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Background: Heart failure (HF) is associated with poor prognosis, and the identification of biomarkers of its severity could help in its treatment. In a pilot study, we observed high levels of acetone in the exhaled breath of patients with HF. The present study was designed to evaluate exhaled acetone as a biomarker of HF diagnosis and HF severity.Methods: Of 235 patients with systolic dysfunction evaluated between May 2009 and September 2010, 89 patients (HF group) fulfilled inclusion criteria and were compared with sex- and age-matched healthy subjects (control group, n = 20). Patients with HF were grouped according to clinical stability (acute decompensated HF [ADHF], n = 59; chronic HF, n = 30) and submitted to exhaled breath collection. Identification of chemical species was done by gas chromatography-mass spectrometry and quantification by spectrophotometry. Patients with diabetes were excluded.Results: The concentration of exhaled breath acetone (EBA) was higher in the HF group (median, 3.7 μg/L; interquartile range [IQR], 1.69-10.45 μg/L) than in the control group (median, 0.39 μg/L; IQR, 0.30-0.79 μg/L; P < .001) and higher in the ADHF group (median, 7.8 μg/L; IQR, 3.6-15.2 μg/L) than in the chronic HF group (median, 1.22 μg/L; IQR, 0.68-2.19 μg/L; P < .001). The accuracy and sensitivity of this method in the diagnosis of HF and ADHF were about 85%, a value similar to that obtained with B-type natriuretic peptide (BNP). EBA levels differed significantly as a function of severity of HF (New York Heart Association classification, P < .001). There was a positive correlation between EBA and BNP (r = 0.772, P < .001).Conclusions: EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP but also a new biomarker of HF severity. [ABSTRACT FROM AUTHOR]

Rationale: Chronic exposure to air pollution has been associated with adverse effects on children's lung growth.Objectives: We analyzed the effects of chronic exposure to urban levels of particulate matter (PM) on selected phases of mouse lung development.Methods: The exposure occurred in two open-top chambers (filtered and nonfiltered) placed 20 m from a street with heavy traffic in São Paulo, 24 hours/day for 8 months. There was a significant reduction of the levels of PM(2.5) inside the filtered chamber (filtered = 2.9 +/- 3.0 microg/m(3), nonfiltered = 16.8 +/- 8.3 microg/m(3); P = 0.001). At this exposure site, vehicular sources are the major components of PM(2.5) (PM Measurements and Main Results: Mice exposed to PM(2.5) pre+postnatally presented a smaller surface to volume ratio when compared with nonexposed animals (P = 0.036). The pre+postnatal group presented reduced inspiratory and expiratory volumes at higher levels of transpulmonary pressure (P = 0.001). There were no differences among prenatal and postnatal exposure and nonexposed animals.Conclusions: Our data provide anatomical and functional support to the concept that chronic exposure to urban PM affects lung growth. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to investigate nasal mucociliary clearance in acutely ill patients who were clinically stable and had no airway manipulation. DESIGN: Prospective clinical study. SETTING: Medical ICU. PATIENTS AND PARTICIPANTS: Sixteen medical patients admitted to the ICU and 16 healthy subjects were studied. Patients who were receiving airway manipulation, including tracheal suctioning, nasogastric or enteral tubes, noninvasive and invasive mechanical ventilation, were excluded. INTERVENTIONS: Mucociliary clearance was evaluated by saccharine transit time (STT) measurements at ICU admission (admission) and 90 days after hospital discharge (recovery). Healthy subjects were also subjected to two measurements 90 days apart. MEASUREMENTS AND RESULTS: The STT of patients was 26.4 +/- 11.3 min and 17.9 +/- 8.6 min at admission and recovery (p = 0.002) [mean +/- SD] but did not change along the 90-day interval in healthy subjects (17.2 +/- 10.2 min and 16.7 +/- 10.3 min), respectively. Smokers (patients and healthy subjects) presented prolonged STT when compared to nonsmokers (p = 0.026). STT at admission correlated positively with heart rate (r = 0.560; p = 0.024) and hospital stay (r = 0.634; p = 0.008). CONCLUSION: Mucociliary clearance is impaired in stable acutely ill patients with no airway manipulation and correlates with simple markers of underlying disease severity. Mucociliary dysfunction may help to explain the increased susceptibility of hospital-acquired respiratory infection in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: The increase in work-related respiratory complaints in artificially ventilated buildings have multiple causes, and intervention studies are a valuable approach to understanding possible mechanisms.Study Objectives: To analyze the effects of an intervention in a ventilation system with > 20 years of continuous use, and with a high rate of building-related respiratory complains.Design: An epidemiologic study was done among individuals working in places with ventilation machinery and ducts with > 20 years of use, before and after intervention. Analysis of symptoms and logistic regression were performed to check the associations between air-conditioning intervention and reported symptoms.Results: The air-conditioning intervention showed a protective effect on building-related worsening of respiratory symptoms (odds ratio, 0.132; 95% confidence interval, 0.030 to 0.575), naso-ocular symptoms (odds ratio, 0.231; 95% confidence interval, 0.058 to 0.915), and persistent cough (odds ratio, 0.071; 95% confidence interval, 0.014 to 0.356).Conclusion: Intervention in high-risk occupational locations can be effective in improving perceived indoor air quality. [ABSTRACT FROM AUTHOR]

Background: The increase of work-related respiratory complaints in artificially ventilated buildings has multiple causes, and the role of allergen exposure and symptoms is still controversial.Study Objectives: To analyze the risk factors and the association of work-related symptoms with allergen exposure and different conditions of the same air conditioning system in São Paulo, Brazil.Design: Workers were classified according to characteristics of the air conditioning system: the first group (group 1) with ventilation machinery and ducts with > 20 years of use, the second group (group 2) with ventilation machinery with > 20 years of use and ventilation ducts with < 2 years of use, and the third group (group 3) with ventilation machinery and ducts with < 2 years of use. Logistic regression was performed to check the associations between air conditioning groups, allergen exposure (fungi, mites, animal dander, and cockroach), and symptoms.Results: There was a higher prevalence of building-related worsening of respiratory symptoms (p = 0.004; odds ratio [OR], 8.53) and symptoms of rhinoconjunctivitis (p = 0.01; OR, 8.49) in group 1. There was a lower relative humidity (p = 0.05) and nonsignificant lower temperature in group 1, when compared to the other groups. The viable mold spores totals were higher outdoors than in the indoor samples (n = 45, p = 0.017). There were higher levels of Der p 1 in group 2 (p = 0.032). All allergen levels were considered low.Conclusion: There was a strong association of building-related upper-airway symptoms with places having ventilation systems with > 20 years of use. [ABSTRACT FROM AUTHOR]

Background: Heterogeneity in temperature-mortality relationships across locations may partly result from differences in the demographic structure of populations and their cause-specific vulnerabilities. Here we conduct the largest epidemiological study to date on the association between ambient temperature and mortality by age and cause using data from 532 cities in 33 countries., Methods: We collected daily temperature and mortality data from each country. Mortality data was provided as daily death counts within age groups from all, cardiovascular, respiratory, or noncardiorespiratory causes. We first fit quasi-Poisson regression models to estimate location-specific associations for each age-by-cause group. For each cause, we then pooled location-specific results in a dose-response multivariate meta-regression model that enabled us to estimate overall temperature-mortality curves at any age. The age analysis was limited to adults., Results: We observed high temperature effects on mortality from both cardiovascular and respiratory causes compared to noncardiorespiratory causes, with the highest cold-related risks from cardiovascular causes and the highest heat-related risks from respiratory causes. Risks generally increased with age, a pattern most consistent for cold and for nonrespiratory causes. For every cause group, risks at both temperature extremes were strongest at the oldest age (age 85 years). Excess mortality fractions were highest for cold at the oldest ages., Conclusions: There is a differential pattern of risk associated with heat and cold by cause and age; cardiorespiratory causes show stronger effects than noncardiorespiratory causes, and older adults have higher risks than younger adults., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

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.

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., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marisa Dolhnikoff reports financial support was provided by Bill and Melinda Gates Foundation. Marisa Dolhnikoff reports financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico. Thais Mauad reports financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico. Marisa Dolhnikoff reports financial support was provided by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP). Ellison Fernando Cardoso reports financial support was provided by University of Sao Paulo Hospital of Clinics. Luiz Fernando Ferraz da Silva reports financial support was provided by University of Sao Paulo Hospital of Clinics., (© 2024 The Authors.)

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 PM 10 . The concentrations of PM 10 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)., Competing Interests: We declare no competing interests., (© 2023 The Authors.)

Background: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size., Objectives: The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies., Data Sources: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory., Study Eligibility Criteria: Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection., Participants: Confirmed COVID-19 patients with post-mortem cardiovascular findings., Interventions: None., Methods: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs)., Results: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%)., Conclusions: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The perinatal period and early infancy are considered critical periods for lung development. During this period, adversities such as environmental exposures, allergic sensitization, and asthma are believed to impact lung health in adulthood. Therefore, we hypothesized that concomitant exposure to allergic sensitization and urban-derived fine particulate matter (PM 2.5 ) in the early postnatal period of mice would cause more profound alterations in lung alveolarization and growth and differently modulate lung inflammation and gene expression than either insult alone in adult life. BALB/c mice were sensitized with ovalbumin (OVA) and exposed to PM 2.5 from the fifth day of life. Then, we assessed lung responsiveness, inflammation in BALF, lung tissue, and alveolarization by stereology. In addition, we performed a transcriptomic analysis of lung tissue on the 40th day of life. Our results showed that young adult mice submitted to allergic sensitization and exposure to ambient PM 2.5 since early life presented decreased lung growth with impaired alveolarization, a mixed neutrophilic-eosinophilic pattern of lung inflammation, increased airway responsiveness, and increased expression of genes linked to neutrophil recruitment when compared to animals that were OVA-sensitized or PM 2.5 exposed only. Both, early life allergic sensitization and PM 2.5 exposure, induced inflammation and impaired lung growth, but concomitant exposure was associated with worsened inflammation parameters and caused alveolar enlargement. Our experimental data provide pathological support for the hypothesis that allergic or environmental insults in early life have permanent adverse consequences for lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice. Together with our data, current evidence points to the urgent need for healthier environments with fewer childhood disadvantage factors during the critical windows of lung development and growth., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the role of the male sex as a risk factor for coronavirus disease deaths in Sao Paulo and to what extent socioeconomic vulnerability and individual health issues can interfere in such risk., Methods: The primary cause of death, age, sex, comorbidities, and code of the Human Development Units of the residence of 37,583 individuals in Sao Paulo, Brazil, were obtained from the records on confirmed coronavirus disease resident hospitalizations of the city of Sao Paulo from the National Influenza Surveillance Information System. A social vulnerability index was assigned to each Human Development Unit. Using "death" as the outcome variable and sex, admission to the intensive care unit, obesity, renal and heart diseases, diabetes, and social vulnerability as confounders, the odds of death for males and females were compared via logistic regression., Results: The odds of death for males were 1.242 (confidence interval 95% = 1.237, 1.247) times the corresponding odds for females with the same values for all confounders. We estimated the odds of death for patients living in regions with high social vulnerability as 2.243 (CI 95% = 2.151, 2.339) times the corresponding odds of patients living in regions with very low social vulnerability with the same values of the remaining variables., Conclusion: The male:female death ratio by severe acute respiratory syndrome coronavirus 2 infection in Sao Paulo cannot be attributed only to comorbidities or social vulnerabilities. Our results suggest that the male sex is an independent biological risk factor for coronavirus disease death. Besides sex-specific factors, further research should focus on crucial biological factors in male sex coronavirus disease mortality., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

The ongoing COVID-19 pandemic represents an extra burden in the majority of public and private health systems worldwide beyond the most pessimistic expectations, driving an urgent rush to develop effective vaccines and effective medical treatments against the SARS-CoV-2 pandemic. The Nucleocapsid structural viral protein is remarkably immunogenic and hugely expressed during infection. High IgG antibodies against Nucleocapsid protein (N protein) levels were detected in the serum of COVID-19 patients, confirming its pivotal antigen role for a T lymphocyte response in a vaccine microenvironment. Currently, adverse events associated with immunizations have raised some degree of concern, irrespective of its huge benefits in dealing with disease severity and decreasing mortality and morbidity. This hitherto study evaluates histological changes in rats' testes, epididymis, prostate, and seminal vesicles and analyzes hormone levels after solely N protein inoculation. Therefore, we exposed a group of Lewis rats to weekly injections of the recombinant N protein for 28 days, while a control group was inoculated with a buffer solution. The N group revealed a more significant number of spermatozoa. Spermatozoa in the seminiferous tubules were counted in twenty 400 × microscopy fields (mean of 9.2 vs. 4.6 in the control group; p < 0,01), but significantly lower testosterone levels (mean of 125.70 ng/dl vs. 309,00 ng/dl in the control group; p < 0,05) were found. No other histological and biochemical changes were displayed. Conclusively, these data suggest testicular hormonal imbalance mediated by the SARS-CoV-2 N protein that could be linked to reported post-COVID-19 syndrome hypogonadism. More relevant research might be performed to confirm this viral antigen's deleterious mechanism in the human testicular microenvironment, particular in Leydig cell function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lucio Carrasco, Noda, Barbosa, Vieira Borges da Silva, Gasque Bomfim, Ventura Fernandes, Teixeira, Nunes Duarte Neto, Nascimento Saldiva, Achoa Filho, Rodrigues Guzzo, Durigon, Affonso Fonseca, Corazzini, Fanelli, Noronha and Hallak.)

Background: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5° × 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000-19., Methods: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5° × 0·5° from 2000-19. Temperature variability was calculated as the SD of the average of the same and previous days' minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades., Findings: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901-2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2-4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7-5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3-10·4), followed by Europe (4·4%, 2·2-5·6) and Africa (3·3, 1·9-4·6)., Interpretation: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability., Funding: Australian Research Council, Australian National Health & Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Studies have investigated the effects of heat and temperature variability (TV) on mortality. However, few assessed whether TV modifies the heat-mortality association. Data on daily temperature and mortality in the warm season were collected from 717 locations across 36 countries. TV was calculated as the standard deviation of the average of the same and previous days' minimum and maximum temperatures. We used location-specific quasi-Poisson regression models with an interaction term between the cross-basis term for mean temperature and quartiles of TV to obtain heat-mortality associations under each quartile of TV, and then pooled estimates at the country, regional, and global levels. Results show the increased risk in heat-related mortality with increments in TV, accounting for 0.70% (95% confidence interval [CI]: -0.33 to 1.69), 1.34% (95% CI: -0.14 to 2.73), 1.99% (95% CI: 0.29-3.57), and 2.73% (95% CI: 0.76-4.50) of total deaths for Q1-Q4 (first quartile-fourth quartile) of TV. The modification effects of TV varied geographically. Central Europe had the highest attributable fractions (AFs), corresponding to 7.68% (95% CI: 5.25-9.89) of total deaths for Q4 of TV, while the lowest AFs were observed in North America, with the values for Q4 of 1.74% (95% CI: -0.09 to 3.39). TV had a significant modification effect on the heat-mortality association, causing a higher heat-related mortality burden with increments of TV. Implementing targeted strategies against heat exposure and fluctuant temperatures simultaneously would benefit public health., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Background: Both cold and hot temperature have been associated with the onset of asthma, but it remains largely unknown about the risk of asthma hospitalisation associated with short-term temperature fluctuation or temperature variability (TV)., Objective: To explore the association between short-term exposure to TV and asthma hospitalisation in Brazil., Methods: Data for asthma hospitalisation and weather conditions were collected from 1816 Brazilian cities between 2000 and 2015. TV was calculated as the SD of all daily minimum and maximum temperatures within 0-7 days prior to current day. A time-stratified case-crossover design was performed to quantify the association between TV and hospitalisation for asthma., Results: A total of 2 818 911 hospitalisations for asthma were identified during the study period. Each 1°C increase in 0-7 days' TV exposure was related to a 1.0% (95% CI 0.7% to 1.4%) increase in asthma hospitalisations. The elderly were more vulnerable to TV than other age groups, while region and season appeared to significantly modify the associations. There were 159 305 (95% CI 55 293 to 2 58 054) hospitalisations, US$48.41 million (95% CI US$16.92 to US$78.30 million) inpatient costs at 2015 price and 450.44 thousand inpatient days (95% CI 156.08 to 729.91 thousand days) associated with TV during the study period. The fraction of asthma hospitalisations attributable to TV increased from 5.32% in 2000 to 5.88% in 2015., Conclusion: TV was significantly associated with asthma hospitalisation and the corresponding substantial health costs in Brazil. Our findings suggest that preventive measures of asthma should take TV into account., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM 2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM 2·5 and mortality across various regions of the world., Methods: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM 2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM 2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM 2·5 exposure was calculated., Findings: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m 3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM 2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM 2·5 exposure during the study period., Interpretation: Short-term exposure to wildfire-related PM 2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires., Funding: Australian Research Council, Australian National Health & Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Exposure to cold or hot temperatures is associated with premature deaths. We aimed to evaluate the global, regional, and national mortality burden associated with non-optimal ambient temperatures., Methods: In this modelling study, we collected time-series data on mortality and ambient temperatures from 750 locations in 43 countries and five meta-predictors at a grid size of 0·5° × 0·5° across the globe. A three-stage analysis strategy was used. First, the temperature-mortality association was fitted for each location by use of a time-series regression. Second, a multivariate meta-regression model was built between location-specific estimates and meta-predictors. Finally, the grid-specific temperature-mortality association between 2000 and 2019 was predicted by use of the fitted meta-regression and the grid-specific meta-predictors. Excess deaths due to non-optimal temperatures, the ratio between annual excess deaths and all deaths of a year (the excess death ratio), and the death rate per 100 000 residents were then calculated for each grid across the world. Grids were divided according to regional groupings of the UN Statistics Division., Findings: Globally, 5 083 173 deaths (95% empirical CI [eCI] 4 087 967-5 965 520) were associated with non-optimal temperatures per year, accounting for 9·43% (95% eCI 7·58-11·07) of all deaths (8·52% [6·19-10·47] were cold-related and 0·91% [0·56-1·36] were heat-related). There were 74 temperature-related excess deaths per 100 000 residents (95% eCI 60-87). The mortality burden varied geographically. Of all excess deaths, 2 617 322 (51·49%) occurred in Asia. Eastern Europe had the highest heat-related excess death rate and Sub-Saharan Africa had the highest cold-related excess death rate. From 2000-03 to 2016-19, the global cold-related excess death ratio changed by -0·51 percentage points (95% eCI -0·61 to -0·42) and the global heat-related excess death ratio increased by 0·21 percentage points (0·13-0·31), leading to a net reduction in the overall ratio. The largest decline in overall excess death ratio occurred in South-eastern Asia, whereas excess death ratio fluctuated in Southern Asia and Europe., Interpretation: Non-optimal temperatures are associated with a substantial mortality burden, which varies spatiotemporally. Our findings will benefit international, national, and local communities in developing preparedness and prevention strategies to reduce weather-related impacts immediately and under climate change scenarios., Funding: Australian Research Council and the Australian National Health and Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics., Methods: We analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay., Results: Patient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression., Conclusion: Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.

In the present study, we evaluated the effects of chronic exposure to traffic from a heavy-duty diesel-fueled vehicle area on respiratory symptoms and airway inflammation in a nonsmoking adult and elderly population. Respiratory symptoms were evaluated by the ISAAC questionnaire (International Study of Asthma and Allergies questionnaire), and airway inflammation was assessed by fractional exhaled nitric oxide (FeNO). Forty volunteers were selected from the 112 volunteers who completed the ISAAC questionnaire for the measurement of FeNO. The FeNO population comprised seven men (six aged ≥ 64 years old, four aged ≥ 75 years old) and 32 women (27 aged ≥ 64 years old, nine aged ≥ 75 years old). FeNO levels were tracked for six months, from November 2014 to June 2015. Results: Twenty-four percent of the volunteers reported having had wheezing in the chest in the last 12 months. However, only 2.7% of the volunteers reported doctor-diagnosed asthma. There was a positive association between FeNO and pollutants in most of the study months. An increase of 1 μg m -3 in NO 2 was associated with a mean increase of 1.08 ppb in FeNO, and an increase of 1 μg m -3 in O 3 was associated with a mean increase of 1.06 ppb in FeNO. The relative risk for NO 2 ranged from 1.009 to 1.32 and that for O 3 ranged from 1.014 to 1.020. Conclusion: The frequency of respiratory symptoms was much higher than the previously described levels of 6% in the Brazilian adult population. In summary, a high frequency of respiratory symptoms and high levels of FeNO were described in an underdiagnosed adult population living very close to a heavy-duty diesel-traffic area. Older elderly adults presented greater susceptibility to airway inflammation than younger adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Various retrospective studies have reported on the increase of mortality risk due to higher diurnal temperature range (DTR). This study projects the effect of DTR on future mortality across 445 communities in 20 countries and regions., Methods: DTR-related mortality risk was estimated on the basis of the historical daily time-series of mortality and weather factors from Jan 1, 1985, to Dec 31, 2015, with data for 445 communities across 20 countries and regions, from the Multi-Country Multi-City Collaborative Research Network. We obtained daily projected temperature series associated with four climate change scenarios, using the four representative concentration pathways (RCPs) described by the Intergovernmental Panel on Climate Change, from the lowest to the highest emission scenarios (RCP 2.6, RCP 4.5, RCP 6.0, and RCP 8.5). Excess deaths attributable to the DTR during the current (1985-2015) and future (2020-99) periods were projected using daily DTR series under the four scenarios. Future excess deaths were calculated on the basis of assumptions that warmer long-term average temperatures affect or do not affect the DTR-related mortality risk., Findings: The time-series analyses results showed that DTR was associated with excess mortality. Under the unmitigated climate change scenario (RCP 8.5), the future average DTR is projected to increase in most countries and regions (by -0·4 to 1·6°C), particularly in the USA, south-central Europe, Mexico, and South Africa. The excess deaths currently attributable to DTR were estimated to be 0·2-7·4%. Furthermore, the DTR-related mortality risk increased as the long-term average temperature increased; in the linear mixed model with the assumption of an interactive effect with long-term average temperature, we estimated 0·05% additional DTR mortality risk per 1°C increase in average temperature. Based on the interaction with long-term average temperature, the DTR-related excess deaths are projected to increase in all countries or regions by 1·4-10·3% in 2090-99., Interpretation: This study suggests that globally, DTR-related excess mortality might increase under climate change, and this increasing pattern is likely to vary between countries and regions. Considering climatic changes, our findings could contribute to public health interventions aimed at reducing the impact of DTR on human health., Funding: Korea Ministry of Environment., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Air pollution is a public health concern that has been associated with adverse effects on the development and functions of the central nervous system (CNS). However, studies on the effects of exposure to pollutants on the CNS across the entire developmental period still remain scarce. In this study, we investigated the impacts of prenatal and/or postnatal exposure to fine particulate matter (PM 2.5 ) from São Paulo city, on the brain structure and behavior of juvenile male mice. BALB/c mice were exposed to PM 2.5 concentrated ambient particles (CAP) at a daily concentration of 600 μg/m³ during the gestational [gestational day (GD) 1.5-18.5] and the postnatal periods [postnatal day (PND) 22-90] to filtered air (FA) in both periods (FA/FA), to CAP only in the postnatal period (FA/CAP), to CAP only in the gestational period (CAP/FA), and to CAP in both periods (CAP/CAP). Behavioral tests were performed when animals were at PND 30 and PND 90. Glial activation, brain volume, cortical neuron number, serotonergic and GABAergic receptors, as well as oxidative stress, were measured. Mice at PND 90 presented greater behavioral changes in the form of greater locomotor activity in the FA-CAP and CAP-CAP groups. In general, these same groups explored objects longer and the CAP-FA group presented anxiolytic behavior. There was no difference in total brain volume among groups, but a lower corpus callosum (CC) volume was observed in the CAP-FA group. Also, the CAP-CAP group presented an increase in microglia in the cortex and an increased in astrocytes in the cortex, CC, and C1A and dentate gyrus of hippocampus regions. Gene expression analysis showed a decrease in BDNF in the hippocampus of CAP-CAP group. Treatment of immortalized glial cells with non-cytotoxic doses of ambient PM 2.5 increased micronuclei frequencies, indicating genomic instability. These findings highlight the potential for negative neurodevelopmental outcomes induced by exposure to moderate levels of PM 2.5 in Sao Paulo city., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesising the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardised, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina. Methods: We searched five online databases for the combined terms for outcome ("retina") and exposure ("cannabis"). Eligibility of studies were conducted by two independent reviewers, and risk of bias was assessed. Results: We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects. Conclusions: This review suggests that cannabinoids may have an important role in retinal processing and function.

Background: It remains challenging to determine which individuals are likely to benefit from microsurgical correction of subclinical varicocele, as basic semen parameters often do not improve postoperatively. We aimed to develop an easily accessible tool for prognostic stratification of infertile men indicated for microsurgical correction of bilateral subclinical varicocele characterized by prolonged and clear venous reflux and no other cause for infertility., Methods: We retrospectively analyzed the testicular biopsy, seminal analysis, and ultrasound evaluation records of 20 men managed between 2006 and 2014. Subclinical varicocele was diagnosed through bilateral testicular palpation and auscultation of venous reflux using a Doppler stethoscope, with confirmation on color Doppler sonography. We conducted receiver operating characteristic curve analysis to identify the optimal combinations of cut-offs for the Johnsen score, Copenhagen index, and testicular volume defining histological patterns with positive prognostic value for improved postoperatively reproductive capacity., Results: Positive prognostic value was noted for the following combinations of parameters: (I) Johnsen score >8.2 in the left testicle and right testicular volume >12.8 mL predicted improved sperm concentration; (II) Johnsen score >8.2 and Copenhagen index digit II <2.5 bilaterally predicted improved total sperm motility; (III) Johnsen score >9.1 and Copenhagen index digit III <1.5 bilaterally predicted improved progressive sperm motility; (IV) Johnsen score >7.9 and right testicular volume >13.6 mL predicted improved sperm morphology., Conclusions: Johnsen score and Copenhagen index as histopathological prognostic factors can be easily obtained upon evaluation of testicular biopsy specimens and can be simple and reliable tool to establish a more realistic prognosis for reproductive capacity in men who undergo microsurgical correction of subclinical varicocele with no other detectable cause for infertility., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Hypertension and air pollution are two important risk factors for cardiovascular morbidity and mortality. Although several studies suggest that air pollution has a significant impact on blood pressure, studies on long-term effects are sparse and still controversial., Objective: To evaluate the effects of exposure of outdoor workers to different levels of traffic-generated PM 2.5 on blood pressure., Design: This is an observational panel study., Participants: 88 non-smoking workers exposed to different concentrations of air pollution were evaluated weekly along four successive weeks., Measurements: In each week, personal monitoring of 24-h PM 2.5 concentration and 24-h ambulatory blood pressure were measured. The association between blood pressure variables and PM 2.5 , adjusted for age, body mass index, time in job, daily work hours, diabetes, hypertension and cholesterol was assessed by means of multiple linear regression models fitted by least squares., Results: Exposure to PM 2.5 (ranging from 8.5 to 89.7 μg/m 3 ) is significantly and consistently associated with an increase in average blood pressure. An elevation of 10 μg/m 3 in the concentration of PM 2.5 is associated with increments of 3.9 mm Hg (CI 95% = [1.5; 6.3]) in average systolic 24-h blood pressure for hypertensive and/or diabetic workers., Conclusion: Exposure to fine particles, predominantly from vehicular traffic, is associated with elevated blood pressure in hypertensive and/or diabetic workers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Life expectancy is increasing worldwide. Lung aging is a process marked by changes in multiple morphological, physiological and age-related biomarkers (e.g., sirtuins) and is influenced by external factors, such as air pollution. Hence, the elderly are considered more vulnerable to the air pollution hazards. We hypothesized that diesel exhaust (DE) exposure intensifies changes in lung inflammatory and structural parameters in aging subjects. Two- and fifteen-month-old mice were exposed to DE for 30 days. Lung function was measured using the forced oscillation method. The inflammatory profile was evaluated in the bronchoalveolar lavage fluid (BALF) and blood, and lung volumes were estimated by stereology. Antioxidant enzyme activity was evaluated by spectrophotometry, sirtuin 1 (SIRT1), sirtuin 2 (SIRT2) and sirtuin 6 (SIRT6) expression was assessed by reverse transcription polymerase chain reaction (RT-PCR), and levels of the sirtuin proteins were evaluated by immunohistochemical staining in lung tissues. Older mice presented decreased pulmonary resistance and elastance, increased macrophage infiltration and decreased tumor necrosis factor (TNF) and interleukin 10 (IL-10) levels in the BALF, reduced activities of the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), and increased activity glutathione S-transferase (GST); increased lung volumes with decreased elastic fiber and increased airway collagen content. SIRT1 gene expression was decreased in older animals, but protein levels were increased. DE exposure increased macrophage infiltration and oxidative stress in the lungs of animals of both ages. SIRT6 gene expression was decreased by DE exposure, with increased protein levels. In older animals, DE affected lung structure and collagen content. Lung aging features, such as decreased antioxidant reserves, lower IL-10 expression, and decreased SIRT1 levels may predispose subjects to exacerbated responses after DE exposure. Our data support the hypothesis that strategies designed to reduce ambient air pollution are an important step towards healthy aging., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Enhanced resolution of 7 T magnetic resonance imaging (MRI) scanners has considerably advanced our knowledge of structure and function in human and animal brains. Post-industrialized countries are particularly prone to an ever-increasing number of ageing individuals and ageing-associated neurodegenerative diseases. Neurodegenerative diseases are associated with volume loss in the affected brain. MRI diagnoses and monitoring of subtle volume changes in the ageing/diseased brains have the potential to become standard diagnostic tools. Even with the superior resolution of 7 T MRI scanners, the microstructural changes comprising cell types, cell numbers, and cellular processes, are still undetectable. Knowledge of origin, nature, and progression for microstructural changes are necessary to understand pathogenetic stages in the relentless neurodegenerative diseases, as well as to develop therapeutic tools that delay or stop neurodegenerative processes at their earliest stage. We illustrate the gap in resolution by comparing the identical regions of the post-mortem in situ 7 T MR images (virtual autopsy or virtopsy) with the histological observations in serial sections through the same brain. We also described the protocols and limitations associated with these comparisons, as well as the necessity of supercomputers and data management for "Big data". Analysis of neuron and/or glial number by using a body of mathematical tools and guidelines (stereology) is time-consuming, cumbersome, and still restricted to trained human investigators. Development of tools based on machine learning (ML) and artificial intelligence (AI) could considerably accelerate studies on localization, onset, and progression of neuron loss. Finally, these observations could disentangle the mechanisms of volume loss into stages of reversible atrophy and/or irreversible fatal cell death. This AI- and ML-based cooperation between virtopsy and histology could bridge the present gap between virtual reality and neuropathology. It could also culminate in the creation of an imaging-associated comprehensive database. This database would include genetic, clinical, epidemiological, and technical aspects that could help to alleviate or even stop the adverse effects of neurodegenerative diseases on affected individuals, their families, and society.

The concern about environmental pollution has risen in the last decades because of its effects on human's health. However, evaluation of the exposure to certain pollutants is currently hampered by the availability of past environmental data. Tree rings are an alternative to reconstruct environmental variability of pre-instrumental periods. Nevertheless, this approach has some reported limitations including migration of chemical elements in the tree rings. The aim of this study was to evaluate the distribution of Cd, Cu, Hg, Na, Ni, Pb, Zn in the tree rings of Tipuana tipu (Fabaceae) to aid the reconstruction of past environmental pollution. We sampled trees in the central region of the city of São Paulo, Brazil, and scanned their tree rings using LA-ICP-MS. We used these data to evaluate the temporal trends of chemical elements under investigation. Results show a non-random distribution of these chemical elements within the tree rings, with higher content in the cell-walls of vessels and lower content in the fibers. Sodium was the only element intimately related to the axial parenchyma cells. Due to differences in elemental composition of xylem cells, temporal trends where evaluated using distinct quartiles of data distribution in each tree ring. The first quartile represents the lower content found in fibers and parenchyma, while the third quartile corresponds to the higher content found in vessels. Data from vessels better represent the decreasing trend of Cd, Cu, Pb, and Ni in the last three decades. This reduction is less significant for Na and Zn. Our results highlight the potential to improve the records of environmental pollution using data from different cells. Pronounced reduction in Pb may be attributed to the lead phase-out in gasoline, while the decreasing trend of Cd, Cu, Ni pollution is probably related to increasing efficiency of vehicles and the deindustrialization of São Paulo. Chemical elements are non-randomly distributed in tree rings. Chemical content of vessels cell-walls is a reliable record of metal pollution, which is decreasing in São Paulo., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Climate change can directly affect human health by varying exposure to non-optimal outdoor temperature. However, evidence on this direct impact at a global scale is limited, mainly due to issues in modelling and projecting complex and highly heterogeneous epidemiological relationships across different populations and climates., Methods: We collected observed daily time series of mean temperature and mortality counts for all causes or non-external causes only, in periods ranging from Jan 1, 1984, to Dec 31, 2015, from various locations across the globe through the Multi-Country Multi-City Collaborative Research Network. We estimated temperature-mortality relationships through a two-stage time series design. We generated current and future daily mean temperature series under four scenarios of climate change, determined by varying trajectories of greenhouse gas emissions, using five general circulation models. We projected excess mortality for cold and heat and their net change in 1990-2099 under each scenario of climate change, assuming no adaptation or population changes., Findings: Our dataset comprised 451 locations in 23 countries across nine regions of the world, including 85 879 895 deaths. Results indicate, on average, a net increase in temperature-related excess mortality under high-emission scenarios, although with important geographical differences. In temperate areas such as northern Europe, east Asia, and Australia, the less intense warming and large decrease in cold-related excess would induce a null or marginally negative net effect, with the net change in 2090-99 compared with 2010-19 ranging from -1·2% (empirical 95% CI -3·6 to 1·4) in Australia to -0·1% (-2·1 to 1·6) in east Asia under the highest emission scenario, although the decreasing trends would reverse during the course of the century. Conversely, warmer regions, such as the central and southern parts of America or Europe, and especially southeast Asia, would experience a sharp surge in heat-related impacts and extremely large net increases, with the net change at the end of the century ranging from 3·0% (-3·0 to 9·3) in Central America to 12·7% (-4·7 to 28·1) in southeast Asia under the highest emission scenario. Most of the health effects directly due to temperature increase could be avoided under scenarios involving mitigation strategies to limit emissions and further warming of the planet., Interpretation: This study shows the negative health impacts of climate change that, under high-emission scenarios, would disproportionately affect warmer and poorer regions of the world. Comparison with lower emission scenarios emphasises the importance of mitigation policies for limiting global warming and reducing the associated health risks., Funding: UK Medical Research Council.

Background and Objective: Acute respiratory distress syndrome (ARDS) has a high mortality rate of 35-46% depending on its severity. Animal models are crucial to better understand the pathophysiology of diseases, including ARDS. This study presents a feasible animal model of acute lung injury (ALI) using nebulized lipopolysaccharide (LPS) in a non-invasive approach, focusing on its short and long-term effects., Methods: Mice received nebulized LPS or vehicle only (control group). Blood, BALF and lung tissue were collected 24 hours (LPS 24h) or 5 weeks (LPS 5w) after the nebulized LPS-induced lung injury. Inflammatory cytokines were assessed in the blood serum, BALF and lung tissue. Stereological analyses and remodeling changes were assessed by histology and immunohistochemistry at the specified time points., Results: The LPS 24h group showed increased pro-inflammatory cytokine levels, intense cell influx, increased total septal volume, septal thickening and decreased surface density of the alveolar septa. The LPS 5w group showed persistent lung inflammation, septal thickening, increased total lung volume, accentuated collagen deposition, especially of collagen type I, and decreased MMP-2 protein expression., Conclusion: We present a feasible, reproducible and non-invasive nebulized-LPS animal model that allows the assessment of both the acute and late phases of acute lung injury. The presence of lung remodeling with collagen deposition after 5 weeks makes it useful to study the pathophysiology, complications, and possible therapeutic intervention studies that aim to understand and reduce pulmonary fibrosis in the late phases of ALI.

Industrialization in developing countries associated with urban growth results in a number of economic benefits, especially in small or medium-sized cities, but leads to a number of environmental and public health consequences. This problem is further aggravated when adequate infrastructure is lacking to monitor the environmental impacts left by industries and refineries. In this study, a new protocol was designed combining biomonitoring and geostatistics to evaluate the possible effects of shale industry emissions on human health and wellbeing. Futhermore, the traditional and expensive air quality method based on PM 2.5 measuring was also used to validate the low-cost geostatistical approach. Chemical analysis was performed using Energy Dispersive X-ray Fluorescence Spectrometer (EDXRF) to measure inorganic elements in tree bark and shale retorted samples in São Mateus do Sul city, Southern Brazil. Fe, S, and Si were considered potential pollutants in the study area. Distribution maps of element concentrations were generated from the dataset and used to estimate the spatial behavior of Fe, S, and Si and the range from their hot spot(s), highlighting the regions sorrounding the shale refinery. This evidence was also demonstrated in the measurements of PM 2.5 concentrations, which are in agreement with the information obtained from the biomonitoring and geostatistical model. Factor and descriptive analyses performed on the concentrations of tree bark contaminants suggest that Fe, S, and Si might be used as indicators of industrial emissions. The number of cases of respiratory diseases obtained from local basic health unit were used to assess a possible correlation between shale refinery emissions and cases of repiratory disease. These data are public and may be accessed on the website of the the Brazilian Ministry of Health. Significant associations were found between the health data and refinery activities. The combination of the spatial characterization of air pollution and clinical health data revealed that adverse effects were significant for individuals over 38 years of age. These results also suggest that a protocol designed to monitor urban air quality may be an effective and low-cost strategy in environmentally contaminated cities, especially in low- and middle-income countries.

The majority of epidemiological studies correlate the cardiorespiratory effects of air pollution exposure by considering the concentrations of pollutants measured from conventional monitoring networks. The conventional air quality monitoring methods are expensive, and their data are insufficient for providing good spatial resolution. We hypothesized that bioassays using plants could effectively determine pollutant gradients, thus helping to assess the risks associated with air pollution exposure. The study regions were determined from different prevalent respiratory death distributions in the Sao Paulo municipality. Samples of tree flower buds were collected from twelve sites in four regional districts. The genotoxic effects caused by air pollution were tested through a pollen abortion bioassay. Elements derived from vehicular traffic that accumulated in tree barks were determined using energy-dispersive X-ray fluorescence spectrometry (EDXRF). Mortality data were collected from the mortality information program of Sao Paulo City. Principal component analysis (PCA) was applied to the concentrations of elements accumulated in tree barks. Pearson correlation and exponential regression were performed considering the elements, pollen abortion rates and mortality data. PCA identified five factors, of which four represented elements related to vehicular traffic. The elements Al, S, Fe, Mn, Cu, and Zn showed a strong correlation with mortality rates (R 2 >0.87) and pollen abortion rates (R 2 >0.82). These results demonstrate that tree barks and pollen abortion rates allow for correlations between vehicular traffic emissions and associated outcomes such as genotoxic effects and mortality data., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The objective of this study was to demonstrate the presence of mycobacterial nucleic acid sequences in peripheral blood and arteries from patients with Takayasu arteritis (TA). Polymerase chain reaction was performed to detect mycobacterial DNA from three different nucleic acid sequences including the insertion sequence (IS) 6110, the 65-kDa heat shock protein gene (HSP65), and the 16S ribosomal RNA (rRNA) gene in peripheral blood from 32 TA patients and in arterial specimens from 10 TA patients. Twenty-eight HIV-negative patients with pulmonary tuberculosis prior to therapy were tested for IS6110 in peripheral blood as positive controls, and 24 blood donors were evaluated as healthy controls (HC). All TA patients were negative for the insertion sequence IS6110 and for HSP65 and 16S rRNA genes in blood samples and in arterial specimens. IS6110 sequence was found in peripheral blood from 22 (78.5 %) patients with pulmonary tuberculosis but not in HC. In conclusion, the strategy of mycobacterial-specific nucleic acid amplification in the peripheral blood and arterial specimens of TA patients was unable to lend support to the association between TA and tuberculosis long suggested in the literature.

Background: The identification of new biomarkers of heart failure (HF) could help in its treatment. Previously, our group studied 89 patients with HF and showed that exhaled breath acetone (EBA) is a new noninvasive biomarker of HF diagnosis. However, there is no data about the relevance of EBA as a biomarker of prognosis., Objectives: To evaluate whether EBA could give prognostic information in patients with heart failure with reduced ejection fraction (HFrEF)., Methods: After breath collection and analysis by gas chromatography-mass spectrometry and by spectrophotometry, the 89 patients referred before were followed by one year. Study physicians, blind to the results of cardiac biomarker testing, ascertained vital status of each study participant at 12 months., Results: The composite endpoint death and heart transplantation (HT) were observed in 35 patients (39.3%): 29 patients (32.6%) died and 6 (6.7%) were submitted to HT within 12 months after study enrollment. High levels of EBA (≥3.7μg/L, 50th percentile) were associated with a progressively worse prognosis in 12-month follow-up (log-rank = 11.06, p = 0.001). Concentrations of EBA above 3.7μg/L increased the risk of death or HT in 3.26 times (HR = 3.26, 95%CI = 1.56-6.80, p = 0.002) within 12 months. In a multivariable cox regression model, the independent predictors of all-cause mortality were systolic blood pressure, respiratory rate and EBA levels., Conclusions: High EBA levels could be associated to poor prognosis in HFrEF patients., Competing Interests: The authors have declared that no competing interests exist.

In this study, the effects of aerobic exercise on the upper airways and their defense mechanisms were investigated in athletes. The athletes ran in two different environments: the downtown streets of the city of São Paulo (Street), more polluted, and an urban forest (Forest), less polluted. Thirty-eight young healthy athletes ran for 45 min d -1 randomly during five consecutive days, with an interval of 48 h before changing environment. Clinical parameters and respiratory tract defense markers were evaluated before and after the first run on Mondays (1 d) and on Fridays (5 d). Street presented higher mean PM 2.5 concentrations (65.1  ±  39.1 µg m -3 , p  <  0.001) and lower temperature (22.0 °C, p  =  0.010) than Forest (22.6  ±  15.3 µg m -3 and 22.8 °C). After 1 d Street running, subjects showed an increment in heart rate (p  <  0.001). At day 5, there was twice the number of athletes with impaired nasal mucociliary clearance (MCC) in the Street runners group when compared to the Forest runners group. Exhaled breath condensate pH values increased in the Forest group, with significant differences between groups in day 1 (p  =  0.006) and day 5 (p  <  0.001), despite the fact that both groups showed values within the normal range. After exposure to both environments, the number of cells in the nasal lavage fluid was reduced after exercise (p  =  0.014), without alterations in cell type and IL-8 and IL-10 concentrations. Aerobic exercise can either maintain or acutely enhance MCC and it may help to regulate inflammatory responses in the airways. Here we show that exercise practice in polluted outdoor environment, over a 5 d period, impairs MCC. In contrast, athletes running in the less polluted environment (Forest) show higher exhaled breath condensate pH values when compared to those who exercised in a more polluted environment (Street).