar , Humanos , Hiperglicemia/etiologia
20.
Palliat Med Rep ; 2(1): 280-286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34927154

RESUMO

Background: The provision of spiritual care is a key component of high-quality patient-centered care, particularly in the intensive care unit (ICU). However, the integration of spiritual care into the care of patients in the ICU is variable, especially at the end of life, which may be due in part to poor or incomplete provider knowledge of the work of chaplains. Objective: To characterize the care and services provided by chaplains to patients in an ICU at the end of life and/or their families. Design: A retrospective chart review was performed to identify all patients admitted over a three-month period to an ICU who had visits with a chaplain and an ICU course that ended in death, discharge to a palliative care facility or discharge to hospice. Subjects/setting: Twenty-five chaplains at a U.S. medical center. Measurements: Qualitative analysis was performed using directed content analysis on the notes written by the chaplains. Results: Qualitative analyses of the chaplain notes revealed four broad themes regarding the activities of chaplains in the ICU with respect to patients and families. These were that chaplains provide comfort to patients and family facing the end of life, provide prayers with a variety of purposes, assist in supporting family members through complex medical decision making, and provide connections to appropriate resources. Conclusions: Chaplains contribute to the care of patients in the ICU through a wide range of activities that demonstrate the unique intermediary and collaborative role chaplains can play within the health care team at the end of life in the ICU.

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