New Insights into Alterations in PL Proteins Affecting Their Binding to DNA after Exposure of Mytilus galloprovincialis to Mercury-A Possible Risk to Sperm Chromatin Structure?

Mercury (Hg) is a highly toxic and widespread pollutant. We previously reported that the exposure of Mytilus galloprovincialis for 24 h to doses of HgCl2 similar to those found in seawater (range 1-100 pM) produced alterations in the properties of protamine-like (PL) proteins that rendered them unable to bind and protect DNA from oxidative damage. In the present work, to deepen our studies, we analyzed PL proteins by turbidimetry and fluorescence spectroscopy and performed salt-induced release analyses of these proteins from sperm nuclei after the exposure of mussels to HgCl2 at the same doses. Turbidity assays indicated that mercury, at these doses, induced PL protein aggregates, whereas fluorescence spectroscopy measurements showed mercury-induced conformational changes. Indeed, the mobility of the PLII band changed in sodium dodecyl sulphate-polyacrylamide gel electrophoresis, particularly after exposure to 10-pM HgCl2, confirming the mercury-induced structural rearrangement. Finally, exposure to HgCl2 at all doses produced alterations in PL-DNA binding, detectable by DNA absorption spectra after the PL protein addition and by a decreased release of PLII and PLIII from the sperm nuclei. In conclusion, in this paper, we reported Hg-induced PL protein alterations that could adversely affect mussel reproductive activity, providing an insight into the molecular mechanism of Hg-related infertility

Morphological, Gene, and Hormonal Changes in Gonads and In-Creased Micrococcal Nuclease Accessibility of Sperm Chromatin Induced by Mercury

Mercury is one of the most dangerous environmental pollutants. In this work, we analysed the effects of exposure of Mytilus galloprovincialis to 1, 10 and 100 pM HgCl2 for 24 h on the gonadal morphology and on the expression level of three stress genes: mt10, hsp70 and pi gst. In this tissue we also evaluated the level of steroidogenic enzymes 3 beta-HSD and 17 beta-HSD and the expression of PL protein genes. Finally, we determined difference in sperm chromatin accessibility to micrococcal nuclease. We found alterations in gonadal morphology especially after exposure to 10 and 100 pM HgCl2 and hypo-expression of the three stress genes, particularly for hsp70. Furthermore, decreased labelling with both 3 beta-HSD and 17 beta-HSD antibodies was observed following exposure to 1 and 10 pM HgCl2 and complete absence at 100 pM HgCl2 exposure. Gonads of mussels exposed to all HgCl2 doses showed decreased expression of PL protein genes especially for PLIII. Finally, micrococcal nuclease digestions showed that all doses of HgCl2 exposure resulted in increased sperm chromatin accessibility to this enzyme, indicative of improper sperm chromatin structure. All of these changes provide preliminary data of the potential toxicity of mercury on the reproductive health of this mussel

Liver Involvement during SARS-CoV-2 Infection Is Associated with a Worse Respiratory Outcome in COVID-19 Patients

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be complicated by life-threatening interstitial pneumonia. SARS-CoV-2 infection may also damage several tissues and/or organs beyond the lungs, including the liver. However, controversy still exists as to whether SARS-CoV-2-induced liver alterations can have an impact on the outcome of COVID-19. The aim of this study was therefore to assess whether SARS-CoV-2-infected patients with liver abnormalities at the time of hospital referral had a worse outcome with respect to patients with no liver biochemistry alterations. To this end, the medical records of 123 patients admitted to our COVID center between the end of 2020 and spring 2021 were retrospectively reviewed. Patients were divided into two groups: those with normal liver biochemistries (group 1, 77 patients) and those with altered liver function tests (group 2, 46 patients). Serum levels of aminotransferases (AST and ALT) and bile duct cell injury markers (γ-GT and ALP) were used to dichotomize patients. A higher percentage of patients with liver enzyme alterations were found to develop COVID-19 pneumonia with respect to group 1 patients (74% vs. 65%); moreover, they needed more days of respiratory support and, more importantly, more intensive administration of supplemental oxygen. A statistically significant correlation was also found between aminotransferase levels and duration of respiratory support. The mortality rate was not superior in group 2 vs. group 1 patients. In conclusion, liver abnormalities on admission predisposed COVID-19 patients to development of more severe interstitial pneumonia, because of a longer requirement for supplemental oxygen and a more intensive respiratory support, indicative of a worse disease evolution in these patients

Prediction of SARS-CoV-2-Related Lung Inflammation Spreading by V:ERITAS (Vanvitelli Early Recognition of Inflamed Thoracic Areas Spreading)

Background Coronavirus disease 2019 (COVID-19) can be complicated by interstitial pneumonia, possibly leading to severe acute respiratory failure and death. Because of variable evolution ranging from asymptomatic cases to the need for invasive ventilation, COVID-19 outcomes cannot be precisely predicted on admission. The aim of this study was to provide a simple tool able to predict the outcome of COVID-19 pneumonia on admission to a low-intensity ward in order to better plan management strategies for these patients. Methods The clinical records of 123 eligible patients were reviewed. The following variables were analyzed on admission: chest computed tomography severity score (CTSS), PaO2/FiO2 ratio, lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio, C-reactive protein (CRP), fibrinogen, D-dimer, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, and albumin. The main outcome was the intensity of respiratory support (RS). To simplify the statistical analysis, patients were split into two main groups: those requiring no or low/moderate oxygen support (group 1); and those needing subintensive/intensive RS up to mechanical ventilation (group 2). Results The RS intensity was significantly associated with higher CTSS and NLR scores; lower PaO2/FiO2 ratios; and higher serum levels of LDH, CRP, D-dimer, and AST. After multivariate logistic regression and ROC curve analysis, CTSS and LDH were shown to be the best predictors of respiratory function worsening. Conclusions Two easy-to-obtain parameters (CTSS and LDH) were able to reliably predict a worse evolution of COVID-19 pneumonia with values of >7 and >328 U/L, respectively

Remdesivir plus dexamethasone versus dexamethasone alone for the treatment of COVID-19 patients requiring supplemental O2 therapy: a prospective controlled non-randomized study

Background: Remdesivir is an antiviral used to treat COVID-19 which improves some clinical outcomes. Dexamethasone has been shown to be effective in reducing mortality. It has been hypothesized that combination of these two drugs can improve mortality. We evaluated the effect of combination on mortality of COVID-19 patients requiring O2 therapy. Methods: A prospective quasi-experimental study, including two independent, sequential controlled cohorts, one received remdesivir-dexamethasone and the other dexamethasone alone, was designed. All COVID-19 patients requiring supplemental O2 therapy were enrolled consecutively. The sample size to power mortality was a priori calculated. The primary endpoints were 30-day mortality and viral clearance differences. Secondary endpoints were differences in hospitalization times, improvement in respiratory failure (PO2/FiO2) and inflammatory indices (fibrinogen, CRP, neutrophil/lymphocyte ratio, D-Dimer). Kaplan-Meier curves and the log-rank test were used to evaluate significant differences in mortality between groups. Results: 151 COVID-19 patients were enrolled (remdesivir/dexamethasone group, 76 and dexamethasone alone,75). No differences in demographic, clinical and laboratory characteristics were observed between the two groups at baseline. Faster viral clearance occurred in the remdesivir/dexamethasone group compared to dexamethasone alone (median 6 vs 16 days; p<0.001). 30-days mortality in the remdesivir/dexamethasone group was 1.3%, while in dexamethasone alone was 16% (p<0.005). In the remdesivir/dexamethasone group compared to dexamethasone alone there was a reduction in hospitalization days (p<0.0001) and a faster improvement in both respiratory function and inflammatory markers. Conclusions: Remdesivir/dexamethasone treatment is associated with significant reduction in mortality, length of hospitalization, and faster SARS-CoV-2 clearance, compared to dexamethasone alone