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Reducing cardiovascular disease disparities will require a concerted, focused effort to better adopt evidence-based interventions, in particular, those that address social determinants of health, in historically marginalized populations (ie, communities excluded on the basis of social identifiers like race, ethnicity, and social class and subject to inequitable distribution of social, economic, physical, and psychological resources). Implementation science is centered around stakeholder engagement and, by virtue of its reliance on theoretical frameworks, is custom built for addressing research-to-practice gaps. However, little guidance exists for how best to leverage implementation science to promote cardiovascular health equity. This American Heart Association scientific statement was commissioned to define implementation science with a cardiovascular health equity lens and to evaluate implementation research that targets cardiovascular inequities. We provide a 4-step roadmap and checklist with critical equity considerations for selecting/adapting evidence-based practices, assessing barriers and facilitators to implementation, selecting/using/adapting implementation strategies, and evaluating implementation success. Informed by our roadmap, we examine several organizational, community, policy, and multisetting interventions and implementation strategies developed to reduce cardiovascular disparities. We highlight gaps in implementation science research to date aimed at achieving cardiovascular health equity, including lack of stakeholder engagement, rigorous mixed methods, and equity-informed theoretical frameworks. We provide several key suggestions, including the need for improved conceptualization and inclusion of social and structural determinants of health in implementation science, and the use of adaptive, hybrid effectiveness designs. In addition, we call for more rigorous examination of multilevel interventions and implementation strategies with the greatest potential for reducing both primary and secondary cardiovascular disparities.
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Equidade em Saúde , Humanos , Ciência da Implementação , American Heart Association , Disparidades em Assistência à Saúde , Classe SocialRESUMO
Heat shock factor 1 (HSF1) is a master stress-responsive transcriptional factor, protecting cells from death. However, its gene regulation in vivo in the brain in response to neuronal stimuli remains elusive. Here, we investigated its direct regulation of the brain-derived neurotrophic factor (BDNF) gene (Bdnf) in response to acute neuronal stress stimuli in the brain. The results of immunohistochemistry and chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) showed that administration of kainic acid (a glutamate receptor agonist inducing excitotoxity) to young adult mice induced HSF1 nuclear translocation and its binding to multiple Bdnf promoters in the hippocampus. Footshock, a physical stressor used for learning, also induced HSF1 binding to selected Bdnf promoters I and IV. This is, to our knowledge, the first demonstration of HSF1 gene regulation in response to neuronal stimuli in the hippocampus in vivo. HSF1 binding sites (HSEs) in Bdnf promoters I and IV were also detected when immunoprecipitated by an antibody of phosphorylated (p)CREB (cAMP-responsive element-binding protein), suggesting their possible interplay in acute stress-induced Bdnf transcription. Interestingly, their promoter binding patterns differed by KA and footshock, suggesting that HSF1 and pCREB orchestrate to render fine-tuned promoter control depending on the types of stress. Further, HSF1 overexpression increased Bdnf promoter activity in a luciferase assay, while virus infection of constitutively active-form HSF1 increased levels of BDNF mRNA and protein in vitro in primary cultured neurons. These results indicated that HSF1 activation of Bdnf promoter was sufficient to induce BDNF expression. Taken together, these results suggest that HSF1 promoter-specific control of Bdnf gene regulation plays an important role in neuronal protection and plasticity in the hippocampus in response to acute stress, possibly interplaying with pCREB.
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Fator Neurotrófico Derivado do Encéfalo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Camundongos , Animais , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Hipocampo/metabolismo , Resposta ao Choque TérmicoRESUMO
Playgrounds have features that benefit visitors, including opportunities to engage in outdoor physical activity. We surveyed 1350 adults visiting 60 playgrounds across the USA in Summer 2021 to determine if distance to the playground from their residence was associated with weekly visit frequency, length of stay, and transportation mode to the site. About 2/3 of respondents living within ½ mile from the playground reported visiting it at least once per week compared with 14.1% of respondents living more than a mile away. Of respondents living within » mile of playgrounds, 75.6% reported walking or biking there. After controlling for socio-demographics, respondents living within ½ mile of the playground had 5.1 times the odds (95% CI: 3.68, 7.04) of visiting the playground at least once per week compared with those living further away. Respondents walking or biking to the playground had 6.1 times the odds (95% CI: 4.23, 8.82) of visiting the playground at least once per week compared with respondents arriving via motorized transport. For public health purposes, city planners and designers should consider locating playgrounds ½ mile from all residences. Distance is likely the most important factor associated with playground use.
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Parques Recreativos , Saúde da População Urbana , Humanos , População Urbana , Meios de Transporte , Inquéritos e Questionários , Masculino , Feminino , Adulto , Estações do Ano , CriançaRESUMO
IMPORTANCE: Recent evidence links air pollution to the severity COVID-19 symptoms and to death from the disease. To date, however, few studies have assessed whether air pollution affects the sequelae to more severe states or recovery from COVID-19 in a cohort with individual data. OBJECTIVE: To assess how air pollution affects the transition to more severe COVID-19 states or to recovery from COVID-19 infection in a cohort with detailed patient information. DESIGN AND OUTCOMES: We used a cohort design that followed patients admitted to hospital in the Kaiser Permanente Southern California (KPSC) Health System, which has 4.7 million members with characteristics similar to the general population. Enrollment began on 06/01/2020 and ran until 01/30/2021 for all patients admitted to hospital while ill with COVID-19. All possible states of sequelae were considered, including deterioration to intensive care, to death, discharge to recovery, or discharge to death. Transition risks were estimated with a multistate model. We assessed exposure using chemical transport model that predicted ambient concentrations of nitrogen dioxide, ozone, and fine particulate matter (PM2.5) at a 1 km scale. RESULTS: Each increase in PM2.5 concentration equivalent to the interquartile range was associated with increased risk of deterioration to intensive care (HR of 1.16; 95% CI: 1.12-1.20) and deterioration to death (HR of 1.11; 95% CI: 1.04-1.17). Results for ozone were consistent with PM2.5 effects, but ozone also affected the transition from recovery to death: HR of 1.24 (95% CI: 1.01-1.51). NO2 had weaker effects but displayed some elevated risks. CONCLUSIONS: PM2.5 and ozone were significantly associated with transitions to more severe states while in hospital and to death after discharge from hospital. Reducing air pollution could therefore lead to improved prognosis for COVID-19 patients and a sustainable means of reducing the health impacts of coronaviruses now and in the future.
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BACKGROUND: The Kaiser Permanente Research Bank (KPRB) is collecting biospecimens and surveys linked to electronic health records (EHR) from approximately 400,000 adult KP members. Within the KPRB, we developed a Cancer Cohort to address issues related to cancer survival, and to understand how genetic, lifestyle and environmental factors impact cancer treatment, treatment sequelae, and prognosis. We describe the Cancer Cohort design and implementation, describe cohort characteristics after 5 years of enrollment, and discuss future directions. METHODS: Cancer cases are identified using rapid case ascertainment algorithms, linkage to regional or central tumor registries, and direct outreach to KP members with a history of cancer. Enrollment is primarily through email invitation. Participants complete a consent form, survey, and donate a blood or saliva sample. All cancer types are included. RESULTS: As of December 31, 2020, the cohort included 65,225 cases (56% female, 44% male) verified in tumor registries. The largest group was diagnosed between 60 and 69 years of age (31%) and are non-Hispanic White (83%); however, 10,076 (16%) were diagnosed at ages 18-49 years, 4208 (7%) are Hispanic, 3393 (5%) are Asian, and 2389 (4%) are Black. The median survival time is 14 years. Biospecimens are available on 98% of the cohort. CONCLUSIONS: The KPRB Cancer Cohort is designed to improve our understanding of treatment efficacy and factors that contribute to long-term cancer survival. The cohort's diversity - with respect to age, race/ethnicity and geographic location - will facilitate research on factors that contribute to cancer survival disparities.
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Bancos de Espécimes Biológicos , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias , Melhoria de Qualidade , Adolescente , Adulto , Idoso , Estudos de Coortes , Registros Eletrônicos de Saúde , Feminino , Humanos , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estados Unidos , Adulto JovemRESUMO
Stressors associated with COVID-19 pandemic stay-at-home orders are associated with increased depression and anxiety and decreased physical activity. Given that physical activity and time spent outdoors in nature are associated with improved mental health, we examined the longitudinal association of these variables during the pandemic. Over 20,000 adults who participated in the U.S. Kaiser Permanente Research Bank, did not report COVID-19 symptoms, and responded to an online baseline and 3 follow-up surveys over approximately 3 months formed the cohort. Physical activity was assessed from a modified survey, time spent outdoors was assessed from one question, and anxiety and depression scores were assessed from validated instruments. Almost 60% were women, 82.8% were non-Hispanic white, and more than 93% of respondents were over the age of 50. Less in-person contact with friends and visiting crowded places was highly prevalent (>80%) initially and decreased somewhat (>70%). Participants in the lowest physical activity category (no physical activity) had the highest depression and anxiety scores compared to each successive physical activity category (p < 0.001). Spending less time outdoors was associated with higher depression and anxiety scores. This effect was greater for participants in the younger age categories compared with older age categories. The effect of less time spent outdoors on anxiety (p = 0.012) and depression (p < 0.001) scores was smaller for males than females. Results suggest that physical activity and time outdoors is associated with better mental health. People should be encouraged to continue physical activity participation during public health emergencies.
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COVID-19 , Adulto , Ansiedade/epidemiologia , Depressão/epidemiologia , Exercício Físico , Feminino , Humanos , Masculino , Pandemias , Distanciamento Físico , Quarentena , SARS-CoV-2 , Estados UnidosRESUMO
Physical activity is vital for the health and well-being of youth and adults, although the prevalence of physical activity continues to be low. Promoting active transportation or human-powered transportation through policy, systems, and environmental change is one of the leading evidence-based strategies to increase physical activity regardless of age, income, racial/ethnic background, ability, or disability. Initiatives often require coordination across federal, state, and local agencies. To maximize the effectiveness of all types of interventions, it is imperative to establish strong and broad partnerships across professional disciplines, community members, and advocacy groups. Health organizations can play important roles in facilitating these partnerships. This policy statement provides recommendations and resources that can improve transportation systems, enhance land use design, and provide education to support policies and environments to promote active travel. The American Heart Association supports safe, equitable active transportation policies in communities across the country that incorporate consistent implementation evaluation. Ultimately, to promote large increases in active transportation, policies need to be created, enforced, and funded across multiple sectors in a coordinated and equitable fashion. Active transportation policies should operate at 3 levels: the macroscale of land use, the mesoscale of pedestrian and bicycle networks and infrastructure such as Complete Streets policies and Safe Routes to School initiatives, and the microscale of design interventions and placemaking such as building orientation and access, street furnishings, and safety and traffic calming measures. Health professionals and organizations are encouraged to become involved in advocating for active transportation policies at all levels of government.
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American Heart Association , Ambiente Construído , Exercício Físico , Comportamentos Relacionados com a Saúde , Política de Saúde , Promoção da Saúde , Meios de Transporte , Humanos , Estados UnidosRESUMO
Bariatric surgery is associated with changing food preferences, but it is not known whether these changes differ by type of operation or are associated with weight loss. The current study presents validation results for a new 27-item scale, Bariatric Surgical Alterations in Tolerability, Enjoyment and Cravings in the Diet (BSATED). This scale measured enjoyment, craving, and intolerance changes for nine food and beverage categories common to dietary habits in the Southern California region of the U.S. one year following bariatric surgery in the Bariatric Experience Long Term (BELONG) study. Validation of BSATED was done using exploratory factor analyses, construct validity with other conceptually related survey instruments, and criterion validity using hypothesized differences for operation type and percent total weight loss (%TWL) at 12-18 months after surgery. Participants (n = 999) were 86% female, 41% non-Hispanic White, with a mean age of 43.1 ± 11.3 years and a body mass index (BMI) of 43.4 ± 6.8 kg/m2 at the time of surgery. Participants reported less enjoyment and craving for high-fat meats (62%), grains (54%), candy and other desserts (e.g. candy bars, chocolate, ice cream) (52%), and sweet baked goods (48%) 12 months after surgery. These changes were more common among participants undergoing Roux-en-Y gastric bypass (RYGB) compared to those receiving sleeve gastrectomy (SG). Participants who reported decreased enjoyment and craving for foods and beverages that post-bariatric patients are counseled to reduce or avoid had greater %TWL at 12-18 months following surgery (p < .001 and p = .003 respectively). The foods and beverages in BSATED that post-bariatric patients are counseled to reduce or avoid could be used to understand how changes in enjoyment, craving and tolerability of these foods/beverages contribute to weight loss following surgery.
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Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Adulto , Fissura , Dieta , Feminino , Preferências Alimentares , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , PrazerRESUMO
OBJECTIVES: To compare hospitalisation rates, intensive care unit (ICU) admissions and mortality for patients with COVID-19 who were consistently inactive, doing some activity or consistently meeting physical activity guidelines. METHODS: We identified 48 440 adult patients with a COVID-19 diagnosis from 1 January 2020 to 21 October 2020, with at least three exercise vital sign measurements from 19 March 2018 to 18 March 2020. We linked each patient's self-reported physical activity category (consistently inactive=0-10 min/week, some activity=11-149 min/week, consistently meeting guidelines=150+ min/week) to the risk of hospitalisation, ICU admission and death after COVID-19 diagnosis. We conducted multivariable logistic regression controlling for demographics and known risk factors to assess whether inactivity was associated with COVID-19 outcomes. RESULTS: Patients with COVID-19 who were consistently inactive had a greater risk of hospitalisation (OR 2.26; 95% CI 1.81 to 2.83), admission to the ICU (OR 1.73; 95% CI 1.18 to 2.55) and death (OR 2.49; 95% CI 1.33 to 4.67) due to COVID-19 than patients who were consistently meeting physical activity guidelines. Patients who were consistently inactive also had a greater risk of hospitalisation (OR 1.20; 95% CI 1.10 to 1.32), admission to the ICU (OR 1.10; 95% CI 0.93 to 1.29) and death (OR 1.32; 95% CI 1.09 to 1.60) due to COVID-19 than patients who were doing some physical activity. CONCLUSIONS: Consistently meeting physical activity guidelines was strongly associated with a reduced risk for severe COVID-19 outcomes among infected adults. We recommend efforts to promote physical activity be prioritised by public health agencies and incorporated into routine medical care.
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COVID-19/epidemiologia , COVID-19/mortalidade , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva , Comportamento Sedentário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
Ischaemic brain damage induces autoimmune responses, including the production of autoantibodies with potential neuroprotective effects. Platelets share unexplained similarities with neurons, and the formation of anti-platelet antibodies has been documented in neurological disorders. The aim of this study was to investigate the presence of anti-platelet antibodies in the peripheral blood of patients after ischaemic stroke and determine any clinical correlations. Using a flow cytometry-based platelet immunofluorescence method, we detected platelet-reactive antibodies in 15 of 48 (31%) stroke patients and two of 50 (4%) controls (p < 0.001). Western blotting revealed heterogeneous reactivities with platelet proteins, some of which overlapped with brain proteins. Stroke patients who carried anti-platelet antibodies presented with larger infarcts and more severe neurological dysfunction, which manifested as higher scores on the National Institutes of Health Stroke Scale (NIHSS; p = 0.009), but they had a greater recovery in the NIHSS by the time of hospital discharge (day 7 ± 2) compared with antibody-negative patients (p = 0.043). Antibodies from stroke sera reacted more strongly with activated platelets (p = 0.031) and inhibited platelet aggregation by up to 30.1 ± 2.8% (p < 0.001), suggesting the potential to interfere with thrombus formation. In conclusion, platelet-reactive antibodies can be found in patients soon after ischaemic stroke and correlate with better short-term outcomes, suggesting a potential novel mechanism limiting thrombosis.
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Autoanticorpos/imunologia , Plaquetas/imunologia , Isquemia Encefálica/imunologia , AVC Isquêmico/imunologia , Idoso , Autoimunidade/imunologia , Coagulação Sanguínea/imunologia , Feminino , Humanos , Masculino , Agregação Plaquetária/imunologia , Contagem de Plaquetas/métodos , Trombose/imunologiaRESUMO
Adeno-associated viral (AAV) vectors are a promising system for transgene delivery into the central nervous system (CNS) based on their safety profile and long-term gene expression. Gene delivery to the CNS has largely been neuron centric but advances in AAV technology are facilitating the development of approaches to enable transduction of glial cells. Considering the role of astrocytes in the on-going secondary damage in spinal cord injury (SCI), an AAV vector that targets astrocytes could show benefit as a potential treatment. Transduction efficiency, transgene expression and cellular tropism were compared for the AAV serotypes AAV5, AAV9 and AAVRec2 whereby destabilised yellow fluorescent protein (dYFP) was controlled by the GFAP or the truncated GfaABC1D promoter. The vectors were tested in primary spinal cord astrocyte cell culture, spinal cord slice culture and an in vivo model of SCI contusion. AAV5 resulted in greater transduction efficiency, transgene expression and astrocyte tropism compared with AAV9 and AAVRec2. In a rodent model of SCI, robust transgene expression by AAV5-GFAP/GfaABC1D-dYFP was observed through 12 mm of spinal cord tissue and expression was largely restricted to astrocytes. Thus, AAV5-GFAP/GfaABC1D carries the potential as a potential gene therapy vector, particularly for transducing astrocytes in the damaged spinal cord.
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Astrócitos/metabolismo , Dependovirus/genética , Terapia Genética/métodos , Traumatismos da Medula Espinal/terapia , Animais , Células Cultivadas , Técnicas de Transferência de Genes , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Regiões Promotoras Genéticas , Ratos , Ratos Sprague-DawleyRESUMO
This scientific statement is about sedentary behavior and its relationship to obesity and other cardiometabolic outcomes in youth. A deleterious effect of sedentary behavior on cardiometabolic health is most notable for screen-based behaviors and adiposity; however, this relation is less apparent for other cardiometabolic outcomes or when sedentary time is measured with objective movement counters or position monitors. Increasing trends of screen time are concerning; the portability of screen-based devices and abundant access to unlimited programming and online content may be leading to new patterns of consumption that are exposing youth to multiple pathways harmful to cardiometabolic health. This American Heart Association scientific statement provides an updated perspective on sedentary behaviors specific to modern youth and their impact on cardiometabolic health and obesity. As we reflect on implications for practice, research, and policy, what emerges is the importance of understanding the context in which sedentary behaviors occur. There is also a need to capture the nature of sedentary behavior more accurately, both quantitatively and qualitatively, especially with respect to recreational screen-based devices. Further evidence is required to better inform public health interventions and to establish detailed quantitative guidelines on specific sedentary behaviors in youth. In the meantime, we suggest that televisions and other recreational screen-based devices be removed from bedrooms and absent during meal times. Daily device-free social interactions and outdoor play should be encouraged. In addition, parents/guardians should be supported to devise and enforce appropriate screen time regulations and to model healthy screen-based behaviors.
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Comportamento do Adolescente , Comportamento Infantil , Exercício Físico , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Estilo de Vida Saudável , Obesidade Infantil/prevenção & controle , Comportamento de Redução do Risco , Comportamento Sedentário , Adolescente , Fatores Etários , American Heart Association , Criança , Pré-Escolar , Humanos , Lactente , Obesidade Infantil/epidemiologia , Obesidade Infantil/fisiopatologia , Obesidade Infantil/psicologia , Jogos e Brinquedos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Tempo de Tela , Fatores de Tempo , Estados UnidosRESUMO
Physical inactivity is one of the most prevalent major health risk factors, with 8 in 10 US adults not meeting aerobic and muscle-strengthening guidelines, and is associated with a high burden of cardiovascular disease. Improving and maintaining recommended levels of physical activity leads to reductions in metabolic, hemodynamic, functional, body composition, and epigenetic risk factors for noncommunicable chronic diseases. Physical activity also has a significant role, in many cases comparable or superior to drug interventions, in the prevention and management of >40 conditions such as diabetes mellitus, cancer, cardiovascular disease, obesity, depression, Alzheimer disease, and arthritis. Whereas most of the modifiable cardiovascular disease risk factors included in the American Heart Association's My Life Check - Life's Simple 7 are evaluated routinely in clinical practice (glucose and lipid profiles, blood pressure, obesity, and smoking), physical activity is typically not assessed. The purpose of this statement is to provide a comprehensive review of the evidence on the feasibility, validity, and effectiveness of assessing and promoting physical activity in healthcare settings for adult patients. It also adds concrete recommendations for healthcare systems, clinical and community care providers, fitness professionals, the technology industry, and other stakeholders in order to catalyze increased adoption of physical activity assessment and promotion in healthcare settings and to contribute to meeting the American Heart Association's 2020 Impact Goals.
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Doenças Cardiovasculares/prevenção & controle , Exercício Físico , Promoção da Saúde , Estilo de Vida Saudável , Comportamento de Redução do Risco , American Heart Association , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Nível de Saúde , Humanos , Prognóstico , Fatores de Proteção , Fatores de Risco , Comportamento Sedentário , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The health impacts of community design have been studied extensively over the past two decades. In particular, public transportation use is associated with more walking between transit stops and shops, work, home and other destinations. Change in transit access has been linked with physical activity and obesity but seldom to health outcomes and associated costs, especially within a causal framework. Health related fiscal impacts of transit investment should be a key consideration in major transit investment decisions. METHODS: The Rails & Health study is a natural experiment evaluating changes in clinical measures, health care utilization and health care costs among Kaiser Permanente Northwest (KPNW) members following the opening of a new light rail transit (LRT) line in Portland, Oregon. The study is prospectively following 3036 adults exposed to the new LRT line and a similar cohort of 4386 adults who do not live close to the new line. Individual-level outcomes and covariates are extracted from the electronic medical record at KPNW, including member demographics and comorbidities, blood pressure, body mass index, lipids, glycosylated hemoglobin, and health care utilization and costs. In addition, participants are surveyed about additional demographics, travel patterns, physical activity (PA), and perceived neighborhood walkability. In a subsample of the study population, we are collecting direct measures of travel-related behavior-physical activity (accelerometry), global positioning system (GPS) tracking, and travel diaries-to document mechanisms responsible for observed changes in health outcomes and cost. Comprehensive measures of the built environment at baseline and after rail construction are also collected. Statistical analyses will (1) examine the effects of opening a new LRT line on chronic disease indicators, health care utilization, and health care costs and (2) evaluate the degree to which observed effects of the LRT line on health measures and costs are mediated by changes in total and transportation-associated PA. DISCUSSION: The results of the Rails & Health study will provide urban planners, transportation engineers, health practitioners, developers, and decision makers with critical information needed to document how transit investments impact population health and related costs.
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Doença Crônica/epidemiologia , Planejamento Ambiental/economia , Planejamento Ambiental/estatística & dados numéricos , Inquéritos Epidemiológicos/estatística & dados numéricos , Ferrovias/economia , Ferrovias/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oregon/epidemiologia , Estudos Prospectivos , Características de Residência , Adulto JovemRESUMO
Epidemiological evidence is accumulating that indicates greater time spent in sedentary behavior is associated with all-cause and cardiovascular morbidity and mortality in adults such that some countries have disseminated broad guidelines that recommend minimizing sedentary behaviors. Research examining the possible deleterious consequences of excess sedentary behavior is rapidly evolving, with the epidemiology-based literature ahead of potential biological mechanisms that might explain the observed associations. This American Heart Association science advisory reviews the current evidence on sedentary behavior in terms of assessment methods, population prevalence, determinants, associations with cardiovascular disease incidence and mortality, potential underlying mechanisms, and interventions. Recommendations for future research on this emerging cardiovascular health topic are included. Further evidence is required to better inform public health interventions and future quantitative guidelines on sedentary behavior and cardiovascular health outcomes.
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Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Morbidade/tendências , Atividade Motora/fisiologia , Comportamento Sedentário , American Heart Association , Humanos , Prevalência , Fatores de Risco , Estados UnidosRESUMO
GluN1 is a mandatory component of N-methyl-D-aspartate receptors (NMDARs) best known for their roles in the brain, but with increasing evidence for relevance in peripheral tissues, including platelets. Certain anti-GluN1 antibodies reduce brain infarcts in rodent models of ischaemic stroke. There is also evidence that human anti-GluN1 autoantibodies reduce neuronal damage in stroke patients, but the underlying mechanism is unclear. This study investigated whether anti-GluN1-mediated neuroprotection involves inhibition of platelet function. Four commercial anti-GluN1 antibodies were screened for their abilities to inhibit human platelet aggregation. Haematological parameters were examined in rats vaccinated with GluN1. Platelet effects of a mouse monoclonal antibody targeting the glycine-binding region of GluN1 (GluN1-S2) were tested in assays of platelet activation, aggregation and thrombus formation. The epitope of anti-GluN1-S2 was mapped and the mechanism of antibody action modelled using crystal structures of GluN1. Our work found that rats vaccinated with GluN1 had a mildly prolonged bleeding time and carried antibodies targeting mostly GluN1-S2. The monoclonal anti-GluN1-S2 antibody (from BD Biosciences) inhibited activation and aggregation of human platelets in the presence of adrenaline, adenosine diphosphate, collagen, thrombin and a protease-activated receptor 1-activating peptide. When human blood was flowed over collagen-coated surfaces, anti-GluN1-S2 impaired thrombus growth and stability. The epitope of anti-GluN1-S2 was mapped to α-helix H located within the glycine-binding clamshell of GluN1, where the antibody binding was computationally predicted to impair opening of the NMDAR channel. Our results indicate that anti-GluN1-S2 inhibits function of human platelets, including dense granule release and thrombus growth. Findings add to the evidence that platelet NMDARs regulate thrombus formation and suggest a novel mechanism by which anti-GluN1 autoantibodies limit stroke-induced neuronal damage.
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Autoanticorpos/sangue , Plaquetas/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Trombose/genética , Animais , Humanos , Masculino , Ratos , Ratos WistarRESUMO
INTRODUCTION: Various phenotypes of overweight and obesity pose various health risks. The objective of this study was to determine the prevalence of 4 commonly measured cardiometabolic risk factors (CRFs) among adults with overweight or obesity, but not diabetes, at the time of the study. METHODS: We analyzed data for 1,294,174 adults (aged ≥20 y) who were members of one of 4 integrated health systems. Each cohort member had a body mass index in 2012 or 2013 that indicated overweight or obesity. We determined the presence of 4 CRFs within 1 year of the first BMI measurement: elevated blood pressure (systolic ≥130 mm Hg or diastolic >85 mm Hg or ICD-9-CM [International Classification of Diseases, Ninth Revision, Clinical Modification] diagnosis code 401.0-405.9); elevated triglycerides (≥150 mg/dL or ICD-9-CM 272.1); low high-density lipoprotein cholesterol (<40 mg/dL for men or <50 mg/dL for women or ICD-9-CM 272.5); and prediabetes (fasting glucose 100-125 mg/dL or HbA1c 5.7%-6.4% or ICD-9-CM 790.2x). We tested the risk of having 1 or more CRFs after adjusting for obesity class and demographic characteristics with multivariable logistic regression. RESULTS: Among participants with overweight (52.5% of the sample), 18.6% had none of the 4 CRFs. Among the 47.5% of participants with obesity, 9.6% had none; among participants with morbid obesity, 5.8% had none. Age was strongly associated with CRFs in multivariable analysis. CONCLUSION: Almost 10% of participants with obesity had no CRFs. Overweight or obesity increases cardiometabolic risk, but the number and type of CRFs varied substantially by age, even among participants with morbid obesity.
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Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Overweight and obesity are epidemic among persons with serious mental illness, yet weight-loss trials systematically exclude this vulnerable population. Lifestyle interventions require adaptation in this group because psychiatric symptoms and cognitive impairment are highly prevalent. Our objective was to determine the effectiveness of an 18-month tailored behavioral weight-loss intervention in adults with serious mental illness. METHODS: We recruited overweight or obese adults from 10 community psychiatric rehabilitation outpatient programs and randomly assigned them to an intervention or a control group. Participants in the intervention group received tailored group and individual weight-management sessions and group exercise sessions. Weight change was assessed at 6, 12, and 18 months. RESULTS: Of 291 participants who underwent randomization, 58.1% had schizophrenia or a schizoaffective disorder, 22.0% had bipolar disorder, and 12.0% had major depression. At baseline, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.3, and the mean weight was 102.7 kg (225.9 lb). Data on weight at 18 months were obtained from 279 participants. Weight loss in the intervention group increased progressively over the 18-month study period and differed significantly from the control group at each follow-up visit. At 18 months, the mean between-group difference in weight (change in intervention group minus change in control group) was -3.2 kg (-7.0 lb, P=0.002); 37.8% of the participants in the intervention group lost 5% or more of their initial weight, as compared with 22.7% of those in the control group (P=0.009). There were no significant between-group differences in adverse events. CONCLUSIONS: A behavioral weight-loss intervention significantly reduced weight over a period of 18 months in overweight and obese adults with serious mental illness. Given the epidemic of obesity and weight-related disease among persons with serious mental illness, our findings support implementation of targeted behavioral weight-loss interventions in this high-risk population. (Funded by the National Institute of Mental Health; ACHIEVE ClinicalTrials.gov number, NCT00902694.).
Assuntos
Terapia Comportamental , Transtornos Mentais/complicações , Obesidade/terapia , Redução de Peso , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Sobrepeso/psicologia , Sobrepeso/terapia , Cooperação do Paciente/estatística & dados numéricosRESUMO
A 4-week-old female infant presented to the emergency department (ED) due to a 1-week history of not moving her left lower extremity as well as crying during diaper changes. She had been seen 6 days prior at an ED, had normal x-rays, and was discharged home. The infant was afebrile and well appearing and had been feeding well all week. Laboratory tests in our department, including a complete blood count with differential and inflammatory markers, were all normal. Repeat x-rays showed a subtle distal tibial lucency, initially overlooked. The infant was admitted to the hospital and received a magnetic resonance imaging,which demonstrated distal tibial osteomyelitis with an accompanying ankle effusion. Cultures from the bone grew group B Streptococcus, and the infant received 6 weeks of antibiotic therapy.