Atrial Fibrillation Diagnosis using ECG Records and Self-Report in the Community:Cross-Sectional Analysis from ELSA-Brasil

FUNDAMENTO: A fibrilação ou flutter atrial (FFA) é a arritmia cardíaca sustentada mais comum. Existem poucos dados sobre a epidemiologia da FFA na América do Sul. OBJETIVO: O presente estudo procurou descrever a epidemiologia clínica da FFA e o uso de anticoagulantes na avaliação da linha de base do Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil). MÉTODOS: Foram analisados dados de 13.260 participantes do ELSA-Brasil. A FFA foi definida pelo eletrocardiograma ou por autorrelato. Modelos de regressão logística foram construídos para analisar fatores associados à FFA. Este estudo também analisou se idade e sexo estavam associados ao uso de anticoagulantes para evitar acidente vascular cerebral. O nível de significância foi de 5%. RESULTADOS: A idade mediana foi de 51 anos, e 7.213 (54,4%) participantes eram mulheres. A FFA foi detectada em 333 (2,5%) participantes. O aumento da idade (razão de chances [RC]:1,05; intervalo de confiança de 95% [IC95%]: 1,04-1,07), hipertensão (RC:1,44; IC95%:1,14-1,81) coronariopatia (RC: 5,11; IC95%:3,85–6,79), insuficiência cardíaca (RC:7,37; IC95%:5,00–10,87) e febre reumática (RC:3,38; IC95%:2,28–5,02) foram associadas à FFA. Dos 185 participantes com FFA e pontuação no CHA(2)DS(2)-VASc≥2, apenas 20 (10,8%) usavam anticoagulantes (50,0% entre aqueles com FFA no eletrocardiograma de linha de base). O uso de anticoagulantes nesse grupo foi associado a maior idade (1,8% vs 17,7% naqueles com idade ≤ 54 e ≥ 65 anos, respectivamente; p=0,013). Observou-se uma tendência ao menor uso de anticoagulantes em mulheres (7,1% vs. 16,4% em mulheres e homens, respectivamente; p=0,055). CONCLUSÕES: No recrutamento do ELSA-Brasil, 2,5% dos participantes tinham FFA. O baixo uso de anticoagulantes era comum, o que representa um desafio para os cuidados de saúde nesse cenário

“Keep That in Mind!” The Role of Positive Affect in Working Memory for Maintaining Goal-Relevant Information

Some studies have demonstrated a beneficial role of Positive Affect on working memory (WM) by either applying protocols of mood induction or assessing naturally occurring state Positive Affect. However, there are no studies directly linking Positive Affect as a stable personality-like trait with WM. We aimed to address this potential relationship using the Positive and Negative Affect Schedule scale and contra-lateral delay activity (CDA) as measures of trait Positive Affect and WM Capacity, respectively. We also sought to investigate the impact of a neutral or unpleasant emotional state on this relationship. Participants performed a change detection task, while a neutral or an unpleasant emotional state was induced. Our results showed a positive robust correlation between trait Positive Affect and WM Capacity for both neutral and unpleasant emotional states, as revealed by the neuroelectrophysiological gold-standard measure of WM, namely, CDA. These data suggest a tangible role of trait Positive Affect in the cognitive ability of maintaining goal-relevant information in WM, such that even a highly disruptive state is not sufficient to corrupt this relationship

Logistica de coleta e transporte de material biologico e organizacao do laboratorio central no ELSA-Brasil

The ELSA (Estudo Longitudinal de Saúde do Adulto - Brazilian Longitudinal Study for Adult Health) is a multicenter cohort study which aims at the identification of risk factors associated with type 2 diabetes and cardiovascular diseases in the Brazilian population. The paper describes the strategies for the collection, processing, transportation, and quality control of blood and urine tests in the ELSA. The study decided to centralize the tests at one single laboratory. The processing of the samples was performed at the local laboratories, reducing the weight of the material to be transported, and diminishing the costs of transportation to the central laboratory at the Universidade de São Paulo Hospital. The study included tests for the evaluation of diabetes, insulin resistance, dyslipidemia, electrolyte abnormalities, thyroid hormones, uric acid, hepatic enzyme abnormalities, inflammation, and total blood cell count. In addition, leukocyte DNA, urine, plasma and serum samples were stored. The central laboratory performed approximately 375,000 tests.O Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) é um estudo de coorte multicêntrico com o objetivo de identificar os fatores de risco associados ao diabetes tipo 2 e à doença cardiovascular na população brasileira. O artigo descreve as estratégias de coleta, processamento, transporte e de controle de qualidade dos exames de sangue e urina no ELSA. O estudo optou pela centralização dos exames em um único laboratório. O processamento das amostras foi realizado nos laboratórios locais, reduzindo o peso do material a ser transportado e diminuindo os custos do transporte para o laboratório central no Hospital da Universidade de São Paulo. O estudo incluiu exames para avaliação de diabetes, resistência à insulina, dislipidemias, alterações eletrolíticas, hormônios tireoidianos, ácido úrico, alterações de enzimas hepáticas, inflamação e hemograma completo. Além desses exames, foram estocados DNA de leucócitos, amostras de urina, plasma e soro. O laboratório central realizou aproximadamente 375.000 exames

Regulation of Stress-Inducible Phosphoprotein 1 Nuclear Retention by Protein Inhibitor of Activated STAT PIAS1

Stress-inducible phosphoprotein 1 (STI1), a cochaperone for Hsp90, has been shown to regulate multiple pathways in astrocytes, but its contributions to cellular stress responses are not fully understood. We show that in response to irradiation-mediated DNA damage stress STI1 accumulates in the nucleus of astrocytes. Also, STI1 haploinsufficiency decreases astrocyte survival after irradiation. Using yeast two-hybrid screenings we identified several nuclear proteins as STI1 interactors. Overexpression of one of these interactors, PIAS1, seems to be specifically involved in STI1 nuclear retention and in directing STI1 and Hsp90 to specific sub-nuclear regions. PIAS1 and STI1 co-immunoprecipitate and PIAS1 can function as an E3 SUMO ligase for STI. Using mass spectrometry we identified five SUMOylation sites in STI1. A STI1 mutant lacking these five sites is not SUMOylated, but still accumulates in the nucleus in response to increased expression of PIAS1, suggesting the possibility that a direct interaction with PIAS1 could be responsible for STI1 nuclear retention. To test this possibility, we mapped the interaction sites between PIAS1 and STI1 using yeast-two hybrid assays and surface plasmon resonance and found that a large domain in the N-terminal region of STI1 interacts with high affinity with amino acids 450-480 of PIAS1. Knockdown of PIAS1 in astrocytes impairs the accumulation of nuclear STI1 in response to irradiation. Moreover, a PIAS1 mutant lacking the STI1 binding site is unable to increase STI1 nuclear retention. Interestingly, in human glioblastoma multiforme PIAS1 expression is increased and we found a significant correlation between increased PIAS1 expression and STI1 nuclear localization. These experiments provide evidence that direct interaction between STI1 and PIAS1 is involved in the accumulation of nuclear STI1. This retention mechanism could facilitate nuclear chaperone activity. Molecular & Cellular Proteomics 12: 10.1074/mcp.M113.031005, 3253-3270, 2013

Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

CONTEXT AND OBJECTIVE: Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD) have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study.DESIGN AND SETTINGS: Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university.METHODS: Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe) and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT). We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI) and the hepatic steatosis index (HSI).RESULTS: Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point ≥ 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91)]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83) than CT.CONCLUSION: The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening

CD8+ T-Cells Expressing Interferon Gamma or Perforin Play Antagonistic Roles in Heart Injury in Experimental Trypanosoma Cruzi-Elicited Cardiomyopathy

In Chagas disease, CD8+ T-cells are critical for the control of Trypanosoma cruzi during acute infection. Conversely, CD8+ T-cell accumulation in the myocardium during chronic infection may cause tissue injury leading to chronic chagasic cardiomyopathy (CCC). Here we explored the role of CD8+ T-cells in T. cruzi-elicited heart injury in C57BL/6 mice infected with the Colombian strain. Cardiomyocyte lesion evaluated by creatine kinase-MB isoenzyme activity levels in the serum and electrical abnormalities revealed by electrocardiogram were not associated with the intensity of heart parasitism and myocarditis in the chronic infection. Further, there was no association between heart injury and systemic anti-T. cruzi CD8+ T-cell capacity to produce interferon-gamma (IFNγ) and to perform specific cytotoxicity. Heart injury, however, paralleled accumulation of anti-T. cruzi cells in the cardiac tissue. In T. cruzi infection, most of the CD8+ T-cells segregated into IFNγ+ perforin (Pfn)neg or IFNγnegPfn+ cell populations. Colonization of the cardiac tissue by anti-T. cruzi CD8+Pfn+ cells paralleled the worsening of CCC. The adoptive cell transfer to T. cruzi-infected cd8−/− recipients showed that the CD8+ cells from infected ifnγ−/−pfn+/+ donors migrate towards the cardiac tissue to a greater extent and caused a more severe cardiomyocyte lesion than CD8+ cells from ifnγ+/+pfn−/− donors. Moreover, the reconstitution of naïve cd8−/− mice with CD8+ cells from naïve ifnγ+/+pfn−/− donors ameliorated T. cruzi-elicited heart injury paralleled IFNγ+ cells accumulation, whereas reconstitution with CD8+ cells from naïve ifnγ−/−pfn+/+ donors led to an aggravation of the cardiomyocyte lesion, which was associated with the accumulation of Pfn+ cells in the cardiac tissue. Our data support a possible antagonist effect of CD8+Pfn+ and CD8+IFNγ+ cells during CCC. CD8+IFNγ+ cells may exert a beneficial role, whereas CD8+Pfn+ may play a detrimental role in T. cruzi-elicited heart injury

Action potential variability in human pluripotent stem cell-derived cardiomyocytes obtained from healthy donors

Human pluripotent stem cells (PSC) have been used for disease modelling, after differentiation into the desired cell type. Electrophysiologic properties of cardiomyocytes derived from pluripotent stem cells are extensively used to model cardiac arrhythmias, in cardiomyopathies and channelopathies. This requires strict control of the multiple variables that can influence the electrical properties of these cells. In this article, we report the action potential variability of 780 cardiomyocytes derived from pluripotent stem cells obtained from six healthy donors. We analyze the overall distribution of action potential (AP) data, the distribution of action potential data per cell line, per differentiation protocol and batch. This analysis indicates that even using the same cell line and differentiation protocol, the differentiation batch still affects the results. This variability has important implications in modeling arrhythmias and imputing pathogenicity to variants encountered in patients with arrhythmic diseases. We conclude that even when using isogenic cell lines to ascertain pathogenicity to variants associated to arrythmias one should use cardiomyocytes derived from pluripotent stem cells using the same differentiation protocol and batch and pace the cells or use only cells that have very similar spontaneous beat rates. Otherwise, one may find phenotypic variability that is not attributable to pathogenic variants

Global and national Burden of diseases and injuries among children and adolescents between 1990 and 2013

Importance The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce. Objective To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study. Evidence Review Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates. Findings Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world’s deaths from neonatal encephalopathy. Half of the world’s diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia. Conclusions and Relevance Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed

Global, regional, and national burden of neurological disorders during 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250.7 [95% uncertainty interval (UI) 229.1 to 274.7] million, comprising 10.2% of global DALYs) and the second-leading cause group of deaths (9.4 [9.1 to 9.7] million], comprising 16.8% of global deaths). The most prevalent neurological disorders were tensiontype headache (1505 9 [UI 1337.3 to 1681.6 million cases]), migraine (958.8 [872.1 to 1055.6] million), medication overuse headache (58.5 [50.8 to 67.4 million]), and Alzheimer's disease and other dementias (46.0 [40.2 to 52.7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36.7%, and the number of DALYs by 7.4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26.1% and 29.7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services.Peer reviewe