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Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
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COVID-19 , SARS-CoV-2 , Femenino , Adulto , Humanos , Persona de Mediana Edad , Masculino , COVID-19/complicaciones , Estudios Prospectivos , Síndrome Post Agudo de COVID-19 , Estudios de Cohortes , Progresión de la Enfermedad , FatigaRESUMEN
BACKGROUND: The determinants of coronavirus disease 2019 (COVID-19) disease severity and extrapulmonary complications (EPCs) are poorly understood. We characterized relationships between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia and disease severity, clinical deterioration, and specific EPCs. METHODS: We used quantitative and digital polymerase chain reaction (qPCR and dPCR) to quantify SARS-CoV-2 RNA from plasma in 191 patients presenting to the emergency department with COVID-19. We recorded patient symptoms, laboratory markers, and clinical outcomes, with a focus on oxygen requirements over time. We collected longitudinal plasma samples from a subset of patients. We characterized the role of RNAemia in predicting clinical severity and EPCs using elastic net regression. RESULTS: Of SARS-CoV-2-positive patients, 23.0% (44 of 191) had viral RNA detected in plasma by dPCR, compared with 1.4% (2 of 147) by qPCR. Most patients with serial measurements had undetectable RNAemia within 10 days of symptom onset, reached maximum clinical severity within 16 days, and symptom resolution within 33 days. Initially RNAemic patients were more likely to manifest severe disease (odds ratio, 6.72 [95% confidence interval, 2.45-19.79]), worsening of disease severity (2.43 [1.07-5.38]), and EPCs (2.81 [1.26-6.36]). RNA loads were correlated with maximum severity (râ =â 0.47 [95% confidence interval, .20-.67]). CONCLUSIONS: dPCR is more sensitive than qPCR for the detection of SARS-CoV-2 RNAemia, which is a robust predictor of eventual COVID-19 severity and oxygen requirements, as well as EPCs. Because many COVID-19 therapies are initiated on the basis of oxygen requirements, RNAemia on presentation might serve to direct early initiation of appropriate therapies for the patients most likely to deteriorate.
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Prostaglandin D2 (PGD2) released from immune cells or other cell types activates its receptors, D prostanoid receptor (DP)1 and 2 (DP1 and DP2), to promote inflammatory responses in allergic and lung diseases. Prostaglandin-mediated inflammation may also contribute to vascular diseases such as abdominal aortic aneurysm (AAA). However, the role of DP receptors in the pathogenesis of AAA has not been systematically investigated. In the present study, DP1-deficient mice and pharmacological inhibitors of either DP1 or DP2 were tested in two distinct mouse models of AAA formation: angiotensin II (AngII) infusion and calcium chloride (CaCl2) application. DP1-deficient mice [both heterozygous (DP1+/-) and homozygous (DP1-/-)] were protected against CaCl2-induced AAA formation, in conjunction with decreased matrix metallopeptidase (MMP) activity and adventitial inflammatory cell infiltration. In the AngII infusion model, DP1+/- mice, but not DP1-/- mice, exhibited reduced AAA formation. Interestingly, compensatory up-regulation of the DP2 receptor was detected in DP1-/- mice in response to AngII infusion, suggesting a potential role for DP2 receptors in AAA. Treatment with selective antagonists of DP1 (laropiprant) or DP2 (fevipiprant) protected against AAA formation, in conjunction with reduced elastin degradation and aortic inflammatory responses. In conclusion, PGD2 signaling contributes to AAA formation in mice, suggesting that antagonists of DP receptors, which have been extensively tested in allergic and lung diseases, may be promising candidates to ameliorate AAA.
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Aneurisma de la Aorta Abdominal/etiología , Receptores Inmunológicos/fisiología , Receptores de Prostaglandina/fisiología , Angiotensina II/farmacología , Animales , Aneurisma de la Aorta Abdominal/prevención & control , Masculino , Ratones , Receptores Inmunológicos/antagonistas & inhibidores , Receptores de Prostaglandina/antagonistas & inhibidoresRESUMEN
Objective: Firefighter first responders and other emergency medical services (EMS) personnel have been among the highest risk healthcare workers for illness during the SARS-CoV-2 pandemic. We sought to determine the rate of seropositivity for SARS-CoV-2 IgG antibodies and of acute asymptomatic infection among firefighter first responders in a single county with early exposure in the pandemic. Methods: We conducted a cross-sectional study of clinically active firefighters cross-trained as paramedics or EMTs in the fire departments of Santa Clara County, California. Firefighters without current symptoms were tested between June and August 2020. Our primary outcomes were rates of SARS-CoV-2 IgG antibody seropositivity and SARS-CoV-2 RT-PCR swab positivity for acute infection. We report cumulative incidence, participant characteristics with frequencies and proportions, and proportion positive and associated relative risk (with 95% confidence intervals). Results: We enrolled 983 out of 1339 eligible participants (response rate: 73.4%). Twenty-five participants (2.54%, 95% CI 1.65-3.73) tested positive for IgG antibodies and 9 (0.92%, 95% CI 0.42-1.73) tested positive for SARS-CoV-2 by RT-PCR. Our cumulative incidence, inclusive of self-reported prior positive PCR tests, was 34 (3.46%, 95% CI 2.41-4.80). Conclusion: In a county with one of the earliest outbreaks in the United States, the seroprevalence among firefighter first responders was lower than that reported by other studies of frontline health care workers, while the cumulative incidence remained higher than that seen in the surrounding community.
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BACKGROUND: Contemporary emergency department (ED) standard-of-care treatment of hyperkalemia is poorly described. OBJECTIVE: Our aim was to determine the treatment patterns of hyperkalemia management in the ED. METHODS: This multicenter, prospective, observational study evaluated patients aged ≥ 18 years with hyperkalemia (potassium [K+] level ≥ 5.5 mmol/L) in the ED from October 25, 2015 to March 30, 2016. K+-lowering therapies and K+ were documented at 0.5, 1, 2, and 4 h after initial ED treatment. The primary end point was change in K+ over 4 h. RESULTS: Overall, 203 patients were enrolled at 14 U.S.-based sites. The initial median K+ was 6.3 (interquartile range [IQR] 5.7-6.8) mmol/L and median time to treatment was 2.7 (IQR 1.9-3.5) h post-ED arrival. Insulin/glucose (n = 130; 64%) was frequently used to treat hyperkalemia; overall, 43 different treatment combinations were employed within the first 4 h. Within 4 h, the median K+ for patients treated with medications alone decreased from 6.3 (IQR, 5.8-6.8) mmol/L to 5.3 (4.8-5.7) mmol/L, while that for patients treated with dialysis decreased from 6.2 (IQR 6.0-6.6) mmol/L to 3.8 (IQR 3.6-4.2) mmol/L. Hypoglycemia occurred in 6% of patients overall and in 17% of patients with K+ > 7.0 mmol/L. Hyperkalemia-related electrocardiogram changes were observed in 23% of all patients; 45% of patients with K+ > 7.0 mmol/L had peaked T waves or widened QRS. Overall, 79% were hospitalized; 3 patients died. CONCLUSIONS: Hyperkalemia practice patterns vary considerably and, although treatment effectively lowered K+, only dialysis normalized median K+ within 4 h.
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Servicio de Urgencia en Hospital , Hiperpotasemia/terapia , Anciano , Medicina Basada en la Evidencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tiempo de Tratamiento , Resultado del Tratamiento , Estados UnidosRESUMEN
Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated. Here, we show that MPO gene deletion attenuates AAA formation in two animal models: ANG II infusion in apolipoprotein E-deficient mice and elastase perfusion in C57BL/6 mice. Oral administration of taurine [1% or 4% (wt/vol) in drinking water], an amino acid known to react rapidly with MPO-generated oxidants like hypochlorous acid, also prevented AAA formation in the ANG II and elastase models as well as the CaCl2 application model of AAA formation while reducing aortic peroxidase activity and aortic protein-bound dityrosine levels, an oxidative cross link formed by MPO. Both MPO gene deletion and taurine supplementation blunted aortic macrophage accumulation, elastin fragmentation, and matrix metalloproteinase activation, key features of AAA pathogenesis. Moreover, MPO gene deletion and taurine administration significantly attenuated the induction of serum amyloid A, which promotes ANG II-induced AAAs. These data implicate MPO in AAA pathogenesis and suggest that studies exploring whether taurine can serve as a potential therapeutic for the prevention or treatment of AAA in patients merit consideration.NEW & NOTEWORTHY Neutrophils are abundant in abdominal aortic aneurysm (AAA), and myeloperoxidase (MPO), prominently expressed in neutrophils, is associated with AAA in humans. This study demonstrates that MPO gene deletion or supplementation with the natural product taurine, which can scavenge MPO-generated oxidants, can prevent AAA formation, suggesting an attractive potential therapeutic strategy for AAA.
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Antioxidantes/farmacología , Aorta Abdominal/efectos de los fármacos , Aneurisma de la Aorta Abdominal/prevención & control , Neutrófilos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Taurina/farmacología , Angiotensina II , Animales , Aorta Abdominal/enzimología , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/enzimología , Aneurisma de la Aorta Abdominal/genética , Cloruro de Calcio , Modelos Animales de Enfermedad , Eliminación de Gen , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Neutrófilos/enzimología , Elastasa Pancreática , Peroxidasa/deficiencia , Peroxidasa/genética , Especies Reactivas de Oxígeno/metabolismo , Proteína Amiloide A Sérica/metabolismoRESUMEN
OBJECTIVE: Perivascular adipose tissue (PVAT) expands during obesity, is highly inflamed, and correlates with coronary plaque burden and increased cardiovascular risk. We tested the hypothesis that PVAT contributes to the vascular response to wire injury and investigated the underlying mechanisms. APPROACH AND RESULTS: We transplanted thoracic aortic PVAT from donor mice fed a high-fat diet to the carotid arteries of recipient high-fat diet-fed low-density lipoprotein receptor knockout mice. Two weeks after transplantation, wire injury was performed, and animals were euthanized 2 weeks later. Immunohistochemistry was performed to quantify adventitial macrophage infiltration and neovascularization and neointimal lesion composition and size. Transplanted PVAT accelerated neointimal hyperplasia, adventitial macrophage infiltration, and adventitial angiogenesis. The majority of neointimal cells in PVAT-transplanted animals expressed α-smooth muscle actin, consistent with smooth muscle phenotype. Deletion of monocyte chemoattractant protein-1 in PVAT substantially attenuated the effects of fat transplantation on neointimal hyperplasia and adventitial angiogenesis, but not adventitial macrophage infiltration. Conditioned medium from perivascular adipocytes induced potent monocyte chemotaxis in vitro and angiogenic responses in cultured endothelial cells. CONCLUSIONS: These findings indicate that PVAT contributes to the vascular response to wire injury, in part through monocyte chemoattractant protein-1-dependent mechanisms.
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Tejido Adiposo/trasplante , Traumatismos de las Arterias Carótidas/metabolismo , Quimiocina CCL2/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Neointima , Actinas/metabolismo , Adipocitos/metabolismo , Adipocitos/trasplante , Tejido Adiposo/metabolismo , Animales , Biomarcadores/metabolismo , Arterias Carótidas/metabolismo , Arterias Carótidas/patología , Traumatismos de las Arterias Carótidas/etiología , Traumatismos de las Arterias Carótidas/genética , Traumatismos de las Arterias Carótidas/patología , Células Cultivadas , Quimiocina CCL2/deficiencia , Quimiocina CCL2/genética , Quimiotaxis , Técnicas de Cocultivo , Medios de Cultivo Condicionados/metabolismo , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Humanos , Hiperplasia , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/lesiones , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Neovascularización Patológica , Fenotipo , Receptores de LDL/deficiencia , Receptores de LDL/genética , Transducción de Señal , Factores de Tiempo , Migración Transendotelial y TransepitelialRESUMEN
BACKGROUND: Precision health is a burgeoning scientific discipline that aims to incorporate individual variability in biological, behavioral, and social factors to develop personalized health solutions. To date, emergency medicine has not deeply engaged in the precision health movement. However, rapid advances in health technology, data science, and medical informatics offer new opportunities for emergency medicine to realize the promises of precision health. METHODS: In this article, we conceptualize precision emergency medicine as an emerging paradigm and identify key drivers of its implementation into current and future clinical practice. We acknowledge important obstacles to the specialty-wide adoption of precision emergency medicine and offer solutions that conceive a successful path forward. RESULTS: Precision emergency medicine is defined as the use of information and technology to deliver acute care effectively, efficiently, and authentically to individual patients and their communities. Key drivers and opportunities include leveraging human data, capitalizing on technology and digital tools, providing deliberate access to care, advancing population health, and reimagining provider education and roles. Overcoming challenges in equity, privacy, and cost is essential for success. We close with a call to action to proactively incorporate precision health into the clinical practice of emergency medicine, the training of future emergency physicians, and the research agenda of the specialty. CONCLUSIONS: Precision emergency medicine leverages new technology and data-driven artificial intelligence to advance diagnostic testing, individualize patient care plans and therapeutics, and strategically refine the convergence of the health system and the community.
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IMPORTANCE: The COVID-19 pandemic has led to 775 million documented cases and over 7 million deaths worldwide as of March 2024 and is an ongoing health crisis. To limit viral spread within households and in the community, public health officials have recommended self-isolation, self-quarantine of exposed household contacts, and mask use. Yet, risk of household transmission (HHT) may be underestimated due to low frequency of sampling, and risk factors for HHT are not well understood. OBJECTIVES: To estimate the secondary attack rate of SARS-CoV-2 within households and to define the risk factors for new infections in household members who are in close contact with the index case. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, from March 2020-December 2021 we enrolled 60 households with index cases who tested positive for SARS-CoV-2. All household contacts and index cases were tested daily for SARS-CoV-2 via reverse transcription polymerase chain reaction (RT-PCR) using self-collected anterior nares specimens. Households were followed until all study participants in the household tested negative for SARS-CoV-2 for seven consecutive days. We collected sex, age, race/ethnicity, comorbidities, and relationship to index case for secondary contacts, household level characteristics including primary income, household density, and square feet per person on property. We compared the sociodemographic variables between COVID-19 positive and negative household members and between households where secondary transmission did and did not occur. MAIN OUTCOMES AND MEASURES: Daily anterior nares swabs were tested for SARS-CoV-2 using RT-PCR, in order to assess duration of nasal shedding of SARS-CoV-2, as well as risk of transmission to secondary household contacts. RESULTS: Of the 163 participants in this study, 84 (51.5%) were women; median age (IQR) was 36.0 (17.0-54.0) years of age; 78 (47.8%) were white and 48 (29.5%) were Hispanic/LatinX. Of the fifty households with household contacts, at least one secondary case occurred in twenty-six households (52.0%) and forty-five household contacts (43.7%) were infected. Secondary attack rate was lowest among children of index cases (6/23, 26.1%). Modified Poisson regression identified that the risk of transmission to household contacts increases significantly with age (Risk ratio for each increase in years of age = 1.01, 95% CI = 1.00-1.02). Mixed effects regression models identified that participants with chronic diseases, such as asthma, diabetes, cancer, or cardiac disease, had higher Cts at baseline when compared to participants without chronic diseases (6.62, 95% CI: 1.46-11.77, p = 0.02) and show a slower rate of increase in Ct over time (-0.43, 95% CI: -0.77 to -0.09, p = 0.02). CONCLUSIONS AND RELEVANCE: This study suggests that HHT represents a key source of community-based infection of SARS-CoV-2. Allocation of resources for contact investigations and prevention interventions should focus on the individuals at highest risk of infection in households, especially those with higher density homes.
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COVID-19 , Composición Familiar , SARS-CoV-2 , Esparcimiento de Virus , Humanos , COVID-19/transmisión , COVID-19/epidemiología , COVID-19/virología , Femenino , Masculino , Adulto , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Estudios Prospectivos , Adolescente , Niño , Adulto Joven , Factores de Riesgo , Preescolar , AncianoRESUMEN
Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially expressed genes between adipocytes derived from human SQ vs. PV adipose tissues. Although >90% of well-expressed genes were similarly regulated, we identified a signature of 307 differentially expressed genes that were highly enriched for functions associated with the regulation of angiogenesis, vascular morphology, inflammation, and blood clotting. Of the 156 PV upregulated genes, 59 associate with angiogenesis, vascular biology, or inflammation, noteworthy of which include TNFRSF11B (osteoprotegerin), PLAT, TGFB1, THBS2, HIF1A, GATA6, and SERPINE1. Of 166 PV downregulated genes, 21 associated with vascular biology and inflammation, including ANGPT1, ANGPTL1, and VEGFC. Consistent with the emergent hypothesis that PV adipocytes differentially regulate angiogenesis and inflammation, cell culture-derived adipocyte-conditioned media from PV adipocytes strongly enhanced endothelial cell tubulogenesis and monocyte migration compared with media from SQ adipocytes. These findings demonstrate that PV adipocytes have the potential to significantly modulate vascular inflammatory crosstalk in the setting of atherosclerosis by their ability to signal to both endothelial and inflammatory cells.
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Adipocitos/metabolismo , Aterosclerosis/metabolismo , Hemostasis/fisiología , Inflamación/metabolismo , Adipogénesis/genética , Adipogénesis/fisiología , Tejido Adiposo/citología , Adolescente , Adulto , Línea Celular , Vasos Coronarios/metabolismo , Femenino , Hemostasis/genética , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana EdadRESUMEN
IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024.
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COVID-19 , Humanos , COVID-19/epidemiología , Estudios Observacionales como Asunto , Síndrome Post Agudo de COVID-19 , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2 , Adolescente , Adulto , Estudios Multicéntricos como AsuntoRESUMEN
Differentiation of preadipocytes into mature adipocytes capable of efficiently storing lipids is an important regulatory mechanism in obesity. Here, we examined the involvement of histone deacetylases (HDACs) and histone acetyltransferases (HATs) in the regulation of adipogenesis. We find that among the various members of the HDAC and HAT families, only HDAC9 exhibited dramatic down-regulation preceding adipogenic differentiation. Preadipocytes from HDAC9 gene knock-out mice exhibited accelerated adipogenic differentiation, whereas HDAC9 overexpression in 3T3-L1 preadipocytes suppressed adipogenic differentiation, demonstrating its direct role as a negative regulator of adipogenesis. HDAC9 expression was higher in visceral as compared with subcutaneous preadipocytes, negatively correlating with their potential to undergo adipogenic differentiation in vitro. HDAC9 localized in the nucleus, and its negative regulation of adipogenesis segregates with the N-terminal nuclear targeting domain, whereas the C-terminal deacetylase domain is dispensable for this function. HDAC9 co-precipitates with USF1 and is recruited with USF1 at the E-box region of the C/EBPα gene promoter in preadipocytes. Upon induction of adipogenic differentiation, HDAC9 is down-regulated, leading to its dissociation from the USF1 complex, whereas p300 HAT is up-regulated to allow its association with USF1 and accumulation at the E-box site of the C/EBPα promoter in differentiated adipocytes. This reciprocal regulation of HDAC9 and p300 HAT in the USF1 complex is associated with increased C/EBPα expression, a master regulator of adipogenic differentiation. These findings provide new insights into mechanisms of adipogenic differentiation and document a critical regulatory role for HDAC9 in adipogenic differentiation through a deacetylase-independent mechanism.
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Tejido Adiposo/citología , Diferenciación Celular/fisiología , Histona Desacetilasas/fisiología , Proteínas Represoras/fisiología , Células 3T3-L1 , Animales , Regulación hacia Abajo , Histona Desacetilasas/genética , Inmunoprecipitación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Proteínas Represoras/genéticaRESUMEN
The medical community recognizes that firearm injury is a public health problem. Yet we lack both the tools for and the implementation of evidence-based firearm injury screening and counseling techniques. One reason for these deficits is the lack of clinical training related to engaging patients in firearm injury risk reduction. In this issue, Rickert et al describe a pre-post evaluation of a 2-part firearm injury prevention training curriculum for first-year medical residents at a single academic medical center. Their manuscript serves an important, but still preliminary, step forward for the field of postgraduate medical education on firearm injury and its prevention. Important elements of this project and paper consist of the inclusion of multiple medical disciplines and the use of standardized patients to evaluate participants' learning. This project also points to the need for further growth. We must commit to consistently and conscientiously framing injuries from guns not as "gun violence" but rather as "firearm injuries" to ensure that they are considered squarely in both the public health space and the clinical space. An ideal curriculum would also highlight the importance of trauma-informed care, cultural competency, and antiracist medical practice while countering implicit biases (e.g., toward gun owners, victims of firearm violence, perpetrators of violence). It should address barriers, as well as facilitators, to change. And most importantly, future educational work must evaluate the effect of these trainings on actual clinical practice-and, even better, the efficacy of education in changing behavior and patient-level outcomes.
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Armas de Fuego , Heridas por Arma de Fuego , Curriculum , Humanos , Salud Pública , Violencia , Heridas por Arma de Fuego/prevención & controlRESUMEN
Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 83.3% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, worst disease severity, and length of symptoms.
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Objectives: This study aimed to identify rates of and contributors to burnout and professional fulfillment among emergency medicine (EM) resident physicians. Methods: This was a cross-sectional, national survey of resident members of the Society for Academic Emergency Medicine (SAEM). Primary outcomes were burnout and professional fulfillment measured using a previously validated instrument with additional domains pertaining to the academic environment. The survey included question domains examining organizational factors (e.g., academic work environment, satisfaction with training, electronic health records, values alignment, and control over schedule) and individual factors (e.g., self-compassion, meaningfulness of clinical work, impact of work on health and personal relationships, perceived appreciation, thoughts of attrition, and expectations of the field of EM). Logistic regression was performed to determine the relationships between the primary outcomes and each domain. Results: The survey was sent electronically to 2641 SAEM resident members. A total of 275 residents completed the survey with a response rate of 10.4%. A total of 151 (55%) respondents were male, and 210 (76%) were White. A total of 132 (48%) residents reported burnout, and 75 (28%) reported professional fulfillment. All organizational and individual factors were significantly associated with both primary outcomes. EM residents reported that meaningfulness of clinical work had the most significant positive association with professional fulfillment (adjusted odds ratio [OR] 2.2 [95% confidence interval {CI} 1.8-2.7]) and negative association with burnout (adjusted OR 0.46 [95% CI 0.37-0.56]). Thoughts of attrition from academics and accurate expectations of EM were also associated with both primary outcomes, with adjusted ORs (95% CIs) of 0.40 (0.21-0.72) and 5.6 (1.9-23.8) for professional fulfillment and 4.1 (2.5-7.1) and 0.19 (0.08-0.40) for burnout, respectively. Conclusions: This study found a high prevalence of burnout and a low prevalence of professional fulfillment among EM residents. Multiple factors were significantly associated with each occupational phenomenon, with meaningfulness of clinical work demonstrating the strongest relationships with burnout and professional fulfillment.
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The field of data science has great potential to address critical questions relevant for academic medical centers. Data science initiatives are consequently being established within academic medicine. At the cornerstone of such initiatives are scientists who practice data science. These scientists include biostatisticians, clinical informaticians, database and software developers, computational scientists, and computational biologists. Too often, however, those involved in the practice of data science are viewed by academic leadership as providing a noncomplex service to facilitate research and further the careers of other academic faculty. The authors contend that the success of data science initiatives relies heavily on the understanding that the practice of data science is a critical intellectual contribution to the overall science conducted at an academic medical center. Further, careful thought by academic leadership is needed for allocation of resources devoted to the practice of data science. At the Stanford University School of Medicine, the authors have developed an innovative model for a data science collaboratory based on 4 fundamental elements: an emphasis on collaboration over consultation, a subscription-based funding mechanism that reflects commitment by key partners, an investment in the career development of faculty who practice data science, and a strong educational component for data science members in team science and for clinical and translational investigators in data science. As data science becomes increasingly essential to learning health systems, centers that specialize in the practice of data science are a critical component of the research infrastructure and intellectual environment of academic medical centers.
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Centros Médicos Académicos , Ciencia de los Datos , Docentes , Docentes Médicos , Humanos , Liderazgo , InvestigadoresRESUMEN
All academic medical specialties have the obligation to continuously create new knowledge that will improve patient care and outcomes. Emergency medicine (EM) is no exception. Since its origins over 50 years ago, EM has struggled to fulfill its research mission. EM ranks last among clinical specialties in the percentage of medical school faculty who are National Institutes of Health (NIH)-funded principal investigators (PIs; 1.7%) and the percentage of medical school departments with NIH-funded PIs (33%). Although there has been a steady increase in the number of NIH-funded projects and total NIH dollars, the slowing growth in the number of NIH-funded PIs and lack of growth in the number of EM departments with NIH-funded PIs is cause for concern. In response, the Association of Academic Chairs of Emergency Medicine (AACEM) Research Task Force proposes a set of 2030 strategic goals for the EM research enterprise that are based on sustaining historic growth rates in NIH funding. These goals have been endorsed by the AACEM Executive Committee and the boards of Society for Academic Emergency Medicine (SAEM), American College of Emergency Physicians (ACEP), and American Academy of Emergency Medicine (AAEM). The 2030 strategic goals include 200 NIH-funded projects led by 150 EM PIs in at least 50 EM departments with over $100M in annual funding resulting in over 3% of EM faculty being NIH-funded PIs. Achieving these goals will require a targeted series of focused strategies to increase the number of EM faculty who are competitive for NIH funding. This requires a coordinated, intentional effort with investments at the national, departmental, and individual levels. These efforts are ideally led by medical school department chairs, who can create the culture and provide the resources needed to be successful. The specialty of EM has the obligation to improve the health of the public and to fulfill its research mission.
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Investigación Biomédica , Medicina de Emergencia , Docentes Médicos , Objetivos , Humanos , National Institutes of Health (U.S.) , Estados UnidosRESUMEN
BACKGROUND: Professional fulfillment and the mitigation of burnout can enhance clinician well-being and the resiliency of the health care organization. This study examined the extent to which specific individual and workplace factors are associated with professional fulfillment and burnout among a national sample of academic emergency physicians. METHODS: This was a cross-sectional survey of faculty members of the Society for Academic Emergency Medicine. Primary outcomes were professional fulfillment and burnout. The survey also examined individual and workplace factors as well as faculty's thoughts of attrition from academic and clinical medicine. Logistic regression was performed to determine the relationships between each outcome and each factor, respectively. RESULTS: A total of 771 of 3130 faculty completed the survey (response rate 24.6%). A total of 38.7% reported professional fulfillment and 39.1% reported burnout. Meaningfulness of work (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.9-2.5), perceived appreciation (OR 1.9, 95% CI 1.7-2.1), and the academic work environment (OR 1.7, 95% CI 1.5-1.9) had the highest odds of being associated with professional fulfillment. In contrast, low score responses for meaningfulness of work (OR 0.6, 95% CI 0.5-0.6), self-compassion (0.6, 95% CI 0.5-0.6), and control over schedule (OR 0.6, 95% CI 0.6-0.7) were most associated with burnout. Faculty with professional fulfillment were less likely to report plans for attrition from academics (OR 0.1, 95% CI 0.1-0.2) and from clinical medicine (OR 0.2, 95% CI 0.1-0.4). Faculty with burnout were more likely to report plans for attrition from academics (OR 7, 95% CI 4.8-10.4) and clinical medicine (OR 5.7, 95% CI 3.9-8.6). CONCLUSIONS: Individual and workplace factors that contributed to professional fulfillment and burnout were identified, with meaningfulness of clinical work demonstrating the strongest association with both occupational phenomena. Knowledge of which factors are most impactful in promoting professional fulfillment and mitigating burnout may be useful in guiding efforts to enhance clinician well-being.
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Agotamiento Profesional , Medicina de Emergencia , Agotamiento Profesional/epidemiología , Estudios Transversales , Docentes , Humanos , Satisfacción Personal , Encuestas y CuestionariosRESUMEN
Importance: There is an urgent need to assess the feasibility of COVID-19 surveillance measures in educational settings. Objective: To assess whether young children can feasibly self-collect SARS-CoV-2 samples for surveillance testing over the course of an academic year. Design, Setting, and Participants: This prospective pilot cohort study was conducted from September 10, 2020, to June 10, 2021, at a K-8 school in San Mateo County, California. The research consisted of quantitative data collection efforts: (1) demographic data collected, (2) student sample self-collection error rates, and (3) student sample self-collection time durations. Students were enrolled in a hybrid learning model, a teaching model in which students were taught in person and online, with students having the option to attend virtually as needed. Data were collected under waiver of consent from students participating in weekly SARS-CoV-2 testing. Main Outcomes and Measures: Errors over time for self-collection of nasal swabs such as contaminated swabs and inadequate or shallow swabbing; time taken for sample collection. Results: Of 296 participants, 148 (50.0%) were boys and 148 (50.0%) were girls. A total of 87 participants (29.2%) identified as Asian; 2 (0.6%), Black or African American; 13 (4.4%), Hispanic/Latinx; 103 (34.6%), non-Hispanic White; 87 (29.2%), multiracial; and 6 (2.0%), other. The median school grade was fourth grade. From September 2020 to March 2021, a total of 4203 samples were obtained from 221 students on a weekly basis, while data on error rates were collected. Errors occurred in 2.7% (n = 107; 95% CI, 2.2%-3.2%) of student encounters, with the highest rate occurring on the first day of testing (20 [10.2%]). There was an overall decrease in error rates over time. From April to June 2021, a total of 2021 samples were obtained from 296 students on a weekly basis while data on encounter lengths were collected. Between April and June 2021, 193 encounters were timed. The mean duration of each encounter was 70 seconds (95% CI, 66.4-73.7 seconds). Conclusions and Relevance: Mastery of self-collected lower nasal swabs is possible for children 5 years and older. Testing duration can be condensed once students gain proficiency in testing procedures. Scalability for larger schools is possible if consideration is given to the resource-intensive nature of the testing and the setting's weather patterns.
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Prueba de COVID-19 , COVID-19/diagnóstico , SARS-CoV-2 , Autoevaluación , COVID-19/patología , COVID-19/prevención & control , California , Niño , Preescolar , Estudios de Cohortes , Epidemias , Estudios de Factibilidad , Femenino , Humanos , Masculino , Vigilancia de la Población , Estudios Prospectivos , Manejo de EspecímenesRESUMEN
BACKGROUNDProlonged symptoms after SARS-CoV-2 infection are well documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with biomarkers are points that remain elusive.METHODSAdult SARS-CoV-2 reverse transcription PCR-positive (RT-PCR-positive) patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to 1 year after diagnosis; they completed symptom surveys and underwent blood draws and nasal swab collections at each visit.RESULTSOur cohort (n = 617) ranged from asymptomatic to critical COVID-19 infections. In total, 40% of participants reported at least 1 symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days; median time from diagnosis to sustained symptom resolution with no recurring symptoms for 1 month or longer was 214 days. Anti-nucleocapsid IgG level in the first week after positive RT-PCR test and history of lung disease were associated with time to sustained symptom resolution. COVID-19 disease severity, ethnicity, age, sex, and remdesivir use did not affect time to sustained symptom resolution.CONCLUSIONWe found that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration.TRIAL REGISTRATIONClinicalTrials.gov, NCT04373148.FUNDINGNIH UL1TR003142 CTSA grant, NIH U54CA260517 grant, NIEHS R21 ES03304901, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative, Sunshine Foundation, Crown Foundation, and Parker Foundation.