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BACKGROUND: Women, in comparison to men, experience worse outcomes after acute coronary syndrome (ACS). However, whether the female sex per se is an independent predictor of such adverse events remains unclear. OBJECTIVE: This study aims to assess the association between the female sex and in-hospital mortality after ST-elevation myocardial infarction (STEMI). METHODS: We conducted a retrospective cohort study by enrolling consecutive STEMI patients admitted to a tertiary hospital from January 2018 to February 2019. All patients were treated per current guideline recommendations. Multivariable logistic regression models were applied to evaluate in-hospital mortality using GRACE variables. Model accuracy was evaluated using c-index. A p-value < 0.05 was statistically significant. RESULTS: Out of the 1678 ACS patients, 709 presented with STEMI. The population consisted of 36% women, and the median age was 61 years. Women were older (63.13 years vs. 60.53 years, p = 0.011); more often presented with hypertension (75.1% vs. 62.4%, p = 0.001), diabetes (42.2% vs. 27.8%, p < 0.001), and hyperlipidemia (34.1% vs. 23.9%, p = 0.004); and were less likely to undergo percutaneous coronary intervention (PCI) via radial access (23.7% vs. 46.1%, p < 0.001). In-hospital mortality rate was significantly higher in women (13.2% vs. 5.6%, p = 0.001), and the female sex remained at higher risk for in-hospital mortality (OR 2.79, 95% CI 1.15-6.76, p = 0.023). A multivariate model including age, sex, systolic blood pressure, cardiac arrest, and Killip class was 94.1% accurate in predicting in-hospital mortality, and the c-index was 0.85 (95% CI 0.77-0.93). CONCLUSION: After adjusting for the risk factors in the GRACE prediction model, women remain at higher risk for in-hospital mortality.

FUNDAMENTO: As mulheres, em comparação aos homens, apresentam piores resultados após a síndrome coronariana aguda (SCA). No entanto, ainda não está claro se o sexo feminino em si é um preditor independente de tais eventos adversos. OBJETIVO: Este estudo tem como objetivo avaliar a associação entre o sexo feminino e a mortalidade hospitalar após infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). MÉTODOS: Conduzimos um estudo de coorte retrospectivo, recrutando pacientes consecutivos com IAMCSST, internados em um hospital terciário de janeiro de 2018 a fevereiro de 2019. Todos os pacientes foram tratados de acordo com as recomendações das diretrizes atuais. Modelos de regressão logística multivariada foram aplicados para avaliar a mortalidade hospitalar utilizando variáveis de GRACE. A precisão do modelo foi avaliada usando o índice c. Um valor de p < 0,05 foi estatisticamente significativo. RESULTADOS: Dos 1.678 pacientes com SCA, 709 apresentaram IAMCSST. A população era composta por 36% de mulheres e a idade média era de 61 anos. As mulheres tinham maior idade (63,13 anos vs. 60,53 anos, p = 0,011); apresentavam hipertensão (75,1% vs. 62,4%, p = 0,001), diabetes (42,2% vs. 27,8%, p < 0,001) e hiperlipidemia (34,1% vs. 23,9%, p = 0,004) mais frequentemente; e apresentaram menor probabilidade de serem submetidas a intervenção coronária percutânea (ICP) por acesso radial (23,7% vs. 46,1%, p < 0,001). A taxa de mortalidade hospitalar foi significativamente maior em mulheres (13,2% vs. 5,6%, p = 0,001), e o sexo feminino permaneceu em maior risco de mortalidade hospitalar (OR 2,79, IC de 95% 1,15­6,76, p = 0,023). Um modelo multivariado incluindo idade, sexo, pressão arterial sistólica, parada cardíaca e classe de Killip atingiu 94,1% de precisão na previsão de mortalidade hospitalar, e o índice c foi de 0,85 (IC de 95% 0,77­0,93). CONCLUSÃO: Após ajuste para os fatores de risco no modelo de previsão do GRACE, as mulheres continuam em maior risco de mortalidade hospitalar.

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Resumo Fundamento As mulheres, em comparação aos homens, apresentam piores resultados após a síndrome coronariana aguda (SCA). No entanto, ainda não está claro se o sexo feminino em si é um preditor independente de tais eventos adversos. Objetivo Este estudo tem como objetivo avaliar a associação entre o sexo feminino e a mortalidade hospitalar após infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). Métodos Conduzimos um estudo de coorte retrospectivo, recrutando pacientes consecutivos com IAMCSST, internados em um hospital terciário de janeiro de 2018 a fevereiro de 2019. Todos os pacientes foram tratados de acordo com as recomendações das diretrizes atuais. Modelos de regressão logística multivariada foram aplicados para avaliar a mortalidade hospitalar utilizando variáveis de GRACE. A precisão do modelo foi avaliada usando o índice c. Um valor de p < 0,05 foi estatisticamente significativo. Resultados Dos 1.678 pacientes com SCA, 709 apresentaram IAMCSST. A população era composta por 36% de mulheres e a idade média era de 61 anos. As mulheres tinham maior idade (63,13 anos vs. 60,53 anos, p = 0,011); apresentavam hipertensão (75,1% vs. 62,4%, p = 0,001), diabetes (42,2% vs. 27,8%, p < 0,001) e hiperlipidemia (34,1% vs. 23,9%, p = 0,004) mais frequentemente; e apresentaram menor probabilidade de serem submetidas a intervenção coronária percutânea (ICP) por acesso radial (23,7% vs. 46,1%, p < 0,001). A taxa de mortalidade hospitalar foi significativamente maior em mulheres (13,2% vs. 5,6%, p = 0,001), e o sexo feminino permaneceu em maior risco de mortalidade hospitalar (OR 2,79, IC de 95% 1,15-6,76, p = 0,023). Um modelo multivariado incluindo idade, sexo, pressão arterial sistólica, parada cardíaca e classe de Killip atingiu 94,1% de precisão na previsão de mortalidade hospitalar, e o índice c foi de 0,85 (IC de 95% 0,77-0,93). Conclusão Após ajuste para os fatores de risco no modelo de previsão do GRACE, as mulheres continuam em maior risco de mortalidade hospitalar.

Abstract Background Women, in comparison to men, experience worse outcomes after acute coronary syndrome (ACS). However, whether the female sex per se is an independent predictor of such adverse events remains unclear. Objective This study aims to assess the association between the female sex and in-hospital mortality after ST-elevation myocardial infarction (STEMI). Methods We conducted a retrospective cohort study by enrolling consecutive STEMI patients admitted to a tertiary hospital from January 2018 to February 2019. All patients were treated per current guideline recommendations. Multivariable logistic regression models were applied to evaluate in-hospital mortality using GRACE variables. Model accuracy was evaluated using c-index. A p-value < 0.05 was statistically significant. Results Out of the 1678 ACS patients, 709 presented with STEMI. The population consisted of 36% women, and the median age was 61 years. Women were older (63.13 years vs. 60.53 years, p = 0.011); more often presented with hypertension (75.1% vs. 62.4%, p = 0.001), diabetes (42.2% vs. 27.8%, p < 0.001), and hyperlipidemia (34.1% vs. 23.9%, p = 0.004); and were less likely to undergo percutaneous coronary intervention (PCI) via radial access (23.7% vs. 46.1%, p < 0.001). In-hospital mortality rate was significantly higher in women (13.2% vs. 5.6%, p = 0.001), and the female sex remained at higher risk for in-hospital mortality (OR 2.79, 95% CI 1.15-6.76, p = 0.023). A multivariate model including age, sex, systolic blood pressure, cardiac arrest, and Killip class was 94.1% accurate in predicting in-hospital mortality, and the c-index was 0.85 (95% CI 0.77-0.93). Conclusion After adjusting for the risk factors in the GRACE prediction model, women remain at higher risk for in-hospital mortality.

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Although Metarhizium anisopliae is one of the most studied fungal biocontrol agents, its infection mechanism is far from being completely understood. Using multidimensional protein identification technology (MudPIT), we evaluated the differential secretome of M. anisopliae E6 induced by the host Rhipicephalus microplus cuticle. The proteomic result showed changes in the expression of 194 proteins after exposure to host cuticle, such as proteins involved in adhesion, penetration, stress and fungal defense. Further, we performed a comparative genomic distribution of differentially expressed proteins of the M. anisopliae secretome against another arthropod pathogen, using the Beauveria bassiana ARSEF2860 protein repertory. Among 47 analyzed protein families, thirty were overexpressed in the M. anisopliae E6 predicted genome compared to B. bassiana. An in vivo toxicity assay using a Galleria mellonella model confirmed that the M. anisopliae E6 secretome was more toxic in cattle tick infections compared to other secretomes, including B. bassiana with cattle ticks and M. anisopliae E6 with the insect Dysdereus peruvianus, which our proteomic results had also suggested. These results help explain molecular aspects associated with host infection specificity due to genetic differences and gene expression control at the protein level in arthropod-pathogenic fungi.

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Zika virus (ZIKV) is a strongly neurotropic flavivirus whose infection has been associated with microcephaly in neonates. However, clinical and experimental evidence indicate that ZIKV also affects the adult nervous system. In this regard, in vitro and in vivo studies have shown the ability of ZIKV to infect glial cells. In the central nervous system (CNS), glial cells are represented by astrocytes, microglia, and oligodendrocytes. In contrast, the peripheral nervous system (PNS) constitutes a highly heterogeneous group of cells (Schwann cells, satellite glial cells, and enteric glial cells) spread through the body. These cells are critical in both physiological and pathological conditions; as such, ZIKV-induced glial dysfunctions can be associated with the development and progression of neurological complications, including those related to the adult and aging brain. This review will address the effects of ZIKV infection on CNS and PNS glial cells, focusing on cellular and molecular mechanisms, including changes in the inflammatory response, oxidative stress, mitochondrial dysfunction, Ca2+ and glutamate homeostasis, neural metabolism, and neuron-glia communication. Of note, preventive and therapeutic strategies that focus on glial cells may emerge to delay and/or prevent the development of ZIKV-induced neurodegeneration and its consequences.

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Zika virus (ZIKV) is an arbovirus that was responsible for multiple outbreaks from 2007 to 2015. It has been linked to cases of microcephaly in Brazil in 2015, among other neurological disorders. Differences among strains might be the reason for different clinical outcomes of infection. To evaluate this hypothesis, we performed a comparative proteomic analysis of Vero cells infected with the African strain MR766 (ZIKVAFR) and the Brazilian strain 17 SM (ZIKVBR). A total of 550 proteins were identified as differentially expressed in ZIKVAFR- or ZIKVBR-infected cells compared to the control. The main findings included upregulation of immune system pathways (neutrophil degranulation and adaptive/innate immune system) and potential activation of immune-system-related pathways by ZIKVAFR (mTOR, JAK-STAT, NF-κB, and others) compared with the ZIKVBR/control. In addition, phagocytosis by macrophages and engulfment of leukocytes were activated in ZIKVAFR infection. An in vivo analysis using an immunocompetent C57BL/6N mouse model identified interstitial pneumonia with neutrophil infiltration in the lungs only in mice infected with ZIKVBR at 48 hours postinfection, with a significant amount of virus detected. Likewise, only animals infected with ZIKVBR had viral material in the cytoplasm of lung macrophages. These results suggest that activation of the immune system by ZIKVAFR infection may lead to faster viral clearance by immune cells.

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Following health agencies warning, the use of animal origin supplements should be avoided in biological products proposed as therapy in humans. Platelet lysate and several other growth factors sources are alternatives to replace fetal calf serum, the current gold standard in clinical-grade cell culture. However, the platelet supplement's content lacks data due to different production methods. The principle behind these products relays on the lysis of platelets that release several proteins, some of which are contained in heterogeneous granules and coordinate biological functions. This study aims to analyze the composition and reproducibility of a platelet lysate produced with a standardized method, by describing several batches' protein and particle content using proteomics and dynamic light scattering. Proteomics data revealed a diversified protein content, with some related to essential cellular processes such as proliferation, morphogenesis, differentiation, biosynthesis, adhesion, and metabolism. It also detected proteins responsible for activation and binding of transforming growth factor beta, hepatocyte growth factor, and insulin-like growth factor. Total protein, biochemical, and growth factors quantitative data showed consistent and reproducible values across batches. Novel data on two major particle populations is presented, with high dispersion level at 231 ± 96 d.nm and at 30 ± 8 d.nm, possibly being an important way of protein trafficking through the cellular microenvironment. This experimental and descriptive analysis aims to support the content definition and quality criteria of a cell supplement for clinical applications.

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OBJECTIVE: To investigate the influence of protective psychosocial factors on the incidence of dental pain in the last six months among 12-year-old children living in Manaus (AM). METHODS: A prospective school-based cohort study was conducted with 210 12-year-old students enrolled in public schools in the eastern zone of Manaus (AM). Students were followed up for two years. Validated questionnaires were used to assess sociodemographic characteristics, protective psychosocial factors, including sense of coherence, social support, and self-esteem at baseline and after two years. Calibrated examiners clinically assessed dental caries and gingival bleeding. Multivariate multilevel Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (95%CI) between the changes on psychosocial factors scores and incidence of dental pain, adjusted for psychosocial factors scores at baseline, dental health insurance, frequency of tooth brushing, and dental caries. RESULTS: Mean scores for sense of coherence and social support reduced significantly from baseline to 2-year follow-up. The incidence of dental pain along the two-year follow-up was 28.6%. The risk of dental pain was 14% higher for every 10 points in the mean reduction of sense of coherence score (RR = 1.14; 95%CI: 1.02-1.20), and 6% higher for every 10 points of the mean reduction in social support score (RR = 1.06; 95%CI: 1.01-1.11). Change on self-esteem was not associated with risk of dental pain. CONCLUSION: Change on sense of coherence and social support over the two-year period influenced the incidence of dental pain among children, suggesting that protective psychosocial factors, health behaviours, dental health insurance, and clinical oral condition have an important role in the incidence of dental pain.

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Five years after the identification of Zika virus as a human teratogen, we reviewed the early clinical manifestations, collectively called congenital Zika syndrome (CZS). Children with CZS have a very poor prognosis with extremely low performance in motor, cognitive, and language development domains, and practically all feature severe forms of cerebral palsy. However, these manifestations are the tip of the iceberg, with some children presenting milder forms of deficits. Additionally, neurodevelopment can be in the normal range in the majority of the non-microcephalic children born without brain or eye abnormalities. Vertical transmission and the resulting disruption in development of the brain are much less frequent when maternal infection occurs in the second half of the pregnancy. Experimental studies have alerted to the possibility of other behavioral outcomes both in prenatally infected children and in postnatal and adult infections. Cofactors play a vital role in the development of CZS and involve genetic, environmental, nutritional, and social determinants leading to the asymmetric distribution of cases. Some of these social variables also limit access to multidisciplinary professional treatment.

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Myrciaria plinioides D. Legrand (Myrtaceae) is a native plant of Southern Brazil, which have potential in the food industry due to its edible fruits. Many plants belonging to this genus have been used for a variety of illnesses, including inflammatory disorders due to antioxidant properties. However, therapeutic uses of M. plinioides have been poorly studied. The aim of study was to assess the anti-inflammatory and anticoagulant activities of the ethanol leaf extract of M. plinioides. In M. plinioides extract-treated RAW 264.7 cells, assessments of cell viability, TNF-α release and p38 MAPK pathway-dependent protein expression were detected. In addition, rat paw edema models were used to analyze the anti-inflammatory effect of the extract. Macrophages cell line treated with M. plinioides extract showed a slight decrease in cell viability. In LPS-stimulated macrophages treated with different concentrations of the extract for 24 h, TNF-α release was inhibited, while modulation of p38 signaling pathway and inhibition of NF-κB p65 protein expression were dose-dependent. In rats, the extract inhibited the formation of paw edema, while an inhibitory effect on trypsin-like enzymes derived from mast cells was seen. Furthermore, the extract presented anticoagulant activity via extrinsic pathway, being able to block specifically factor Xa and thrombin. The study suggests that extract possess potent anti-inflammatory and anticoagulant effects. M. plinioides present great biological potential as a source for the development of anti-inflammatory and anticoagulant drugs. Additional studies can be proposed to better elucidate the mechanism by which M. plinioides exerts its effects.

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ABSTRACT OBJECTIVE To investigate the influence of protective psychosocial factors on the incidence of dental pain in the last six months among 12-year-old children living in Manaus (AM). METHODS A prospective school-based cohort study was conducted with 210 12-year-old students enrolled in public schools in the eastern zone of Manaus (AM). Students were followed up for two years. Validated questionnaires were used to assess sociodemographic characteristics, protective psychosocial factors, including sense of coherence, social support, and self-esteem at baseline and after two years. Calibrated examiners clinically assessed dental caries and gingival bleeding. Multivariate multilevel Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (95%CI) between the changes on psychosocial factors scores and incidence of dental pain, adjusted for psychosocial factors scores at baseline, dental health insurance, frequency of tooth brushing, and dental caries. RESULTS Mean scores for sense of coherence and social support reduced significantly from baseline to 2-year follow-up. The incidence of dental pain along the two-year follow-up was 28.6%. The risk of dental pain was 14% higher for every 10 points in the mean reduction of sense of coherence score (RR = 1.14; 95%CI: 1.02-1.20), and 6% higher for every 10 points of the mean reduction in social support score (RR = 1.06; 95%CI: 1.01-1.11). Change on self-esteem was not associated with risk of dental pain. CONCLUSION Change on sense of coherence and social support over the two-year period influenced the incidence of dental pain among children, suggesting that protective psychosocial factors, health behaviours, dental health insurance, and clinical oral condition have an important role in the incidence of dental pain.

RESUMO OBJETIVO Investigar a influência de fatores psicossociais protetores sobre a incidência de dor dentária nos últimos seis meses em crianças de 12 anos residentes em Manaus (AM). MÉTODOS Um estudo de coorte prospectivo de base escolar foi realizado com 210 alunos de 12 anos, matriculados em escolas públicas da zona leste de Manaus (AM) que foram acompanhados por dois anos. Questionários validados foram usados para avaliar características sociodemográficas, fatores psicossociais protetores, incluindo senso de coerência, apoio social e autoestima na linha de base e após dois anos. Examinadores calibrados avaliaram clinicamente cárie dentária e sangramento gengival. Regressão de Poisson multinível multivariada foi usada para estimar o risco relativo (RR) e o intervalo de confiança de 95% (IC95%) entre a variação dos escores dos fatores psicossociais e a incidência de dor dentária, ajustada para os escores dos fatores psicossociais na linha de base, plano de saúde odontológico, frequência de escovação dentária e cárie dentária. RESULTADOS As médias dos escores do senso de coerência e do apoio social reduziram significativamente entre linha de base e seguimento de dois anos. A incidência de dor dentária no seguimento de dois anos foi 28,6%. O risco de dor dentária foi 14% maior para cada 10 pontos na redução média do escore do senso de coerência (RR = 1,14; IC95% 1,02-1,20), e 6% maior para cada 10 pontos na redução média do escore do apoio social (RR = 1,06; IC95% 1,01-1,11). A mudança na autoestima não foi associada ao risco de dor dentária. CONCLUSÃO A variação do senso de coerência e do apoio social no período de dois anos influenciou a incidência de dor dentária em crianças, sugerindo que fatores psicossociais protetores, comportamentos em saúde, plano odontológico e a condição clínica bucal desempenham um papel importante na incidência da dor dentária.

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