Exposure to wildfire-related PM2.5 and site-specific cancer mortality in Brazil from 2010 to 2016: A retrospective study.

BACKGROUND: Long-term exposure to fine particles ≤2.5 µm in diameter (PM2.5) has been linked to cancer mortality. However, the effect of wildfire-related PM2.5 exposure on cancer mortality risk is unknown. This study evaluates the association between wildfire-related PM2.5 and site-specific cancer mortality in Brazil, from 2010 to 2016. METHODS AND FINDINGS: Nationwide cancer death records were collected during 2010-2016 from the Brazilian Mortality Information System. Death records were linked with municipal-level wildfire- and non-wildfire-related PM2.5 concentrations, at a resolution of 2.0° latitude by 2.5° longitude. We applied a variant difference-in-differences approach with quasi-Poisson regression, adjusting for seasonal temperature and gross domestic product (GDP) per capita. Relative risks (RRs) and 95% confidence intervals (CIs) for the exposure for specific cancer sites were estimated. Attributable fractions and cancer deaths were also calculated. In total, 1,332,526 adult cancer deaths (age ≥ 20 years), from 5,565 Brazilian municipalities, covering 136 million adults were included. The mean annual wildfire-related PM2.5 concentration was 2.38 µg/m3, and the annual non-wildfire-related PM2.5 concentration was 8.20 µg/m3. The RR for mortality from all cancers was 1.02 (95% CI 1.01-1.03, p < 0.001) per 1-µg/m3 increase of wildfire-related PM2.5 concentration, which was higher than the RR per 1-µg/m3 increase of non-wildfire-related PM2.5 (1.01 [95% CI 1.00-1.01], p = 0.007, with p for difference = 0.003). Wildfire-related PM2.5 was associated with mortality from cancers of the nasopharynx (1.10 [95% CI 1.04-1.16], p = 0.002), esophagus (1.05 [95% CI 1.01-1.08], p = 0.012), stomach (1.03 [95% CI 1.01-1.06], p = 0.017), colon/rectum (1.08 [95% CI 1.05-1.11], p < 0.001), larynx (1.06 [95% CI 1.02-1.11], p = 0.003), skin (1.06 [95% CI 1.00-1.12], p = 0.003), breast (1.04 [95% CI 1.01-1.06], p = 0.007), prostate (1.03 [95% CI 1.01-1.06], p = 0.019), and testis (1.10 [95% CI 1.03-1.17], p = 0.002). For all cancers combined, the attributable deaths were 37 per 100,000 population and ranged from 18/100,000 in the Northeast Region of Brazil to 71/100,000 in the Central-West Region. Study limitations included a potential lack of assessment of the joint effects of gaseous pollutants, an inability to capture the migration of residents, and an inability to adjust for some potential confounders. CONCLUSIONS: Exposure to wildfire-related PM2.5 can increase the risks of cancer mortality for many cancer sites, and the effect for wildfire-related PM2.5 was higher than for PM2.5 from non-wildfire sources.

Ambient Particulate Air Pollution and Daily Mortality in 652 Cities.

BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 µm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 µm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived. RESULTS: On average, an increase of 10 µg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS: Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).

Radiological patterns of incidental epididymitis in mild-to-moderate COVID-19 patients revealed by colour Doppler ultrasound.

The testis is a potential target organ for SARS-CoV-2 infection. Our study intended to investigate any testicular involvement in mild-to-moderate COVID-19 men. We conduct a cross-sectional study in 18 to 55-year-old men hospitalised for confirmed COVID-19. A senior radiologist executed the ultrasound with multi-frequency linear probe in all participants, regardless of any scrotal complaints. Exclusion criteria involved any situation that could impair testicular function. Statistical analysis compared independent groups, classified by any pathological change. Categorical and numerical outcome hypotheses were tested by Fisher's Exact and Mann-Whitney tests, using the Excel for Mac, version 16.29 (p < .05). The sample size was 26 men (mean 33.7 ± 6.2 years; range: 21-42 years), all without scrotal complaints. No orchitis was seen. Eleven men (32.6 ± 5.8 years) had epididymitis (42.3%), bilateral in 19.2%. More than half of men with epididymitis displayed epididymal head augmentation > 1.2 cm (p = .002). Two distinct epididymitis' patterns were reported: (a) disseminated micro-abscesses (n = 6) and (b) inhomogeneous echogenicity with reactional hydrocele (n = 5). Both patterns revealed increased epididymal head, augmented Doppler flow and scrotal skin thickening. The use of colour Doppler ultrasound in mild-to-moderate COVID-19 men, even in the absence of testicular complaints, might be useful to diagnose epididymitis that could elicit fertility complications.

Socioeconomic level and associations between heat exposure and all-cause and cause-specific hospitalization in 1,814 Brazilian cities: A nationwide case-crossover study.

BACKGROUND: Heat exposure, which will increase with global warming, has been linked to increased risk of a range of types of cause-specific hospitalizations. However, little is known about socioeconomic disparities in vulnerability to heat. We aimed to evaluate whether there were socioeconomic disparities in vulnerability to heat-related all-cause and cause-specific hospitalization among Brazilian cities. METHODS AND FINDINGS: We collected daily hospitalization and weather data in the hot season (city-specific 4 adjacent hottest months each year) during 2000-2015 from 1,814 Brazilian cities covering 78.4% of the Brazilian population. A time-stratified case-crossover design modeled by quasi-Poisson regression and a distributed lag model was used to estimate city-specific heat-hospitalization association. Then meta-analysis was used to synthesize city-specific estimates according to different socioeconomic quartiles or levels. We included 49 million hospitalizations (58.5% female; median [interquartile range] age: 33.3 [19.8-55.7] years). For cities of lower middle income (LMI), upper middle income (UMI), and high income (HI) according to the World Bank's classification, every 5°C increase in daily mean temperature during the hot season was associated with a 5.1% (95% CI 4.4%-5.7%, P < 0.001), 3.7% (3.3%-4.0%, P < 0.001), and 2.6% (1.7%-3.4%, P < 0.001) increase in all-cause hospitalization, respectively. The inter-city socioeconomic disparities in the association were strongest for children and adolescents (0-19 years) (increased all-cause hospitalization risk with every 5°C increase [95% CI]: 9.9% [8.7%-11.1%], P < 0.001, in LMI cities versus 5.2% [4.1%-6.3%], P < 0.001, in HI cities). The disparities were particularly evident for hospitalization due to certain diseases, including ischemic heart disease (increase in cause-specific hospitalization risk with every 5°C increase [95% CI]: 5.6% [-0.2% to 11.8%], P = 0.060, in LMI cities versus 0.5% [-2.1% to 3.1%], P = 0.717, in HI cities), asthma (3.7% [0.3%-7.1%], P = 0.031, versus -6.4% [-12.1% to -0.3%], P = 0.041), pneumonia (8.0% [5.6%-10.4%], P < 0.001, versus 3.8% [1.1%-6.5%], P = 0.005), renal diseases (9.6% [6.2%-13.1%], P < 0.001, versus 4.9% [1.8%-8.0%], P = 0.002), mental health conditions (17.2% [8.4%-26.8%], P < 0.001, versus 5.5% [-1.4% to 13.0%], P = 0.121), and neoplasms (3.1% [0.7%-5.5%], P = 0.011, versus -0.1% [-2.1% to 2.0%], P = 0.939). The disparities were similar when stratifying the cities by other socioeconomic indicators (urbanization rate, literacy rate, and household income). The main limitations were lack of data on personal exposure to temperature, and that our city-level analysis did not assess intra-city or individual-level socioeconomic disparities and could not exclude confounding effects of some unmeasured variables. CONCLUSIONS: Less developed cities displayed stronger associations between heat exposure and all-cause hospitalizations and certain types of cause-specific hospitalizations in Brazil. This may exacerbate the existing geographical health and socioeconomic inequalities under a changing climate.

Pulmonary and systemic involvement in COVID-19 patients assessed with ultrasound-guided minimally invasive autopsy.

AIMS: Brazil ranks high in the number of coronavirus disease 19 (COVID-19) cases and the COVID-19 mortality rate. In this context, autopsies are important to confirm the disease, determine associated conditions, and study the pathophysiology of this novel disease. The aim of this study was to assess the systemic involvement of COVID-19. In order to follow biosafety recommendations, we used ultrasound-guided minimally invasive autopsy (MIA-US), and we present the results of 10 initial autopsies. METHODS AND RESULTS: We used MIA-US for tissue sampling of the lungs, liver, heart, kidneys, spleen, brain, skin, skeletal muscle and testis for histology, and reverse transcription polymerase chain reaction to detect severe acute respiratory syndrome coronavirus 2 RNA. All patients showed exudative/proliferative diffuse alveolar damage. There were intense pleomorphic cytopathic effects on the respiratory epithelium, including airway and alveolar cells. Fibrinous thrombi in alveolar arterioles were present in eight patients, and all patients showed a high density of alveolar megakaryocytes. Small thrombi were less frequently observed in the glomeruli, spleen, heart, dermis, testis, and liver sinusoids. The main systemic findings were associated with comorbidities, age, and sepsis, in addition to possible tissue damage due to the viral infection, such as myositis, dermatitis, myocarditis, and orchitis. CONCLUSIONS: MIA-US is safe and effective for the study of severe COVID-19. Our findings show that COVID-19 is a systemic disease causing major events in the lungs and with involvement of various organs and tissues. Pulmonary changes result from severe epithelial injury and microthrombotic vascular phenomena. These findings indicate that both epithelial and vascular injury should be addressed in therapeutic approaches.

Occupational effect of sugarcane biomass burning on the conjunctival mucin profile of harvest workers and residents of an adjacent town - A Brazilian panel study.

Pre-harvest burning of sugarcane fields produces large amounts of air pollutants which are known to cause health problems, including ocular surface abnormalities. In this study, we evaluated the effect of biomass burning on mucus quality and mucin gene expression (MUC1, MUC5AC, MUC16) in the conjunctiva of sugarcane workers (SWs) and residents of an adjacent town (RTs). Impression cytology samples of the inferior tarsal and bulbar conjunctiva of 78 SWs and 32 RTs were collected before (T1) and immediately after (T2) a 6-month harvest period. The neutral, acid and total mucus content of goblet cells was determined by PAS and AB staining. The levels of MUC5AC, MUC1 and MUC16 mRNA in the conjunctiva were measured by real-time PCR. Compared to RTs, SWs had higher levels of bulbar acid mucus and MUC16 mRNA and tarsal MUC5AC mRNA at T2 and lower levels of neutral mucus at T1 and T2. In the SW group, MUC1 mRNA levels were higher at T2 than at T1, but the levels of neutral and acid mucus were similar. In the RT group, acid mucus decreased and neutral mucus increased in the bulbar and tarsal conjunctiva at T2. In conclusion, our findings show that sugarcane harvesting is associated with abnormalities in mucus quality and content and changes in mucin mRNA levels on the ocular surface. This may help explain the ocular inflammatory signs and symptoms observed in subjects exposed to air pollutants and high temperatures from sugarcane biomass burning.

Immune-pineal axis protects rat lungs exposed to polluted air.

Environmental pollution in the form of particulate matter <2.5 µm (PM2.5 ) is a major risk factor for diseases such as lung cancer, chronic respiratory infections, and major cardiovascular diseases. Our goal was to show that PM2.5 eliciting a proinflammatory response activates the immune-pineal axis, reducing the pineal synthesis and increasing the extrapineal synthesis of melatonin. Herein, we report that the exposure of rats to polluted air for 6 hours reduced nocturnal plasma melatonin levels and increased lung melatonin levels. Melatonin synthesis in the lung reduced lipid peroxidation and increased PM2.5 engulfment and cell viability by activating high-affinity melatonin receptors. Diesel exhaust particles (DEPs) promoted the synthesis of melatonin in a cultured cell line (RAW 264.7 cells) and rat alveolar macrophages via the expression of the gene encoding for AANAT through a mechanism dependent on activation of the NFκB pathway. Expression of the genes encoding AANAT, MT1, and MT2 was negatively correlated with cellular necroptosis, as disclosed by analysis of Gene Expression Omnibus (GEO) microarray data from the human alveolar macrophages of nonsmoking subjects. The enrichment score for antioxidant genes obtained from lung gene expression data (GTEx) was significantly correlated with the levels of AANAT and MT1 but not the MT2 melatonin receptor. Collectively, these data provide a systemic and mechanistic rationale for coordination of the pineal and extrapineal synthesis of melatonin by a standard damage-associated stimulus, which activates the immune-pineal axis and provides a new framework for understanding the effects of air pollution on lung diseases.

The association between heat exposure and hospitalization for undernutrition in Brazil during 2000-2015: A nationwide case-crossover study.

BACKGROUND: Global warming is predicted to indirectly result in more undernutrition by threatening crop production. Whether temperature rise could affect undernutrition directly is unknown. We aim to quantify the relationship between short-term heat exposure and risk of hospitalization due to undernutrition in Brazil. METHODS AND FINDINGS: We collected hospitalization and weather data for the hot season (the 4 adjacent hottest months for each city) from 1,814 Brazilian cities during 1 January 2000-31 December 2015. We used a time-stratified case-crossover design to quantify the association between heat exposure and hospitalization due to undernutrition. Region-specific odds ratios (ORs) were used to calculate the attributable fractions (AFs). A total of 238,320 hospitalizations for undernutrition were recorded during the 2000-2015 hot seasons. Every 1°C increase in daily mean temperature was associated with a 2.5% (OR 1.025, 95% CI 1.020-1.030, p < 0.001) increase in hospitalizations for undernutrition across lag 0-7 days. The association was greatest for individuals aged ≥80 years (OR 1.046, 95% CI 1.034-1.059, p < 0.001), 0-4 years (OR 1.039, 95% CI 1.024-1.055, p < 0.001), and 5-19 years (OR 1.042, 95% CI 1.015-1.069, p = 0.002). Assuming a causal relationship, we estimate that 15.6% of undernutrition hospitalizations could be attributed to heat exposure during the study period. The AF grew from 14.1% to 17.5% with a 1.1°C increase in mean temperature from 2000 to 2015. The main limitations of this study are misclassification of different types of undernutrition, lack of individual temperature exposure data, and being unable to adjust for relative humidity. CONCLUSIONS: Our study suggests that global warming might directly increase undernutrition morbidity, by a route other than by threatening food security. This short-term effect is increasingly important with global warming. Global strategies addressing the syndemic of climate change and undernutrition should focus not only on food systems, but also on the prevention of heat exposure.

The association between heatwaves and risk of hospitalization in Brazil: A nationwide time series study between 2000 and 2015.

BACKGROUND: To our knowledge, no study has assessed the association between heatwaves and risk of hospitalization and how it may change over time in Brazil. We quantified the heatwave-hospitalization association in Brazil during 2000-2015. METHODS AND FINDINGS: Daily data on hospitalization and temperature were collected from 1,814 cities (>78% of the national population) in the hottest five consecutive months during 2000-2015. Twelve types of heatwaves were defined with daily mean temperatures of ≥90th, 92.5th, 95th, or 97.5th percentiles of year-round temperature and durations of ≥2, 3, or 4 consecutive days. The city-specific association was estimated using a quasi-Poisson regression with constrained distributed lag model and then pooled at the national level using random-effect meta-analysis. Stratified analyses were performed by five regions, sex, 10 age groups, and nine cause categories. The temporal change in the heatwave-hospitalization association was assessed using a time-varying constrained distributed lag model. Of the 58,400,682 hospitalizations (59% women), 24%, 34%, 21%, and 19% of cases were aged <20, 20-39, 40-59, and ≥60 years, respectively. The city-specific year-round daily mean temperatures were 23.5 ± 2.8 °C on average, varying from 26.8 ± 1.8 °C for the 90th percentile to 28.0 ± 1.6 °C for the 97.5th percentile. We observed that the risk of hospitalization was most pronounced for heatwaves characterized by high daily temperatures and long durations across Brazil, except for the minimal association in the north (the hottest region). After controlling for temperature, the association remained for severe heatwaves in the south and southeast (cold regions). Children 0-9 years, the elderly ≥70 years, and admissions for perinatal conditions were most strongly associated with heatwaves. Over the study period, the strength of the heatwave-hospitalization association declined substantially in the south, while an apparent increase was observed in the southeast. The main limitations of this study included the lack of data on individual temperature exposure and measured air pollution. CONCLUSIONS: There are geographic, demographic, cause-specific, and temporal variations in the heatwave-hospitalization associations across the Brazilian population. Considering the projected increase in frequency, duration, and intensity of heatwaves, future strategies should be developed, such as building early warning systems, to reduce the health risk associated with heatwaves in Brazil.

Yellow fever and orthotopic liver transplantation: new insights from the autopsy room for an old but re-emerging disease.

AIMS: The clinical spectrum of yellow fever (YF) ranges from asymptomatic to fulminant hepatitis. During the sylvatic YF epidemic in the metropolitan area of São Paulo, Brazil in 2018, seven orthotopic liver transplantations (OLTs) were performed in our institution to treat fulminant YF hepatitis. Three patients recovered, while four patients died following OLT. The autopsy findings of all these cases are presented herein as the first description of YF in transplanted patients. METHODS AND RESULTS: All patients were men, aged 16-40 years, without vaccination to YF virus (YFV). All organs were examined, with tissue sampling for histopathological analysis. Detection of YF virus antigens (YFV Ag) was performed with two primary antibodies (mouse polyclonal anti-YFV antibody directed to wild strain and a goat anti-YF virus antibody), and RT-PCR assays were utilised to detect YFV-RNA. All the cases depicted typical findings of YF hepatitis in the engrafted liver. The main extrahepatic findings were cerebral oedema, pulmonary haemorrhage, pneumonia, acute tubular necrosis and ischaemic/reperfusion pancreatitis. Of the four cases, the YVF Ag was detected in the heart in one case, liver and testis in three cases, and the kidney and spleen in all four cases. All four cases had YF virus RNA detected by RT-PCR in the liver and in other organs. CONCLUSIONS: Infection of the engrafted liver and other organs by YFV, possibly combined with major ischaemic systemic lesions, may have led to the death of four of the seven patients undergoing OLT.

Vesicular acetylcholine transport deficiency potentiates some inflammatory responses induced by diesel exhaust particles.

Endogenous acetylcholine (ACh), which depends of the levels of vesicular ACh transport (VAChT) to be released, is the central mediator of the cholinergic anti-inflammatory system. ACh controls the release of cytokine in different models of inflammation. Diesel exhaust particles (DEP) are one of the major environmental pollutants produced in large quantity by automotive engines in urban center. DEP bind the lung parenchyma and induce inflammation. We evaluated whether cholinergic dysfunction worsens DEP-induced lung inflammation. Male mice with decreased ACh release due to reduced expression of VAChT (VAChT-KD mice) were submitted to DEP exposure for 30 days (3 mg/mL of DEP, once a day, five days a week) or saline. Pulmonary function and inflammation as well as extracellular matrix fiber deposition were evaluated. Additionally, airway and nasal epithelial mucus production were quantified. We found that DEP instillation worsened lung function and increased lung inflammation. Higher levels of mononuclear cells were observed in the peripheral blood of both wild-type (WT) and VAChT-KD mice. Also, both wild-type (WT) and VAChT-KD mice showed an increase in macrophages in bronchoalveolar lavage fluid (BALF) as well as increased expression of IL-4, IL-6, IL-13, TNF-α, and NF-κB in lung cells. The collagen fiber content in alveolar septa was also increased in both genotypes. On the other hand, we observed that granulocytes were increased only in VAChT-KD peripheral blood. Likewise, increased BALF lymphocytes and neutrophils as well as increased elastic fibers in alveolar septa, airway neutral mucus, and nasal epithelia acid mucus were observed only in VAChT-KD mice. The cytokines IL-4 and TNF-α were also higher in VAChT-KD mice compared with WT mice. In conclusion, decreased ability to release ACh exacerbates some of the lung alterations induced by DEP in mice, suggesting that VAChT-KD animals are more vulnerable to the effects of DEP in the lung.

Pulmonary interstitial emphysema in fatal asthma: case report and histopathological review.

BACKGROUND: Mortality related to asthma has decreased worldwide since the introduction of inhaled corticosteroid therapy in the past decades. However, there are still some asthma fatalities identified mainly in populations with less access to regular treatment. Pulmonary interstitial emphysema due to alveolar rupture has been rarely described as a complication of an acute severe asthma attack, and its identification in pathological analysis can be difficult. Previous studies reported the association of pulmonary interstitial emphysema and bronchial ductal gland ectasia in asthma. CASE PRESENTATION: We present the case of a 42-year- old man that died due to a fatal asthma attack. Postmortem computed tomography revealed the unusual finding of acute Pulmonary Interstitial Emphysema, confirmed by pathological analysis. We reviewed 28 cases of fatal asthma tissue and identified the presence of pulmonary interstitial emphysema in 10% of the cases. CONCLUSIONS: Postmortem computed tomography is a useful complimentary diagnostic tool for autopsies. Pulmonary Interstitial Emphysema in acute exacerbations of asthma seems to be more frequent than reported. Alveolar hyperdistension and bronchial duct gland ectasia causing tissue rupture are possible mechanisms involved in the formation of Pulmonary Interstitial Emphysema. The clinical impact of Pulmonary Interstitial Emphysema in asthma is unknown.

Periprostatic innervation: New issues based on segmental analysis of 10 human cadaver pelvic blocs.

BACKGROUND: The exact paths of periprostatic nerves have been under debate over the last decades. In the present study, the topographic distribution of nerves around the prostate and their relative distances from the prostatic capsule were analyzed in male cadaver visceral blocs. METHODS: The pelvic organs from ten fresh male cadavers were removed and serial sectioned en bloc for histological investigation. The macroslices was divided into four sectors. Each sector was centrally covered with a raster dividing each sector in three subsectors numbered clockwise. The prostatic capsule was identified, and distances of 2.5 and 5 mm from the prostate were demarked with lines. We quantified the number of nerve fibers present in each subsector of each slide and recorded their position relative to the prostatic capsule. RESULTS: In general, the topographic analysis revealed that the majority of nerves were identified in sectors 4 through 9, corresponding to the posterolateral and posterior surfaces of the prostate gland. At the prostate base, the majority of nerves were found at the posterolateral and posterior surfaces of the gland. Within the mid-region of the prostate, the same topographic distribution pattern was observed, but the nerve fibers were closer to the prostatic capsule. At the apical region, the percentage of nerve fibers identified in the anterior region was higher, despite their major concetration in the posterior surface. The nerves identified at the apex were mainly located up to 2.5 mm from the prostate. This proximity to the prostate was specifically observed in the anterolateral and anterior sectors. In the craniocaudal sense, the percentage of nerves identified between 2.5 and 5 mm from the prostatic capsule remained constant. CONCLUSIONS: A significant number of nerve fibers were present in the anterior and anterolateral positions, especially at the apex. The anterior nerves were closer to the prostate. This proximity suggests that the anterior nerves may participate in local physiology and that the cavernous nerves are probably formed by the posterior nerve fibers. It is likely that the safe distance of 2.5 mm from all surfaces of the prostate may be related to cavernous fiber preservation.

Influence of ACTN3 R577X polymorphism on ventilatory thresholds related to endurance performance.

The purpose of this study was to verify the association between ACTN3 polymorphism and physiological parameters related to endurance performance. A total of 150 healthy male volunteers performed a maximal incremental running test to determine the speeds corresponding to ventilatory threshold (VT) and respiratory compensation point (RCP). Participants were genotyped and divided into terciles based on the analysed variables. Genotype frequencies were compared through χ(2) test between lower and higher terciles, with the lowest or highest values of each analysed variable. ACTN3 XX genotype was over-represented in higher tercile for VT and RCP. Odds ratio also showed significantly higher chances of XX individuals to be in higher tercile compared to RR (7.3) and RR + RX (3.5) for VT and compared to RR genotype (8.1) and RR + RX (3.4) for RCP. Thus, XX individuals could attain the VT and RCP at higher speeds, suggesting that they are able to sustain higher running speeds in lower exercise intensity domains. It could result in higher lipid acids oxidation, saving muscle glycogen and delaying the fatigue during prolonged exercises, which could be the advantage mechanism of this genotype to endurance performance.

The genetics of human running: ACTN3 polymorphism as an evolutionary tool improving the energy economy during locomotion.

BACKGROUND: Covering long distances was an important trait to human evolution and continues to be highlighted for health and athletic status. This ability is benefitted by a low cost of locomotion (CoL), meaning that the individuals who are able to expend less energy would be able to cover longer distances. The CoL has been shown to be influenced by distinct and even 'opposite' factors, such as physiological and muscular characteristics, which are genetically inherited. In this way, DNA alterations could be important determinants of the characteristics associated with the CoL. A polymorphism in the ACTN3 gene (R577X) has been related to physical performance, associating the X allele with endurance and the R allele with strength/power abilities. AIM: To investigate the influence of ACTN3 genotypes on the CoL. SUBJECTS AND METHODS: One hundred and fifty healthy male individuals performed two constant speed tests (at 10 and 12 km/h) to determine the CoL. RESULTS: Interestingly, the results showed that heterozygous individuals (RX genotype) presented significantly lower CoL compared to RR and XX individuals. CONCLUSIONS: It is argued that RX genotype might generate an intermediate strength-to-endurance phenotype, leading to a better phenotypic profile for energy economy during running and, consequently, for long-term locomotion.

Chronic exposure of diesel exhaust particles induces alveolar enlargement in mice.

BACKGROUND: Diesel exhaust particles (DEPs) are deposited into the respiratory tract and are thought to be a risk factor for the development of diseases of the respiratory system. In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clarified. METHODS: We evaluated the effects of chronic exposure to DEP at doses below those found in a typical bus corridor in Sao Paulo (150 µg/m3). Male BALB/c mice were divided into mice receiving a nasal instillation: saline (saline; n = 30) and 30 µg/10 µL of DEP (DEP; n = 30). Nasal instillations were performed five days a week, over a period of 90 days. Bronchoalveolar lavage (BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13 and interferon-gamma (INF-γ) were determined by ELISA-immunoassay. Assessment of respiratory mechanics was performed. The gene expression of Muc5ac in lung was evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T cells and CD20+ B cells in tissues was analysed by immunohistochemistry. Bronchial thickness and the collagen/elastic fibers density were evaluated by morphometry. We measured the mean linear intercept (Lm), a measure of alveolar distension, and the mean airspace diameter (D0) and statistical distribution (D2). RESULTS: DEP decreased IFN-γ levels in BAL (p = 0.03), but did not significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p ≤ 0.001) and CD8+ T cells (p ≤ 0.001) increased in the parenchyma. Although IL-13 (p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene expression was not altered in the lung of DEP-exposed animals. Although respiratory mechanics, elastic and collagen density were not modified, the mean linear intercept (Lm) was increased in the DEP-exposed animals (p ≤ 0.001), and the index D2 was statistically different (p = 0.038) from the control animals. CONCLUSION: Our data suggest that nasal instillation of low doses of DEP over a period of 90 days results in alveolar enlargement in the pulmonary parenchyma of healthy mice.

Organic and inorganic fractions of diesel exhaust particles produce changes in mucin profile of mouse trachea explants.

Diesel exhaust particles (DEP) contain organic and inorganic elements that produce damage to the respiratory epithelium. The aim of this study was to determine the mucus profile of tracheal explants exposed to either crude diesel exhaust particles (DEP) or DEP treated with nitric acid (DEP/NA), with hexane (DEP/HEX), or with methanol (DEP/MET) at concentrations of 50 and 100 µg/ml for 30 and 60 min. Tracheal explants were subjected to morphometric analyses to study acidic (AB+), neutral (PAS+), and mixed (AB+/PAS+) mucus production and vacuolization (V). Incubation with 50 µg/ml crude DEP resulted in a rise in acid mucus production, an increase in vacuolization at 30 min, and reduction in neutral mucus at 30 and 60 min. Tracheas exposed to DEP/MET at 50 µg/ml for 30 or 60 min resulted in a significant decrease in neutral mucus production and an elevation in acid mucus production. DEP/HEX increased vacuolization at both 50 and 100 µg/ml at 30 and 60 min of exposure. Treatment with 50 µg/ml for 30 or 60 min significantly elevated mixed mucus levels. These results suggest that DEP appear to be more toxic when administered in combination with HEX or MET. DEP/MET modified the mucus profile of the epithelium, while DEP/HEX altered mucus extrusion, and these responses might be due to bioavailability of individual elements in DEP fractions.

Exogenous and endogenous antioxidants attenuate the lipid peroxidation in workers occupationally exposed to paints.

Occupational exposure to organic solvents present in paints is responsible for an increased production of reactive species, thus enabling the development of several diseases. Besides, both exo- and endogenous antioxidant defense systems are necessary to avoid oxidative tissue damage. This study investigated possible protective effects of the exo- and endogenous antioxidants on oxidative damage in painters occupationally exposed to organic solvents (n = 42) and controls (n = 28). Retinol, lycopene and ß-carotene were significantly lower in the exposed group. Despite the fact that blood toluene was below the biological exposure limits, malondialdehyde levels and antioxidant enzyme activities were increased, whereas reduced glutathione levels were decreased in painters, compared to nonexposed subjects. Moreover, multivariate regression models showed that reduced glutathione and carotenoids (mainly ß-carotene) have the major influence on lipid peroxidation (LPO). The present work suggests that the exogenous antioxidants, such as carotenoids, could protect occupationally exposed subjects to xenobiotics from LPO.