Regional ion channel gene expression heterogeneity and ventricular fibrillation dynamics in human hearts.

RATIONALE: Structural differences between ventricular regions may not be the sole determinant of local ventricular fibrillation (VF) dynamics and molecular remodeling may play a role. OBJECTIVES: To define regional ion channel expression in myopathic hearts compared to normal hearts, and correlate expression to regional VF dynamics. METHODS AND RESULTS: High throughput real-time RT-PCR was used to quantify the expression patterns of 84 ion-channel, calcium cycling, connexin and related gene transcripts from sites in the LV, septum, and RV in 8 patients undergoing transplantation. An additional eight non-diseased donor human hearts served as controls. To relate local ion channel expression change to VF dynamics localized VF mapping was performed on the explanted myopathic hearts right adjacent to sampled regions. Compared to non-diseased ventricles, significant differences (p<0.05) were identified in the expression of 23 genes in the myopathic LV and 32 genes in the myopathic RV. Within the myopathic hearts significant regional (LV vs septum vs RV) expression differences were observed for 13 subunits: Nav1.1, Cx43, Ca3.1, Cavalpha2delta2, Cavbeta2, HCN2, Na/K ATPase-1, CASQ1, CASQ2, RYR2, Kir2.3, Kir3.4, SUR2 (p<0.05). In a subset of genes we demonstrated differences in protein expression between control and myopathic hearts, which were concordant with the mRNA expression profiles for these genes. Variability in the expression of Cx43, hERG, Na(+)/K(+) ATPase ss1 and Kir2.1 correlated to variability in local VF dynamics (p<0.001). To better understand the contribution of multiple ion channel changes on VF frequency, simulations of a human myocyte model were conducted. These simulations demonstrated the complex nature by which VF dynamics are regulated when multi-channel changes are occurring simultaneously, compared to known linear relationships. CONCLUSIONS: Ion channel expression profile in myopathic human hearts is significantly altered compared to normal hearts. Multi-channel ion changes influence VF dynamic in a complex manner not predicted by known single channel linear relationships

The association of neighbourhood and individual social capital with consistent self-rated health: a longitudinal study in Brazilian pregnant and postpartum women.

BACKGROUND: Social conditions, social relationships and neighbourhood environment, the components of social capital, are important determinants of health. The objective of this study was to investigate the association of neighbourhood and individual social capital with consistent self-rated health in women between the first trimester of pregnancy and six months postpartum. METHODS: A multilevel cohort study in 34 neighbourhoods was performed on 685 Brazilian women recruited at antenatal units in two cities in the State of Rio de Janeiro, Brazil. Self-rated health (SRH) was assessed in the 1st trimester of pregnancy (baseline) and six months after childbirth (follow-up). The participants were divided into two groups: 1. Good SRH--good SRH at baseline and follow-up, and, 2. Poor SRH--poor SRH at baseline and follow-up. Exploratory variables collected at baseline included neighbourhood social capital (neighbourhood-level variable), individual social capital (social support and social networks), demographic and socioeconomic characteristics, health-related behaviours and self-reported diseases. A hierarchical binomial multilevel analysis was performed to test the association between neighbourhood and individual social capital and SRH, adjusted for covariates. RESULTS: The Good SRH group reported higher scores of social support and social networks than the Poor SRH group. Although low neighbourhood social capital was associated with poor SRH in crude analysis, the association was not significant when individual socio-demographic variables were included in the model. In the final model, women reporting poor SRH both at baseline and follow-up had lower levels of social support (positive social interaction) [OR 0.82 (95% CI: 0.73-0.90)] and a lower likelihood of friendship social networks [OR 0.61 (95% CI: 0.37-0.99)] than the Good SRH group. The characteristics that remained associated with poor SRH were low level of schooling, Black and Brown ethnicity, more children, urinary infection and water plumbing outside the house. CONCLUSIONS: Low individual social capital during pregnancy, considered here as social support and social network, was independently associated with poor SRH in women whereas neighbourhood social capital did not affect women's SRH during pregnancy and the months thereafter. From pregnancy and up to six months postpartum, the effect of individual social capital explained better the consistency of SRH over time than neighbourhood social capital

The effects of TNF-alpha inhibitor therapy on the incidence of infection in JIA children

Juvenile Idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The diagnosis is based on the underlying symptoms of arthritis with an exclusion of other diseases Biologic agents are increasingly used on the side of disease-modifying anti-rheumatic drugs (DMARD) in JIA treatment.The aim of this meta-analysis was to investigate the observed infections in JIA children during tumor necrosis factor (TNF)-alpha inhibitor therapy. A systematic search of three databases (Medline via PubMed, Embase, Cochrane Library) was carried out up to May 2018. Published trials that evaluated the infectious adverse events in patients receiving TNF-alpha inhibitor vs. a control group were included in the analysis. Full-text data extraction was carried out independently by the investigators from ten relevant publications. 1434 patients received TNF-alpha inhibitor therapy; the control group consisted of 696 subjects. The analysis presented the risk of infection in the active treatment group (OR = 1.13; 95% CI: 0.76-1.69; p = 0.543). The majority of infections were upper respiratory tract infections (URTIs). Furthermore, the subgroup analysis demonstrated a higher infection rate in the observed localization.Anti-TNF therapy slightly but not significantly increases the incidence of infection in JIA children compared to other therapies (GRADE: moderate evidence). The most common infections reported were mild URTIs. Further studies with larger patients number with a strong evidence level are crucially needed to finalize the answer whether anti-TNF therapy elevates and if yes on what extent the incidence of infection in JIA children.Prospero: CRD42017067873

Quantification of Human Cytomegalovirus DNA by Real-Time PCR

A quantitative real-time PCR assay was developed to measure human cytomegalovirus (HCMV) DNA load in peripheral blood leukocytes (PBLs). The HCMV DNA load in PBLs was normalized by means of the quantification of a cellular gene (albumin). The results of the real-time PCR assay correlated with those of the HCMV pp65-antigenemia assay (P < 0.0001)

Parentesco, escravidão e liberdade (Porto Feliz, São Paulo, século XIX) Kinship, slavery and freedom (Porto Feliz, São Paulo, 19th century)

Focado na cidade de Porto Feliz, capitania/província de São Paulo, o trabalho analisa como motivos de ordem familiar influenciaram conflitos entre senhores e escravos em torno da liberdade e da escravidão. Nas últimas décadas da escravidão, em meio a pressões em prol da liberdade e de relativa perda de legitimidade da escravidão, nota-se, por parte de uma família senhorial, o esforço em preservar essa condição construída ao longo de gerações. Senhores com (ante)passado escravo e famílias cativas que almejavam a liberdade conduziram-se por motivos parentais, ainda que com objetivos diferentes<br>Focused in Porto Feliz, captaincy/province of São Paulo, this study analyzes how family reasons influenced conflicts between masters and slaves about freedom and slavery. At the ends of slavery, with pressures for freedom and relative loss of legitimacy of slavery, a master family tried to preserve its social position, built up over generations and over slavery. By other hand, slaves families sought to achieve freedom. Thus, a former slave family and a slave family joined forces to defend their kinships interest