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

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

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

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

Allergic sensitization and exposure to ambient air pollution beginning early in life lead to a COPD-like phenotype in young adult mice.

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 (PM2.5) 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 PM2.5 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 PM2.5 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 PM2.5 exposed only. Both, early life allergic sensitization and PM2.5 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.

SARS-CoV-2 Nucleocapsid Protein is Associated With Lower Testosterone Levels: An Experimental Study.

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.

Tracking the time course of pathological patterns of lung injury in severe COVID-19.

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.

The role of artificial intelligence and machine learning in harmonization of high-resolution post-mortem MRI (virtopsy) with respect to brain microstructure.

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.

Tree rings reveal the reduction of Cd, Cu, Ni and Pb pollution in the central region of São Paulo, Brazil.

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.

Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model.

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.

Aerobic exercise in polluted urban environments: effects on airway defense mechanisms in young healthy amateur runners.

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 PM2.5 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).

In utero exposure to air pollution lowers erythrocyte antioxidant defense and decreases weight in adult mice.

In this study, we tested the influence of ambient air pollution on different phases of development of adult mice. With respect to adult weight, the animals that had spent their in utero period exposed to pollution showed less weight gain over their lifetime, as well as lower activity levels of the antioxidant enzymes catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx). Our study suggests that contact with atmospheric pollutants during the foetal period produces important changes on enzymatic erythrocyte antioxidant defense and weight in adult mice.

The association between air pollution and blood pressure in traffic controllers in Santo André, São Paulo, Brazil.

BACKGROUND: Urban air pollutants are associated with cardiovascular events. Traffic controllers are at high risk for pollution exposure during outdoor work shifts. OBJECTIVE: The purpose of this study was to evaluate the relationship between air pollution and systemic blood pressure in traffic controllers during their work shifts. METHODS: This cross-sectional study enrolled 19 male traffic controllers from Santo André city (São Paulo, Brazil) who were 30-60 years old and exposed to ambient air during outdoor work shifts. Systolic and diastolic blood pressure readings were measured every 15 min by an Ambulatory Arterial Blood Pressure Monitoring device. Hourly measurements (lags of 0-5h) and the moving averages (2-5h) of particulate matter (PM(10)), ozone (O(3)) ambient concentrations and the acquired daily minimum temperature and humidity means from the São Paulo State Environmental Agency were correlated with both systolic and diastolic blood pressures. Statistical methods included descriptive analysis and linear mixed effect models adjusted for temperature, humidity, work periods and time of day. RESULTS: Interquartile increases of PM(10) (33 µg/m(3)) and O(3) (49 µg/m(3)) levels were associated with increases in all arterial pressure parameters, ranging from 1.06 to 2.53 mmHg. PM(10) concentration was associated with early effects (lag 0), mainly on systolic blood pressure. However, O(3) was weakly associated most consistently with diastolic blood pressure and with late cumulative effects. CONCLUSIONS: Santo André traffic controllers presented higher blood pressure readings while working their outdoor shifts during periods of exposure to ambient pollutant fluctuations. However, PM(10) and O(3) induced cardiovascular effects demonstrated different time courses and end-point behaviors and probably acted through different mechanisms.

Pre- and postnatal exposure to ambient levels of urban particulate matter (PM(2.5)) affects mice spermatogenesis.

This work characterizes the effects of ambient levels of urban particulate matter (PM(2.5)) from the city of Sao Paulo on spermatogenesis using mice exposed during the embryo-fetal and/or postnatal phases of development. Parental generations (BALB/c mice) were exposed to air pollution in chambers with or without filtering PM(2.5) for 4 months. Animals were mated, and half of the 1-day-old offspring were moved between chambers, which yielded prenatal and postnatal groups. Remaining offspring comprised the non-exposed and pre+postnatal exposed groups. After 90 days, the animals were sacrificed for testis collection and weighing. Optical microscopy was used for the morphometric analyses of the cell counts, spermatogenic cycle, proliferation, and apoptosis. Prenatally exposed animals presented reduced body and testicular weight with an increased gonadosomatic index (GSI). Testicular volume also decreased, as well as the tubular diameter in testes of the same animals. Proliferation, apoptosis, and spermatogenic cycle analyses showed no significant differences among groups. However, the tubules at stage VII of pre- and postnatal animals presented a reduced number of elongated spermatids. Pre+postnatal group presented higher spermatid head retention at stages VIII-XII. These results show that ambient levels of PM(2.5) from Sao Paulo city affect spermatogenesis by damaging sperm production.

Effects of biomass burning on nasal mucociliary clearance and mucus properties after sugarcane harvesting.

OBJECTIVE: Biofuel from sugarcane is widely produced in developing countries and is a clean and renewable alternative source of energy. However, sugarcane harvesting is mostly performed after biomass burning. The aim of this study was to evaluate the effects of harvesting after biomass burning on nasal mucociliary clearance and the nasal mucus properties of farm workers. METHODS: Twenty seven sugarcane workers (21-45 years old) were evaluated at the end of two successive time-periods: first at the end of a 6-month harvesting period (harvesting), and then at the end of a 3-month period without harvesting (non-harvesting). Nasal mucociliary clearance was evaluated by the saccharine transit test, and mucus properties were analyzed using in vitro mucus contact angle and mucus transportability by sneeze. Arterial blood pressure, heart rate, respiratory rate, pulse oximetry, body temperature, associated illness, and exhaled carbon monoxide were registered. RESULTS: Data are presented as mean values (95% confidence interval). The multivariate model analysis adjusted for age, body-mass index, smoking status and years of working with this agricultural practice showed that harvesting yielded prolonged saccharine transit test in 7.83 min (1.88-13.78), increased mucus contact angle in 8.68 degrees (3.18-14.17) and decreased transportability by sneeze in 32.12 mm (-44.83 to -19.42) compared with the non-harvesting period. No significant differences were detected in any of the clinical parameter at either time-period. CONCLUSION: Sugarcane harvesting after biomass burning negatively affects the first barrier of the respiratory system in farm workers by impairing nasal mucociliary clearance and inducing abnormal mucus properties.

Biological effects and dose-response assessment of diesel exhaust particles on in vitro early embryo development in mice.

An increased risk of early pregnancy loss in women briefly exposed to high levels of ambient particulate matter during the preconceptional period was recently observed. The effects of this exposure on early embryo development are unknown. This study was designed to assess the dose-response and biological effects of diesel exhaust particles (DEP) on in vitro embryo development using the in vitro fertilization (IVF) mouse model. Zygotes obtained from superovulated mice after IVF were randomly cultured in different DEP concentrations (0, 0.2, 2, and 20 microg/cm(2)) for 5 days and observed for their capacity to attach and develop on a fibronectin matrix until day 8. Main outcome measures included blastocyst rates 96 and 120 h after insemination, hatching discriminatory score, total cell count, proportion of cell allocation to inner cell mass (ICM) and trophectoderm (TE), ICM morphology, attachment rate and outgrowth area, apoptosis and necrosis rates, and Oct-4 and Cdx-2 expression. Multivariate analysis showed a negative dose-dependent effect on early embryo development and hatching process, blastocyst cell allocation, and ICM morphology. Although blastocyst attachment and outgrowth were not affected by DEP, a significant impairment of ICM integrity was observed in day 8 blastocysts. Cell death through apoptosis was significantly higher after DEP exposure. Oct-4 expression and the Oct-4/Cdx-2 ratio were significantly decreased in day 5 blastocysts irrespective of DEP concentration. Results suggest that DEP appear to play an important role in disrupting cell lineage segregation and ICM morphological integrity even at lower concentrations, compromising future growth and viability of the blastocyst.

Pulmonary function and histological impairment in mice after acute exposure to aluminum dust.

Along the aluminum refining process, alumina (Al2O3) constitutes the main source of dust. Although aluminum refinery workers present respiratory symptoms with lung functional changes, no conclusive data about lung function impairment after alumina exposure has been so far reported. We examined the pulmonary alterations of exposure to material collected in an aluminum refinery in Brazil. BALB/c mice were exposed in a whole-body chamber for 1 h to either saline (CTRL, n = 11) or to a suspension (in saline) of 8 mg/m(3) of the dust (ALUM, n = 11) both delivered by an ultrasonic nebulizer. Twenty-four hours after exposure lung mechanics were measured by the end-inflation method. Lungs were prepared for histology. ALUM showed significantly higher static elastance (34.61 +/- 5.76 cmH2O/mL), elastic component of viscoelasticity (8.16 +/- 1.20 cmH2O/mL), pressure used to overcome the resistive component of viscoelasticity (1.62 +/- 0.24 cmH2O), and total resistive pressure (2.21 +/- 0.49 cmH2O) than CTRL (27.95 +/- 3.63 cmH2O/mL, 6.12 +/- 0.99 cmH2O/mL, 1.23 +/- 0.19 cmH2O, and 1.68 +/- 0.23 cmH2O, respectively). ALUM also presented significantly higher fraction area of alveolar collapse (69.7 +/- 1.2%) and influx of polymorphonuclear cells (27.5 +/- 1.1%) in lung parenchyma than CTRL (27.2 +/- 1.1% and 14.6 +/- 0.7%, respectively). The composition analysis of the particulate matter showed high concentrations of aluminum. For the first time it was demonstrated in an experimental model that an acute exposure to dust collected in an aluminum producing facility impaired lung mechanics that could be associated with inflammation.

Metal embryotoxicity from urban particles in Sao Paulo city: an experimental study in chicken embryos.

Chicken eggs were inoculated with suspensions of ambient air particles (

Small airway remodeling in idiopathic interstitial pneumonias: a pathological study.

BACKGROUND: Few studies have addressed small airway (SA) histopathological changes and their possible role in the remodeling process in idiopathic interstitial pneumonias. OBJECTIVES: To study morphological, morphometrical and immunohistochemical features of SA in idiopathic pulmonary fibrosis (usual interstitial pneumonia, UIP) and nonspecific interstitial pneumonia (NSIP). METHODS: We analyzed SA pathology in lung biopsies from 29 patients with UIP and 8 with NSIP. Biopsies were compared with lung tissue from 13 patients with constrictive bronchiolitis (CB) as positive controls and 10 normal autopsied control lungs. We semi-quantitatively analyzed SA structure, inflammation, architectural features and the bronchiolar epithelial immunohistochemical expression of TGF-beta, MMP-2, 7, 9, and their tissue inhibitors (TIMP-1, 2). RESULTS: Compared to controls, patients with UIP, NSIP and CB presented increased bronchiolar inflammation, peribronchiolar inflammation and fibrosis and decreased luminal areas. UIP patients had thicker walls due to an increase in most airway compartments. NSIP patients presented increased epithelial areas, whereas patients with CB had larger inner wall areas. All of the groups studied presented increased bronchiolar expression of MMP-7 and MMP-9, compared to the controls. CONCLUSION: We conclude that SAs are pathologically altered and may take part in the lung-remodeling process in idiopathic interstitial pneumonias.

Effects of exposure to high levels of particulate air pollution during the follicular phase of the conception cycle on pregnancy outcome in couples undergoing in vitro fertilization and embryo transfer.

The objective of this retrospective cohort study was to assess the potential effects of preconceptional short-term exposure to particulate air pollution in a real-world situation on pregnancy outcome in infertile women evaluating the possible role of IVF/embryo transfer treatment on this outcome using women who had conceived naturally for the first time during the same time frame as a matched control group. The study provides evidence for an association between brief exposure to high levels of ambient particulate matter (aerodynamic diameter