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.

Homocysteine and cysteine concentrations are modified by recent exposure to environmental air pollution in São Paulo, Brazil.

Millions of people worldwide are affected by anthropogenic air pollution derived from the combustion of fossil fuels. In this work, we tested the effects of fetal, lactation and post-weaning ambient air pollution exposure on total homocysteine (tHcy) concentrations and on a downstream pathway element, the plasma cysteine (Cys) concentration. Two similar exposure chambers (polluted and filtered chamber) were located near an area with heavy traffic in São Paulo, Brazil, and male Swiss mice were housed there from the pre-natal period until 3 months of age. Groups during fetal, lactation and adult periods of exposure were apportioned, and tHcy and Cys plasma concentrations were assessed when the animals were 3 months old. In our study, both the tHcy and Cys concentrations were decreased in groups that spent their final stage of life in polluted chambers, suggesting recent alterations in tHcy and Cys concentrations due to air pollution exposure. The possible relationship of these data with cardiovascular dysfunction is still a matter of controversy in animals; nevertheless, epigenetic mechanisms emerge as a possible issue to consider in the investigation of the link between air pollution and Hcy measurement.

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.

Ambient levels of air pollution induce goblet-cell hyperplasia in human conjunctival epithelium.

BACKGROUND: Ocular mucosa is exposed constantly to the external environment, and chronic exposure to air pollution may affect the ocular surface. OBJECTIVE: We assessed the effect of air pollution on the ocular surface by combining determinations of individual exposure and conjunctival impression cytology. METHODS: A panel study was conducted with 29 volunteers recruited in two locations with different pollution levels: São Paulo (n = 13) and Divinolândia (n = 16). We assessed mean individual levels of nitrogen dioxide (NO2) exposure for 7 days, using a passive sampler. Impression cytology samples were obtained from inferior tarsal conjunctiva. Comparisons between the two groups in terms of NO2 exposure and goblet-cell counts were performed using the Student t-test. Correlations between goblet-cells counts and corresponding individual NO2 exposure levels were determined using Spearman's correlation. RESULTS: Individuals living in São Paulo received a significantly (p = 0.005) higher dose of NO2 (mean 32.47; SD 9.83) than those living in Divinolândia (mean 19.33; SD 5.24). There was a steady increase in goblet-cell counts, proportional to NO2 exposure (Spearman's correlation = 0.566, p = 0.001), with a dose-response pattern. CONCLUSIONS: A positive and significant association between exposure to air pollution and goblet-cell hyperplasia in human conjunctiva was detected. The combination of simple measurements of exposure and impression cytology was an effective and noninvasive approach for characterizing human response to ambient levels of air pollution.

An approach to using heart rate monitoring to estimate the ventilation and load of air pollution exposure.

BACKGROUND: The effects of air pollution on health are associated with the amount of pollutants inhaled which depends on the environmental concentration and the inhaled air volume. It has not been clear whether statistical models of the relationship between heart rate and ventilation obtained using laboratory cardiopulmonary exercise test (CPET) can be applied to an external group to estimate ventilation. OBJECTIVES: To develop and evaluate a model to estimate respiratory ventilation based on heart rate for inhaled load of pollutant assessment in field studies. METHODS: Sixty non-smoking men; 43 public street workers (public street group) and 17 employees of the Forest Institute (park group) performed a maximum cardiopulmonary exercise test (CPET). Regression equation models were constructed with the heart rate and natural logarithmic of minute ventilation data obtained on CPET. Ten individuals were chosen randomly (public street group) and were used for external validation of the models (test group). All subjects also underwent heart rate register, and particulate matter (PM2.5) monitoring for a 24-hour period. RESULTS: For the public street group, the median difference between estimated and observed data was 0.5 (CI 95% -0.2 to 1.4) l/min and for the park group was 0.2 (CI 95% -0.2 to 1.2) l/min. In the test group, estimated values were smaller than the ones observed in the CPET, with a median difference of -2.4 (CI 95% -4.2 to -1.8) l/min. The mixed model estimated values suggest that this model is suitable for situations in which heart rate is around 120-140bpm. CONCLUSION: The mixed effect model is suitable for ventilation estimate, with good accuracy when applied to homogeneous groups, suggesting that, in this case, the model could be used in field studies to estimate ventilation. A small but significant difference in the median of external validation estimates was observed, suggesting that the applicability of the model to external groups needs further evaluation.

Centrilobular fibrosis: a novel histological pattern of idiopathic interstitial pneumonia.

The classification of idiopathic interstitial pneumonias (IIP) is still under debate. In this context, we observed in some of our patients with a clinical and radiological diagnosis of IIP a different histological picture with an aggressive centrilobular scarring centered in the bronchiolar epithelia, but involving the surrounding parenchyma, which underwent extensive remodeling. We hypothesized that this pattern is a form of IIP that could be separated out histologically from the previously described patterns, in particular from usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Forty-nine patients with clinical and radiological diagnosis of IIP and open-lung biopsies were retrospectively selected from 1982 to 1998. The biopsies were reviewed according to the following criteria: derangement of lobular architecture, temporal homogeneity and subpleural or bronchocentric distribution of the lesions, fibroblast foci, bronchial epithelium necrosis and regeneration, exposure of the basal membrane, squamous metaplasia, basophilic intraluminal contents, and foreign bodies within the remodeling airspaces. Three groups were found: UIP (24 patients), NSIP (13), and a third that we named centrilobular fibrosis (CLF) (12). All histological parameters were significantly different among the three groups (p < 0.001). CLF is a specific, homogeneous, and recognizable histological pattern of IIP, and can be isolated from UIP and NSIP.

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.

Effects of air pollution on blood pressure and heart rate variability: a panel study of vehicular traffic controllers in the city of São Paulo, Brazil.

AIMS: Evaluating the effects of air pollution on Sao Paulo city's vehicular traffic controllers by means of risk indicators for cardiovascular diseases. METHODS AND RESULTS: Twenty-four hour blood pressure recordings and an electrocardiogram were obtained in 48 healthy, non-smoking vehicular traffic controllers, aged 31-55 years, during three periods: winter 2000, summer 2001, and winter 2001. Effects of air pollutants on the outcomes were estimated using linear regression based on generalized estimated equations, controlling for age, body mass index, humidity, and temperature. An interquartile range (IQR) increase in CO (1.1 p.p.m.) was associated with increases of 2.6 mmHg (95% CI 1.0, 4.2), 1.8 mmHg (95% CI 0.8, 2.8), and 2.4 mmHg (95% CI 1.1, 3.6) in systolic, diastolic, and mean 24 h ambulatory blood pressures. SO(2) also had relevant effects on blood pressure. On heart rate variability, an IQR increase of SO2 (9.6 microg/m3) was negatively associated with the standard deviation (SD) of normal RR intervals (SDNN) -7.93 ms (95% CI -15.3, -0.6). CONCLUSION: This study supplies biological plausibility for observational studies on air pollution-related cardiovascular morbidity and mortality.