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Brazil reported 18,282 suspected congenital Zika syndrome (CZS) cases up to 2018 and accounts for 61.4% of the total reported Zika cases in the Americas in the period. To detect high-risk areas for children with CZS in the city of Rio de Janeiro, we used cluster detection and thematic maps. We analyzed data using a Poisson model in Satscan 10.1.3 software. We also analyzed the records of children with CZS from 2015 to 2016 to describe the clinical and epidemiological maternal and child profile, as well as live births in 2016 and the social development index (SDI) by neighborhood. In 2015 and 2016, the incidence rates of CZS were 8.84 and 46.96 per 100,000 live births in the city, respectively. Severe congenital findings such as microcephaly and brain damage, osteoarticular impairment, ocular abnormalities, and hearing loss were observed in 47 children. The spatial distribution of CZS was concentrated in the north and west zones in heterogeneous neighborhoods. The neighborhoods with the highest occurrence of CZS cases were found to have the worst SDIs. Stascan detected three spatial clusters in the north zone, where the SDI is lower. The clusters presented high relative risks for CZS (7.86, 1.46, and 2.08), although they were not statistically significant. Our findings highlight a higher occurrence of CZS in areas with less favorable socioeconomic conditions.

The study aimed to detect high-risk areas for deaths of children and adolescents 5 to 14 years of age in the state of Mato Grosso, Brazil, from 2009 to 2020. This was an exploratory ecological study with municipalities as the units of analysis. Considering mortality data from the Mortality Information System (SIM) and demographic data from the Brazilian Institute of Geography and Statistics (IBGE), the study used multivariate statistics to identify space-time clusters of excess mortality risk in this age group. From 5 to 9 years of age, two clusters with high mortality risk were detected; the most likely located in the state's southern mesoregion (RR: 1.6; LRT: 8,53). Among the 5 clusters detected in the 10-14-year age group, the main cluster was in the state's northern mesoregion (RR: 2,26; LRT: 7,84). A reduction in mortality rates was observed in the younger age group and an increase in these rates in the older group. The identification of these clusters, whose analysis merits replication in other parts of Brazil, is the initial stage in the investigation of possible factors associated with morbidity and mortality in this group, still insufficiently explored, and for planning adequate interventions.

Objective: To evaluate immunization coverage and dropout rates of the measles, mumps, and rubella vaccine across Brazilian regions., Methods: This ecological study employing a space-time approach used data from the National Immunization Program (PNI) and the Live Births Information System (SINASC). We estimated the annual variation (2014 to 2021) in immunization coverage and dropout rate of the measles, mumps, and rubella vaccine in children aged 12 and 15 months in the 5 570 Brazilian municipalities. Statistical analysis was conducted for the municipalities contained in each Brazilian region using the space-time scan technique, considering the Poisson probabilistic model and the hypothesis that municipalities with lower immunization coverage or high dropout rates would form space-time clusters., Results: From 2014 to 2021, 38.3% and 12.9% of municipalities achieved a coverage ≥ 95.0% in the first and second doses respectively; 53.6% of municipalities had a high dropout rate (20.0% to 49.9%) and 37.2% had a very high dropout rate. The Northeast region had primary clusters for low coverage of the first (2018 to 2021) and second vaccine doses (2020 to 2021) with higher relative risks (RR) compared to other primary clusters. The RR for high dropout rate was elevated in all Brazilian regions (1.57 to 26.23)., Conclusions: In some Brazilian regions, the dropout rate has been high since 2014, signaling a risk of measles resurgence. In turn, space-time analysis indicated lower vaccination coverage in 2020, suggesting the influence of the COVID-19 pandemic., Competing Interests: Conflitos de interesse. Nada declarado pelos autores.

Main Results: Annual vaccination coverage was below 95% in Brazil. The second dose of the vaccine showed stationary and decreasing trends in the country's Federative Units. The dropout rate varied greatly throughout the study period., Implications for Services: The results found regarding the trends serve to inform and point to the urgency of planning actions aimed at improving coverage of the triple viral vaccine nationally in Brazil., Perspectives: Investments in enhanced training of epidemiological surveillance professionals and enhanced computerized systems are necessary, with a view to continuous monitoring, to support actions to promote better and timely vaccine coverage., Objective: to analyze the temporal trend of coverage and dropout rate for triple viral vaccine in Brazil, according to the country's Federative Units and Macro-Regions, between 2014 and 2021., Methods: this was an ecological time series study, using data from the National Immunization Program Information System and the Live Birth Information System; joinpoint regression models were used., Results: in Brazil as a whole annual vaccination coverage was below 95% and ranged from 92.3% (2015) to 54.4% (2021); the second dose of the vaccine showed a decreasing temporal trend in the period (average change over the period = -5.8; 95%CI -10.5;-0.8); the temporal trends were stationary and decreasing in the country's Federative Units; the dropout rate ranged from 22.2% (2014) to 37.4% (2021)., Conclusion: there was a downward trend in vaccination coverage and an increase in the dropout rate in Brazil as a whole and in the country's Federative Units.

The vascular endothelium constitutes the inner lining of the blood vessel, and malfunction and injuries of the endothelium can cause cardiovascular diseases as well as other diseases including stroke, tumor growth, and chronic kidney failure. Generation of effective sources to replace injured endothelial cells (ECs) could have significant clinical impact, and somatic cell sources like peripheral or cord blood cannot credibly supply enough endothelial cell progenitors for multitude of treatments. Pluripotent stem cells are a promising source for a reliable EC supply, which have the potential to restore tissue function and treat vascular diseases. We have developed methods to differentiate induced pluripotent stem cells (iPSCs) efficiently and robustly across multiple iPSC lines into nontissue-specific pan vascular ECs (iECs) with high purity. These iECs present with canonical endothelial cell markers and exhibit measures of endothelial cell functionality with the uptake of Dil fluorescent dye-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and tube formation. Using proteomic analysis, we revealed that the iECs are more proteomically similar to established human umbilical vein ECs (HUVECs) than to iPSCs. Posttranslational modifications (PTMs) were most shared between HUVECs and iECs, and potential targets for increasing the proteomic similarity of iECs to HUVECs were identified. Here we demonstrate an efficient robust method to differentiate iPSCs into functional ECs, and for the first time provide a comprehensive protein expression profile of iECs, which indicates their similarities with a widely used immortalized HUVECs, allowing for further mechanistic studies of EC development, signaling, and metabolism for future regenerative applications. NEW & NOTEWORTHY We have developed methods to differentiate induced pluripotent stem cells (iPSCs) across multiple iPSC lines into nontissue-specific pan vascular ECs (iECs) and demonstrated the proteomic similarity of these cells to a widely used endothelial cell line (HUVECs). We also identified posttranslational modifications and targets for increasing the proteomic similarity of iECs to HUVECs. In the future, iECs can be used to study EC development, signaling, and metabolism for future regenerative applications.

Objective: To analyze the spatial distribution and identify high-risk spatial clusters of Zika, dengue, and chikungunya (ZDC), in the city of Rio de Janeiro, Brazil, and their socioeconomic status., Methods: An ecological study based on data from a seroprevalence survey. Using a rapid diagnostic test to detect the arboviruses, 2,114 individuals were tested in 2018. The spatial distribution was analyzed using kernel estimation. To detect high-risk spatial clusters of arboviruses, we used multivariate scan statistics. The Social Development Index (SDI) was considered in the analysis of socioeconomic status., Results: Among the 2,114 individuals, 1,714 (81.1%) were positive for at least one arbovirus investigated. The kernel estimation showed positive individuals for at least one arbovirus in all regions of the city, with hot spots in the North, coincident with regions with very low or low SDI. The scan statistic detected three significant (p<0.05) high-risk spatial clusters for Zika, dengue, and chikungunya viruses. These clusters correspond to 35.7% (n=613) of all positive individuals of the sample. The most likely cluster was in the North (cluster 1) and overlapped regions with very low and low SDI. Clusters 2 and 3 were in the West and overlapping regions with low and very low SDI, respectively. The highest values of relative risks were in cluster 1 for CHIKV (1.97), in cluster 2 for ZIKV (1.58), and in cluster 3 for CHIKV (1.44). Regarding outcomes in the clusters, the Flavivirus had the highest frequency in clusters 1, 2, and 3 (42.83%, 54.46%, and 52.08%, respectively)., Conclusion: We found an over-risk for arboviruses in areas with the worst socioeconomic conditions in Rio de Janeiro. Moreover, the highest concentration of people negative for arboviruses occurred in areas considered to have better living conditions.

Objective: to analyze the characteristics and temporal trend of mortality rates in the population aged 5 to 14 years in Mato Grosso state and in Brazil, from 2009 to 2020., Methods: this was an ecological time-series study, based on data taken from the Mortality Information System. Descriptive and trend analyses were performed, using the joinpoint regression model and calculating the average annual percentage change (AAPC)., Results: in Brazil and in Mato Grosso state, deaths were predominantly male, preventable and due to external causes. A falling trend was identified for Brazil (5-9 years AAPC: -2.9; 95%CI -4.3;-1.6 and 10-14 years AAPC: -2.5; 95%CI -3.3;-1.8), while a stationary trend was found in Mato Grosso (5-9 years AAPC: -2.0; 95%CI -5.6;1.7 and 10-14 years AAPC: -0.1; 95%CI -5.9;6.1)., Conclusion: the stable trend of mortality at high levels demands urgent interventions to reduce it.

This study aimed to analyze the occurrence of clusters and factors associated with the resurgence of measles cases from the largest epidemic of the post-elimination period in the State of São Paulo, Brazil, in 2019. Sociosanitary and care factors were analyzed by zero-inflated Poisson (ZIP) and ZIP models with structured and unstructured spatial effect. The SCAN statistic was used to analyze the occurrence of case clusters. Clusters of high-risk cases were identified in municipalities that make up the intermediate region of São Paulo. In the ZIP model, the following variables were observed as risk factors at the municipal level: household heads under 18 years old (adjusted RR =0 1.39; 95%CrI: 1.27-1.53), inequality in income distribution (adjusted RR = 36.67; 95%CrI: 26.36-51.15), unemployment in people over 18 years old (adjusted RR = 1.10; 95%CrI: 1.08-1.12), and non-existent street lighting (adjusted RR = 1.05; 95%CrI: 1.04-1.05). In the ZIP models with structured and unstructured spatial effect, the following variables were observed as risk factors: household heads under 18 years old (adjusted RR = 1.36; 95%CrI: 1.04-1.90) and inequality in income distribution (adjusted RR = 3.12; 95%CrI: 1.02-9.48). In both models, the coverage of health agents was presented as a protective factor. The findings reinforce the importance of intensifying measles surveillance actions articulated to the Family Health Strategy, especially in areas with greater social vulnerability, to ensure equitable and satisfactory vaccination coverage and reduce the risk of reemergence of the disease.

Urinary tract infections (UTIs) are common and frequently precipitate delirium-like states. Advanced age coincident with the postmenopausal period is a risk factor for delirium following UTIs. We previously demonstrated a pathological role for interleukin-6 (IL-6) in mediating delirium-like phenotypes in a murine model of UTI. Estrogen has been implicated in reducing peripheral IL-6 expression, but it is unknown whether the increased susceptibility of postmenopausal females to developing delirium concomitant with UTIs reflects diminished effects of circulating estrogen. Here, we tested this hypothesis in a mouse model of UTI. Female C57BL/6J mice were oophorectomized, UTIs induced by transurethral inoculation of E. coli, and treated with 17β-estradiol. Delirium-like behaviors were evaluated prior to and following UTI and 17β-estradiol treatment. Compared to controls, mice treated with 17β-estradiol had less neuronal injury, improved delirium-like behaviors, and less plasma and frontal cortex IL-6. In vitro studies further showed that 17β-estradiol may also directly mediate neuronal protection, suggesting pleiotropic mechanisms of 17β-estradiol-mediated neuroprotection. In summary, we demonstrate a beneficial role for 17β-estradiol in ameliorating acute UTI-induced structural and functional delirium-like phenotypes. These findings provide pre-clinical justification for 17β-estradiol as a therapeutic target to ameliorate delirium following UTI., (© 2022. The Author(s).)

The hypothalamus, which is part of the brain of all vertebrate animals, is considered the link between the central nervous system (CNS) and (i) the endocrine system via the pituitary gland and (ii) with our organs via the autonomic nervous system. It synthesizes and releases neurohormones, which in turn stimulate or inhibit the secretion of other hormones within the CNS, and sends and receives signals to and from the peripheral nervous and endocrine systems. As the brain region responsible for energy homeostasis, the hypothalamus is the key regulator of thermoregulation, hunger and satiety, circadian rhythms, sleep and fatigue, memory and learning, arousal and reproductive cycling, blood pressure, and heart rate and thus orchestrates complex physiological responses in order to maintain metabolic homeostasis. These critical roles implicate the hypothalamus in neuroendocrine disorders such as obesity, diabetes, anorexia nervosa, bulimia, and others. In this chapter, we focus on the use of human-induced pluripotent stem cells (hiPSCs) and their differentiation into hypothalamic neurons in order to model neuroendocrine disorders such as extreme obesity in a dish. To do so, we discuss important steps of human hypothalamus development, neuroendocrine diseases related to the hypothalamus, multiple protocols to differentiate hiPSCs into hypothalamic neurons, and severe obesity modeling in vitro using hiPSCs-derived hypothalamic neurons., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In the last 40 years, Latin America countries, including Brazil, have suffered from the emergence and reemergence of arboviruses, first Dengue (DENV) and recently Zika (ZIKV) and Chikungunya (CHIKV). All three arboviruses are currently endemic in Brazil and have caused major outbreaks in recent years. Rio de Janeiro city, host of the last Summer Olympic Games and the Football World Cup, has been specially affected by them. A surveillance system based on symptomatic reports is in place in Rio, but the true number of affected individuals is unknown due to the great number of Zika, Dengue and Chikungunya asymptomatic cases. Seroprevalence studies are more suitable to evaluate the real number of cases in a given population. We performed a populational seroprevalence survey in Rio, with recruitment of a sample of volunteers of all ages and gender from July to October 2018, within randomly selected census tracts and household. A total of 2,120 volunteers were interviewed and tested with rapid immunochromatographic test for ZIKV, DENV and CHIKV. Individuals with positive results for IgG and/or IgM from only one virus were classified accordingly, while those with test results positive for both ZIKV and DENV were classified as flaviviruses. We corrected for sample design and non-response in data analysis, and calculated point estimate prevalence and 95% confidence intervals for each virus. Arbovirus prevalence in the Rio's population (n = 6,688,927) was estimated at 48.6% [95% CI 44.8-52.4] (n = 3,254,121) for flaviviruses and at 18.0% [95% CI 14.8-21.2] (n = 1,204,765) for CHIKV. Approximately 17.0% [95% CI 14.1-20.1] (n = 1,145,674) of Rio´s population had no contact with any of the three arboviruses. The reported cases of Zika, Dengue and Chikungunya by the current surveillance system in place is insufficient to estimate their real numbers, and our data indicate that Zika seroprevalence could be at least five times and Chikungunya 45 times bigger. The high number of individuals having never been infected by any of the three arboviruses, may indicate a proper scenario for future outbreaks., Competing Interests: The authors have declared that no competing interests exist.

Background: The signs and symptoms of Zika virus infection are usually mild and self-limited. However, the disease has been linked to neurological complications such as Guillain-Barré syndrome and peripheral nerve involvement, and also to abortion and fetal deaths due to vertical transmission, resulting in various congenital malformations in newborns, including microcephaly. This review aimed to describe the o signs and symptoms that characterize the congenital Zika syndrome., Methods and Findings: A systematic review was performed with a protocol and described according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search strategy yielded 2,048 studies. After the exclusion of duplicates and application of inclusion criteria, 46 studies were included. The main signs and symptoms associated with the congenital Zika syndrome were microcephaly, parenchymal or cerebellar calcifications, ventriculomegaly, central nervous system hypoplasia or atrophy, arthrogryposis, ocular findings in the posterior and anterior segments, abnormal visual function and low birthweight for gestational age., Conclusions: Zika virus infection during pregnancy can cause a series of changes in the growth and development of children, while impacting the healthcare system due to the severity of cases. Our findings outline the disease profile in newborns and infants and may contribute to the development and updating of more specific clinical protocols., Competing Interests: The authors have declared that no competing interests exist.

The scope of this research was to identify and characterize spatial units of epidemiological relevance in the state of Rio de Janeiro, through the highest concentrations of cutaneous leishmaniasis (CL) from 1980 to 2012, considering the geographical aspects. SUCAM, FUNASA and SINAN databases were consulted. A method of adjustment of spatially referenced data for demarcation of the regions with the highest concentrations of cases called circuits and poles was applied. These were superimposed on the socioenvironmental indicator maps. Of the total cases registered in the period, 87% occurred in the municipalities located in the resulting circuits and poles. The variations in the occurrence of cases in the different circuits and poles were not related to the socioenvironmental indicators. The identification of the circuits and poles can subsidize the state CL program of the prioritization of strategies of prevention and control actions and the optimization of the resources of the program. These regions, which are more stable than the localities, allow surveillance and control operations in locations with many cases and in other locations in the identified risk area, because they have the same characteristics as those already affected.

Objective: to analyze the relationship between per capita income and the cumulative incidence of COVID-19 in the neighborhoods of the city of Rio de Janeiro, RJ, Brazil., Method: an ecological study using neighborhoods as units of analysis. The cumulative incidence rate per 100,000 inhabitants and the median of potential confounding variables (sex, race, and age) were calculated. Multiple analysis included quantile regression, estimating the regression coefficients of the variable income for every five percentiles from the 10th to 90th percentiles to verify the relationship between income and incidence., Results: the city's rate was 36.58 new cases per 100,000 inhabitants. In general, the highest rates were observed in the wealthiest regions. Multiple analysis was consistent with this observation since the per capita income affected all percentiles analyzed, with a median regression coefficient of 0.02 (p-value <0.001; R2 32.93). That is, there is an increase of R$ 0.02 in the neighborhood's per capita income for every unit of incidence., Conclusion: cumulative incident rates of COVID-19 are influenced by one's neighborhood of residency, suggesting that access to testing is uneven.

Evidence of psychosocial stress at work as a risk factor for diabetes and prediabetes is restricted., Objectives: Analyze the independent and combined association of the models, demand-control and social support (DC-SS) and the effort-reward imbalance and overcommitment (ERI-OC), and the incidence of glycemic alterations (prediabetes and diabetes)., Methods: A prospective study was carried out with data from 7503 active workers from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study in the period 2008-2014. Work stress was measured by two stress models. Glycemic levels were evaluated by glycated hemoglobin (HbA1c) in two moments and classified in four groups: normal, maintenance of prediabetes, incident prediabetes, and incident diabetes. Multinomial logistic regression was analyzed with 5% significance levels stratified by sex, and multiplicative interactions were investigated., Results: Work stress and glycemic alterations were more frequent in women. Psychosocial stress at work was shown to be associated to the risk of prediabetes and diabetes only among women. For women, the combination of models enlarged the magnitude of the association: prediabetes (DC-ERI = OR 1.51, 95% CI 1.15-1.99) and diabetes (DC-ERI = OR 2.10, 95% CI 1.20-3.65). Highly-educated women exposed to ERI-OC were four times more likely to have diabetes., Conclusion: Both models may contribute to explaining the psychosocial stress load according to each pattern of glycemic alteration among women., Competing Interests: The authors declare no conflicts of interest.

Background: Despite the decreasing of leprosy cases in Brazil, its occurrence remains high in certain Brazilian cities. The aim of the study was to analyze the spatial pattern of leprosy in São Luís, capital of Maranhão State, Northeastern Brazil., Methodology: An ecological study was carried out based on secondary data from leprosy cases and contacts reported in the Notification of Injury Information System in2015, and information on residency domiciles in three districts in the city., Results: A positive correlation was found between the leprosy cases and the average number of residents per household, and households with open sewage, garbage accumulated, with street identification, persons without income, dependents and the poor. A negative correlation between cases and households with a sidewalk, literate people and 60 years old or more were identified. The seropositivity of contacts examined using the ML Flow test was of 23.19%. The disease presents a heterogeneous spatial pattern, with hyperendemic clusters., Conclusions: The spatialization of both leprosy cases and contacts and the identification of areas presenting the highest concentration of the disease in each district is important and constitutes an important tool to subsidize disease-control actions., (Copyright © 2020. Published by Elsevier Ltd.)

One of the leading causes for the development of adverse metabolic effects, including type 2 diabetes, dyslipidemia, and cardiovascular diseases, is the accumulation of excess body weight, often measured by body mass index (BMI). Although BMI, calculated using weight and height, is the standard measure used to determine body adiposity in clinical and public health guidelines, an inherent limitation is that BMI does not distinguish where in the body adiposity is deposited. Central obesity, characterized by greater accumulation of adiposity in the abdominal region, has been associated with a higher risk of mortality, independent of BMI. Importantly, one of the determinants of body fat distribution is sex hormones. Both estrogens and androgens appear to directly and indirectly influence body fat distribution. Our review will focus specifically on the role of estrogens and their influence in determining body fat distribution and overall health of adipose tissues, and the role of epigenetic mechanisms in regulating the production and function of estrogens., (© 2019 New York Academy of Sciences.)

Introduction: The fish farming program in Acre is as an alternative program to generate income and employment and has promising regional, national, and international markets. While the economic importance of fish farming in the Jurua Region is clear, one must address its contribution to increase malaria transmission., Methods: This was a qualitative study. The answers of the 16 key informants were organized into the following: (1) the healthcare services structure; (2) conscience, perception, and behaviors; and (3) socioeconomic and political issues. Each answer was classified as weaknesses, strengths, opportunities, and threats., Results: Regarding healthcare services, the frequency of household visits was reduced, and subjects presenting with malaria symptoms were required to visit a healthcare unit to be diagnosed and treated. Regarding individual's conscience, perception, and behavior, malaria was considered an insignificant disease, and a large proportion of the population were engaged in health practices that put them at risk in contacting with malaria vectors. Regarding political and economic issues, there were economic and infrastructure barriers for the development of a productive activity, and the insufficient credit or formalization of their properties prevented their access to governmental incentives and the financial market., Conclusions: Support to fish farmers for low-cost inputs was not observed, and appropriate knowledge regarding the impact of the absence of maintenance and abandonment of fish tanks was insufficient. Moreover, insufficient healthcare services prevented not only the treatment of individuals with malaria but also the control of this disease.

Obesity increases the risks of developing cardiovascular and metabolic diseases and degrades quality of life, ultimately increasing the risk of death. However, not all forms of obesity are equally dangerous: some individuals, despite higher percentages of body fat, are at less risk for certain chronic obesity-related complications. Many open questions remain about why this occurs. Data suggest that the physical location of fat and the overall health of fat dramatically influence disease risk; for example, higher concentrations of visceral relative to subcutaneous adipose tissue are associated with greater metabolic risks. As such, understanding the determinants of the location and health of adipose tissue can provide insight about the pathological consequences of obesity and can begin to outline targets for novel therapeutic approaches to combat the obesity epidemic. Although age and sex hormones clearly play roles in fat distribution and location, much remains unknown about gene regulation at the level of adipose tissue or how genetic variants regulate fat distribution. In this review, we discuss what is known about the determinants of body fat distribution, and we highlight the important roles of sex hormones, aging, and genetic variation in the determination of body fat distribution and its contribution to obesity-related comorbidities., (Copyright © 2019 Frank et al.)

Objective: to investigate access to health services for tuberculosis (TB) diagnosis and treatment among indigenous peoples in Rondônia State, Brazil, 2009-2011., Methods: we conducted a cross-sectional study with indigenous people attending Indigenous Health Care Units (Casai) between October 2009 and February 2011; geographical, economical and functional dimensions of access to TB services were evaluated through interviews and then described., Results: 52 indigenous people with TB were interviewed; in the geographical dimension, lack of transportation, distance and lack of health professionals were the main obstacles; in the economic dimension, 15 indigenous people reported cost/expense as a barrier to access; in the functional dimension, 21 arrived at the Casai using their own means; 24 reported that the time between first symptoms and arriving at the Casai was > 30days; 25 reported that time between first consultation and starting treatment was >30 days; treatment was supervised in 22 cases., Conclusion: the difficulties found in accessing health services in the dimensions we analyzed can contribute to TB continuing to be transmitted in indigenous villages.

Objective: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population., Methods: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test)., Results: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity., Conclusions: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

Rio de Janeiro maintains a recurrent history of dengue epidemics. There is scarce evidence about the route of the population to get health care. The study aimed to describe the pattern of suspected dengue patients flow in search of health care services in Rio de Janeiro. The following data were analyzed: dengue reports from 2011 to 2013; the neighborhoods of patient's residence; the neighborhoods of health services. Neighborhoods of the city were used as unit of analysis focusing on access to health facilities of municipal Planning Area (AP) 3.3. Flow maps were elaborated to describe the routes between the neighborhood of residence and the heath service. Between 2011 and 2013 48,576 suspected dengue cases living in program area 3.3 were reported, 72% got health care in the AP 3.3, 37% of which in primary care. A total of 12,545 suspected cases attended health facilities outside the AP 3.3. A great geographical variation was observed in the search for Primary Care within the AP 3.3, as well as a relevant movement to the center and south zone of the city on access to care, comprising 2,647 different flows. The findings indicate a large flow within the municipality.

Objectives: Compare mortality from severe acute respiratory infection (SARI) attributable to influenza between pre-vaccination (pre-V) and post-vaccination (post-V) periods, to determine the historical evolution and seasonality of time series between 2002 and 2016, and to estimate the risk of death in children between 6 and 23 months of age, using a statistical model., Methods: Time-series study using official mortality data from the official statistical database on deaths. ICD-10 codes between J09-18.9 and J22X were considered to represent SARI. Crude rates and age-adjusted rates (AAR) were calculated, and pre-V (2002-2009) and post-V (2010-2016) periods were compared using the chi-squared ( χ 2) test. The best statistical model was the one that compared deaths from SARI in children during 2002 with other years. The data were analyzed with R programming ( p <0.05)., Results: 4.6% of deaths (301,747) were from SARI, with a median age of 82 years. The percentage of deaths under age 2 declined in the post-V period (from 2.34% to 0.99%, p < 0.05). Marked seasonality was observed in winter. The AAR in persons over age 64 rose from 259.8 per 100,000 population (pre-V) to 328.6 (post-V) ( p < 0.05). In children, the crude rate dropped significantly. Compared with the year 2002, there was a significantly lower estimated risk of dying from SARI during the three years post-V., Conclusions: The reduction in mortality from influenza in Argentina was more pronounced in children, with an estimated 3.5 fewer child deaths from SARI per month., Competing Interests: Conflicto de intereses. Ninguno declarado por los autores.

Background: Despite the intensification of Chagas disease control in Brazil, around 1980s and 1990s, the transmission still occurs. The aim of this study was to identify the factors associated with Chagas disease among blood donors in Piaui State, Brazilian Northeast Region from 2004 to 2013., Methodology: Records of 597 blood donors from Management System in Hemotherapy Services and Laboratory Environment Manager System of Piaui were studied. Sociodemographic variables and serological tests results for Chagas disease's confirmation were analyzed using adjusted multiple logistic regression and odds ratio (OR) evaluation., Results: The frequency of serological test confirming Chagas disease was 15.6%. Multivariate analysis showed that the most important associated factors were among blood donors who were born until 1960 (OR 5.1; 95%; CI 1.95-13.14), with low educational level (OR 2.8; 95%; CI 0.75-10.29), who lives in cities with ≤50% of urbanization rate (OR 3.5; 95%; CI 1.42-8.72) and first-time blood donors (OR 3.0; 95%; CI 1.74-5.23)., Conclusions: Unfortunately, the factors associated with Chagas disease are still the same pointed out in the scientific literature of decades ago. Our results are in line with the postulate of the 2nd Brazilian Consensus on Chagas disease, regarding the need to develop research that presents new scientific evidence, contributing not only to the Brazilian scenario but also to Latin America., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Mato Grosso do Sul State (MS) has the second-largest indigenous population and the highest incidence rates of TB among indigenous people in Brazil. However, little is known about the risk factors associated with active TB in indigenous people in the region, especially regarding socioeconomic factors. The aim of this study is to assess the effect of the Family Allowance Program (BFP) and of other predictors of active TB in a high-risk indigenous population in Brazil. We conducted a case-control study with incident TB cases matched by age and by village of residence (1:2 proportion) between March 2011 and December 2012. We used a conditional logistic regression for data analysis. A total of 153 cases and 306 controls were enrolled. The final model included the following risk factors: alcohol consumption (low-risk use OR=2.2; 95% CI 1.1-4.3; risky use OR=2.4; 95% CI 1.0-6.0; dependent/ damaging use OR=9.1; 95% CI 2.9-29.1); recent contact with a TB patient (OR=2.0; 95% CI 1.2-3.5); and male sex (OR=1.9; 95% CI 1.1-3.2). BFP participation (OR=0.5; 95% CI 0.3-0.6) and BCG vaccination (OR=0.5; 95% CI 0.3-0.9) were found to be protective factors against TB. Although the BFP was not designed to target TB-affected households specifically, our findings reveal the importance of the BFP in preventing one of the most important infectious diseases among adults in indigenous villages in Brazil. This result is in line with the End-TB strategy, which identifies social protection, poverty alleviation and targeting other determinants of TB as key actions.

Low levels of estrogens are associated with obesity-related comorbidities. Mice with lower levels of estrogens are thereby more sensitive to the effects of a high-fat-diet (HFD) for the development of glucose intolerance and insulin resistance. Studies in vivo have demonstrated that taurine (TAU) supplementation prevents glucose and insulin resistance. Thus, we aimed to investigate the potential beneficial effects of TAU supplementation on glucose homeostasis of mice with low levels of estrogens fed with a HFD. 3-month-old female C57BL/6J mice underwent bilateral ovariectomy (OVX). After 1 week of recovery, mice were divided into 4 groups and either received: a standard chow diet (OVXC), chow diet plus drinking water enriched with 3% of TAU (OVXCT), HFD (OVXH), and HFD plus supplementation of TAU (OVXHT) for 14 weeks. Exposure to the HFD increased adiposity and plasma levels of glucose and insulin. Contrary to our prediction, the addition of TAU enhanced the deleterious effects of the HFD. Glucose and insulin tolerance tests (ipGTT and ipITT) indicated that mice maintained on the HFD + TAU had worse glucose intolerance and insulin resistance that was linked to lower insulin signaling in skeletal muscle and liver. Insulin secretion of isolated pancreatic islets of OVXH mice was higher than OVXC, and the addition of TAU associated with a HFD did not modulate insulin secretion, suggesting a failure of pancreatic β cells of OVXHT mice. These results suggest that despite the beneficial reports of TAU, it should be used cautiously in situations where the levels of estrogens are low.

Despite the decline in prevalence of Chagas disease in Brazil, the Northeast region of the country has favorable conditions for its resurgence. The study aimed to analyze positive Chagas disease serology rates among blood donors in Piauí State from 2004 to 2013. Prevalence of positive Chagas disease serology in blood donor screening was 1%, ranging from 0.4% in the Uruçuí Regional Health District to 2.4% in the São Raimundo Nonato Regional Health District. Of the state's 220 municipalities, 58.6% reported cases. Only 34.5% of the positive samples in screening were referred for complementary tests, and 84.4% of these showed negative results. Our findings suggest the possibility of persistent vector-borne transmission in areas of Piauí State and the need for measures to improve complementary testing in positive cases detected by screening.

Cell culture has enhanced our understanding of cellular physiology and constitutes an important tool in advancing mechanistic insight. Researchers should be reminded, however, that there are limitations in extrapolating data derived from cultured cells to questions focusing on the impact of sex. In this Opinion, we highlight two underappreciated aspects of cell culture systems regarding sex: how cell culture media alters the sex hormone environment, and how the innate sex of the cell is often not factored into the overall analysis. By paying careful attention to these areas, researchers can facilitate reproducibility of their cell culture models, which is consistent with the mandate from the National Institutes of Health to improve scientific rigor and reproducibility in research.

The influence of sex on cellular function and metabolism is often ill defined in many human and animal studies. The National Institute of Health (NIH) recognized this gap in scientific knowledge and mandated that sex be factored into the design and data analysis of all cell culture and animal studies. Therefore, it is critical to understand how to incorporate sex in pre-clinical and clinical research. Here, we discuss how the sexual identify of cells influences experimental responses in cell culture and we highlight the importance of the culture media and its constituents to the function of cells. We further discuss the importance of understanding the influence and interactions between sex hormones and sex chromosomes. A deeper understanding of how sex chromosomes and sex hormones function as variables in complex biological systems may lead to better, more personalized medical therapies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aging is associated with visceral adiposity, metabolic disorders, and chronic low-grade inflammation. 17α-estradiol (17α-E2), a naturally occurring enantiomer of 17β-estradiol (17β-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17α-E2 could alleviate age-related metabolic dysfunction and inflammation. 17α-E2 reduced body mass, visceral adiposity, and ectopic lipid deposition without decreasing lean mass. These declines were associated with reductions in energy intake due to the activation of hypothalamic anorexigenic pathways and direct effects of 17α-E2 on nutrient-sensing pathways in visceral adipose tissue. 17α-E2 did not alter energy expenditure or excretion. Fasting glucose, insulin, and glycosylated hemoglobin were also reduced by 17α-E2, and hyperinsulinemic-euglycemic clamps revealed improvements in peripheral glucose disposal and hepatic glucose production. Inflammatory mediators in visceral adipose tissue and the circulation were reduced by 17α-E2. 17α-E2 increased AMPKα and reduced mTOR complex 1 activity in visceral adipose tissue but not in liver or quadriceps muscle, which is in contrast to the generalized systemic effects of caloric restriction. These beneficial phenotypic changes occurred in the absence of feminization or cardiac dysfunction, two commonly observed deleterious effects of exogenous estrogen administration. Thus, 17α-E2 holds potential as a novel therapeutic for alleviating age-related metabolic dysfunction through tissue-specific effects., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Most preclinical and clinical, animal, and human research has been biased with respect to sex and even more so with respect to gender. In fact, little is known about the impact of sex and even less about the influence of gender on overall metabolic processes. The National Institutes of Health has recognized this gap in scientific knowledge and now mandates that studies be conducted in both sexes and to include gender as variables influencing physiological processes such as metabolism. It is therefore critical to understand and appreciate how to incorporate sex and gender in preclinical and clinical research in order to enhance our understanding of the mechanisms by which metabolic processes differ by sex and gender. In this chapter, we define sex and gender and discuss when sex and gender are not aligned, such as that which occurs in transgender individuals, and how this impacts metabolic processes. We discuss the importance of understanding the influence and interactions between sex hormones and sex chromosomes rather than focusing on their relative contributions to metabolism in isolation. This knowledge will optimize therapies specific for individuals which need to encompass sex and gender.

Anti-tuberculosis (TB) drugs are responsible for the occurrence of several adverse drug reactions (ADRs), including hepatotoxicity. The aim was to estimate the incidence of hepatotoxicity and its association with genetic polymorphisms and clinical-epidemiological factors by comparing indigenous and non-indigenous TB patients. We investigated clinical-epidemiological variables, serum levels of liver enzymes and NAT2, CYP2E1 and GSTM1 polymorphisms. A non-conditional logistic regression was used to identify the factors associated with hepatotoxicity. Odds ratios were used as the association measures. The incidence of hepatotoxicity was 19.7% for all patients. The risk of hepatotoxicity was almost four times higher in indigenous patients, comparing to non-indigenous. We identified a new nonsynonymous single nucleotide polymorphism of NAT2 in indigenous patients. In total, 54.6% of the patients expressed a slow acetylation phenotype profile. The frequency of the null genotype of GSTM1 was higher in non-indigenous patients (p = 0.002), whereas no significant differences in relation to polymorphisms of CYP2E1 were observed between the groups. Hepatotoxicity was associated with patients older than 60 and indigenous (OR = 26.0; 95%CI:3.1-217.6; OR = 3.8; 95%CI:1.3-11.1, respectively). Furthermore, hepatotoxicity was associated with a slow acetylation profile in indigenous patients (OR = 10.7; 95%CI:1.2-97.2). Our findings suggest that there are distinct acetylation profiles in the Brazilian population, emphasizing the importance of pharmacogenetic analyses for achieving personalized therapeutic schemes and better outcomes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Menopause-related withdrawal of ovarian estrogens is associated with reduced energy metabolism and overall impairment of substrate oxidation. Estradiol's withdrawal after menopause is associated with a reduction in energy metabolism and impaired substrate oxidation, which contributes to weight gain and visceral fat accumulation. Here we aimed to investigate the association between plasma estradiol concentrations and energy expenditure (EE)/substrate oxidation in a group of overweight postmenopausal women before and after a fatty meal challenge. Women were divided into three groups according to their plasma estradiol concentrations (E2): group 1 - E 2  ≤ 39, group 2 - 40 ≤ E 2  ≤ 59, and group 3 - E 2  ≥ 60 pg/mL. VO 2 and VCO 2 volumes were collected following indirect calorimetry 5 h following a single lipid overload meal (1100 kcal, 72% of fat). For comparisons between groups and within the same group, a linear regression model with mixed effects was applied (P < 0.05). Forty-four women aged 55 ± 0.7 years-old, 8 ± 1.1 years following menopause, with a BMI of 30.5 ± 0.5 kg/m 2 , and 41.9 ± 0.7% of body fat were enrolled the study. Plasma E2 concentrations were: group 1 - 30.4 ± 1.9, group 2 - 46.9 ± 1.5, and group 3 - 91.3 ± 12.0 pg/mL (P < 0.0001). EE at baseline and in the resting state was 1320 ± 24.3 kcal/d, and increased to 1440 ± 27.0 kcal/d 30 min following ingestion of the fatty meal (P < 0.0001), and rose again to an average of 1475 ± 30.3 kcal/d at the completion of experiment (P < 0.0001). Carbohydrate oxidation (Chox) was 0.155 ± 0.01 g/min at resting, maintained as 0.133 ± 0.00 g/min 30 min after ingestion of the fatty meal, and was 0.123 ± 0.01 g/min at the end of the testing period. Lipid oxidation (Lipox) was 0.041 ± 0.003 g/min at resting, increasing to 0.054 ± 0.003 g/min at 30 min (P = 0.01), and reaching 0.063 ± 0.003 g/min at the end of the experiment (P < 0.0001). There was no difference between groups for EE, Chox or Lipox. Our data suggest that EE and substrate oxidation were modulated following a lipid-meal challenge equally in all groups and this did not differ with plasma E2 concentrations., (Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Introduction: Geographic information systems (GIS) enable public health data to be analyzed in terms of geographical variability and the relationship between risk factors and diseases. This study discusses the application of the geographic weighted regression (GWR) model to health data to improve the understanding of spatially varying social and clinical factors that potentially impact leprosy prevalence., Methods: This ecological study used data from leprosy case records from 1998-2006, aggregated by neighborhood in the Duque de Caxias municipality in the State of Rio de Janeiro, Brazil. In the GWR model, the associations between the log of the leprosy detection rate and social and clinical factors were analyzed., Results: Maps of the estimated coefficients by neighborhood confirmed the heterogeneous spatial relationships between the leprosy detection rates and the predictors. The proportion of households with piped water was associated with higher detection rates, mainly in the northeast of the municipality. Indeterminate forms were strongly associated with higher detections rates in the south, where access to health services was more established., Conclusions: GWR proved a useful tool for epidemiological analysis of leprosy in a local area, such as Duque de Caxias. Epidemiological analysis using the maps of the GWR model offered the advantage of visualizing the problem in sub-regions and identifying any spatial dependence in the local study area.

Background: The leprosy transmission chain is very complex and, in order to intervene in this transmission, more must be known about the factors linked to falling ill. There are doubts as to the influence of population size, population density and the disease's magnitude in detection rate trends. This paper aimed to identify factors associated with detection of leprosy in an endemic municipality of Rio de Janeiro State, Brazil., Methods: This ecological study in Duque de Caxias municipality, Rio de Janeiro State, Brazil, used neighbourhoods (bairros) as the unit of analysis. Selecting new cases of leprosy detected from 1998 to 2006, the analysis examined clinical, socioeconomic and service variables using a Poisson log-Normal model., Results: In the municipality overall, 2572 new cases were detected, a rate of 3.70 cases/10,000 inhabitants. The results describe a heterogeneous distribution of cases and rates in the municipality. The final model displayed a significant association with indeterminate clinical form (β = 2.599), proportion of homes with running water (β = -2.334) and presence of a decentralised health care unit (β = 0.524)., Conclusion: Although the results indicate progress towards elimination of the disease in the municipality, high rates continue to be detected in municipal sub-regions. The following question can thus be posed: over how wide a geographical area could the disease be thoroughly eliminated, given this heterogeneity within a small municipality?