Short-term ozone exposure and cancer mortality in Brazil: A nationwide case-crossover study.

Exposure to ambient ozone (O3) is linked to increased mortality risks from various diseases, but epidemiological investigations delving into its potential implications for cancer mortality are limited. We aimed to examine the association between short-term O3 exposure and site-specific cancer mortality and investigate vulnerable subgroups in Brazil. In total 3,459,826 cancer death records from 5570 Brazilian municipalities between 2000 and 2019, were included. Municipal average daily O3 concentration was calculated from a global estimation at 0.25°×0.25° spatial resolution. The time-stratified case-crossover design was applied to assess the O3-cancer mortality association. Subgroup analyses by age, sex, season, time-period, region, urban hierarchy, climate classification, quantiles of GDP per capita and illiteracy rates were performed. A linear and non-threshold exposure-response relationship was observed for short-term exposure to O3 with cancer mortality, with a 1.00% (95% CI: 0.79%-1.20%) increase in all-cancer mortality risks for each 10-µg/m3 increment of three-day average O3. Kidney cancer was most strongly with O3 exposure, followed by cancers of the prostate, stomach, breast, lymphoma, brain and lung. The associated cancer risks were relatively higher in the warm season and in southern Brazil, with a decreasing trend over time. When restricting O3 concentration to the national minimum value during 2000-2019, a total of 147,074 (116,690-177,451) cancer deaths could be avoided in Brazil, which included 17,836 (7014-28,653) lung cancer deaths. Notably, these associations persisted despite observed adaptation within the Brazilian population, highlighting the need for a focus on incorporating specific measures to mitigate O3 exposure into cancer care recommendations.

Short-Term Exposure to Wildfire-Specific PM2.5 and Hospitalization for Diabetes Morbidity: A Study in Multiple Countries and Territories.

OBJECTIVE: To evaluate associations of wildfire fine particulate matter (PM2.5) with diabetes across multiple countries and territories. RESEARCH DESIGN AND METHODS: We collected data on 3,612,135 diabetes hospitalizations from 1,008 locations in Australia, Brazil, Canada, Chile, New Zealand, Thailand, and Taiwan during 2000-2019. Daily wildfire-specific PM2.5 levels were estimated through chemical transport models and machine-learning calibration. Quasi-Poisson regression with distributed lag nonlinear models and random-effects meta-analysis were applied to estimate associations between wildfire-specific PM2.5 and diabetes hospitalization. Subgroup analyses were by age, sex, location income level, and country or territory. Diabetes hospitalizations attributable to wildfire-specific PM2.5 and nonwildfire PM2.5 were compared. RESULTS: Each 10 µg/m3 increase in wildfire-specific PM2.5 levels over the current day and previous 3 days was associated with relative risks (95% CI) of 1.017 (1.011-1.022), 1.023 (1.011-1.035), 1.023 (1.015-1.032), 0.962 (0.823-1.032), 1.033 (1.001-1.066), and 1.013 (1.004-1.022) for all-cause, type 1, type 2, malnutrition-related, other specified, and unspecified diabetes hospitalization, respectively. Stronger associations were observed for all-cause, type 1, and type 2 diabetes in Thailand, Australia, and Brazil; unspecified diabetes in New Zealand; and type 2 diabetes in high-income locations. Relative risks (95% CI) of 0.67% (0.16-1.18%) and 1.02% (0.20-1.81%) for all cause and type 2 diabetes hospitalizations were attributable to wildfire-specific PM2.5. Compared with nonwildfire PM2.5, wildfire-specific PM2.5 posed greater risks of all-cause, type 1, and type 2 diabetes and were responsible for 38.7% of PM2.5-related diabetes hospitalizations. CONCLUSIONS: We show the relatively underappreciated links between diabetes and wildfire air pollution, which can lead to a nonnegligible proportion of PM2.5-related diabetes hospitalizations. Precision prevention and mitigation should be developed for those in advantaged communities and in Thailand, Australia, and Brazil.

Cancer mortality risk from short-term PM2.5 exposure and temporal variations in Brazil.

Although some studies have found that short-term PM2.5 exposure is associated with lung cancer deaths, its impact on other cancer sites is unclear. To answer this research question, this time-stratified case-crossover study used individual cancer death data between January 1, 2000, and December 31, 2019, extracted from the Brazilian mortality information system to quantify the associations between short-term PM2.5 exposure and cancer mortality from 25 common cancer sites. Daily PM2.5 concentration was aggregated at the municipality level as the key exposure. The study included a total of 34,516,120 individual death records, with the national daily mean PM2.5 exposure 15.3 (SD 4.3) µg/m3. For every 10-µg/m3 increase in three-day average PM2.5 exposure, the odds ratio (OR) for all-cancer mortality was 1.04 (95% CI 1.03-1.04). Apart from all-cancer deaths, PM2.5 exposure may impact cancers of oesophagus (1.04, 1.00-1.08), stomach (1.05, 1.02-1.08), colon-rectum (1.04, 1.01-1.06), lung (1.04, 1.02-1.06), breast (1.03, 1.00-1.06), prostate (1.07, 1.04-1.10), and leukaemia (1.05, 1.01-1.09). During the study period, acute PM2.5 exposure contributed to an estimated 1,917,994 cancer deaths, ranging from 0 to 6,054 cases in each municipality. Though there has been a consistent downward trend in PM2.5-related all-cancer mortality risks from 2000 to 2019, the impact remains significant, indicating the continued importance of cancer patients avoiding PM2.5 exposure. This nationwide study revealed a notable association between acute PM2.5 exposure and heightened overall and site-specific cancer mortality for the first time to our best knowledge. The findings suggest the importance of considering strategies to minimize such exposure in cancer care guidelines. ENVIRONMENTAL IMPLICATION: The 20-year analysis of nationwide death records in Brazil revealed that heightened short-term exposure to PM2.5 is associated with increased cancer mortality at various sites, although this association has gradually decreased over time. Despite the declining impact, the research highlights the persistent adverse effects of PM2.5 on cancer mortality, emphasizing the importance of continued research and preventive measures to address the ongoing public health challenges posed by air pollution.

Transmission electron microscopy reveals the presence of SARS-CoV-2 in human spermatozoa associated with an ETosis-like response.

BACKGROUND: Severe acute syndrome coronavirus 2 can invade a variety of tissues, including the testis. Even though this virus is scarcely found in human semen polymerase chain reaction tests, autopsy studies confirm the viral presence in all testicular cell types, including spermatozoa and spermatids. OBJECTIVE: To investigate whether the severe acute syndrome coronavirus 2 is present inside the spermatozoa of negative polymerase chain reaction-infected men up to 3 months after hospital discharge. MATERIALS AND METHODS: This cross-sectional study included 13 confirmed moderate-to-severe COVID-19 patients enrolled 30-90 days after the diagnosis. Semen samples were obtained and examined with real-time polymerase chain reaction for RNA detection and by transmission electron microscopy. RESULTS: In moderate-to-severe clinical scenarios, we identified the severe acute syndrome coronavirus 2 inside spermatozoa in nine of 13 patients up to 90 days after discharge from the hospital. Moreover, some DNA-based extracellular traps were reported in all studied specimens. DISCUSSION AND CONCLUSION: Although severe acute syndrome coronavirus 2 was not present in the infected men's semen, it was intracellularly present in the spermatozoa till 3 months after hospital discharge. The Electron microscopy (EM) findings also suggest that spermatozoa produce nuclear DNA-based extracellular traps, probably in a cell-free DNA-dependent manner, similar to those previously described in the systemic inflammatory response to COVID-19. In moderate-to-severe cases, the blood-testes barrier grants little defence against different pathogenic viruses, including the severe acute syndrome coronavirus 2. The virus could also use the epididymis as a post-testicular route to bind and fuse to the mature spermatozoon and possibly accomplish the reverse transcription of the single-stranded viral RNA into proviral DNA. These mechanisms can elicit extracellular cell-free DNA formation. The potential implications of our findings for assisted conception must be addressed, and the evolutionary history of DNA-based extracellular traps as preserved ammunition in animals' innate defence might improve our understanding of the severe acute syndrome coronavirus 2 pathophysiology in the testis and spermatozoa.

Maternal greenness exposure and preterm birth in Brazil: A nationwide birth cohort study.

In the dynamic landscape of maternal and child health, understanding the intricate interplay between environmental factors and pregnancy outcomes is of paramount importance. This study investigates the relationship between maternal greenness exposure and preterm births in Brazil using data spanning from 2010 to 2019. Satellite-derived indices, including the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI), were employed to assess greenness exposure during whole pregnancy in maternal residential area. Employing Cox proportional hazard models, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) for changes in NDVI, while adjusting for individual and area-level covariates. In total, 24,010,250 live births were included. Prevalence of preterm birth was 11.5%, with a modest but statistically significant decreasing trend (p = 0.013) observed across the nation over the study period. The findings reveal a significant association between greenness exposure and a reduced risk of preterm birth. Specifically, for every 0.1 increase in NDVI, there was a 2.0% decrease in the risk of preterm birth (95%CI: 1.9%-2.2%). Stratified analyses based on maternal education and ethnicity indicated potential effect modifications, with stronger protective effects observed among younger mothers and those with less years of education. Sensitivity analyses using EVI yielded consistent results. In conclusion, this study suggests that higher maternal greenness exposure is linked to a decreased risk of preterm birth in Brazil. These findings imply that enhancing residential greenspaces could be a valuable public health strategy to promote maternal and child health in Brazil.

Younger age is associated with cardiovascular pathological phenotype of severe COVID-19 at autopsy.

Introduction: COVID-19 affects patients of all ages. There are few autopsy studies focusing on the younger population. We assessed an autopsy cohort aiming to understand how age influences pathological outcomes in fatal COVID-19. Methods: This study included autopsied patients, aged 6 months to 83 years, with confirmed COVID-19 in 2020-2021. We collected tissue samples from deceased patients using a minimally invasive autopsy protocol and assessed pathological data following a systematic approach. Results: Eighty-six patients were included, with a median age of 55 years (IQR 32.3-66.0). We showed that age was significantly lower in patients with acute heart ischemia (p = 0.004), myocarditis (p = 0.03) and lung angiomatosis (p < 0.001), and significantly higher in patients with exudative diffuse alveolar damage (p = 0.02), proliferative diffuse alveolar damage (p < 0.001), lung squamous metaplasia (p = 0.003) and lung viral atypia (p = 0.03), compared to patients without those findings. We stratified patients by their age and showed that cardiovascular findings were more prevalent in children and young adults. We performed principal component analysis and cluster of pathological variables, and showed that cardiovascular variables clustered and covariated together, and separated from pulmonary variables. Conclusion: We showed that age modulates pathological outcomes in fatal COVID-19. Younger age is associated with cardiovascular abnormalities and older age with pulmonary findings.

Eosinophilic pneumonitis induced by aerosol-administered diesel oil and pyrethrum to mice / Neumonía eosinofílica inducida por aerosol de aceite diésel y piretroide en ratones

OBJECTIVE: To confirm the episode of eosinophilic pneumonitis that occurred in March 2001 in Manaus, Amazon, northern Brazil, as secondary to home aerosolization with 2 percent cypermethrin diluted in diesel compared with the more conventional 1 percent cypermethrin and soybean solution used in prophylaxis of dengue. METHODS: Four groups of Swiss mice were kept in polycarbonate cages aerosolized with one of the following solutions: diesel, diesel and cypermethrin, soy oil and cypermethrin, and saline. Three and 6 days after exposure, resistance and compliance of the respiratory system and white cell kinetics in peripheral blood and lung tissue were analyzed. RESULTS: The group exposed to diesel and cypermethrin showed higher respiratory system resistance (p < 0.001), lower compliance (p = 0.03), and increased eosinophils in blood (p = 0.03) and lung tissue (p = 0.005) compared with the other groups. There was an increase of neutrophils in the blood of all experimental groups on the third day after exposure (p < 0.001). CONCLUSIONS: We concluded that diesel associated with cypermethrin induced lung hyperresponsiveness in this experimental model and was associated with increased polymorphonuclear cells (eosinophils and neutrophils) in blood and lungs. This effect is strongest on the third day after exposure. These results are similar to the episode that occurred in Manaus in 2001 and suggest that diesel plus cypermethrin home aerosolization for arbovirosis prophylaxis should be revised.

OBJETIVO: Confirmar el episodio de neumonía eosinofílica ocurrido en marzo de 2001 en Manaus, Amazonas, en el norte de Brasil, secundario al uso de aerosol de cipermetrina diluida al 2 por ciento en aceite diésel en las viviendas en comparación con la profilaxis más convencional contra el dengue, basada en cipermetrina al 1 por ciento con aceite de soya. MÉTODOS: Se mantuvieron cuatro grupos de ratones suizos en jaulas de policarbonato y se aplicó aerosol con una de las siguientes soluciones: aceite diésel, aceite diésel y cipermetrina, aceite de soya y cipermetrina, y solución salina. Se analizaron la resistencia y el funcionamiento del sistema respiratorio y la cinética de leucocitos en sangre periférica y tejido pulmonar a los tres y seis días después de la exposición. RESULTADOS: El grupo expuesto a aceite diésel y cipermetrina mostró mayor resistencia del sistema respiratorio (P < 0,001), peor funcionamiento (P = 0,03) y más eosinófilos en sangre (P = 0,03) y tejido pulmonar (P = 0,005) que los otros grupos. Se observó un aumento de neutrófilos en sangre en todos los grupos experimentales al tercer día después de la exposición (P < 0,001). CONCLUSIONES: El aceite diésel con cipermetrina indujo una hiperrespuesta pulmonar en este modelo experimental y se asoció con un aumento en las células polimorfonucleares (eosinófilos y neutrófilos) en sangre y tejido pulmonar. Este efecto es mayor al tercer día después de la exposición. Estos efectos son similares a los observados en el episodio ocurrido en Manaus en 2001 e indican que se debe reevaluar el uso de aerosol de aceite diésel con cipermetrina para la profilaxis de arbovirus en las viviendas.

Clinico-pathological discrepancies in a general university hospital in São Paulo, Brazil

INTRODUCTION: The autopsy rate has continuously diminished over the past few decades, reducing the quality of medical care and the accuracy of statistical health data. OBJECTIVE: To assess the accuracy of clinical diagnoses by comparing pre- and postmortem findings, and to identify potential risk factors for misdiagnoses. METHODS: Retrospective evaluations performed between June 2001 and June 2003 in a 2500-bed tertiary university hospital in São Paulo, Brazil, including 288 patients who died at that institution and had a postmortem examination. RESULTS: Clinical and autopsy records were reviewed and compared for categorization using the adapted Goldman criteria. The overall major and minor discrepancy rates were 16.3 percent and 28.1 percent, respectively. The most common missed diagnoses were pulmonary embolism, pneumonia, and myocardial infarction, and the most prevalent underlying diseases were infectious diseases, cerebro-cardiovascular conditions, and malignancies. Patients age 60 or older had an increased risk of diagnostic disagreement, as did female patients. The period of hospitalization, last admission unit at the hospital and underlying disease were not significantly related to the pre-mortem diagnostic accuracy. DISCUSSION: The discrepancy rate found in this study is similar to those reported globally. The factors influencing diagnostic accuracy as well as the most commonly missed diagnoses are also consistent with the literature. CONCLUSION: Autopsy remains a crucial tool for improving medical care, and effort must be focused on increasing its practice worldwide.

The effects of air pollution on cardiovascular diseases: lag structures / Efeitos da poluição do ar nas doenças cardiovasculares: estruturas de defasagem

OBJECTIVE: To assess the lag structure between air pollution exposure and elderly cardiovascular diseases hospital admissions, by gender. METHODS: Health data of people aged 64 years or older was stratified by gender in São Paulo city, Southeastern Brazil, from 1996 to 2001. Daily levels of air pollutants (CO, PM10, O3, NO2, and SO2) , minimum temperature, and relative humidity were also analyzed. It were fitted generalized additive Poisson regressions and used constrained distributed lag models adjusted for long time trend, weekdays, weather and holidays to assess the lagged effects of air pollutants on hospital admissions up to 20 days after exposure. RESULTS: Interquartile range increases in PM10 (26.21 mug/m³) and SO2 (10.73 mug/m³) were associated with 3.17 percent (95 percent CI: 2.09-4.25) increase in congestive heart failure and 0.89 percent (95 percent CI: 0.18-1.61) increase in total cardiovascular diseases at lag 0, respectively. Effects were higher among female group for most of the analyzed outcomes. Effects of air pollutants for different outcomes and gender groups were predominately acute and some "harvesting" were found. CONLUSIONS: The results show that cardiovascular diseases in São Paulo are strongly affected by air pollution.

OBJETIVO: Investigar a estrutura de defasagem entre exposição à poluição do ar e internações hospitalares por doenças cardiovasculares em idosos, separada por gênero. MÉTODOS: Os dados de saúde de pessoas com mais de 64 anos de idade foram estratificados por gênero, na cidade de São Paulo, entre 1996 e 2001. Os níveis diários de poluentes do ar (CO, PM10, O3, NO2, SO2) e os dados de temperatura mínima e umidade relativa do ar foram também foram analisados. Foram utilizados modelos restritos de distribuição polinomial em modelos aditivos generalizados de regressão de Poisson para estimar os efeitos dos poluentes no dia da exposição e até 20 dias após, controlando-se para sazonalidades de longa e curta durações, feriados e fatores meteorológicos. RESULTADOS: Variações interquartis de PM10 (26,21 mig/m³) e SO2 (10,73 mig/m³) foram associados com aumentos de 3,17 por cento (IC 95 por cento: 2,09-4,25) nas admissões por insuficiência cardíaca congestiva e de 0,89 por cento (IC 95 por cento: 0,18-1,61) para admissões por todas as doenças cardiovasculares no dia da exposição, respectivamente. Os efeitos foram predominantemente agudos e maiores para o gênero feminino. Além disso, foi observado efeito colheita. CONCLUSÕES: Os achados mostraram que as doenças cardiovasculares em São Paulo são fortemente afetadas pela poluição do ar.

Air pollution effects on myocardial infarction

OBJETIVO: O infarto do miocárdio é uma doença cardiovascular grave que tem como indicação a internação em unidades de terapia intensiva, com poucos indicados para admissão em enfermarias. O objetivo do estudo foi investigar se as estimativas dos efeitos da poluição atmosférica nas internações por infarto do miocárdio são modificadas de acordo com a fonte de informações de saúde. MÉTODOS: Em hospitais do Sistema Unico de Saúde (SUS), na cidade de São Paulo, foi realizado estudo de séries temporais (1998-1999) tendo como desfechos as internações por infarto em unidades de terapia intensiva e em enfermarias, em pessoas acima de 64 anos. Foram utilizados modelos lineares generalizados, controlados para sazonalidade (de longa e curta duração) e variáveis climáticas. Foram construídos modelos distribuídos de defasagem polinomial de terceiro grau, para avaliar os efeitos acumulados nos oito dias anteriores à exposição.RESULTADOS: Aproximadamente 70 por cento das internações por infarto no miocárdio ocorreram em enfermarias. Apesar disso, os efeitos da poluição sobre os casos foram maiores nas internações em unidades de terapia intensiva. Todos os poluentes mostraram uma associação positiva com os desfechos, mas o SO2 apresentou uma associação mais robusta e estatisticamente significante. O aumento do intervalo interquartil para as concentrações observadas do SO2 foi associado ao aumento em 13 por cento (IC 95 por cento: 6-19) e 8por cento (IC 95por cento: 2-13) nas internações em unidade de terapia intensiva e enfermarias, respectivamente. CONCLUSÕES: Pode-se supor que exista um erro de classificação das internações por infarto nas enfermarias, superestimando o número de internações. No entanto, o menor número de internações por infarto do miocárdio em unidades de terapia intensiva, é o indicador mais adequado para estimar os efeitos da poluição atmosférica nas internações por infarto.

Internações e óbitos e sua relação com a poluição atmosférica em São Paulo, 1993 a 1997 / Hospital admissions and mortality: association with air pollution in São Paulo, Brazil, 1993 to 1997

OBJETIVO: Investigar efeitos de curto prazo da poluição atmosférica na morbidade respiratória de menores de 15 anos e na mortalidade de idosos. MÉTODOS: O estudo foi realizado na cidade de São Paulo, Brasil. Foram analisadas as contagens diárias de admissões hospitalares, de menores de 15 anos e de mortes de idosos (>64 anos) no período de 1993 a 1997, em relação às variações diárias de poluentes atmosféricos (PM10, CO, O3). Foi utilizada para análise a regressão de Poisson em modelos aditivos generalizados. Os modelos foram ajustados para efeitos da tendência temporal, sazonalidade, dias da semana, fatores meteorológicos e autocorrelação. RESULTADOS: Variações do 10º ao 90º percentil dos poluentes foi significativamente associada com o aumento de admissões por doenças respiratórias em menores de 15 anos para PM10 ( por cento RR=10,0), CO ( por cento RR=6,1) e O3 ( por cento RR=2,5). Associação similar foi encontrada para mortalidade em idosos e PM10 ( por cento RR=8,1) e CO ( por cento RR=7,9). CONCLUSÕES: Os resultados encontrados são coerentes com os estudos que apontam associação entre variações de curto prazo dos poluentes atmosféricos e incremento na morbidade e mortalidade nos grandes centros urbanos.