Hydrogen sulfide dysfunction in metabolic syndrome-associated vascular complications involves cGMP regulation through soluble guanylyl cyclase persulfidation.

Here, by using in vitro and ex vivo approaches, we elucidate the impairment of the hydrogen sulfide (H2S) pathway in vascular complications associated with metabolic syndrome (MetS). In the in vitro model simulating hyperlipidemic/hyperglycemic conditions, we observe significant hallmarks of endothelial dysfunction, including eNOS/NO signaling impairment, ROS overproduction, and a reduction in CSE-derived H2S. Transitioning to an ex vivo model using db/db mice, a genetic MetS model, we identify a downregulation of CBS and CSE expression in aorta, coupled with a diminished L-cysteine-induced vasorelaxation. Molecular mechanisms of eNOS/NO signaling impairment, dissected using pharmacological and molecular approaches, indicate an altered eNOS/Cav-1 ratio, along with reduced Ach- and Iso-induced vasorelaxation and increased L-NIO-induced contraction. In vivo treatment with the H2S donor Erucin ameliorates vascular dysfunction observed in db/db mice without impacting eNOS, further highlighting a specific action on smooth muscle component rather than the endothelium. Analyzing the NO signaling pathway in db/db mice aortas, reduced cGMP levels were detected, implicating a defective sGC/cGMP signaling. In vivo Erucin administration restores cGMP content. This beneficial effect involves an increased sGC activity, due to enzyme persulfidation observed in sGC overexpressed cells, coupled with PDE5 inhibition. In conclusion, our study demonstrates a pivotal role of reduced cGMP levels in impaired vasorelaxation in a murine model of MetS involving an impairment of both H2S and NO signaling. Exogenous H2S supplementation through Erucin represents a promising alternative in MetS therapy, targeting smooth muscle cells and supporting the importance of lifestyle and nutrition in managing MetS.

Safety profile and SARS-CoV-2 breakthrough infections among HCWs receiving anti-SARS-CoV-2 and influenza vaccines simultaneously: an Italian observational study.

In October/December 2021, World Health Organization and other international agencies recommended the offer of the third dose of anti-SARS-CoV-2 vaccine. In this period, the routine offer of seasonal influenza vaccination was also guaranteed and simultaneous administration of the two vaccines was encouraged. This study aims to evaluate the safety profile and to estimate the incidence of SARS-CoV-2 breakthrough infections in subjects receiving the anti-SARS-CoV-2 and influenza vaccines simultaneously. The study population was represented by healthcare workers (HCWs) of Bari Policlinico General Hospital who received the influenza (Flucelvax Tetra®) and/or anti-SARS-CoV-2 vaccination (BNT162b2 mRNA COVID-19 vaccine, Comirnaty®) either in coadministration or separately in October 2021. Reports of adverse events following immunization (AEFIs) were investigated to study the safety of both vaccines in coadministration and in separate-instance administration. Post-vaccination SARS-CoV-2 breakthrough infection was also studied. 942 HCWs accepted to join our study. 610/942 received both vaccines simultaneously. 25.26 % subjects (238/942) were only vaccinated against SARS-CoV-2, while the remaining 94 HCWs received the influenza vaccination first and subsequently received the anti-SARS-CoV2 booster dose. 717 HCWs reported AEFIs (Reporting Rate 76.1 per 100 subjects). Simultaneous administration of the two vaccines was not related with an increase of the rate of AEFIs compared to the single administration of SARS-CoV-2 vaccine, but the AEFIs' rate was lower among subjects who received only influenza vaccine. Post-vaccination SARS-CoV-2 infections were notified for 41.5 % of enrolled subjects (391/942). Incidence of breakthrough infection and symptomatic disease was not significantly different between the simultaneous administration group and other subjects. Our data suggests that simultaneous administration of a quadrivalent influenza vaccine and an mRNA anti-SARS-CoV-2 vaccine neither affected the safety of said products nor was associated with a higher risk of SARS-CoV-2 breakthrough infection.

Incidence of SARS-COV-2 infection among swimming athletes: data from real life in Apulia (Italy), July 2020/August 2021.

Background: As other indoor sports facilities, swimming pools were closed in Italy from March to May 2020 and from October 2020 to July 2021 due to the outbreak of the COVID-19 pandemic; access to these facilities was restricted to athletes of national relevance. This decision was based on "precautionary principles" and without evidence of a high risk of SARS-COV-2 circulation among swimming pools' attendants. The aim of this paper is to describe the pattern of SARS-COV-2 circulation among swimming athletes in Apulia (Southern Italy). Study design: The study aims to investigate the hypothesis that attending a pool increases the risk of SARS-COV-2 infection. The outcome measure is the incidence of SARS-COV-2 infection among swimming athletes compared with the general population. Methods: This is a retrospective cross-sectional study carried out in Apulia, Southern Italy. The study was performed through the analysis of both the database of the Italian Swimming Federation and the SARS-COV-2 infections in Apulia Region, from July 2020 to August 2021. Results: Among 2,939 federally licensed athletes, 221 had an history of SARS-COV-2 infection from July 2020 to August 2021, with an incidence of 75.2 /1,000. In the general Apulian population, during the same time span, the incidence of SARS-COV-2 infection was 67.3/1,000 and - considering the incidence rate ratio - there is no difference between the two populations (IRR=1.1; 95% CI=0.9-1.3; p>0.05). Conclusions: The incidence of SARS-COV-2 infection in Apulian swimmers showed no significant differences with the general population.

The safety of pneumococcal vaccines at the time of sequential schedule: data from surveillance of adverse events following 13-valent conjugated pneumococcal and 23-valent polysaccharidic pneumococcal vaccines in newborns and the elderly, in Puglia (Italy), 2013-2020.

Background: Nowadays, two types of anti-pneumococcal vaccine are available: pneumococcal 13-valent conjugate vaccine (PCV13), first licensed in the United States (US) in 2013, and pneumococcal 23-valent polysaccaridic vaccine (PPSV23), first licensed in the US in 1999. These vaccines are recommended in Italy for the immunization of newborns and of the elderly, using a combined sequential schedule for the latter. This report aims to describe the PCV13- and PPSV23-related AEFIs notified in Puglia in 2013-2020, in order to design these products' safety profile in a real-life scenario, three years after the official recommendation about the sequential schedule for people over 60 years of age. Methods: This is a retrospective observational study. Data were gathered from the list of AEFIs notified following PCV13 and PPSV23 administration in Puglia in 2013-2020. The number of administered vaccine doses was obtained from the regional immunization database. AEFIs were classified according to WHO's algorithm, and causality assessment was carried out in case of serious AEFIs. Results: From January 2013 to December 2020, 764,183 doses of PCV13 and 40,382 doses of PPSV23 were administered in Puglia. In the same period, 71 PCV13 AEFIs (Reporting Rate: 9.29 x100,000 doses) and 5 PPSV23 AEFIs (Reporting Rate: 12.4 x100,000 doses) were reported. The overall male/female ratio in AEFIs was 0.85. The majority of AEFIs occurred in subjects aged less than 2 (64/76, 84.2%), while 10 out of 76 (13.2%) occurred in patients aged 60 or older. 22 AEFIs were classified as serious and for 12 (54.5%) causality assessment showed a consistent relationship with immunization. The most commonly reported symptoms were fever (Reporting Rate: 4.72 x100,000 doses) and neurological symptoms (Reporting Rate: 3.23 x100,000 doses). Only one death was notified, classified as non-vaccine-related. Conclusions: The benefit of pneumococcal vaccination appears to be greater than the risk of AEFIs for both PCV13 and PPSV23. In fact, AEFIs occur in less than 0.1‰ of patients and the majority of AEFIs are mild and self-limiting.

A new paradigm of hospital care for SARS-COV-2 patients in the post-emergency phase in Italy.

Abstract: In Italy, at the beginning of the SARS-CoV-2 pandemic, the main organizational model of hospital care was represented by the physical or functional division of hospitals and wards into COVID and non-COVID areas, in order to separate SARS-CoV-2-infected patients from the others. Now that the emergency phase has reached its long-awaited end, it is necessary to develop a new hospital care paradigm that may deal with SARS-CoV-2-positive patients discriminating between those who are hospitalized because of COVID-19 and those who are diagnosed with SARS-CoV-2 infection immediately before or after the first access to healthcare facilities.

Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity.

Duchenne muscular dystrophy (DMD) is the most frequent X chromosome-linked disease caused by mutations in the gene encoding for dystrophin, leading to progressive and unstoppable degeneration of skeletal muscle tissues. Despite recent advances in the understanding of the molecular processes involved in the pathogenesis of DMD, there is still no cure. In this study, we aim at investigating the potential involvement of the transsulfuration pathway (TSP), and its by-end product namely hydrogen sulfide (H2S), in primary human myoblasts isolated from DMD donors and skeletal muscles of dystrophic (mdx) mice. In myoblasts of DMD donors, we demonstrate that the expression of key genes regulating the H2S production and TSP activity, including cystathionine γ lyase (CSE), cystathionine beta-synthase (CBS), 3 mercaptopyruvate sulfurtransferase (3-MST), cysteine dioxygenase (CDO), cysteine sulfonic acid decarboxylase (CSAD), glutathione synthase (GS) and γ -glutamylcysteine synthetase (γ-GCS) is reduced. Starting from these findings, using Nuclear Magnetic Resonance (NMR) and quantitative Polymerase Chain Reaction (qPCR) we show that the levels of TSP-related metabolites such as methionine, glycine, glutathione, glutamate and taurine, as well as the expression levels of the aforementioned TSP related genes, are significantly reduced in skeletal muscles of mdx mice compared to healthy controls, at both an early (7 weeks) and overt (17 weeks) stage of the disease. Importantly, the treatment with sodium hydrosulfide (NaHS), a commonly used H2S donor, fully recovers the impaired locomotor activity in both 7 and 17 old mdx mice. This is an effect attributable to the reduced expression of pro-inflammatory markers and restoration of autophagy in skeletal muscle tissues. In conclusion, our study uncovers a defective TSP pathway activity in DMD and highlights the role of H2S-donors for novel and safe adjuvant therapy to treat symptoms of DMD.

Oncology and Cardiac Rehabilitation: An Underrated Relationship.

Cancer and cardiovascular diseases are globally the leading causes of mortality and morbidity. These conditions are closely related, beyond that of sharing many risk factors. The term bidirectional relationship indicates that cardiovascular diseases increase the likelihood of getting cancer and vice versa. The biological and biochemical pathways underlying this close relationship will be analyzed. In this new overlapping scenario, physical activity and exercise are proven protective behaviors against both cardiovascular diseases and cancer. Many observational studies link an increase in physical activity to a reduction in either the development or progression of cancer, as well as to a reduction in risk in cardiovascular diseases, a non-negligible cause of death for long-term cancer survivors. Exercise is an effective tool for improving cardio-respiratory fitness, quality of life, psychological wellbeing, reducing fatigue, anxiety and depression. Finally, it can counteract the toxic effects of cancer therapy. The protection obtained from physical activity and exercise will be discussed in the various stages of the cancer continuum, from diagnosis, to adjuvant therapy, and from the metastatic phase to long-term effects. Particular attention will be paid to the shelter against chemotherapy, radiotherapy, cardiovascular risk factors or new onset cardiovascular diseases. Cardio-Oncology Rehabilitation is an exercise-based multi-component intervention, starting from the model of Cardiac Rehabilitation, with few modifications, to improve care and the prognosis of a patient's cancer. The network of professionals dedicated to Cardiac Rehabilitation is a ready-to-use resource, for implementing Cardio-Oncology Rehabilitation.

An integrated web system to support veterinary activities in Italy for the management of information in epidemic emergencies.

The management of public health emergencies is improved by quick, exhaustive and standardized flow of data on disease outbreaks, by using specific tools for data collection, registration and analysis. In this context, the National Information System for the Notification of Outbreaks of Animal Diseases (SIMAN) has been developed in Italy to collect and share data on the notifications of outbreaks of animal diseases. SIMAN is connected through web services to the national database of animals and holdings (BDN) and has been integrated with tools for the management of epidemic emergencies. The website has been updated with a section dedicated to the contingency planning in case of epidemic emergency. EpiTrace is one such useful tool also integrated in the BDN and based on the Social Network Analysis (SNA) and on network epidemiological models. This tool gives the possibility of assessing the risk associated to holdings and animals on the basis of their trade, in order to support the veterinary services in tracing back and forward the animals in case of outbreaks of infectious diseases.

A 12-month follow-up for neurological complication after subarachnoid anesthesia in a parturient affected by multiple sclerosis.

Multiple sclerosis is common among women of childbearing age. Neuraxial blocks have been administered to them with reluctance because of the hypothetical risk that local anesthetics might be more histotoxic to neural tissue already compromised by multiple sclerosis. In spite of the lack of uniform guidelines on disorders in pregnancy like multiple sclerosis, and of the published data that sometimes contrast each other, experience gained in recent years has indicated that regional anesthesia is safe even in these patients, but there aren't many published cases. We describe the case of a pregnant woman affected by multiple sclerosis in which we administered spinal anesthesia for a cesarean section, and we analyzed the aspects that literature defines as critical points in this group of patients. The results were favorable with regard to the level, intensity and duration of anesthesia. No neurological exacerbations were recognized during the hospital stay, nor during the follow-up that lasted 12 months.

Protective role of PI3-kinase-Akt-eNOS signalling pathway in intestinal injury associated with splanchnic artery occlusion shock.

BACKGROUND AND PURPOSE: Endothelial NO synthase (eNOS) is a dynamic enzyme tightly controlled by co- and post-translational lipid modifications, phosphorylation and regulated by protein-protein interactions. Here we have pharmacologically modulated the activation of eNOS, at different post-translational levels, to assess the role of eNOS-derived NO and of these regulatory mechanisms in intestinal injury associated with splanchnic artery occlusion (SAO) shock. EXPERIMENTAL APPROACH: SAO shock was induced by clamping both the superior mesenteric artery and the celiac trunk for 45 min followed by 30 min of reperfusion. During ischemia, 15 min prior to reperfusion, mice were given geldanamycin, an inhibitor of hsp90 recruitment to eNOS, or LY-294002 an inhibitor of phosphatidylinositol 3-kinase (PI3K), an enzyme that initiates Akt-catalysed phosphorylation of eNOS on Ser1179. After 30 min of reperfusion, samples of ileum were taken for histological examination or for biochemical studies. KEY RESULTS: Either LY-294002 or geldanamycin reversed the increased activation of eNOS and Akt observed following SAO shock. These molecular effects were mirrored in vivo by an exacerbation of the intestinal damage. Histological damage also correlated with neutrophil infiltration, assessed as myeloperoxidase activity, and with an increased expression of the adhesion proteins: ICAM-I, VCAM, P-selectin and E-selectin. CONCLUSIONS AND IMPLICATIONS: Overall these results suggest that activation of the Akt pathway in ischemic regions of reperfused ileum is a protective event, triggered in order to protect the intestinal tissue from damage induced by ischaemia/reperfusion through a fine tuning of the endothelial NO pathway.

Integrable model for interacting electrons in metallic grains.

We find an integrable generalization of the BCS model with nonuniform Coulomb and pairing interaction. The Hamiltonian is integrable by construction since it is a functional of commuting operators; these operators, which therefore are constants of motion of the model, contain the anisotropic Gaudin Hamiltonians. The exact solution is obtained diagonalizing them by means of Bethe ansatz. Uniform pairing and Coulomb interaction are obtained as the "isotropic limit" of the Gaudin Hamiltonians. We discuss possible applications of this model to a single grain and to a system of few interacting grains.

Re-entrant spin susceptibility of a superconducting grain

We study the spin susceptibility chi of a small, isolated superconducting grain. Because of the interplay between parity effects and pairing correlations, the dependence of chi on temperature T is qualitatively different from the standard BCS result valid in the bulk limit. If the number of electrons on the grain is odd, chi shows a re-entrant behavior as a function of temperature. This behavior persists even in the case of ultrasmall grains where the mean level spacing is much larger than the BCS gap. If the number of electrons is even, chi(T) is exponentially small at low temperatures.

Elevated alanine aminotransferase in blood donors: role of different factors and multiple viral infections.

Many different aetiological agents stimulate alanine aminotransferase (ALT) production. Viral markers and other aetiologies were investigated in 2166 individuals, randomly selected from 10,000 consecutive blood donors. Elevation of ALT was found in 10.8% of subjects. Grouping donors according to ALT level and correlating with, respectively, hepatitis B core antibody (HBcAb), cytomegalovirus antibody alone, or associated with HBcAb, showed similar findings (high ALT 11.1%, normal 11.6%; high 85.4%, normal 81.4%; high 10.2%, normal 11.0%, respectively). Hepatitis C virus (HCV) antibody was found to be significantly associated with elevated ALT levels (high 1.7%, normal 0.26%). Other causes of ALT elevation were alcohol abuse (17%), obesity (25%) and dyslipidaemia (38%), but in 11% there was no obvious aetiology. Although HCV is a rare cause of elevated ALT in blood donors, it seems to be the only virus, among those tested, to account for liver damage. This may be due to the non-protective role of HCV antibody, the low specificity of ALT, or the pathogenic role of uninvestigated viruses.

Trends in combustion technology in relation to health risk.

The general aspects of air pollutant formation during combustion are summarized, and emphasis placed on smoke emissions highly suspected of inducing cancer in human beings. A health risk index is defined, taking into account both quantities and toxicities of emission compounds. Pollutant formation during real combustion processes is discussed considering different fuels and different combustion devices both for stationary applications and for transportation. The possible technological actions for emission reduction with regard mainly to soot and polynuclear aromatic hydrocarbons are described for different cases. The paper ends with some considerations of the prospects for research in the field of combustion and on the strategies of cooperation between combustion scientists and toxicologists.