Inflammatory Status in Trained and Untrained Mice at Different Pollution Levels.

Atmospheric pollution can be defined as a set of changes that occur in the composition of the air, making it unsuitable and/or harmful and thereby generating adverse effects on human health. The regular practice of physical exercise (PE) is associated with the preservation and/or improvement of health; however, it can be influenced by neuroimmunoendocrine mechanisms and external factors such as air pollution, highlighting the need for studies involving the practice of PE in polluted environments. Herein, 24 male C57BL/6 mice were evaluated, distributed into four groups (exposed to a high concentration of pollutants/sedentary, exposed to a high concentration of pollutants/exercised, exposed to ambient air/sedentary, and exposed to ambient air/exercised). The exposure to pollutants occurred in the environmental particle concentrator (CPA) and the physical training was performed on a treadmill specially designed for use within the CPA. Pro- and anti-inflammatory markers in blood and bronchoalveolar lavage (BALF), BALF cellularity, and lung tissue were evaluated. Although the active group exposed to a high concentration of pollution showed a greater inflammatory response, both the correlation analysis and the ratio between pro- and anti-inflammatory cytokines demonstrated that the exercised group presented greater anti-inflammatory activity, suggesting a protective/adaptative effect of exercise when carried out in a polluted environment.

Air pollution aggravates renal ischaemia-reperfusion-induced acute kidney injury.

Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and a decline in renal function. PM2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia-reperfusion injury (IRI) involves biological processes similar to those involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Usefulness of minimally invasive autopsy in the diagnosis of arboviruses to increase the sensitivity of the Epidemiological Surveillance System in Ceará, Brazil.

OBJECTIVE: To create a protocol for performing minimally invasive autopsies (MIA) in detecting deaths from arboviruses and report preliminary data from its application in Ceará state, Brazil. METHODS: Training was provided to medical pathologists on MIA. RESULTS: A protocol was established for performing MIA, defining criteria for sample collection, storage methods, and diagnoses to be carried out according to the type of biological sample; 43 MIAs were performed in three months. Of these, 21 (48.8%) arrived at the Death Verification Service (SVO) with arboviruses as a diagnostic hypothesis, and seven (16.3%) were confirmed (six chikungunya cases and one dengue case); cases of COVID-19 (n = 9), tuberculosis (n = 5), meningitis (n = 4), cryptococcosis (n = 1), Creutzfeldt-Jakob disease (n = 1), breast cancer (n = 1), and human rabies (n = 1) were also confirmed. CONCLUSION: The protocol implemented enabled identification of a larger number of suspected arbovirus-related deaths, as well as confirmation of other diseases of interest for surveillance. MAIN RESULTS: A protocol was developed to perform minimally invasive autopsies (MIAs) in Death Verification Services (SVO), capable of expanding the system's capacity to identify a greater number of deaths suspected to be due to arboviruses. IMPLICATIONS FOR SERVICES: The experience suggests that in-service trained health professionals are able to perform MIA, and that use of this technique in SVOs has been shown to be capable of increasing the system's sensitivity in detecting deaths of interest to public health. PERSPECTIVES: Trained professionals will be able to collect biological material in hospitals, through MIA, in cases of interest for health surveillance and when family members do not allow a complete conventional autopsy to be performed.

The landscape of biomedical research funding in Brazil: a current overview

ABSTRACT Objective: The objective of this narrative review is to discuss the current state of research funding in Brazil. Materials and Methods: This study is based on the most recent edition of the course Funding for Research and Innovation in the University of Sao Paulo School of Medicine which was a three-day course with 12 hours of instruction. The course brought together leading experts in the field to comprehensively discuss the current state of research funding in Brazil. Each speaker provided a presentation on a specific topic related to research funding. After the workshop, speakers assembled relevant topics in this manuscript. Results: collaborative research is critical for securing research funding. It optimizes proposal competitiveness, amplifies societal impact, and manages risks effectively. As such, fostering and supporting these collaborations is paramount for both researchers and funding agencies. To maintain the highest integrity in research, investigators involved in these collaborations must disclose any relationships that could potentially influence the outcomes or interpretation of their projects. Conclusions: In Brazil, the mainstay of research funding stems from public entities, with agencies such as CNPq, CAPES, and state bodies like FAPESP, FAPERJ, FAPEMIG and others at the forefront. Concurrently, industry funding offers viable pathways, especially through industry-sponsored studies, investigator-led projects, and collaborative initiatives. The Brazilian funding landscape is further enriched by innovative platforms, including crowdfunding and the contributions of institutions like the Serrapilheira Institute. Internationally, esteemed organizations such as the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation stand out as potential funders.

Effects of land cover and air pollution on the risk of preterm births.

OBJECTIVE: To evaluate the association between gestational age and green areas, urban built areas, and the concentration of particulate matter 2.5 (PM2.5) in the city of São Paulo, analyzing the irregular distribution of these areas and pollution levels above the recommended level. METHODS: The study population consisted of a cohort of live births from 2012, and data from the Live Birth Information System (Sinasc) of the city of São Paulo were used. Using satellite images and supervised classification, the distribution and quantity of green areas and built areas in the city of São Paulo was obtained, as well as the concentrations of PM2.5. Logistic regressions were used to obtain possible associations. RESULTS: The results of the study show that a lower percentage of green areas is significantly associated with a higher chance of preterm births. A higher building density was positively associated with the odds ratio for preterm birth. We did not find any significant associations between air pollution (PM2.5) and preterm births. CONCLUSIONS: The results of this study show that greener areas are less associated with preterm births when compared with less green areas.

Wildfire-related PM2.5 and cardiovascular mortality: A difference-in-differences analysis in Brazil.

Brazil has experienced unprecedented wildfires recently. We aimed to investigate the association of wildfire-related fine particulate matter (PM2.5) with cause-specific cardiovascular mortality, and to estimate the attributable mortality burden. Exposure to wildfire-related PM2.5 was defined as exposure to annual mean wildfire-related PM2.5 concentrations in the 1-year prior to death. The variant difference-in-differences method was employed to explore the wildfire-related PM2.5-cardiovascular mortality association. We found that, in Brazil, compared with the population in the first quartile (Q1: ≤1.82 µg/m3) of wildfire-related PM2.5 exposure, those in the fourth quartile (Q4: 4.22-17.12 µg/m3) of wildfire-related PM2.5 exposure had a 2.2% (RR: 1.022, 95% CI: 1.013-1.032) higher risk for total cardiovascular mortality, 3.1% (RR: 1.031, 95% CI: 1.014-1.048) for ischaemic heart disease mortality, and 2.0% (RR: 1.020, 95% CI: 1.002-1.038) for stroke mortality. From 2010 to 2018, an estimation of 35,847 (95% CI: 22,424-49,177) cardiovascular deaths, representing 17.77 (95% CI: 11.12-24.38) per 100,000 population, were attributable to wildfire-related PM2.5 exposure. Targeted health promotion strategies should be developed for local governments to protect the public from the risk of wildfire-related cardiovascular premature deaths.

Association of pulmonary black carbon accumulation with cardiac fibrosis in residents of Sao Paulo, Brazil.

Evidence suggests that myocardial interstitial fibrosis, resulting from cardiac remodeling, may possibly be influenced by mechanisms activated through the inhalation of airborne pollutants. However, limited studies have explored the relationship between lifetime exposure to carbon-based particles and cardiac fibrosis, specially using post-mortem samples. This study examined whether long-term exposure to air pollution (estimated by black carbon accumulated in the lungs) is associated with myocardial fibrosis in urban dwellers of megacity of Sao Paulo. Data collection included epidemiological and autopsy-based approaches. Information was obtained by interviewing the next of kin and through the pathologist's report. The individual index of exposure to carbon-based particles, which we designed as the fraction of black carbon (FBC), was estimated through quantification of particles on the macroscopic lung surface. Myocardium samples were collected for histopathological analysis to evaluate the fraction of cardiac fibrosis. The association between cardiac fibrosis and FBC, age, sex, smoking status and hypertension was assessed by means of multiple linear regression models. Our study demonstrated that the association of FBC with cardiac fibrosis is influenced by smoking status and hypertension. Among hypertensive individuals, the cardiac fibrosis fraction tended to increase with the increase of the FBC in both groups of smokers and non-smokers. In non-hypertensive individuals, the association between cardiac fibrosis fraction and FBC was observed primarily in smokers. Long-term exposure to tobacco smoke and environmental particles may contribute to the cardiac remodeling response in individuals with pre-existing hypertension. This highlights the importance of considering hypertension as an additional risk factor for the health effects of air pollution on the cardiovascular system. Moreover, the study endorses the role of autopsy to investigate the effects of urban environment and personal habits in determining human disease.

Ambient PM2.5 and productivity-adjusted life years lost in Brazil: a national population-based study.

Enormous health burden has been associated with air pollution and its effects continue to grow. However, the impact of air pollution on labour productivity at the population level is still unknown. This study assessed the association between premature death due to PM2.5 exposure and the loss of productivity-adjusted life years (PALYs), in Brazil. We applied a novel variant of the difference-in-difference (DID) approach to assess the association. Daily all-cause mortality data in Brazil were collected from 2000-2019. The PALYs lost increased by 5.11% (95% CI: 4.10-6.13%), for every 10 µg/m3 increase in the 2-day moving average of PM2.5. A total of 9,219,995 (95% CI: 7,491,634-10,921,141) PALYs lost and US$ 268.05 (95% CI: 217.82-317.50) billion economic costs were attributed to PM2.5 exposure, corresponding to 7.37% (95% CI: 5.99-8.73%) of the total PALYs lost due to premature death. This study also found that 5,005,306 PALYs could be avoided if the World Health Organization (WHO) air quality guideline (AQG) level was met. In conclusion, this study demonstrates that ambient PM2.5 exposure is associated with a considerable labour productivity burden relating to premature death in Brazil, while over half of the burden could be prevented if the WHO AQG was met. The findings highlight the need to reduce ambient PM2.5 levels and provide strong evidence for the development of strategies to mitigate the economic impacts of air pollution.

The landscape of biomedical research funding in Brazil: a current overview.

OBJECTIVE: The objective of this narrative review is to discuss the current state of research funding in Brazil. MATERIALS AND METHODS: This study is based on the most recent edition of the course Funding for Research and Innovation in the University of Sao Paulo School of Medicine which was a three-day course with 12 hours of instruction. The course brought together leading experts in the field to comprehensively discuss the current state of research funding in Brazil. Each speaker provided a presentation on a specific topic related to research funding. After the workshop, speakers assembled relevant topics in this manuscript. RESULTS: collaborative research is critical for securing research funding. It optimizes proposal competitiveness, amplifies societal impact, and manages risks effectively. As such, fostering and supporting these collaborations is paramount for both researchers and funding agencies. To maintain the highest integrity in research, investigators involved in these collaborations must disclose any relationships that could potentially influence the outcomes or interpretation of their projects. CONCLUSIONS: In Brazil, the mainstay of research funding stems from public entities, with agencies such as CNPq, CAPES, and state bodies like FAPESP, FAPERJ, FAPEMIG and others at the forefront. Concurrently, industry funding offers viable pathways, especially through industry-sponsored studies, investigator-led projects, and collaborative initiatives. The Brazilian funding landscape is further enriched by innovative platforms, including crowdfunding and the contributions of institutions like the Serrapilheira Institute. Internationally, esteemed organizations such as the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation stand out as potential funders.

Postmortem chest computed tomography in COVID-19: A minimally invasive autopsy method.

Objectives: Performing autopsies in a pandemic scenario is challenging, as the need to understand pathophysiology must be balanced with the contamination risk. A minimally invasive autopsy might be a solution. We present a model that combines radiology and pathology to evaluate postmortem CT lung findings and their correlation with histopathology. Methods: Twenty-nine patients with fatal COVID-19 underwent postmortem chest CT, and multiple lung tissue samples were collected. The chest CT scans were analyzed and quantified according to lung involvement in five categories: normal, ground-glass opacities, crazy-paving, small consolidations, and large or lobar consolidations. The lung tissue samples were examined and quantified in three categories: normal lung, exudative diffuse alveolar damage (DAD), and fibroproliferative DAD. A linear index was used to estimate the global severity of involvement by CT and histopathological analysis. Results: There was a positive correlation between patient mean CT and histopathological severity score indexes - Pearson correlation coefficient (R) = 0.66 (p = 0.0078). When analyzing the mean lung involvement percentage of each finding, positive correlations were found between the normal lung percentage between postmortem CT and histopathology (R=0.65, p = 0.0082), as well as between ground-glass opacities in postmortem CT and normal lungs in histopathology (R=0.65, p = 0.0086), but negative correlations were observed between ground-glass opacities extension and exudative diffuse alveolar damage in histological slides (R=-0.68, p = 0.005). Additionally, it was found is a trend toward a decrease in the percentage of normal lung tissue on the histological slides as the percentage of consolidations in postmortem CT scans increased (R =-0.51, p = 0.055). The analysis of the other correlations between the percentage of each finding did not show any significant correlation or correlation trends (p ≥ 0.10). Conclusions: A minimally invasive autopsy is valid. As the severity of involvement is increased in CT, more advanced disease is seen on histopathology. However, we cannot state that one specific radiological category represents a specific pathological correspondent. Ground-glass opacities, in the postmortem stage, must be interpreted with caution, as expiratory lungs may overestimate disease.

Effects of land cover and air pollution on the risk of preterm births / Efeitos da cobertura de solo e poluição do ar no risco de nascimentos prematuros

ABSTRACT OBJECTIVE To evaluate the association between gestational age and green areas, urban built areas, and the concentration of particulate matter 2.5 (PM2.5) in the city of São Paulo, analyzing the irregular distribution of these areas and pollution levels above the recommended level. METHODS The study population consisted of a cohort of live births from 2012, and data from the Live Birth Information System (Sinasc) of the city of São Paulo were used. Using satellite images and supervised classification, the distribution and quantity of green areas and built areas in the city of São Paulo was obtained, as well as the concentrations of PM2.5. Logistic regressions were used to obtain possible associations. RESULTS The results of the study show that a lower percentage of green areas is significantly associated with a higher chance of preterm births. A higher building density was positively associated with the odds ratio for preterm birth. We did not find any significant associations between air pollution (PM2.5) and preterm births. CONCLUSIONS The results of this study show that greener areas are less associated with preterm births when compared with less green areas.

RESUMO OBJETIVO Avaliar a associação entre a idade gestacional e as áreas verdes, áreas construídas urbanas e a concentração de material particulado 2,5 (MP2,5) em São Paulo, analisando a distribuição irregular dessas áreas e os níveis de poluição acima do recomendado. MÉTODOS A população utilizada no estudo foi a dos nascidos vivos no ano de 2012, com os dados do Sistema de Informações sobre Nascidos Vivo (Sinasc) na cidade de São Paulo. Por meio de imagens de satélites e realizando a classificação supervisionada, obtivemos a distribuição e quantidade de áreas verdes e de áreas construídas, na cidade de São Paulo, assim como as concentrações de MP2,5. Regressões logísticas foram utilizadas para obter possíveis associações. RESULTADOS Os resultados do estudo mostram que menor percentual de áreas verdes está associado significativamente com maior chance de prematuridade. Maior densidade de construção foi associada positivamente com a razão de chance de nascimento prematuro. Não encontramos resultados significativos entre a poluição do ar (MP2,5) e prematuridade. CONCLUSÕES Os resultados deste estudo demostraram que áreas mais verdes em relação às áreas menos verdes são menos associadas a nascimentos prematuros.

Usefulness of minimally invasive autopsy in the diagnosis of arboviruses to increase the sensitivity of the Epidemiological Surveillance System in Ceará, Brazil / Utilidad de la autopsia mínimamente invasiva en el diagnóstico de arbovirus para aumentar la sensibilidad del Sistema de Vigilancia Epidemiológica en Brasil: experiencia de Ceará, Brasil / Utilidade da autópsia minimamente invasiva no diagnóstico das arboviroses para ampliação da sensibilidade do Sistema de Vigilância Epidemiológica no Brasil: experiência do Ceará

Abstract Objective: To create a protocol for performing minimally invasive autopsies (MIA) in detecting deaths from arboviruses and report preliminary data from its application in Ceará state, Brazil. Methods: Training was provided to medical pathologists on MIA. Results: A protocol was established for performing MIA, defining criteria for sample collection, storage methods, and diagnoses to be carried out according to the type of biological sample; 43 MIAs were performed in three months. Of these, 21 (48.8%) arrived at the Death Verification Service (SVO) with arboviruses as a diagnostic hypothesis, and seven (16.3%) were confirmed (six chikungunya cases and one dengue case); cases of COVID-19 (n = 9), tuberculosis (n = 5), meningitis (n = 4), cryptococcosis (n = 1), Creutzfeldt-Jakob disease (n = 1), breast cancer (n = 1), and human rabies (n = 1) were also confirmed. Conclusion: The protocol implemented enabled identification of a larger number of suspected arbovirus-related deaths, as well as confirmation of other diseases of interest for surveillance.

Resumen Objetivo: Estabelecer un protocolo utilizado para la realización de autopsias mínimamente invasivas (AMI) para la detección de muertes por arbovirus y presentar datos preliminares de este protocolo en Ceará, Brasil. Métodos: Se llevó a cabo la capacitación de médicos patólogos en AMI. Resultados: Se estableció un protocolo para la realización de AMI, que define los criterios para la toma de muestras, métodos de almacenamiento y diagnóstico; en tres meses se realizaron 43 AMI; de estas, 21 (48,8%) llegaron al Servicio de Verificación de Óbito (SVO) con una hipótesis diagnóstica de alguna arbovirosis y siete (16,3%) fueron confirmadas (seis casos de chikungunya y uno de dengue); también se confirmaron casos de Covid-19 (n = 9), tuberculosis (n = 5), meningitis (n = 4), criptococosis (n = 1), enfermedad de Creutzfeldt-Jakob (n = 1), neoplasia de mama (n = 1) y rabia humana (n = 1). Conclusión: El protocolo implementado permitió la identificación de un mayor número de muertes sospechosas de arbovirus, además de la confirmación de otras patologías de interés.

Resumo Objetivo: Estabelecer protocolo para realização de autópsias minimamente invasivas (AMIs) na detecção de óbitos por arboviroses e relatar dados preliminares desse protocolo no Ceará, Brasil. Métodos: Médicos patologistas foram treinados em AMI. Resultados: Estabeleceu-se protocolo para AMI, definindo-se critérios para amostras a serem coletadas, suas formas de armazenamento e diagnóstico, segundo o tipo de amostra biológica; em três meses, foram realizadas 43 AMIs, das quais 21 (48,8%) chegaram ao Serviço de Verificação de Óbito (SVO) com hipótese diagnóstica de alguma arbovirose e sete (16,3%) foram confirmados (seis de chikungunya; uma de dengue); também foram confirmados casos de covid-19 (n = 9), tuberculose (n = 5), meningite (n = 4), criptococose (n = 1), doença de Creutzfeldt-Jakob (n = 1), neoplasia de mama (n = 1) e raiva humana (n = 1). Conclusão: O protocolo implantado permitiu a captação de um maior número de óbitos suspeitos de arboviroses, além da confirmação de outras patologias de interesse da vigilância.

COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS.

BACKGROUND: Lung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS. METHODS: We have quantified different ECM elements and TGF-ß expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile. RESULTS: We observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-ß, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-ß was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course. CONCLUSIONS: Fatal COVID-19 is associated with an early TGF-ß expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.

Ultrastructural characterization of alveolar microvascular damage in severe COVID-19 respiratory failure.

Endothelial dysfunction is a key phenomenon in COVID-19, induced by direct viral endothelial infection and secondary inflammation, mainly affecting the microvascular circulation. However, few studies described the subcellular aspects of the lung microvasculature and the associated thrombotic phenomena, which are widely present in severe COVID-19 cases. To that end, in this transversal observational study we performed transmission and scanning electron microscopy in nine lung samples of patients who died due to COVID-19, obtained via minimally invasive autopsies in Sao Paulo, Brazil, in 2020. All patients died due to acute respiratory failure and had microvascular thrombosis at histology. Electron microscopy revealed areas of endothelial damage with basal lamina disruption and virus infection in endothelial cells. In the capillary lumens, the ultrastructure of the thrombi is depicted, with red blood cells stacking, dysmorphism and hemolysis, fibrin meshworks, and extracellular traps. Our description illustrates the complex pathophysiology of microvascular thrombosis at the cellular level, which leads to some of the peculiar characteristics of severe COVID-19.NEW & NOTEWORTHY In this study, electron microscopy was used to explain the pathophysiology of respiratory failure in severe COVID-19. Before the advent of vaccination, as the virus entered the respiratory system, it rapidly progressed to the alveolar capillary network and, before causing exudative alveolar edema, it caused mainly thrombosis of the pulmonary microcirculation with preserved lung compliance explaining "happy hypoxia." Timing of anticoagulation is of pivotal importance in this disease.

What else in times of COVID-19? The role of minimally invasive autopsy for the differential diagnosis of acute respiratory failure in a case of kala-azar.

Visceral leishmaniasis (VL) is a chronic vector-borne zoonotic disease caused by trypanosomatids, considered endemic in 98 countries, mainly associated with poverty. About 50,000-90,000 cases of VL occur annually worldwide, and Brazil has the second largest number of cases in the world. The clinical picture of VL is fever, hepatosplenomegaly, and pancytopenia, progressing to death in 90% of cases due to secondary infections and multi-organ failure, if left untreated. We describe the case of a 25-year-old female who lived in the metropolitan area of Sao Paulo, who had recently taken touristic trips to several rural areas in Southeastern Brazil and was diagnosed post-mortem. During the hospitalization in a hospital reference for the treatment of COVID-19, the patient developed acute respiratory failure, with chest radiographic changes, and died due to refractory shock. The ultrasound-guided minimally invasive autopsy diagnosed VL (macrophages containing amastigote forms of Leishmania in the spleen, liver and bone marrow), as well as pneumonia and bloodstream infection by gram-negative bacilli.

Assessing socioeconomic bias of exposure to urban air pollution: an autopsy-based study in São Paulo, Brazil.

Background: The characterisation of individual exposure to air pollution in urban scenarios is a challenge in environmental epidemiological studies. We investigated if the city's pollution monitoring stations over or underestimate the exposure of individuals depending on their socioeconomic conditions and daily commuting times. Methods: The amount of black carbon accumulated in the lungs of 604 deceased who underwent autopsy in São Paulo was considered as a proxy for PM10. The concentrations of PM10 in the residence of the deceased were estimated by interpolating an ordinary kriging model. These two-exposure metrics allowed us to construct an environmental exposure misclassification index ranging from -1 to 1. The association between the index and daily commuting, socioeconomic context index (GeoSES), and street density as predictors was assessed by means of a multilevel linear regression model. Findings: With a decrease of 0.1 units in GeoSES, the index increases, on average, by 0.028 units and with an increase of 1 h in daily commuting, the index increases, on average, by 0.022 units indicating that individual exposure to air pollution is underestimated in the lower GeoSES and in people with many hours spent in daily commuting. Interpretation: Reduction of health consequences of air pollution demands not only alternative fuel and more efficient mobility strategies, but also should include profound rethink of cities. Funding: São Paulo Research Foundation (FAPESP-13/21728-2) and National Council for Scientific and Technological Development (CNPq-304126/2015-2, 401825/2020-5).

Maternal exposure to air pollution alters energy balance transiently according to gender and changes gut microbiota.

Introduction: The timing of maternal exposure to air pollution is crucial to define metabolic changes in the offspring. Here we aimed to determine the most critical period of maternal exposure to particulate matter (PM2.5) that impairs offspring's energy metabolism and gut microbiota composition. Methods: Unexposed female and male C57BL/6J mice were mated. PM2.5 or filtered air (FA) exposure occurred only in gestation (PM2.5/FA) or lactation (FA/PM2.5). We studied the offspring of both genders. Results: PM2.5 exposure during gestation increased body weight (BW) at birth and from weaning to young in male adulthood. Leptin levels, food intake, Agrp, and Npy levels in the hypothalamus were also increased in young male offspring. Ikbke, Tnf increased in male PM2.5/FA. Males from FA/PM2.5 group were protected from these phenotypes showing higher O2 consumption and Ucp1 in the brown adipose tissue. In female offspring, we did not see changes in BW at weaning. However, adult females from PM2.5/FA displayed higher BW and leptin levels, despite increased energy expenditure and thermogenesis. This group showed a slight increase in food intake. In female offspring from FA/PM2.5, BW, and leptin levels were elevated. This group displayed higher energy expenditure and a mild increase in food intake. To determine if maternal exposure to PM2.5 could affect the offspring's gut microbiota, we analyzed alpha diversity by Shannon and Simpson indexes and beta diversity by the Linear Discriminant Analysis (LDA) in offspring at 30 weeks. Unlike males, exposure during gestation led to higher adiposity and leptin maintenance in female offspring at this age. Gestation exposure was associated with decreased alpha diversity in the gut microbiota in both genders. Discussion: Our data support that exposure to air pollution during gestation is more harmful to metabolism than exposure during lactation. Male offspring had an unfavorable metabolic phenotype at a young age. However, at an older age, only females kept more adiposity. Ultimately, our data highlight the importance of controlling air pollution, especially during gestation.

Wildfire-related PM2.5 and health economic loss of mortality in Brazil.

BACKGROUND: Wildfire imposes a high mortality burden on Brazil. However, there is a limited assessment of the health economic losses attributable to wildfire-related fine particulate matter (PM2.5). METHODS: We collected daily time-series data on all-cause, cardiovascular, and respiratory mortality from 510 immediate regions in Brazil during 2000-2016. The chemical transport model GEOS-Chem driven with Global Fire Emissions Database (GFED), in combination with ground monitored data and machine learning was used to estimate wildfire-related PM2.5 data at a resolution of 0.25°â€ˆ× 0.25°. A time-series design was applied in each immediate region to assess the association between economic losses due to mortality and wildfire-related PM2.5 and the estimates were pooled at the national level using a random-effect meta-analysis. We used a meta-regression model to explore the modification effect of GDP and its sectors (agriculture, industry, and service) on economic losses. RESULTS: During 2000-2016, a total of US$81.08 billion economic losses (US$5.07 billion per year) due to mortality were attributable to wildfire-related PM2.5 in Brazil, accounting for 0.68% of economic losses and equivalent to approximately 0.14% of Brazil's GDP. The attributable fraction (AF) of economic losses due to wildfire-related PM2.5 was positively associated with the proportion of GDP from agriculture, while negatively associated with the proportion of GDP from service. CONCLUSION: Substantial economic losses due to mortality were associated with wildfires, which could be influenced by the agriculture and services share of GDP per capita. Our estimates of the economic losses of mortality could be used to determine optimal levels of investment and resources to mitigate the adverse health impacts of wildfires.

Productivity-adjusted life years lost due to non-optimum temperatures in Brazil: A nationwide time-series study.

Non-optimal temperatures are associated with premature deaths globally. However, the evidence is limited in low- and middle-income countries, and the productivity losses due to non-optimal temperatures have not been quantified. We aimed to estimate the work-related impacts and economic losses attributable to non-optimal temperatures in Brazil. We collected daily mortality data from 510 immediate regions in Brazil during 2000 and 2019. A two-stage time-series analysis was applied to evaluate the association between non-optimum temperatures and the Productivity-Adjusted Life-Years (PALYs) lost. The temperature-PALYs association was fitted for each location in the first stage and then we applied meta-analyses to obtain the national estimations. The attributable fraction (AF) of PALY lost due to ambient temperatures and the corresponding economic costs were calculated for different subgroups of the working-age population. A total of 3,629,661 of PALYs lost were attributed to non-optimal temperatures during 2000-2019 in Brazil, corresponding to 2.90 % (95 % CI: 1.82 %, 3.95 %) of the total PALYs lost. Non-optimal temperatures have led to US$104.86 billion (95 % CI: 65.95, 142.70) of economic costs related to PALYs lost and the economic burden was more substantial in males and the population aged 15-44 years. Higher risks of extreme cold temperatures were observed in the South region in Brazil while extreme hot temperatures were observed in the Central West and Northeast regions. In conclusion, non-optimal temperatures are associated with considerable labour losses as well as economic costs in Brazil. Tailored policies and adaptation strategies should be proposed to mitigate the impacts of non-optimal temperatures on the labour supply in a changing climate.

What else in times of COVID-19? The role of minimally invasive autopsy for the differential diagnosis of acute respiratory failure in a case of kala-azar

ABSTRACT Visceral leishmaniasis (VL) is a chronic vector-borne zoonotic disease caused by trypanosomatids, considered endemic in 98 countries, mainly associated with poverty. About 50,000-90,000 cases of VL occur annually worldwide, and Brazil has the second largest number of cases in the world. The clinical picture of VL is fever, hepatosplenomegaly, and pancytopenia, progressing to death in 90% of cases due to secondary infections and multi-organ failure, if left untreated. We describe the case of a 25-year-old female who lived in the metropolitan area of Sao Paulo, who had recently taken touristic trips to several rural areas in Southeastern Brazil and was diagnosed post-mortem. During the hospitalization in a hospital reference for the treatment of COVID-19, the patient developed acute respiratory failure, with chest radiographic changes, and died due to refractory shock. The ultrasound-guided minimally invasive autopsy diagnosed VL (macrophages containing amastigote forms of Leishmania in the spleen, liver and bone marrow), as well as pneumonia and bloodstream infection by gram-negative bacilli.