Circulating miRNAs in acute new-onset atrial fibrillation and their target mRNA network.

BACKGROUND: MicroRNAs (miRNAs) are involved in the pathogenesis of atrial fibrillation (AF), acting on development and progression. Our pilot study investigated the expression of six miRNAs and their miRNA-mRNA interactions in patients with acute new-onset AF, well-controlled AF, and normal sinus rhythm (controls). METHODS AND RESULTS: Plasma of acute new-onset AF patients (n = 5) was collected in the emergency room when patients presented with irregular and fast-atrial fibrillation rhythm. Samples from well-controlled AF (n = 16) and control (n =  15) patients were collected during medical appointments following an ECG. Expression of miR-21, miR-133a, miR-133b, miR-150, miR-328, and miR-499 was analyzed by real-time PCR. Ingenuity Pathway Analysis and the TargetScan database identified the top 30 mRNA targets of these miRNA, seeking the miRNA-mRNA interactions in cardiovascular process. Increased expression of miR-133b (1.4-fold), miR-328 (2.0-fold), and miR-499 (2.3-fold) was observed in patients with acute new-onset AF, compared with well-controlled AF and control patients. Decreased expression of miR-21 was seen in patients with well-controlled AF compared to those with acute new-onset AF and controls (0.6-fold). The miRNA-mRNA interaction demonstrated that SMAD7 and FASLG genes were the targets of miR-21, miR-133b, and miR-499 and were directly related to AF, being involved in apoptosis and fibrosis. CONCLUSION: The miRNAs had different expression profiles dependent on the AF condition, with higher expression in the acute new-onset AF than well-controlled AF. Clinically, this may contribute to an effective assessment for patients, leading to early detection of AF and monitoring to reduce the risk of other serious cardiovascular events.

Effect of the COVID-19 pandemic on malnutrition in socially vulnerable children in Brazil. / Efeito da pandemia da COVID-19 sobre a má nutrição em crianças em vulnerabilidade social, no Brasil.

This article aims to evaluate the effect of the COVID-19 pandemic on malnutrition among children under two years of age enrolled in the Bolsa Família Program (BFP). Ecological study of interrupted time series (ITS), with low weight for age, stunting, and overweight as time-dependent variables of malnutrition, extracted monthly (Jan/2008 to June/2021) from the Food and Nutrition Surveillance System. The COVID-19 pandemic was the exposure, dichotomized into pre-pandemic and pandemic. In RStudio, the trend was obtained by Prais-Winsten regression, and the effect of the pandemic on the time-dependent variables was determined by SARIMA modeling, estimating the regression coefficients (RC) adjusted for trend and seasonality (α = 5%). The pandemic was associated with an increase in: i) low weight for age in the South (RC = 0.94; p < 0.001) and Southeast (RC = 1.97; p < 0.001); ii) height deficit in the Midwest (RC = 2.4; p = 0.01), South (RC = 2.15; p < 0.001) and Southeast (RC = 2.96; p < 0.001); and iii) and overweight in the North (RC = 1.51; p = 0.04), Midwest (RC = 2.29; p = 0.01), South (RC = 2.83; p < 0.001), and Southeast (RC = 0.72; p = 0.04). The pandemic increased underweight in the South and Southeast, and the double burden of malnutrition in the Midwest, South, and Southeast. In the Northeast and North, higher rates of malnutrition still persist.

O objetivo do artigo é avaliar o efeito da pandemia de COVID-19 sobre a má nutrição em crianças menores de dois anos inscritas no Programa Bolsa Família. Estudo ecológico de série temporal interrompida, tendo o baixo peso por idade, o déficit de estatura e o excesso de peso como variáveis tempo-dependentes de má nutrição, extraídas mensalmente (jan/2008 a junho/2021) do Sistema de Vigilância Alimentar e Nutricional. A pandemia de COVID-19 foi a exposição, dicotomizada em pré e pandemia. No programa RStudio, a tendência foi obtida pela regressão de Prais-Winsten, e o efeito da pandemia sobre as variáveis tempo-dependentes, pela modelagem SARIMA, calculando-se coeficientes de regressão (CR) ajustados para tendência prévia e sazonalidade (α = 5%). A pandemia se associou ao aumento do: i) baixo peso por idade no Sul (CR = 0,94; p < 0,001) e Sudeste (CR = 1,97; p < 0,001); ii) déficit de estatura no Centro-Oeste (CR = 2,4; p = 0,01), Sul (CR = 2,15; p < 0,001) e Sudeste (CR = 2,96; p < 0,001); e iii) excesso de peso no Norte (CR = 1,51; p=0,04), Centro-Oeste (CR = 2,29; p = 0,01), Sul (CR = 2,83; p < 0,001) e Sudeste (CR = 0,72; p = 0,04). A pandemia aumentou o baixo peso no Sul e Sudeste e a dupla carga de má nutrição no Centro-Oeste, no Sul e no Sudeste. No Nordeste e no Norte persistem taxas mais altas de má nutrição.

The Brazilian National Oral Health Policy and oral cancer mortality trends: An autoregressive integrated moving average (ARIMA) model.

OBJECTIVE: This study analyzes the effect of the Brazilian National Oral Health Policy (NOHP) on oral cancer mortality rates (OCMR). METHOD: This is an ecological study with secondary oral cancer death data, using interrupted time series analysis (ARIMA, Autoregressive Integrated Moving Average). Annual death data were collected from the Mortality Information System (1996-2019). The outcome was the OCMR, standardized by gender and age We considered the NOHP, categorized as "0" (before its implementation), from 1996 to 2004, and "1 to 15", from 2005 to 2019. ARIMA modeling was carried out for temporal analysis, and regression coefficient estimation (RC). RESULTS: The Brazilian NOHP implementation was associated with an increase in OCMR in the North region (CR = 0.16; p = 0.022) and with a decrease in the Southeast region (CR = -0.04; p<0.001), but did not affect the other macro-regions nor Brazil. The forecast models estimated an increase in OCMR for the North, and Northeast, a decrease for the Southeast, and stability for the South and Brazil. CONCLUSION: The Brazilian NOHP is not being effective in reducing the OCMR. The trends behaved differently in the Brazilian territory, highlighting health inequities. We recommend that the NOHP strengthen the oral health care network, incorporating oral cancer as a notifiable disease, adopting strategies for prevention, screening, and providing opportunities for early treatment of the disease.

Efeitos da pandemia de COVID-19 nos serviços odontológicos da atenção primária no Maranhão, Brasil / Effects of the COVID-19 pandemic on dental services in primary care in Maranhão, Brazil

Resumo O objetivo deste artigo é analisar indicadores de uso de serviços de saúde bucal da atenção primária à saúde no Maranhão antes e durante a pandemia de COVID-19. Estudo ecológico de série temporal interrompida cuja unidade de análise foi o Maranhão. A exposição foi a pandemia de COVID-19, dicotomizada em pré e pandemia. Os desfechos foram calculados pela razão da quantidade de procedimentos preventivos (RPP), de urgência (RPU) e procedimentos curativos (RPC), e a projeção censitária da população do estado, multiplicada por mil, mensalmente. Os dados foram coletados do Sistema de Informação em Saúde para a Atenção Básica e do Instituto Brasileiro de Geografia e Estatística, no período de 2015.1 a 2022.2. As análises foram realizadas por meio do modelo autorregressivo, integrado e de médias móveis com sazonalidade. Houve tendência crescente dos três indicadores até jan./2019. A pandemia causou redução significativa na RPP (Xreg = -6,55; p-valor = 0,0008) e na RPC (Xreg = -4,74; p-valor = 0,0005), mas não influenciou a RPU (Xreg = -0,03; p-valor = 0,12) desde o primeiro semestre de 2020, persistindo até o segundo semestre de 2022. A pandemia de COVID-19 provocou redução nos serviços preventivos e curativos de saúde bucal no Maranhão.

Abstract This article aims to analyze indicators of the utilization of oral health services (UOHS) in primary health care in the state of Maranhão, Brazil, before and during the COVID-19 pandemic. We conducted an ecological time series study. The unit of analysis was the state of Maranhão, and the exposure variable was the COVID-19 pandemic, dichotomized into pre-pandemic and pandemic. The outcome variables were the monthly rates per 1,000 population of three UOHS indicators: rate of preventive procedures (RPP-PHC); rate of urgent procedures (RUP-PHC), and rate of curative procedures (RCP-PHC). The data were collected from the Primary Health Care Information System (SISAB) and the Brazilian Institute of Geography and Statistics (IBGE) for the period from 2015-2022. The analyses were performed using the Seasonal Autoregressive Integrated Moving Average (SARIMA) model. The three indicators showed an upward trend up to January 2019. The pandemic caused a significant reduction in the RPP (Xreg = -6.55; p-value = 0.0008) and RCP (Xreg = -4.74; p-value = 0.0005), starting in the first semester of 2020 and continuing into the second semester of 2022, but did not influence the RUP (Xreg = -0.03; p-value = 0.12). The COVID-19 pandemic caused a reduction in preventive and curative oral health services in Maranhão.

Integrated analysis of miRNA and mRNA gene expression microarrays: Influence on platelet reactivity, clopidogrel response and drug-induced toxicity.

Genetic and epigenetic variability may influence the efficacy and safety of antiplatelet therapies, including clopidogrel. Therefore, the miRNA-mRNA interactions and drug toxicity were investigated in silico using available microarray data. Expressions profiles of platelet miRNA (GSE59488) from acute coronary syndrome and mRNA in peripheral blood cells (GSE32226) from coronary artery disease patients were used to miRNA-target mRNA integrated analysis by Ingenuity Pathways Analysis 6 software (IPA). Results showed that ST13 mRNA is regulated by hsa-miR-107 (miR-103-3p); BTNL3 and CFD mRNAs are regulated by hsa-miR-4701-3p (miR-1262); SLC7A8 is regulated by hsa-miR-145-5p (miR-145-5p); and SENP5 mRNA is regulated by hsa-miR-15b-5p (miR-16-5p) and hsa-miR-26a-5p (miR-26a-5p). Drug toxicity IPA tool showed that these miRNAs/mRNAs are associated with clopidogrel-related liver and renal injury. In conclusion, these results demonstrate that differential expression of miRNAs in platelets and interactions with their target mRNAs are associated with variability in platelet reactivity, clopidogrel response and drug-induced toxicity.