Impact of outdoor air pollution on severity and mortality in COVID-19 pneumonia.

The relationship between exposure to air pollution and the severity of coronavirus disease 2019 (COVID-19) pneumonia and other outcomes is poorly understood. Beyond age and comorbidity, risk factors for adverse outcomes including death have been poorly studied. The main objective of our study was to examine the relationship between exposure to outdoor air pollution and the risk of death in patients with COVID-19 pneumonia using individual-level data. The secondary objective was to investigate the impact of air pollutants on gas exchange and systemic inflammation in this disease. This cohort study included 1548 patients hospitalised for COVID-19 pneumonia between February and May 2020 in one of four hospitals. Local agencies supplied daily data on environmental air pollutants (PM10, PM2.5, O3, NO2, NO and NOX) and meteorological conditions (temperature and humidity) in the year before hospital admission (from January 2019 to December 2019). Daily exposure to pollution and meteorological conditions by individual postcode of residence was estimated using geospatial Bayesian generalised additive models. The influence of air pollution on pneumonia severity was studied using generalised additive models which included: age, sex, Charlson comorbidity index, hospital, average income, air temperature and humidity, and exposure to each pollutant. Additionally, generalised additive models were generated for exploring the effect of air pollution on C-reactive protein (CRP) level and SpO2/FiO2 at admission. According to our results, both risk of COVID-19 death and CRP level increased significantly with median exposure to PM10, NO2, NO and NOX, while higher exposure to NO2, NO and NOX was associated with lower SpO2/FiO2 ratios. In conclusion, after controlling for socioeconomic, demographic and health-related variables, we found evidence of a significant positive relationship between air pollution and mortality in patients hospitalised for COVID-19 pneumonia. Additionally, inflammation (CRP) and gas exchange (SpO2/FiO2) in these patients were significantly related to exposure to air pollution.

The estrogen replacement therapy of the Women's Health Initiative promotes the cellular mechanisms of memory and neuronal survival in neurons vulnerable to Alzheimer's disease.

OBJECTIVES: The current study investigated the neurotrophic and neuroprotective action of the complex formulation of conjugated equine estrogens (CEEs), the most frequently prescribed estrogen replacement therapy in the United States and the estrogen replacement therapy of the Women's Health Initiative. METHODS: Videomicroscopic, morphologic and biochemical analyses were conducted in primary cultures of hippocampal neurons to determine the neurotrophic and neuroprotective properties of CEEs. RESULTS: Results of these analyses demonstrated that CEEs significantly increased hippocampal neuronal outgrowth, a cellular marker of memory formation. Dose response analyses indicated that the lowest effective concentration of CEEs exerted the maximal neurotrophic effect. Results of neuroprotection studies demonstrated that CEES induced highly significant neuroprotection against beta amyloid(25-35), hydrogen peroxide and glutamate-induced toxicity. CONCLUSIONS: CEEs induced cellular markers of memory function in neurons critical to memory and vulnerable to negative effects of aging and Alzheimer's disease. In addition, CEEs significantly and potently protected neurons against toxic insults associated with Alzheimer's disease. Because CEEs are the estrogen replacement therapy of the Women's Health Initiative, results of the current study could provide cellular mechanisms for effects of CEEs on cognitive function and risk of Alzheimer's disease derived from this prospective clinical trial.

The women's health initiative estrogen replacement therapy is neurotrophic and neuroprotective.

The current study investigated the neurotrophic and neuroprotective action of the complex formulation of conjugated equine estrogens (CEEs), the most frequently prescribed estrogen replacement therapy in the United States and the estrogen replacement therapy of the Women's Health Initiative. Morphologic analyses demonstrated that CEEs significantly increased neuronal outgrowth in hippocampal, basal forebrain, occipital, parietal and frontal cortex neurons. Dose-response analyses indicated that the lowest effective concentration of CEEs exerted the maximal neurotrophic effect with greatest potency occurring in hippocampal and occipital cortex neurons. CEES induced highly significant neuroprotection against beta amyloid(25-35), hydrogen peroxide and glutamate-induced toxicity. Rank order of potency and magnitude of CEE-induced neuroprotection in the brain regions investigated was hippocampal neurons > basal forebrain neurons > cortical neurons. In hippocampal neurons pre-exposed to beta amyloid(25-35), CEEs halted Abeta(25-35)-induced cell death and protected surviving neurons from further cell death induced by Abeta(25-35). Because CEEs are the estrogen replacement therapy of the Women's Health Initiative, results of the current study could provide cellular mechanisms for understanding effects of CEEs on cognitive function and risk of Alzheimer's disease derived from this prospective clinical trial.