Short occupational exposure to glyphosate and its biomonitoring via urinary levels of glyphosate and metabolite AMPA (Amino-MethylPhosphonic acid), in Italian vineyard workers.

Glyphosate, an herbicide largely used in various contexts, can have adverse effects on human health. Although it is currently the most applied pesticide worldwide, few studies evaluated the extent of human exposure via biomonitoring. To expand such information, biological monitoring of exposure to glyphosate was conducted. The study has a before-and-after design to demonstrate the immediate impact of short-term interventions. Accordingly, the urine concentrations of glyphosate and its main biodegradation product (amino-methylphosphonic acid- AMPA) were measured before and the day after the single herbicide application in 17 male winegrowers. Urine samples were analyzed by high performance liquid chromatography coupled with a triple quadrupole mass spectrometer equipped with an electrospray ionization source. Glyphosate and AMPA were not detectable in pre-application urine samples (limit of quantification for glyphosate (LOQG) was 0.1 µg/L; limit of quantification for AMPA (LOQAMPA) was 0.5 µg/L). After application, glyphosate urinary levels were above LOQG in all workers. The median, min, and max values were 2.30, 0.51, and 47.2 µg/L, respectively. The same values were found for 50 %, 5 % and 95 % percentiles. After assigning numerical values, such as one half the LOQ, to each of the non-detects, the "z" of Wilcoxon matched-pairs signed-ranks test was -3.62 (p = 0.0003), suggesting the pre-application values being significantly lower than the post-application urinary glyphosate concentration. A similar analysis was not feasible with AMPA urinary levels, which were detectable only in 3 workers, after application. 12 (71 %) workers were significantly exposed to glyphosate, but adherence to the adoption of personal protective equipment was good: 14 (82 %) workers used gloves, 13 (76 %) used overalls and 13 (76 %) facial masks. Our data show that glyphosate can be absorbed by the workers after a single application and confirms the usefulness of biomonitoring in exposed workers. Further studies are needed in larger working populations and with multiple glyphosate applications, as well as to evaluate the correlations of glyphosate urine levels with exposure questionnaire data, in order to assess the actual relevance of risk and protection factors.

The effect of high polycyclic aromatic hydrocarbon exposure on biological aging indicators.

BACKGROUND: Aging represents a serious health and socioeconomic concern for our society. However, not all people age in the same way and air pollution has been shown to largely impact this process. We explored whether polycyclic aromatic hydrocarbons (PAHs), excellent fossil and wood burning tracers, accelerate biological aging detected by lymphocytes DNA methylation age (DNAmAge) and telomere length (TL), early nuclear DNA (nDNA) hallmarks of non-mitotic and mitotic cellular aging, and mitochondrial DNA copy number (mtDNAcn). METHODS: The study population consisted of 49 male noncurrent-smoking coke-oven workers and 44 matched controls. Occupational and environmental sources of PAH exposures were evaluated by structured questionnaire and internal dose (urinary 1-pyrenol). We estimated Occup_PAHs, the product of 1-pyrenol and years of employment as coke-oven workers, and Environ_PAHs, from multiple items (diet, indoor and outdoor). Biological aging was determined by DNAmAge, via pyrosequencing, and by TL and mtDNAcn, via quantitative polymerase chain reaction. Genomic instability markers in lymphocytes as target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei), gene-specific (p53, IL6 and HIC1) and global (Alu and LINE-1 repeats) DNA methylation, and genetic polymorphisms (GSTM1) were also evaluated in the latent variable nDNA_changes. Structural equation modelling (SEM) analysis evaluated these multifaceted relationships. RESULTS: In univariate analysis, biological aging was higher in coke-oven workers than controls as detected by higher percentage of subjects with biological age older than chronological age (AgeAcc ≥ 0, p = 0.007) and TL (p = 0.038), mtDNAcn was instead similar. Genomic instability, i.e., genotoxic and epigenetic alterations (LINE-1, p53 and Alu) and latent variable nDNA_changes were higher in workers (p < 0.001). In SEM analysis, DNAmAge and TL were positively correlated with Occup_PAHs (p < 0.0001). Instead, mtDNAcn is positively correlated with the latent variable nDNA_changes (p < 0.0001) which is in turn triggered by Occup_PAHs and Environ_PAHs. CONCLUSIONS: Occupational PAHs exposure influences DNAmAge and TL, suggesting that PAHs target both non-mitotic and mitotic mechanisms and made coke-oven workers biologically older. Also, differences in mtDNAcn, which is modified through nDNA alterations, triggered by environmental and occupational PAH exposure, suggested a nuclear-mitochondrial core-axis of aging. By decreasing this risky gerontogenic exposure, biological aging and the consequent age-related diseases could be prevented.

Supporting the Aspecific Physiological Defenses of Upper Airways against Emerging SARS-CoV-2 Variants.

The rapid rollout of COVID-19 vaccines in 2021 sparked general optimism toward controlling the severe form of the disease, preventing hospitalizations and COVID-19-associated mortality, and the transmissibility of SARS-CoV-2 infection [...].

Primary SARS-CoV-2 Infections, Re-infections and Vaccine Effectiveness during the Omicron Transmission Period in Healthcare Workers of Trieste and Gorizia (Northeast Italy), 1 December 2021-31 May 2022.

Objective: To evaluate the incidence of primary and recurrent COVID-19 infections in healthcare workers (HCWs) routinely screened for SARS-CoV-2 by nasopharyngeal swabs during the Omicron wave. Design: Dynamic Cohort study of HCWs (N = 7723) of the University Health Agency Giuliano Isontina (ASUGI), covering health services of the provinces of Trieste and Gorizia (Northeast Italy). Cox proportional hazard model was employed to estimate the risk of primary as well as recurrent SARS-CoV-2 infection from 1 December 2021 through 31 May 2022, adjusting for a number of confounding factors. Results: By 1 December 2021, 46.8% HCWs of ASUGI had received the booster, 37.2% were immunized only with two doses of COVID-19 vaccines, 6.0% only with one dose and 10.0% were unvaccinated. During 1 March 2020-31 May 2022, 3571 primary against 406 SARS-CoV-2 recurrent infections were counted among HCWs of ASUGI, 59.7% (=2130/3571) versus 95.1% (=386/406) of which occurring from 1 December 2021 through 31 May 2022, respectively. All HCWs infected by SARS-CoV-2 during 1 December 2021 through 31 May 2022 presented mild flu-like disease. Compared to staff working in administrative services, the risk of primary as well as recurrent SARS-CoV-2 infection increased in HCWs with patient-facing clinical tasks (especially nurses and other categories of HCWs) and in all clinical wards but COVID-19 units and community health services. Regardless of the number of swab tests performed during the study period, primary infections were less likely in HCWs immunized with one dose of COVID-19 vaccine. By contrast, the risk of SARS-CoV-2 re-infection was significantly lower in HCWs immunized with three doses (aHR = 0.58; 95%CI: 0.41; 0.80). During the study period, vaccine effectiveness (VE = 1-aHR) of the booster dose declined to 42% against re-infections, vanishing against primary SARS-CoV-2 infections. Conclusions: Though generally mild, SARS-CoV-2 infections and re-infections surged during the Omicron transmission period. Compared to unvaccinated colleagues, the risk of primary SARS-CoV-2 infection was significantly lower in HCWs immunized just with one dose of COVID-19 vaccines. By Italian law, HCWs immunized only with one dose were either suspended or re-assigned to job tasks not entailing patient facing contact; hence, while sharing the same biological risk of unvaccinated colleagues, they arguably had a higher level of protection against COVID-19 infection. By contrast, SARS-CoV-2 re-infections were less likely in HCWs vaccinated with three doses, suggesting that hybrid humoral immunity by vaccination combined with natural infection provided a higher level of protection than vaccination only. In this stage of the pandemic, where SARS-CoV-2 is more infectious yet much less pathogenic, health protection measures in healthcare premises at higher biological risk seem the rational approach to control the transmission of the virus.

Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial.

Background: COVID-19 is an asymptomatic condition in 40% of cases, and most symptomatic patients present with mild/moderate disease not requiring hospitalization or intensive care, especially during the Omicron wave, when the hospitalization rate was estimated to be 0.3%. The main port of entry for SARS-CoV-2 in the human body is the nasal cavity and the upper respiratory tract is affected since the early stages of the infection. Nasal irrigation or aerosol by isotonic or hypertonic saline solution is a traditional therapeutic approach for respiratory or nasal inflammation, also featured by prophylactic properties against upper respiratory infections. Methods: We conducted a prospective open-label controlled study to assess the superiority of an already existing medication (Tonimer Lab Panthexyl 800)-a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid-to reduce the viral shedding time in patients affected by asymptomatic or mild COVID-19. COVID-19 patients (N = 108) were split into two groups: a treatment arm (50 participants receiving standard of care plus nasal spray 3 times/day with Tonimer Lab Panthexyl 800) and a control arm (58 participants receiving standard of care but nasal spray with Tonimer Lab Panthexyl 800). The two groups, both testing initially positive for SARS-CoV-2 at real-time PCR (RT-PCR) on nasal swab, were followed up over time to assess the daily number of positive swab tests turning negative (study endpoint). Treatment effectiveness at various time lags since the first positive RT-PCR swab test was measured by rate of events in the experimental arm (EER) and in the control arm (CER), absolute risk increase (ARI) = (EER - CER), and number needed to treat (NNT) = (1/ARI). To investigate the endpoint, we used logistic and Cox regression models, expressing the result as odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (95%CI), respectively. The symptoms recorded with a modified COVID-Q questionnaire at both diagnosis and first negative antigenic swab test were compared in each group (treated versus controls) by exact symmetry test. Results: During the first five days of treatment, COVID-19 patients treated with Tonimer Lab Panthexyl 800 were more likely to become negative two days before controls. According to NNT, four subjects had to be treated for five days to achieve the study endpoint in one individual. The negativization rate in patients treated with Tonimer Lab Panthexyl 800 was significantly higher than patients' treated with standard of care alone (OR = 7.39, 95%CI: 1.83-29.8; HR = 6.12, 95%CI: 1.76-21.32). There was no evidence of side effects. Conclusions: Nasal spray with Tonimer Lab Panthexyl 800 was effective against SARS-CoV-2, stopping viral shedding in the treatment arm two days before the control group. This treatment should be continued for at least five days after the first positive swab test for SARS-CoV-2.

Occupational exposure to mercury from cinnabar enriched sand in workers of Grado Beach, Gulf of Trieste (North-eastern Italy, upper Adriatic Sea).

Health and safety of occupations entailing extensive skin contact with cinnabar-enriched sand in beaches of Friuli-Venezia Giulia (FVG) Region (North-eastern Italy) have been questioned for possible skin absorption of mercury (Hg). One hundred mg hair was collected from the occipital scalp of 50 male workers of Grado beach and 121 males from FVG general population. Factors associated with hair Hg content were investigated by multivariable logistic (considering Hg levels >1 vs ≤1 mg/kg) and log-transformed linear regression. The median hair concentration of Hg in male beach workers was 0.70 (IQR = 0.42; 1.34) mg/kg, lower than FVG general population's [1.29 (IQR = 0.87-2.06) mg/kg (p < 0.001)]. In both regression models the hair Hg increased with fish consumption, both among beach workers of Grado and FVG general population. The mean Hg levels in beach workers of Grado fell within an acceptable range, not requiring restrictions of their occupational activities.

A Prospective Study on Risk Factors for Acute Kidney Injury and All-Cause Mortality in Hospitalized COVID-19 Patients From Tehran (Iran).

Background: Several reports suggested that acute kidney injury (AKI) is a relatively common occurrence in hospitalized COVID-19 patients, but its prevalence is inconsistently reported across different populations. Moreover, it is unknown whether AKI results from a direct infection of the kidney by SARS-CoV-2 or it is a consequence of the physiologic disturbances and therapies used to treat COVID-19. We aimed to estimate the prevalence of AKI since it varies by geographical settings, time periods, and populations studied and to investigate whether clinical information and laboratory findings collected at hospital admission might influence AKI incidence (and mortality) in a particular point in time during hospitalization for COVID-19. Methods: Herein we conducted a prospective longitudinal study investigating the prevalence of AKI and associated factors in 997 COVID-19 patients admitted to the Baqiyatallah general hospital of Tehran (Iran), collecting both clinical information and several dates (of: birth; hospital admission; AKI onset; ICU admission; hospital discharge; death). In order to examine how the clinical factors influenced AKI incidence and all-cause mortality during hospitalization, survival analysis using the Cox proportional-hazard models was adopted. Two separate multiple Cox regression models were fitted for each outcome (AKI and death). Results: In this group of hospitalized COVID-19 patients, the prevalence of AKI was 28.5% and the mortality rate was 19.3%. AKI incidence was significantly enhanced by diabetes, hyperkalemia, higher levels of WBC count, and blood urea nitrogen (BUN). COVID-19 patients more likely to die over the course of their hospitalization were those presenting a joint association between ICU admission with either severe COVID-19 or even mild/moderate COVID-19, hypokalemia, and higher levels of BUN, WBC, and LDH measured at hospital admission. Diabetes and comorbidities did not increase the mortality risk among these hospitalized COVID-19 patients. Conclusions: Since the majority of patients developed AKI after ICU referral and 40% of them were admitted to ICU within 2 days since hospital admission, these patients may have been already in critical clinical conditions at admission, despite being affected by a mild/moderate form of COVID-19, suggesting the need of early monitoring of these patients for the onset of eventual systemic complications.

Mortality for Lung Cancer among PVC Baggers Employed in the Vinyl Chloride Industry.

Vinyl-chloride monomer (VCM) is classified as a known carcinogen of the liver; for lung cancer, some results suggest a potential association with polyvinyl chloride (PVC) dust. We evaluated the relationship between lung cancer mortality and exposure as PVC baggers in a cohort of workers involved in VCM production and polymerization in Porto Marghera (Venice, Italy) considering both employment status and smoking habits. The workers were studied between 1973 and 2017. A subset of them (848 over 1658) was interviewed in the 2000s to collect information about smoking habits and alcohol consumption. Missing values were imputed by the Multivariate Imputation by Chained Equations (MICE) algorithm. We calculated standardized mortality ratios (SMR) and 95% confidence intervals (95% CIs) using regional reference rates by task (never, ever, and exclusively baggers) and by smoking habits. Mortality rate ratios (MRR), adjusted for age, calendar time, time since first exposure, and smoking habits, were obtained via Poisson regression using Rubin's rule to combine results from imputed datasets calculating the fraction of information due to non-response. Lung cancer mortality was lower than the regional reference in the whole cohort (lung cancer SMR = 0.92; 95% CI 0.75-1.11). PVC baggers showed a 50% increase in lung cancer mortality compared to regional rates (SMR = 1.48; 95% CI 0.82-2.68). In the cohort analyses, a doubled risk of lung cancer mortality among PVC baggers was confirmed after adjustment for smoking and time-dependent covariates (MRR = 1.99, 95% CI 1.04-3.81). Exposure to PVC dust resulting from activity as bagger in a polymerization PVC plant was associated with an increase in lung cancer mortality risk after adjustment for smoking habits.

On Therapeutic Plasma Exchange Against Severe COVID-19-Associated Pneumonia: An Observational Clinical Study.

Background: There is a risk of novel mutations of SARS-CoV-2 that may render COVID-19 resistant to most of the therapies, including antiviral drugs and vaccines. The evidence around the application of therapeutic plasma exchange (TPE) for the management of critically ill patients with COVID-19 is still provisional, and further investigations are needed to confirm its eventual beneficial effects. Aims: To assess the effect of TPE on the risk of mortality in patients with COVID-19-associated pneumonia, using three statistical procedures to rule out any threats to validity. Methods: We therefore carried out a single-centered retrospective observational non-placebo-controlled trial enrolling 73 inpatients from Baqiyatallah Hospital in Tehran (Iran) with the diagnosis of COVID-19-associated pneumonia confirmed by real-time polymerase chain reaction (RT-qPCR) on nasopharyngeal swabs and high-resolution computerized tomography chest scan. These patients were broken down into two groups: Group 1 (30 patients) receiving standard care (corticosteroids, ceftriaxone, azithromycin, pantoprazole, hydroxychloroquine, lopinavir/ritonavir), and Group 2 (43 patients) receiving the above regimen plus TPE (replacing 2 l of patients' plasma by a solution, 50% of normal plasma, and 50% of albumin at 5%) administered according to various time schedules. The follow-up time was 30 days and all-cause mortality was the endpoint. Results: Deaths were 6 (14%) in Group 2 and 14 (47%) in Group 1. However, different harmful risk factors prevailed among patients not receiving TPE rather than being equally split between the intervention and control group. We used an algorithm of structural equation modeling (of STATA) to summarize a large pool of potential confounders into a single score (called with the descriptive name "severity"). Disease severity was lower (Wilkinson rank-sum test p < 0.001) among patients with COVID-19 undergoing TPE (median: -2.82; range: -5.18; 7.96) as compared to those not receiving TPE (median: -1.35; range: -3.89; 8.84), confirming that treatment assignment involved a selection bias of patients according to the severity of COVID-19 at hospital admission. The adjustment for confounding was carried out using severity as the covariate in Cox regression models. The univariate hazard ratio (HR) of 0.68 (95%CI: 0.26; 1.80; p = 0.441) for TPE turned to 1.19 (95%CI: 0.43; 3.29; p = 0.741) after adjusting for severity. Conclusions: In this study sample, the lower mortality observed among patients receiving TPE was due to a lower severity of COVID-19 rather than the TPE effects.

A Survey on Knowledge, Prevention, and Occurrence of Sexually Transmitted Infections among Freshmen from Four Italian Universities.

Background. The peak of sexually transmitted infections (STI) among adolescents/young adults suggests a low level of prevention. In order to assess whether the level of sexual health education (SHE), received by several channels, was effective at improving sexual behaviors, we conducted a survey among freshmen from four Italian universities. Methods. This observational cross-sectional study was carried out with an anonymous self-reported paper questionnaire, administered during teaching lectures to university freshmen of the northern (Padua, Bergamo, and Milan campuses) and southern (Palermo campus) parts of the country. Knowledge of STI (a linear numerical score), knowledge of STI prevention (dichotomous variable: yes vs. no) and previous STI occurrence (polytomous variable: "no"; "don't know"; "yes") were the outcomes in the statistical analysis. Results. The final number of freshmen surveyed was 4552 (97.9% response rate). The mean age of respondents was 21.4 ± 2.2 years and most of them (70.3%) were females. A total of 60% of students were in a stable romantic relationship. Only 28% respondents knew the most effective methods to prevent STI (i.e., condom and sexual abstinence), with a slightly higher prevalence of correct answers among females (31.3%) than males (25.8%). Students with history of STIs were 5.1%; they reported referring mostly to their general practitioner (GP) (38.1%) rather than discussing the problem with their partner (13.1%). At multivariable analysis, a significantly higher level of STI knowledge was observed in older students (25+ years of age), biomedical students, and those from a non-nuclear family; lower levels were found among students of the University of Palermo, and those who completed a vocational secondary school education. Those who had less knowledge about the most effective tools to prevent STIs included males, students from the University of Palermo, students registered with educational sciences, economics/political sciences, those of foreign nationality, and those whose fathers had lower educational levels. The risk of contracting a STI was significantly lower only in students not in a stable relationship (relative risk ratio, RRR = 0.67; 95% confidence interval, 95%CI = 0.48; 0.94), whereas such risk was significantly higher in students with higher STI knowledge (RRR = 1.15; 95%CI = 1.08; 1.22). Discussion and Conclusions. University freshmen investigated in this study had poor knowledge of STIs and their prevention. Unexpectedly, those with higher levels of knowledge had an increased risk of STIs. There have been no educational interventions-with good quality and long-term follow-ups-that increased the confidence that such SHE programs could have population level effects. A new high-quality study is therefore recommended to assess the effectiveness of an intervention generating behavioral changes; increasing only STI knowledge may not be sufficient.

The Impact of COVID-19 on Individuals with Hearing and Visual Disabilities during the First Pandemic Wave in Italy.

BACKGROUND: The COVID-19 pandemic has imposed radical behavioral and social changes in the general population, significantly impacting the lives of individuals affected by disabilities. The aim of this study was to investigate the impact of COVID-19 on non-institutionalized subjects with sensorineural disabilities during the first COVID-19 wave in Italy. METHODS: A 39-item online national survey was disseminated from 1 April 2020 to 31 June 2020 via social media throughout Italy to communities of individuals with proven severe sensorineural disabilities, affiliated to five national patient associations. The survey collected extensive information on the socio-demographic profile, health, everyday activities, and lifestyle of individuals with hearing and visual disabilities. RESULTS: One hundred and sixty-three respondents with hearing (66.9%) and visual (33.1%) disabilities returned a usable questionnaire. The mean age of interviewees was 38.4 ± 20.2 years and 56.3% of them were females. Despite the vast majority of respondents (77.9%) perceiving their health status as unchanged (68.8% of interviewees with hearing deficits vs. 96.3% of those with visual impairments), about half the interviewees reported sleep disorders during lock-down, more likely those with visual deficits. Remote services were seemingly more effective for business than school activities. Furthermore, although just 18.8% of respondents rated remote rehabilitation care unsatisfactory, only 12.8% of interviewees felt supported by health and social services during the COVID-19 emergency. The vast majority of respondents were concerned about the future and the risk of SARS-CoV-2 contagion, particularly individuals with hearing impairments. Among the various risk mitigation measures, facemasks caused the greatest discomfort due to communication barriers, particularly among interviewees affected by hearing disabilities (92.2% vs. 45.7%). The most common request (46.5%) of respondents to reduce the inconveniences of the COVID-19 emergency country lock-down was improving the access to and delivery of health and social services for individuals with sensorineural disabilities (19.3%), followed by the use of transparent masks (17.5%). CONCLUSIONS: Although health protection measures such as face masks and social distancing play a key role in preventing and controlling the spread of SARS-CoV-2, the unmet needs of disabled individuals should be carefully considered, especially those affected by sensory disabilities. Tailored access to health and social services for individuals affected by sensorineural disabilities should be implemented. Additional actions should include the use of to face masks to reduce communication barriers linked to hearing-impairment, as well as the improvement of remote services, especially distance learning at school.

Longer Leukocytes Telomere Length Predicts a Significant Survival Advantage in the Elderly TRELONG Cohort, with Short Physical Performance Battery Score and Years of Education as Main Determinants for Telomere Elongation.

Leukocyte telomere length (LTL) represents a key integrating component of the cumulative effects of environmental, lifestyle, and genetic factors. A question, however, remains on whether LTL can be considered predictive for a longer and healthier life. Within the elderly prospective TRELONG cohort (n = 612), we aimed to investigate LTL as a predictor of longevity and identify the main determinants of LTL among many different factors (physiological and lifestyle characteristics, physical performance and frailty measures, chronic diseases, biochemical measurements and apolipoprotein E genotyping). We found an ever-increasing relationship between LTL quartiles and survival. Hazard ratio analysis showed that for each unit increase in LTL and Short Physical Performance Battery (SPPB) scores, the mortality risk was reduced by 22.41% and 8.78%, respectively. Conversely, male gender, Charlson Comorbidity Index, and age threatened survival, with mortality risk growing by 74.99%, 16.57% and 8.5%, respectively. Determinants of LTL elongation were SPPB scores (OR = 1.1542; p = 0.0066) and years of education (OR = 1.0958; p = 0.0065), while male gender (OR = 0.4388; p = 0.0143) and increased Disease Count Index (OR = 0.6912; p = 0.0066) were determinants of LTL attrition. Longer LTL predicts a significant survival advantage in elderly people. By identifying determinants of LTL elongation, we provided additional knowledge that could offer a potential translation into prevention strategies.

Real Life Clinical Management and Survival in Advanced Cutaneous Melanoma: The Italian Clinical National Melanoma Registry Experience.

BACKGROUND: Cutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR). METHODS: Melanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. RESULTS: The median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62). CONCLUSIONS: The nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

Community Use of Face Masks against the Spread of COVID-19.

The role of face masks to prevent and control COVID-19 is critical, especially since asymptomatic or pre-symptomatic infected individuals can shed high loads of SARS-CoV-2 in the surrounding environment. In addition to being a two-way barrier to protect against virions droplets both in terms of "source control" (for the benefits of the community) and "physical protection" (for wearer), face masks also allow maintaining physiological temperatures and humidity of the nasal cavity and mouth, independently from the external environmental conditions. Beyond compromising the viral transmission speed, exposure to cold environments could have a detrimental effect on the host's susceptibility to SARS-CoV-2. The innate human immune system becomes in fact weaker with cooler nose temperatures and thus more vulnerable to viral replication. Furthermore, there is evidence that warm, humid climates are associated with reduced spread of SARS-CoV-2, while cold dry conditions favor its stability and transmissibility. In the early stage of a viral infection, a physiological body temperature in the upper airways supports the innate immune system, endorsing the muco-ciliary clearance, inhibiting, or deactivating any first settlement of viruses. Face masks are therefore strongly recommended also outdoors, especially under cold weather conditions, not only as a physical barrier against the transmission of SARS-CoV-2, but also to prevent the rapid cooling of the nasal mucosa and the inhibition of the human innate defense of the upper airways.

Hypothiocyanite and Hypothiocyanite/Lactoferrin Mixture Exhibit Virucidal Activity In Vitro against SARS-CoV-2.

SARS-CoV-2 replicates efficiently in the upper airways during the prodromal stage, resulting in environmental viral shedding from patients with active COVID-19 as well as from asymptomatic individuals. There is a need to find pharmacological interventions to mitigate the spread of COVID-19. Hypothiocyanite and lactoferrin are molecules of the innate immune system with a large spectrum cidal activity. The Food and Drug Administration and the European Medicines Agency designated the hypothiocyanite and lactoferrin combination as an orphan drug. We report an in vitro study showing that micromolar concentrations of hypothiocyanite exhibit dose- and time-dependent virucidal activity against SARS-CoV-2 and that the latter is slightly enhanced by the simultaneous presence of lactoferrin.

Attitudes and Perceptions of Health Protection Measures Against the Spread of COVID-19 in Italy and Poland.

Background: During the first wave of the COVID-19 pandemic (April to May 2020), 6,169 Polish and 939 Italian residents were surveyed with an online questionnaire investigating socio-demographic information and personality traits (first section) as well as attitudes, position, and efficacy perceptions on the impact of lockdown (second section) and various health protection measures enforced (third section). Methods: The "health protection attitude score" (HPAS), an endpoint obtained by pooling up the answers to questions of the third section of the survey tool, was investigated by multiple linear regression models, reporting regression coefficients (RC) with 95% confidence intervals (95% CI). Results: Concerns for business and health due to COVID-19 were associated with a positive attitude toward risk reduction rules. By contrast, male sex, concerns about the reliability of information available online on COVID-19 and its prevention, along with the feeling of not being enough informed on the transmissibility/prevention of SARS-CoV-2 were associated with a negative attitude toward risk mitigation measures. Discussion: A recent literature review identified two social patterns with different features in relation to their attitude toward health protection rules against the spread of COVID-19. Factors positively associated with adherence to public health guidelines were perceived threat of COVID-19, trust in government, female sex, and increasing age. Factors associated with decreased compliance were instead underestimation of the COVID-19 risk, limited knowledge of the pandemic, belief in conspiracy theories, and political conservativism. Very few studies have tested interventions to change attitudes or behaviors. Conclusion: To improve attitude and compliance toward risk reduction norms, a key intervention is fostering education and knowledge on COVID-19 health risk and prevention among the general population. However, information on COVID-19 epidemiology might be user-generated and contaminated by social media, which contributed to creating an infodemic around the disease. To prevent the negative impact of social media and to increase adherence to health protection, stronger content control by providers of social platforms is recommended.

The effects of everyday-life exposure to polycyclic aromatic hydrocarbons on biological age indicators.

BACKGROUND: Further knowledge on modifiable aging risk factors is required to mitigate the increasing burden of age-related diseases in a rapidly growing global demographic of elderly individuals. We explored the effect of everyday exposure to polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution, on cellular biological aging. This was determined via the analysis of leukocyte telomere length (LTL), mitochondrial DNA copy number (LmtDNAcn), and by the formation of anti-benzo[a]pyrene diolepoxide (B[a]PDE-DNA) adducts. METHODS: The study population consisted of 585 individuals living in North-East Italy. PAH exposure (diet, indoor activities, outdoor activities, traffic, and residential exposure) and smoking behavior were assessed by questionnaire and anti-B[a]PDE-DNA by high-performance-liquid-chromatography. LTL, LmtDNAcn and genetic polymorphisms [glutathione S-transferase M1 and T1 (GSTM1; GSTT1)] were measured by polymerase chain reaction. Structural equation modelling analysis evaluated these complex relationships. RESULTS: Anti-B[a]PDE-DNA enhanced with PAH exposure (p = 0.005) and active smoking (p = 0.0001), whereas decreased with detoxifying GSTM1 (p = 0.021) and in females (p = 0.0001). Subsequently, LTL and LmtDNAcn reduced with anti-B[a]PDE-DNA (p = 0.028 and p = 0.018), particularly in males (p = 0.006 and p = 0.0001). Only LTL shortened with age (p = 0.001) while elongated with active smoking (p = 0.0001). Besides this, the most significant determinants of PAH exposure that raised anti-B[a]PDE-DNA were indoor and diet (p = 0.0001), the least was outdoor (p = 0.003). CONCLUSION: New findings stemming from our study suggest that certain preventable everyday life exposures to PAHs reduce LTL and LmtDNAcn. In particular, the clear association with indoor activities, diet, and gender opens new perspectives for tailored preventive measures in age-related diseases. CAPSULE: Everyday life exposure to polycyclic aromatic hydrocarbons reduces leukocyte telomere length and mitochondrial DNA copy number through anti-B[a]PDE-DNA adduct formation.

The Italian National Surveillance System for Occupational Injuries: Conceptual Framework and Fatal Outcomes, 2002-2016.

Background: A national database of work-related injuries has been established in Italy since 2002, collecting information on the injured person, his/her work tasks, the workplace and the risk factors contributing to incident dynamics, according to a model called Infor.Mo. Methods: A descriptive study of occupational fatal injuries, excluding work-related fatal traffic injuries, that occurred in Italy from 2002 to 2016 (15 years) was performed. Results: Among 4874 victims involved, all were males, mainly >51 years of age (43.2%), predominantly self-employed (27.8%) or workers with non-standard contracts (25%). About 18.4% and 17.3% of fatal events occurred in micro-enterprises belonging to, respectively, construction and agriculture. A wide range of nationalities (59 countries in addition to Italy) was identified. Overall, 18.9% of work-related fatal injuries were due to some form of hazardous energy-mechanical, thermal, electrical or chemical-that was normally present in the workplace. Workers' falls from height (33.5%), heavy loads falling on workers from height (16.7%) and vehicles exiting their route and overturning (15.9%) were the events causing the greatest proportion of occupational fatal injuries in the present study (from 2002 to 2016) and in the initial pilot phase, focused on years 2002-2004, with a similar distribution of fatal events between the two time periods. The activity of the injured person made up 43.3% of 9386 risk factors identified in 4874 fatalities. Less common risk factors were related to work equipment (20.2%), work environment (14.9%), third-party activity (9.8%), personal protective equipment/clothing (8.0%) and materials (3.7%). The activity of the injured person remained the most relevant contributing factor even when the incident was caused by two or more risk factors. Discussion: Occupational fatal injuries occurred mainly in small size firms (up to nine employees) in hazardous workplaces. Small companies, which account for 68% (2888/4249) of all firms in the present study, generally have fewer resources to remain current with the continuously evolving health and safety at work regulations; moreover, these firms tend to be less compliant with health and safety at work regulations since they are less likely to be inspected by occupational vigilance services. Perspectives: An approach being introduced in Italy relies on the use of economic incentives to promote safe and healthy workplaces. The comparison of pre-intervention and post-intervention rates of work-related injuries by means of interrupted time series analyses could detect whether the intervention will have an effect significantly greater than the underlying secular trend.