Explaining the increase of incidence and mortality from cardiovascular disease in Indonesia: A global burden of disease study analysis (2000-2019).

BACKGROUND: In the last two decades, there has been a discernible shift in the distribution of mortality attributed to cardiovascular disease (CVD) between developing and developed nations; in developed nations, the percentage of deaths caused by CVD decreased from 48% in 1990 to 43% in 2010, while in developing nations, they increased from 18% to 25%. In Indonesia, CVD death has increased substantially and remained elevated in the last ten years. Current behavioral and metabolic risk factors, including hyperglycemia, obesity, dyslipidemia, hypertension, and smoking, enhance the risk of CVD mortality, according to several studies. AIMS: We undertook a study to determine whether the increase in mortality and incidence of CVD can be attributed to changes in the most common metabolic and behavioral risk factors from 2000 to 2019 across 34 Indonesian provinces. MATERIALS AND METHODS: Data from 34 province for CVD incidence and mortality and data on changes in metabolic and behavioural risk factors between 2000 and 2019 in Indonesia were obtained from the Global Burden study (GBD) by The Institute of Health Metrics and Evaluation (IHME). A statistical model was applied to calculate the fatalities attributable to the risk factors change using Population attributable fractions (PAF) and baseline year death numbers. Furthermore, we ran multivariate regressions on Summary Exposure Value of risk factors associated with the increasing mortality, incidence rates in a lag year analysis. R software used to measure heteroscedasticity-consistent standard errors with coeftest and coefci. Covariates were added to adjusted models, including the Socio-demographic Index, Primary health care facilities coverage, and GDP per capita. RESULTS: The age-standardized mortality rate for CVD from 2000 to 2019 in Indonesia, increased from 356.05 to 412.46 deaths per 100,000 population among men and decreased from 357.52 to 354.07 deaths per 100,000 population among women, resulting in an increase of 270.928 per 100,0000 inhabitants of CVD deaths. In the same period, there was an increase in exposure to risk factors such as obesity by +9%, smoking by +1%, dyslipidemia by +1.3%, hyperglycemia by +2%, and hypertension by +1.2%. During this time span, an additional 14,517 men and 17,917 women died from CVD, which was attributable to higher obesity exposure. We apply multivariate regression with province-fixed and year-fixed analysis and find strong correlation between hyperglycemia in women (6; 95%CI 0 to 12, death per 1-point increase in hyperglycemia exposure) with an increasing death rate in ischemic heart disease. We also performed a year lag analysis and discovered a robust association between high low density lipoprotein (LDL) levels in men and women and the growing incidence of ischemic heart disease. The association between a 10-year lag of high LDL and the incidence of ischemic heart disease was five times stronger than that observed for other risk factors, particularly in men (5; 95%CI 2 to 8, incidence per 1-point increase in high LDL exposure). CONCLUSION: Hyperglycemia in women is an important risk factor associated with increasing mortality due to Ischemic Heart Disease (IHD) in Indonesia This study also revealed that the presence of high LDL in both men and women were associated with an increase incidence of IHD that manifested several years subsequent to exposure to the risk factor. Additionally, the highest cardiovascular death portion were attributed to obesity. These findings suggest that policymakers should control high LDL and hyperglycemia 10 years earlier prior to the occurrence of IHD and employ personalized therapy to regulate associated risks.

Nanomechanical and Vibrational Signature of Chikungunya Viral Particles.

Chikungunya virus (CHIKV) belongs to the genus Alphaviridae, with a single-stranded positive-sense RNA genome of 11.8 kbp encoding a polyprotein that generates both non-structural proteins and structural proteins. The virus is transmitted by the Aedes aegypti and A. albopictus mosquitoes, depending on the location. CHIKV infection leads to dengue-like musculoskeletal symptoms and has been responsible for several outbreaks worldwide since its discovery in 1952. Patients often experience fever, headache, muscle pain, joint swelling, and skin rashes. However, the ultrastructural and mechanical properties of CHIKV have not been fully characterized. Thus, this study aims to apply a physical approach to investigate CHIKV's ultrastructural morphology and mechanical properties, using atomic force microscopy and Raman spectroscopy as the main tools. Using nanomechanical assays of AFM and a gold nanoparticles substrate for Raman signal enhancement, we explored the conformational plasticity, morphology, vibrational signature, and nanomechanical properties of the chikungunya virus, providing new information on its ultrastructure at the nanoscale and offering a novel understanding of the virus' behavior upon mechanical disruptions besides its molecular composition.

Analysing the impact of modifiable risk factors on cardiovascular disease mortality in Brazil.

OBJECTIVES: We have examined the impact of changes in modifiable risk factors on CVD mortality in 26 Brazilian states from 2005 to 2017. METHODS: Data were acquired from the Global Burden of Diseases study (GBD) and official sources of the Brazilian government, totalling 312 state-year observations. Population attributable fractions (PAFs) were calculated to determine the number of deaths attributed to changes in each risk factor. Fixed-effects multivariable linear regression models were performed, adjusting for income, income inequality, poverty and access to healthcare. RESULTS: Between 2005 and 2017, CVD deaths reduced by 21.42%, accompanied by a decrease in smoking (-33%) and increases in hyperglycaemia (+9.5%), obesity (+31%) and dyslipidaemia (+5.2%). Reduction in smoking prevented or postponed almost 20,000 CVD deaths in this period, while increased hyperglycaemia exposure resulted in more than 6,000 CVD deaths. The association between hyperglycaemia and CVD mortality was 5 to 10 times higher than those found for other risk factors, especially in women (11; 95%CI 7 to 14, deaths per 1-point increase in hyperglycaemia exposure). Importantly, the association between hyperglycaemia and CVD mortality was independent of socioeconomic status and access to healthcare, while associations for other risk factors after the same adjustments. CONCLUSION: Reduction in smoking was the risk factor that led to the highest number of CVD deaths prevented or postponed, while hyperglycaemia showed the most deleterious association with CVD mortality. Health policies should aim to directly reduce the prevalence of hyperglycaemia to mitigate the population burden of CVD in Brazil in the future.

Early Exposure to High-Sucrose Diet Leads to Deteriorated Ovarian Health.

Background: The metabolic syndrome (MetS) is correlated with disorders of the reproductive system, such as the polycystic ovary syndrome (PCOS). While consumption of a diet rich in carbohydrates is linked to the development of MetS, it is still unclear if this diet leads to ovarian dysfunction and PCOS. Objectives: We investigated the influence of a high-sucrose diet (HSD) on the ovarian milieu of Wistar rats and studied the correlation between high consumption of sugary drinks and the prevalence of PCOS in women. Methods: Wistar rats were given a standard laboratory diet (CTR, 10% sucrose, n = 8) or HSD (HSD, 25% sucrose, n = 8) from postnatal day 21 to 120. Animals were evaluated weekly to calculate food intake, feed efficiency and weight gain. Both onset of puberty and estrous cycle were monitored. Metabolic serum biochemistry, organ morphometry and ovarian histology were performed upon euthanasia. In parallel, a fixed-effects multiple linear regression analysis was performed using data from Brazilian states (459 state-year observations) to test the correlation between the consumption of sugar-sweetened beverages (surrogate for HSD intake) and the prevalence of PCOS (surrogate for ovarian dysfunction). Results: HSD animals showed increased adipose tissue accumulation, hyperglycaemia and insulin resistance when compared to CTR. Interestingly HSD rats also entered puberty earlier than CTR. Moreover, ovaries from HSD animals had an increased number of atretic antral follicles and cystic follicles, which were correlated with the hypertrophy of periovarian adipocytes. Finally, there was a positive correlation between the intake of sugary drinks and prevalence of PCOS in women of reproductive age. Conclusions: HSD ingestion leads to ovarian dysfunction in rats and could be correlated with PCOS in women, suggesting these alterations could lead to public health issues. Therefore, we reinforce the deleterious impact of HSD to the ovarian system and suggest that the reduction of added sugars intake could be beneficial to ovarian health.

Thiol Isomerases Orchestrate Thrombosis and Hemostasis.

Significance: Since protein disulfide isomerase (PDI) was first described in 1963, researchers have shown conclusively that PDI and sibling proteins are quintessential for thrombus formation. PDI, endoplasmic reticulum protein (ERp)5, ERp57, and ERp72 are released from platelets and vascular cells and interact with integrin αIIbß3 on the outer surface of platelets. Recent Advances: At the cell surface they influence protein folding and function, propagating thrombosis and maintaining hemostasis. TMX1, which is a transmembrane thiol isomerase, is the first family member shown to negatively regulate platelets. Targets of thiol isomerases have been identified, including integrin α2ß1, Von Willebrand Factor, GpIbα, nicotinamide adenine dinucleotide phosphate oxidase (Nox)-1, Nox-2, and tissue factor, all of which are pro-thrombotic, and several of which are on the cell surface. In spite of this, PDI can paradoxically catalyze the delivery of nitric oxide to platelets, which decrease thrombus formation. Critical Issues: Although the overall effect of PDI is to positively regulate platelet activation, it is still unclear how thiol isomerases function in pro-thrombotic states, such as obesity, diabetes, and cancer. In parallel, there has been a surge in the development of novel thiol isomerase inhibitors, which display selectivity, potency and modulate thrombosis and hemostasis. The availability of selective thiol isomerase inhibitors has culminated in clinical trials, with promising outcomes for the prevention of cancer-associated thrombosis. Future Directions: Altogether, thiol isomerases are perceived as an orchestrating force that regulates thrombus development. In the current review, we will explore the history of PDI in cardiovascular biology, detail known mechanisms of action, and summarize known thiol isomerase inhibitors.

Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors.

BACKGROUND: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors. OBJECTIVES: To establish whether PDI and Nox-1 cooperate to control platelet function. METHODS: Immunofluorescence microscopy was utilised to determine expression and localisation of PDI and Nox-1. Platelet aggregation, fibrinogen binding, P-selectin exposure, spreading and calcium mobilization were measured as markers of platelet function. A cross-sectional population study (n = 136) was conducted to assess the relationship between platelet PDI and Nox-1 levels and cardiometabolic risk factors. RESULTS: PDI and Nox-1 co-localized upon activation induced by the collagen receptor GPVI. Co-inhibition of PDI and Nox-1 led to additive inhibition of GPVI-mediated platelet aggregation, activation and calcium flux. This was confirmed in murine Nox-1-/- platelets treated with PDI inhibitor bepristat, without affecting bleeding. PDI and Nox-1 together contributed to GPVI signalling that involved the phosphorylation of p38 MAPK, p47phox, PKC and Akt. Platelet PDI and Nox-1 levels were upregulated in obesity, with platelet Nox-1 also elevated in hypertensive individuals. CONCLUSIONS: We show that PDI and Nox-1 cooperate to control platelet function and are associated with cardiometabolic risk factors.

Socioeconomic Factors Associated With Reports of Domestic Violence in Large Brazilian Cities.

Background: Domestic violence is a traumatic experience that can lead to physical consequences, mental disorders and financial damage. Over 18 cases per 100,000 inhabitants were reported in Brazil between 2013 and 2014. The ministry of health poses a mandatory notification of all cases of domestic violence, which is essential, bearing in mind its systemic relation to various social issues and the extensive regional differences and high socioeconomic inequalities present in Brazil. Aim: To analyze the characteristics of the notification rates of domestic violence and investigate the correlation of these with health and socioeconomic characteristics of large Brazilian cities. Methods: Retrospective data on notifications of domestic violence was collected from the National Information System for Notifiable Diseases for Brazil, 2017. Dependent variables were collected from the Brazilian Institute of Geography and Statistics and Ministry of Citizenship. Inclusion criteria were: cities larger than 100.000 habitants and that had at least 20 reports, totaling 68.313 reports in 259 cities. These were stratified by age, race and sex of victim, type of violence used, violence perpetrator, place of occurrence and means of aggression. Proportional number of notified cases was calculated for each city to expose different characteristics of reports. A multiple linear regression model was used to investigate the correlation between report rates and different socioeconomic and health variables. Results: The analysis showed a high proportion of repeated violence, use of body strength and over 50% were perpetrated by a partner or boyfriend. Report rates were higher for women, black individuals and children under four, highlighting subgroups of the population that were more vulnerable. Indeed, these groups were correlated differently with socioeconomic variables. Poverty, assessed as Bolsa Família investment, was correlated with domestic violence report rates across vulnerable groups. Conclusion: The study showed that black women and children are more vulnerable to domestic violence, highlighting deleterious effects of patriarchy and structural racism within Brazilian society. Altogether, we suggest that reducing poverty, patriarchy and structural racism could lead to fewer cases of domestic violence.

Platelet-derived extracellular vesicles express NADPH oxidase-1 (Nox-1), generate superoxide and modulate platelet function.

BACKGROUND: Platelets release platelet-derived extracellular vesicles (PDEVs) upon activation - in a process that is regulated by generation of reactive oxygen species (ROS). Platelet NADPH oxidase-1 (Nox-1) contributes to ROS generation and thrombus formation downstream of the collagen receptor GPVI. OBJECTIVES: We aimed to investigate whether PDEVs contain Nox-1 and whether this is relevant for PDEV-induced platelet activation. METHODS: PDEVs were isolated through serial centrifugation after platelet activation with thrombin receptor agonist TRAP-6 (activated PDEVs) or in the absence of agonist (resting PDEVs). The physical properties of PDEVs were analyzed through nanoparticle tracking analysis. Nox-1 levels, fibrinogen binding and P-selectin exposure were measured using flow cytometry, and protein levels quantified by immunoblot analysis. ROS were quantified using DCF fluorescence and electron paramagnetic resonance. RESULTS: Nox-1 was found to be increased on the platelet outer membrane upon activation and was present in PDEVs. PDEVs induced platelet activation, while co-addition of GPVI agonist collagen-related peptide (CRP) did not potentiate this response. PDEVs were shown to be able to generate superoxide in a process at least partially mediated by Nox-1, while Nox-1 inhibition with ML171 (also known as 2-APT) did not influence PDEV production. Finally, inhibition of Nox-1 abrogated PDEV-mediated platelet activation. CONCLUSIONS: PDEVs are able to generate superoxide, bind to and activate platelets in a process mediated by Nox-1. These data provide novel mechanisms by which Nox-1 potentiates platelet responses, thus proposing Nox-1 inhibition as a feasible strategy to treat and prevent thrombotic diseases.

Income inequality and non-communicable disease mortality and morbidity in Brazil States: a longitudinal analysis 2002-2017.

Background: Income inequality can negatively affect population health by increasing social stress and conflict, and reducing trust, public goods and healthcare access. However there is limited evidence from low and middle-income countries (LMICs) with high levels of inequality. This study investigates the association between income inequality, morbimortality and risk factors of non-communicable diseases (NCDs) in 26 Brazilian states from 2002 to 2017. Methods: Data was acquired for men and women from the Global Health Data Exchange, the Brazilian Institute of Geography and Statistics, and the Brazilian Ministry of Health, totalling 416 state-year observations. Disability-adjusted life years (DALYs) and risk factors of NCDs were the dependent variables. Gini Index was the main independent variable. Multivariate linear panel regressions were performed, controlling for state and time fixed effects, gross domestic product per capita, population ageing, poverty and access to healthcare. Findings: A 1% increase in the Gini Index was associated with increases in alcohol abuse (of 923•4 DALYs per 100,000 people, 95%CI 217•6 to 1629•0) and diabetes mellitus morbidity (of 893•3 DALYs per 100,000 people, 95%CI 127•7 to 1659•0), and decreases in morbidity from attention disorder (of -4•0 DALYs per 100,000 people, 95%CI -7•4 to -0•5) and autism spectrum (of -2•4 DALYs per 100,000 people, 95%CI -4•3 to -0•5). These associations were greater for men, further supported by associations with alcohol use as a risk factor. Interpretation: This study provides evidence from a highly unequal LMIC, Brazil, of negative associations between income inequality and NCDs, and the importance of addressing wider social determinants of health. Funding: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001 as a Brazilian CAPES scholarship to AZD and by the São Paulo Research Foundation (FAPESP), grant 2020/15944-8 to RSG.

Lipid Metabolism and Signaling in Platelet Function.

Modern society has changed its diet composition, transitioning to a higher intake of saturated fat with a 50% increase of cardiovascular risk (CVD). Within the context of increased CVD, there is an induction of a prothrombotic phenotype mainly due to increased platelet reactivity as well as decreased platelet response to inhibitors. Platelets maintain haemostasis through both blood components and endothelial cells that secrete inhibitory or stimulatory molecules to regulate thrombus formation. There exist a correlation between platelets' polyunsaturated fatty acid (PUFA) and the increase in platelet reactivity. The aim of this chapter is to review the metabolism of the main PUFAs involved in platelet function associated with the role that their enzyme-derived oxidized metabolites exert in platelet function and fate. Finally, how lipid metabolism in the organism affect platelet aggregation and activation and the pharmacological modulation of these processes will also be discussed.

Corrigendum to "Protective Effects of a Polyphenol-Rich Extract from Syzygium cumini (L.) Skeels Leaf on Oxidative Stress-Induced Diabetic Rats".

[This corrects the article DOI: 10.1155/2018/5386079.].

Myricetin, the Main Flavonoid in Syzygium cumini Leaf, Is a Novel Inhibitor of Platelet Thiol Isomerases PDI and ERp5.

BACKGROUND: Flavonoids have been characterized as a prominent class of compounds to treat thrombotic diseases through the inhibition of thiol isomerases. Syzygium cumini is a flavonoid-rich medicinal plant that contains myricetin and gallic acid. Little is known about the potential antiplatelet properties of S. cumini and its constituent flavonoids. OBJECTIVE: To evaluate the antiplatelet effects and mechanism of action of a polyphenol-rich extract (PESc) from S. cumini leaf and its most prevalent polyphenols, myricetin and gallic acid. METHODS: PESc, myricetin, and gallic acid were incubated with platelet-rich plasma and washed platelets to assess platelet aggregation and activation. In vitro platelet adhesion and thrombus formation as well as in vivo bleeding time were performed. Finally, myricetin was incubated with recombinant thiol isomerases to assess its potential to bind and inhibit these, while molecular docking studies predicted possible binding sites. RESULTS: PESc decreased platelet activation and aggregation induced by different agonists. Myricetin exerted potent antiplatelet effects, whereas gallic acid did not. Myricetin reduced the ability of platelets to spread on collagen, form thrombi in vitro without affecting hemostasis in vivo. Fluorescence quenching studies suggested myricetin binds to different thiol isomerases with similar affinity, despite inhibiting only protein disulfide isomerase (PDI) and ERp5 reductase activities. Finally, molecular docking studies suggested myricetin formed non-covalent bonds with PDI and ERp5. CONCLUSIONS: PESc and its most abundant flavonoid myricetin strongly inhibit platelet function. Additionally, myricetin is a novel inhibitor of ERp5 and PDI, unveiling a new therapeutic perspective for the treatment of thrombotic disorders.

[Trends in reporting of sexual violence in Brazil from 2009 to 2013]. / Evolução da notificação de violência sexual no Brasil de 2009 a 2013.

The objective was to analyze the trends in reporting of sexual violence in Brazil from 2009 to 2013, with special emphasis on rape. An observational times series study was conducted, analyzing data from 2009 to 2013 coming from a secondary database of the Brazilian National Information System for Notificable Diseases (SINAN). The independent variable was the number of reports of sexual violence from 2009 to 2013, which was compared to several sociodemographic, violence-related, and health-related variables. The data were analyzed with a Prais-Winsten generalized linear regression model, determining the variations as stable, upward, or downward by analysis of the coefficient of determination (Pearson's R2) and level of significance set at p < 0.05. The reports of sexual violence showed greater positive variation in the 10-19-year age bracket (364%), indigenous individuals (520%), in the South of Brazil (414%), females (331%), and individuals with low schooling (343%). More than 70% of the reports were rapes, while one-third were repeat offenses, with a downward trend in reports of sexual violence accompanied by beating. The aggressors' characteristics remained stable. The site of violence changed, with fewer cases occurring on public byways. Finally, the reporting rate for rape increased by 590%, with a similar trend in rapes in the household and an increase in case resolutions. The study reveals the sociodemographic profile of cases of sexual violence reported in Brazil and an increase in reported rapes, especially inside the household. There was also an increase in case resolution.

O objetivo foi analisar a evolução das notificações de violência sexual no Brasil entre 2009 e 2013, dando especial enfoque ao estupro. Realizou-se um estudo observacional de série temporal, analisando dados entre 2009 e 2013, provenientes do banco de dados secundários coletados do Sistema de Informação de Agravos de Notificação (SINAN). A variável independente referiu-se ao número de notificações de violência sexual entre 2009 e 2013, sendo esta comparada a diversas variáveis sociodemográficas, de violência e de saúde. Os dados foram analisados por modelo de regressão linear generalizada de Prais-Winsten, determinando as variações como estável, crescente ou decrescente pela análise do coeficiente de determinação (R2 de Pearson) e nível de significância (p < 0,05). As notificações de violência sexual tiveram maior variação positiva em: 10-19 anos (364%), indígenas (520%), da Região Sul (414%), sexo feminino (331%) e baixa escolaridade (343%). Mais de 70% das notificações foram estupros, enquanto um terço foi casos de repetição, com decréscimo de notificações acompanhadas de espancamento. As características do agressor mantiveram-se estáveis. O local de ocorrência modificou-se, com menos casos ocorridos em via pública. Por fim, a taxa de notificação estupro aumentou em 590%, com tendência semelhante aos estupros dentro de casa e aumento da resolutividade dos atendimentos. O presente estudo evidencia o perfil sociodemográfico das vítimas de violência sexual notificadas no Brasil e o aumento da notificação de estupros atrelado aos casos em domicílio. Ainda, houve aumento da resolutividade das notificações.

El objetivo de este trabajo fue analizar la evolución de las notificaciones sobre violencia sexual en Brasil entre 2009 y 2013, otorgando especial relevancia a la violación. Se realizó un estudio observacional de carácter temporal, analizando datos entre 2009 y 2013, provenientes de un banco de datos secundarios, recabados por el Sistema de Información Nacional sobre Enfermedades de Notificación Obligatoria (SINAN por sus siglas en portugués). La variable independiente se refirió al número de notificaciones sobre violencia sexual entre 2009 y 2013, siendo esta última comparada con diversas variables sociodemográficas, de violencia y de salud. Los datos se analizaron mediante un modelo de regresión lineal generalizado de Prais-Winsten, determinando las variaciones como estables, crecientes o decrecientes por el análisis del coeficiente de determinación (R2 de Pearson) y el nivel de significancia (p < 0,05). Las notificaciones de violencia sexual contaron con una mayor variación positiva en: 10-19 años (364%), indígenas (520%), de la región Sur (414%), sexo femenino (331%) y baja escolaridad (343%). Más del 70% de las notificaciones fueron violaciones, mientras que un tercio fueron casos de repetición, con un descenso de las notificaciones acompañadas de palizas. Las características del agresor se mantuvieron estables. El lugar de ocurrencia fue modificado, hubo menos casos que se produjeron en vía pública. Finalmente, la tasa de notificación de violación aumentó un 590%, con una tendencia semejante a las violaciones dentro de casa y al aumento de la resolutividad de las atenciones. El presente estudio evidencia el perfil sociodemográfico de las víctimas de violencia sexual notificadas en Brasil y el aumento de la notificación de violaciones, relacionado con casos en domicilios. Asimismo, hubo un aumento de la resolutividad de las notificaciones.

Protective Effects of a Polyphenol-Rich Extract from Syzygium cumini (L.) Skeels Leaf on Oxidative Stress-Induced Diabetic Rats.

Syzygium cumini (L.) Skeels has been reported to exert anti-inflammatory and cardiometabolic activities due to its high content of polyphenols. We characterized the chemical composition and assessed the antidiabetic effects of a novel polyphenol-rich extract (PESc) obtained from S. cumini leaf. Rats were injected with alloxan (150 mg/kg, ip, ALX group) and followed up for 7 days. Some were orally treated with PESc (50 mg/kg/day) for 7 days before and after diabetes induction (ALX-PP) or only for 7 days after alloxan injection (ALX-P). ALX-P and ALX-PP decreased fasting glycemia in 37 and 43%, respectively, as compared to ALX. Triglycerides and total cholesterol serum levels were also significantly reduced in comparison to ALX. PESc presented high polyphenol concentration (71.78 ± 8.57 GAE/100 g), with flavonoid content of 8.21 ± 0.42 QE/100 g. Upon HPLC-MS/MS and MS/MS studies, five main polyphenols-gallic acid, quercetin, myricetin, and its derivatives-were identified. Myricetin was predominant (192.70 ± 16.50 µg/mg PESc), followed by measurable amounts of gallic acid (11.15 ± 0.90 µg/mg PESc) and quercetin (4.72 ± 0.06 µg/mg PESc). Kinetic assessment of total antioxidant capacity revealed PESc high potency, since maximum response was reached within 5 min reaction time in a concentration-dependent manner. Specific antioxidant activity of PESc was assessed against both DPPH• and ABTS•+, showing strong activity (IC50: 3.88 ± 1.09 and 5.98 ± 1.19 µg/mL, resp.). PESc also inhibited lipoxygenase activity (IC50: 27.63 ± 8.47), confirming its antioxidant activity also on biologically relevant radicals. Finally, PESc induced insulin secretion by directly stimulating INS-1E ß cells in the absence of any cytotoxic effect. Overall, our results support that PESc is a potent antioxidant phytocomplex with potential pharmacological use as a preventive antidiabetic natural product.

Evolução da notificação de violência sexual no Brasil de 2009 a 2013 / Trends in reporting of sexual violence in Brazil from 2009 to 2013 / Evolución de notificaciones sobre violencia sexual en Brasil de 2009 a 2013

O objetivo foi analisar a evolução das notificações de violência sexual no Brasil entre 2009 e 2013, dando especial enfoque ao estupro. Realizou-se um estudo observacional de série temporal, analisando dados entre 2009 e 2013, provenientes do banco de dados secundários coletados do Sistema de Informação de Agravos de Notificação (SINAN). A variável independente referiu-se ao número de notificações de violência sexual entre 2009 e 2013, sendo esta comparada a diversas variáveis sociodemográficas, de violência e de saúde. Os dados foram analisados por modelo de regressão linear generalizada de Prais-Winsten, determinando as variações como estável, crescente ou decrescente pela análise do coeficiente de determinação (R2 de Pearson) e nível de significância (p < 0,05). As notificações de violência sexual tiveram maior variação positiva em: 10-19 anos (364%), indígenas (520%), da Região Sul (414%), sexo feminino (331%) e baixa escolaridade (343%). Mais de 70% das notificações foram estupros, enquanto um terço foi casos de repetição, com decréscimo de notificações acompanhadas de espancamento. As características do agressor mantiveram-se estáveis. O local de ocorrência modificou-se, com menos casos ocorridos em via pública. Por fim, a taxa de notificação estupro aumentou em 590%, com tendência semelhante aos estupros dentro de casa e aumento da resolutividade dos atendimentos. O presente estudo evidencia o perfil sociodemográfico das vítimas de violência sexual notificadas no Brasil e o aumento da notificação de estupros atrelado aos casos em domicílio. Ainda, houve aumento da resolutividade das notificações.

The objective was to analyze the trends in reporting of sexual violence in Brazil from 2009 to 2013, with special emphasis on rape. An observational times series study was conducted, analyzing data from 2009 to 2013 coming from a secondary database of the Brazilian National Information System for Notificable Diseases (SINAN). The independent variable was the number of reports of sexual violence from 2009 to 2013, which was compared to several sociodemographic, violence-related, and health-related variables. The data were analyzed with a Prais-Winsten generalized linear regression model, determining the variations as stable, upward, or downward by analysis of the coefficient of determination (Pearson's R2) and level of significance set at p < 0.05. The reports of sexual violence showed greater positive variation in the 10-19-year age bracket (364%), indigenous individuals (520%), in the South of Brazil (414%), females (331%), and individuals with low schooling (343%). More than 70% of the reports were rapes, while one-third were repeat offenses, with a downward trend in reports of sexual violence accompanied by beating. The aggressors' characteristics remained stable. The site of violence changed, with fewer cases occurring on public byways. Finally, the reporting rate for rape increased by 590%, with a similar trend in rapes in the household and an increase in case resolutions. The study reveals the sociodemographic profile of cases of sexual violence reported in Brazil and an increase in reported rapes, especially inside the household. There was also an increase in case resolution.

El objetivo de este trabajo fue analizar la evolución de las notificaciones sobre violencia sexual en Brasil entre 2009 y 2013, otorgando especial relevancia a la violación. Se realizó un estudio observacional de carácter temporal, analizando datos entre 2009 y 2013, provenientes de un banco de datos secundarios, recabados por el Sistema de Información Nacional sobre Enfermedades de Notificación Obligatoria (SINAN por sus siglas en portugués). La variable independiente se refirió al número de notificaciones sobre violencia sexual entre 2009 y 2013, siendo esta última comparada con diversas variables sociodemográficas, de violencia y de salud. Los datos se analizaron mediante un modelo de regresión lineal generalizado de Prais-Winsten, determinando las variaciones como estables, crecientes o decrecientes por el análisis del coeficiente de determinación (R2 de Pearson) y el nivel de significancia (p < 0,05). Las notificaciones de violencia sexual contaron con una mayor variación positiva en: 10-19 años (364%), indígenas (520%), de la región Sur (414%), sexo femenino (331%) y baja escolaridad (343%). Más del 70% de las notificaciones fueron violaciones, mientras que un tercio fueron casos de repetición, con un descenso de las notificaciones acompañadas de palizas. Las características del agresor se mantuvieron estables. El lugar de ocurrencia fue modificado, hubo menos casos que se produjeron en vía pública. Finalmente, la tasa de notificación de violación aumentó un 590%, con una tendencia semejante a las violaciones dentro de casa y al aumento de la resolutividad de las atenciones. El presente estudio evidencia el perfil sociodemográfico de las víctimas de violencia sexual notificadas en Brasil y el aumento de la notificación de violaciones, relacionado con casos en domicilios. Asimismo, hubo un aumento de la resolutividad de las notificaciones.

Temporal analysis of reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012 / Análise temporal dos casos notificados de tuberculose e de coinfecção tuberculose--HIV na população brasileira no período entre 2002 e 2012

ABSTRACT Objective: To investigate the reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012. Methods: This was an observational study based on secondary time series data collected from the Brazilian Case Registry Database for the 2002-2012 period. The incidence of tuberculosis was stratified by gender, age group, geographical region, and outcome, as was that of tuberculosis-HIV co-infection. Results: Nationally, the incidence of tuberculosis declined by 18%, whereas that of tuberculosis-HIV co-infection increased by 3.8%. There was an overall decrease in the incidence of tuberculosis, despite a significant increase in that of tuberculosis-HIV co-infection in women. The incidence of tuberculosis decreased only in the 0- to 9-year age bracket, remaining stable or increasing in the other age groups. The incidence of tuberculosis-HIV co-infection increased by 209% in the ≥ 60-year age bracket. The incidence of tuberculosis decreased in all geographical regions except the south, whereas that of tuberculosis-HIV co-infection increased by over 150% in the north and northeast. Regarding the outcomes, patients with tuberculosis-HIV co-infection, in comparison with patients infected with tuberculosis only, had a 48% lower chance of cure, a 50% greater risk of treatment nonadherence, and a 94% greater risk of death from tuberculosis. Conclusions: Our study shows that tuberculosis continues to be a relevant public health issue in Brazil, because the goals for the control and cure of the disease have yet to be achieved. In addition, the sharp increase in the incidence of tuberculosis-HIV co-infection in women, in the elderly, and in the northern/northeastern region reveals that the population of HIV-infected individuals is rapidly becoming more female, older, and more impoverished.

RESUMO Objetivo: Investigar os casos notificados de tuberculose e de sua coinfecção com o HIV na população brasileira no período entre 2002 e 2012. Métodos: Realizou-se um estudo observacional de série temporal, no qual foram analisados dados secundários coletados do Sistema de Informação de Agravos de Notificação, no período entre 2002 e 2012. As incidências de tuberculose e tuberculose-HIV foram estratificadas por sexo, faixa etária, macrorregião e situação de encerramento. Resultados: A incidência de tuberculose decaiu 18%, enquanto a de coinfecção tuberculose-HIV aumentou 3,8% no país. Houve uma redução geral da incidência de tuberculose apesar do aumento expressivo de tuberculose-HIV em mulheres. A taxa de incidência de tuberculose diminuiu apenas na faixa etária de 0-9 anos, permanecendo estável ou com variação positiva nas outras faixas etárias. A incidência da coinfecção tuberculose-HIV cresceu 209% na faixa etária ≥ 60 anos. A incidência de tuberculose diminuiu em todas as macrorregiões, exceto no Sul, enquanto a de tuberculose-HIV aumentou mais de 150% no Norte e Nordeste. Quanto à situação de encerramento, revelou-se que pacientes com tuberculose-HIV têm 48% menos chance de cura, 50% mais chance de abandonar o tratamento e 94% mais chance de óbito por tuberculose em relação àqueles sem a coinfecção. Conclusões: O presente estudo evidencia a tuberculose como um importante problema de saúde pública no Brasil, uma vez que as metas estabelecidas de cura e controle da doença ainda não foram alcançadas. Ademais, o aumento vertiginoso na incidência de tuberculose-HIV em mulheres, idosos e nas regiões Norte e Nordeste evidencia a feminização, a transição etária e a pauperização pelo HIV.

Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats.

Obesity and metabolic syndrome are the common causes of reproductive and fertility disorders in women. In particular, polycystic ovary syndrome, which is clinically characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, has been increasingly associated with metabolic disorders. However, given the broad interplay between metabolic and reproductive functions, this remains a field of intense research. In this study, we investigated the effect of monosodium l-glutamate (MSG)-induced obesity on reproductive biology of female rats. Newborn female rats were subcutaneously injected with MSG (4g/kg/day) or equiosmolar saline (CTR) each 2 days up to postnatal day (pnd) 10. On pnd 60, estrous cycle was evaluated using vaginal smears twice a day for 15 days, which showed MSG rats to be oligocyclic. Thereafter, animals were killed on estrous phase for blood and tissue collection. MSG rats had increased body mass, accumulation of retroperitoneal and visceral fat pads, and visceral adipocyte hypertrophy compared with CTR rats. MSG rats were also dyslipidemic and hyperinsulinemic but were normoglycemic and normoandrogenic. Ovarian morphology analysis showed that MSG rats had a two-fold decrease in oocyte count but a six-fold increase on ovarian follicular cysts, along with a higher number of total primordial and atretic follicles. Moreover, MSG rats had a four-fold increase in anti-Müllerian hormone immunohistochemical staining on antral follicles. Taken together, data presented here characterize MSG obesity as a unique model to study the metabolic pathways underlying reproductive disorders in the absence of overactivated hypothalamic-pituitary-gonadal axis.

Temporal analysis of reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012.

OBJECTIVE:: To investigate the reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012. METHODS:: This was an observational study based on secondary time series data collected from the Brazilian Case Registry Database for the 2002-2012 period. The incidence of tuberculosis was stratified by gender, age group, geographical region, and outcome, as was that of tuberculosis-HIV co-infection. RESULTS:: Nationally, the incidence of tuberculosis declined by 18%, whereas that of tuberculosis-HIV co-infection increased by 3.8%. There was an overall decrease in the incidence of tuberculosis, despite a significant increase in that of tuberculosis-HIV co-infection in women. The incidence of tuberculosis decreased only in the 0- to 9-year age bracket, remaining stable or increasing in the other age groups. The incidence of tuberculosis-HIV co-infection increased by 209% in the ≥ 60-year age bracket. The incidence of tuberculosis decreased in all geographical regions except the south, whereas that of tuberculosis-HIV co-infection increased by over 150% in the north and northeast. Regarding the outcomes, patients with tuberculosis-HIV co-infection, in comparison with patients infected with tuberculosis only, had a 48% lower chance of cure, a 50% greater risk of treatment nonadherence, and a 94% greater risk of death from tuberculosis. CONCLUSIONS:: Our study shows that tuberculosis continues to be a relevant public health issue in Brazil, because the goals for the control and cure of the disease have yet to be achieved. In addition, the sharp increase in the incidence of tuberculosis-HIV co-infection in women, in the elderly, and in the northern/northeastern region reveals that the population of HIV-infected individuals is rapidly becoming more female, older, and more impoverished. OBJETIVO:: Investigar os casos notificados de tuberculose e de sua coinfecção com o HIV na população brasileira no período entre 2002 e 2012. MÉTODOS:: Realizou-se um estudo observacional de série temporal, no qual foram analisados dados secundários coletados do Sistema de Informação de Agravos de Notificação, no período entre 2002 e 2012. As incidências de tuberculose e tuberculose-HIV foram estratificadas por sexo, faixa etária, macrorregião e situação de encerramento. RESULTADOS:: A incidência de tuberculose decaiu 18%, enquanto a de coinfecção tuberculose-HIV aumentou 3,8% no país. Houve uma redução geral da incidência de tuberculose apesar do aumento expressivo de tuberculose-HIV em mulheres. A taxa de incidência de tuberculose diminuiu apenas na faixa etária de 0-9 anos, permanecendo estável ou com variação positiva nas outras faixas etárias. A incidência da coinfecção tuberculose-HIV cresceu 209% na faixa etária ≥ 60 anos. A incidência de tuberculose diminuiu em todas as macrorregiões, exceto no Sul, enquanto a de tuberculose-HIV aumentou mais de 150% no Norte e Nordeste. Quanto à situação de encerramento, revelou-se que pacientes com tuberculose-HIV têm 48% menos chance de cura, 50% mais chance de abandonar o tratamento e 94% mais chance de óbito por tuberculose em relação àqueles sem a coinfecção. CONCLUSÕES:: O presente estudo evidencia a tuberculose como um importante problema de saúde pública no Brasil, uma vez que as metas estabelecidas de cura e controle da doença ainda não foram alcançadas. Ademais, o aumento vertiginoso na incidência de tuberculose-HIV em mulheres, idosos e nas regiões Norte e Nordeste evidencia a feminização, a transição etária e a pauperização pelo HIV.

Potential Role of Protein Disulfide Isomerase in Metabolic Syndrome-Derived Platelet Hyperactivity.

Metabolic Syndrome (MetS) has become a worldwide epidemic, alongside with a high socioeconomic cost, and its diagnostic criteria must include at least three out of the five features: visceral obesity, hypertension, dyslipidemia, insulin resistance, and high fasting glucose levels. MetS shows an increased oxidative stress associated with platelet hyperactivation, an essential component for thrombus formation and ischemic events in MetS patients. Platelet aggregation is governed by the peroxide tone and the activity of Protein Disulfide Isomerase (PDI) at the cell membrane. PDI redox active sites present active cysteine residues that can be susceptible to changes in plasma oxidative state, as observed in MetS. However, there is a lack of knowledge about the relationship between PDI and platelet hyperactivation under MetS and its metabolic features, in spite of PDI being a mediator of important pathways implicated in MetS-induced platelet hyperactivation, such as insulin resistance and nitric oxide dysfunction. Thus, the aim of this review is to analyze data available in the literature as an attempt to support a possible role for PDI in MetS-induced platelet hyperactivation.