NO-dependent proliferation and migration induced by Vitamin D in HUVEC.

Recently, Vitamin D (Vit. D) has gained importance in cellular functions of a wide range of extraskeletal organs and target tissues, other than bone. In particular, Vit. D has displayed important beneficial effects in the cardiovascular system. Although little is known about the mechanism by which this response is exerted, a Vit. D-induced eNOS-dependent nitric oxide (NO) production in endothelial cells (EC) has been reported. The aim of this study was to evaluate whether Vit. D administration could affect human EC proliferation and/or migration through NO production. For this purpose, HUVEC (human umbilical vein endothelial cells) were used to evaluate Vit. D effects on cell proliferation and migration in a 3D matrix. Experiments were also performed in the presence of the specific VDR ligand ZK159222 and eNOS inhibitor L-NAME. This study demonstrated that Vit. D can promote both HUVEC proliferation and migration in a 3D matrix. These effects were NO dependent, since HUVEC proliferation and migration were abrogated along with Vit. D induced MMP-2 expression by inhibiting eNOS activity by L-NAME. These findings support the role of Vit. D in the angiogenic process, suggesting new applications for Vit. D in tissue repair and wound healing

Focolaio di COVID-19 in un campo estivo nella Regione Piemonte (2021): descrizione, lezioni apprese e raccomandazioni per futuri campi estivi

COVID-19 outbreak at a summer camp in Piedimont region in 2021: description, lessons learned and recommendations for future summer camps Introduction In August 2021, an outbreak of coronavirus disease 2019 (COVID-19) occurred in a summer camp in Piedmont region, Italy, affecting primarily campers aged ≤16 years. We conducted a retrospective cohort study among campers and personnel (attendees) to determine the attack rate (AR), evaluate possible factors associated with transmission and propose recommended measures for the organization of future summer camps. Materials and methods A de-identified database including demographic, role of attendees, cohorting, means of transportation to the camp, inter-camper interactions, SARS-CoV-2 testing results and symptomatology was used. All analysis data came from a collection of data carried out by the organizing private company and the information related to the mitigation protocol put in place was provided by the health care personnel. All campers were asked to have an antigen/molecular test within 72 hours before departure. Nine dedicated buses departed from different Italian regions towards the camp. All travellers wore a surgical mask during the trip. Upon arrival, regardless of the bus used, the campers were divided into 11 subgroups with no further contact between them unless they were blood relatives. No SARS-CoV-2 screening tests were scheduled for campers after arrival and during the camp period. On the other hand, personnel had a screening test at each shift change. During the camp period, antigen tests were performed at cases with symptoms suggestive of infection. Only attendees enrolled in the private company and those who received at least one test since arrival at the camp were considered in the study. We calculated overall AR and relative risk (RR) along with specific, transmission-focused risk factors. Results Among the 187 study participants, the median age was 14 years (range: 6-45). Seven days after arrival at the camp, 8 campers developed symptoms and tested positive. The overall AR was 33.7% (63 out of 187), and 34.2% (50/146) for campers and 31.7% (13/41) for staff, respectively. Among those with available symptoms information, 72% (36/50) were asymptomatic at the time of testing. Only 17.1% of campers had direct contact with blood relatives from other subgroups. The AR of participants using a bus was 36.2% (59/163) with an RR of 1.18 (95% CI = 0.51-2.73,) and the AR of those belonging to a subgroup was 35% (62/177) with an RR of 3.5 (95% CI = 0.54-22.7). For personnel, participation to a subgroup gave an AR of 38.7% (12/31) and an RR of 3.87 (95% CI = 0.57-26.18). All but four subgroups had a high AR (>33,3). Conclusions Getting tested prior to traveling and campers separation into low-contact subgroups was not sufficient enough to avoid a high number of infections in this summer camp. Analysis did not allow the identification of an index case or helped to understand whether the outbreak originated from the attendees who travelled on the same bus. The high AR observed in all subgroups suggest that there was frequent contact between attendees belonging to different subgroups. Sharing of common areas such as the canteen and contact between attendees are possible factors that have contributed to the spread of the outbreak. The experience gained by the analysis of this data was used for the review of measures for the organization of summer camps in 2022

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Effect of exercise and strenght training of cardiovascular status in HIV-infected patients receiving highly active antiretroviral therapy

A routine evaluation of lipid metabolism and body fat distribution along with a careful cardiovascular risk stratification according to international guidelines are required for HIV-infected patients receiving highly active antiretroviral therapy. Intervention includes evaluation of patients for both epidemiological and clinical factors, and for anthropometric and biochemical parameters. Diet counseling, prescription of antihyperlipidemic drugs and exercise training are the cornerstones of programs devoted to protecting patients from side effects of therapies that compromise quality of life and the functions of organs like the pancreas and heart that are involved in lipid disorder

Dynamic of mixed HCV infection in plasma and PBMC of HIV/HCV patients under treatment with Peg-IFN/ribavirin

The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG

Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV/HCV Patients Under Treatment With Peg-IFN/Ribavirin

The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown. The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate. The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P–R). Ten individuals were nonresponder (NR) or relapser (RE) to P–R treatment and 9 had a sustained virological response (SVR). Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV–RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P–R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237). Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P–R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG

Health status of petrochemical workers: a narrative review

: Professional exposure to benzene has been extensively investigated by occupational medicine, leading to strict regulation of exposure threshold values. However, the petrochemical industry utilizes many chemical substances, whose exposure, without effective control and mitigation actions, could influence the health status over time. The aim of this narrative review is to describe health status of petrochemical workers related to occupational exposures, inquiring literature from 1980 to present. We used the PubMed and Web of Science search engines. As regards non-neoplastic diseases, despite heterogeneous prevalence estimates, we could say that standardized mortality rate (SMR) for hypertension, hypercholesterolemia and diabetes does not increase overall, compared to reference populations; a possible explanation may be the "healthy worker effect". Attention should be paid to color disperception and respiratory symptoms, due to toxic or irritating substances exposure. Studies concerning neoplastic pathology have mainly investigated mortality outcomes, finding no increase in cancer, except for melanoma or other skin cancers and leukemia. As regards the former, however, it is not excluded that other risk factors may contribute (e.g. UV rays in offshore workers), while for leukemia, only the most recent studies have analyzed various subtypes of hematopoietic tumors, highlighting a possible risk for the development of myelodysplastic syndrome. The risk of pleural mesothelioma was also increased, likely due to asbestos exposures, while the risk of death from prostate cancer remains controversial

Awareness, discussion and non-prescribed use of HIV pre-exposure prophylaxis among persons living with HIV/AIDS in Italy: a Nationwide, cross-sectional study among patients on antiretrovirals and their treating HIV physicians

Background: Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and made available, a few surveys among gay and bisexual men, and persons living with HIV/AIDS (PLWHA), identified an informal use of antiretrovirals (ARVs) for PrEP among HIV-negative individuals. Before PrEP availability in Italy, we aimed to assess whether PLWHA in Italy shared their ARVs with HIV-negative individuals, whether they knew people who were on PrEP, and describe the level of awareness and discussion on this preventive measure among them and people in their close circle. Methods: Two anonymous questionnaires investigating personal characteristics and PrEP awareness, knowledge, and experience were proposed to HIV specialists and their patients on ARVs in a one-week, cross-sectional survey (December 2013-January 2014). Among PLWHA, a Multivariable Logistic Regression analysis was conducted to identify factors associated with PrEP discussion with peers (close circle and/or HIV associations), and experience (use in close circle and/or personal ARV sharing). Results: Eighty-seven specialists in 31 representative Infectious Diseases departments administered the questionnaire to 1405 PLWHA. Among specialists, 98% reported awareness, 65% knew the dosage schedule, and 14% had previously suggested or prescribed PrEP. Among PLWHA, 45.6% were somehow aware, discussed or had direct or indirect experience of PrEP: 38% "had heard" of PrEP, 24% were aware of studies in HIV-negative individuals demonstrating a risk reduction through the use of ARVs, 22% had discussed PrEP, 12% with peers; 9% reported PrEP use in close circle and 1% personal ARV sharing. Factors predictive of either PrEP discussion with peers or experience differed between men and women, but across all genders were mainly related to having access to information, with HIV association membership being the strongest predictor. Conclusions: At a time and place where there were neither official information nor proposals or interventions to guide public policies on PrEP in Italy, a significant number of PLWHA were aware of it, and approximately 10% reported PrEP use in their close circle, although they rarely shared their ARVs with uninfected people for this purpose. Official policies and PrEP availability, along with implementation programs, could avoid risks from uncontrolled PrEP procurement and self-administration practices