Biochemical effect evaluation of perfluorooctane sulfonic acid-contaminated wood mice (Apodemus sylvaticus).

Wood mice (Apodemus sylvaticus) were captured at Blokkersdijk, a nature reserve in the immediate vicinity of a fluorochemical plant in Antwerp, Belgium, and at Galgenweel, 3 kilometers farther away. The liver perfluorooctane sulfonic acid (PFOS) concentrations in the Blokkersdijk mice were extremely high (0.47-178.55 micro g/g wet weight). Perfluorononanoic, perfluorodecanoic, perfluoroundecanoic, and perfluorododecanoic acids were found sporadically in the liver tissue of the Blokkersdijk mice. The liver PFOS concentrations at Galgenweel were significantly lower than those at Blokkersdijk (0.14-1.11 micro g/g wet weight). Further results suggest sex independence of the liver PFOS levels, increased levels of PFOS bioaccumulation in older mice, and maternal PFOS transfer to the young. Several liver end points were significantly elevated in the Blokkersdijk mice: liver weight, relative liver weight, peroxisomal beta-oxidation activity, microsomal lipid peroxidation level, and mitochondrial fraction protein content. For the mitochondrial fraction catalase activity, no significant difference between locations was found. The liver weight, relative liver weight, and liver microsomal lipid peroxidation level increased significantly with the liver PFOS concentration. No indications for PFOS-mediated effects on the serum triglyceride, cholesterol, or potassium levels were obtained. The liver PFOS concentration was negatively related to the serum alanine aminotransferase activity

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Perfluorinated chemicals infiltrate ocean waters: Link between exposure levels and stable isotope ratios in marine mammals

This is the first study to report on concentrations of perfluorinated organochemicals (FOCs) in marine mammals stranded along the southern North Sea coast in relation to stable nitrogen and carbon isotope ratios (delta(15)N and delta(13)C). The presence of FOCs in top predators such as marine mammals would indicate a potential biomagnification of these compounds and their widespread occurrence. Liver and kidney tissues of nine marine mammal species have been sampled. Among all the measured FOCs compounds, PFOS (perfluorooctane sulfonate) was predominant in terms of concentration. The highest PFOS concentrations were found in the liver of harbor seal compared to white-beaked dolphin, harbor porpoise, gray seal, sperm whale, white-sided dolphin, striped dolphin, fin whale, and hooded seal. PFOS concentrations differed significantly between sexes and age classes in harbor porpoises. Stable isotope measurements (delta(13)C and delta(15)N) were used in this study to describe the behavior of contaminants in food webs. We found a significant (p < 0.05) linear relationship between PFOS concentrations in livers of harbor porpoises and both Muscle delta(13)C and delta(15)N measurements. Harbor and gray seals and white-beaked dolphin, which displayed the highest trophic position, contained the highest PFOS levels, while offshore feeders such as sperm whales,fin whales, striped dolphin, and white-sided dolphin showed lower PFOS concentrations than inshore species

Cytosolic distribution of Cd, Cu and Zn, and metallothionein levels in relation to physiological changes in gibel carp (**Carassius auratus gibelio**) from metal-impacted habitats

Oxidation products of α-pinene represent a fraction of organic matter in the environmental aerosol. α-pinene is one of most abundant monoterpenes released in the atmosphere by plants, located typically in boreal, temperate and tropical forests. This primary compound reacts with atmospheric oxidants, such as O3, O2, OH radicals and NOx, through the major tropospheric degradation pathway for many monoterpenes under typical atmospheric condition. Although several studies identified a series of by-products deriving from the α-pinene photo-oxidation in the atmosphere, such as pinic and cis-pinonic acid, the knowledge of the mechanism of this process is partially still lacking. Thus, the investigation of the distribution of these acids in the different size aerosol particles provides additional information on this regard. The aim of this study is twofold. First, we aim to improve the existing analytical methods for the determination of pinic and cis-pinonic acid in aerosol samples, especially in terms of analytical sensitivity and limits of detection (LOD) and quantification (LOQ). We even attempted to increase the knowledge of the α-pinene photo-oxidation processes by analysing, for the first time, the particle-size distribution up to nanoparticle level of pinic and cis-pinonic acid. The analysis of aerosol samples was carried out via high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The instrumental LOD values of cis-pinonic and pinic acid are 1.6 and 1.2 ng L−1 while LOQ values are 5.4 and 4.1 ng L−1, respectively. Samples were collected by MOUDI II™ cascade impactor with twelve cut-sizes, from March to May 2016 in the urban area of Mestre-Venice (Italy). The range concentrations in the aerosol samples were from 0.1 to 0.9 ng m−3 for cis-pinonic acid and from 0.1 to 0.8 ng m−3 for pinic acid