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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.

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.

Births by cesarean section (CS) usually require longer recovery time, and as a result women remain hospitalized longer following CS than vaginal delivery (VD). A number of strategies have been proposed to reduce avoidable health care costs associated with childbirth. Among these, the containment of length of hospital stay (LoS) has been identified as an important quality indicator of obstetric care and performance efficiency of maternity centres. Since improvement of obstetric care at hospital level needs quantitative evidence, we compared the maternity services of an Italian region on LoS post CS. We conducted a population-based study in Friuli Venezia Giulia (FVG), a region of North-Eastern Italy, collecting data from all its 12 maternity centres (coded from A to K) during 2005-2015. We fitted a multivariable logistic regression using LoS as a binary outcome, higher/lower than the international early discharge (ED) cutoffs for CS (4 days), controlling for hospitals as well as several factors related to the clinical conditions of the mothers and the newborn, the obstetric history and socio-demographic background. Results were expressed as adjusted odds ratios (aOR) with 95% confidence interval (95%CI). Population attributable risks (PARs) were also calculated as proportional variation of LoS>ED for each hospital in the ideal scenario of having the same performance as centre J (the reference) during calendar year 2015. Results were expressed as PAR with 95%CI. Differences in mean LoS were also investigated with a multivariable linear regression model including the same explanatory factors of the above multiple logistic regression. Results were expressed as adjusted regression coefficients (aRC) with 95%CI. Although decreasing over the years (5.0 ± 1.7 days in 2005 vs. 4.4 ± 1.7 days in 2015), the pooled mean LoS in the whole FVG during these 11 years was still 4.7 ± 1.7 days, higher than respective international ED benchmark. The significant decreasing trend of LoS>ED over time in FVG (aOR = 0.89; 95%CI: 0.88; 0.90) was marginal as compared to the variability of LoS>ED observed among the various maternity services. Regardless it was expressed as aRC or aOR, LoS after CS was lowest in hospital C, highest in hospital D and intermediate in centres I, K, G, F, A, H, E, B and J (in descending order). The aOR of LoS being longer than ED ranged from 1.63 (95%CI:1.46; 1.81) in hospital B up to 32.09 (95%CI: 25.68; 40.10) in facility D. When hospitals were ranked by PAR the same pattern was found, even if restricting the analysis to low risk pregnancies. Although significantly decreasing over time, the mean LoS in FVG during 2005-2015 was 4.7 days, higher than the international threshold recommended for CS. There was substantial variability in LoS by facility centre, suggesting that internal organizational processes of single hospitals should be improved by enforcing standardized guidelines and using audits, economic incentives and penalties if need be.

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.

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.

Lengths of hospital stay (LoS) after childbirth that are too long have a number of health, social and economic drawbacks. For this reason, in several high-income countries LoS has been reduced over the past decades and early discharge (ED) is increasingly applied to low-risk mothers and newborns. We conducted a population-based study investigating LoS after chilbirth across all 12 maternity centres of Friuli Venezia-Giulia (FVG), North-Eastern Italy, using a database capturing all registered births in the region from 2005 to 2015 (11 years). Adjusting for clinical factors (clinical conditions of the mother and the newborn), socio-demographic bakground and obstetric history with multivariable logistic regression, we ranked facility centres for LoS that were longer than our proposed ED benchmarks (defined as >2 days for spontaneous vaginal deliveries and >3 days for instrumental vaginal deliveries). The reference was hospital A, a national excellence centre for maternal and child health. The total number of births examined in our database was 109,550, of which 109,257 occurred in hospitals. During these 11 years, the number of births significantly diminished over time, and the pooled mean LoS for spontaneous vaginal deliveries in the whole FVG was 2.9 days. There was a significantly decreasing trend in the proportion of women remaining admitted more than the respective ED cutoffs for both delivery modes. The percentage of women staying longer that the ED benchmarks varied extensively by facility centre, ranging from 32% to 97% for spontaneous vaginal deliveries and 15% to 64% for instrumental vaginal deliveries. All hospitals but G were by far more likely to surpass the ED cutoff for spontaneous deliveries. As compared with hospital A, the most significant adjusted ORs for LoS overcoming the ED thresholds for spontaneous vaginal deliveries were: 89.38 (78.49-101.78); 26.47 (22.35-31.36); 10.42 (9.49-11.44); 10.30 (9.45-11.21) and 8.40 (7.68-9.19) for centres B, D, I, K and E respectively. By contrast the OR was 0.77 (95%CI: 0.72-0.83) for centre G. Similar mitigated patterns were observed also for instrumental vaginal deliveiries. For spontaneous vaginal deliveries the mean LoS in the whole FVG was shorter than 3.4 days, the average figure most recently reported for the whole of Italy, but higher than other countries' with health systems similar to Italy's. Since our results are controlled for the effect of all other factors, the between-hospital variability we found is likely attributable to the health care provider itself. It can be argued that some maternity centres of FVG may have had ecocomic interest in longer LoS after childbirth, although fear of medico-legal backlashes, internal organizational malfunctions of hospitals and scarce attention of ward staff on performance efficiency shall not be ruled out. It would be therefore important to ensure higher level of coordination between the various maternity services of FVG, which should follow standardized protocols to pursue efficiency of care and allow comparability of health outcomes and costs among them. Improving the performance of FVG and Italian hospitals requires investment in primary care services.

Of patients with COVID-19, 14%–15% develop severe pneumonia and 5%–6% a critical condition requiring admission to intensive care unit (ICU).2–4 Death may eventually occur after an average of 17.8 days since the onset of symptoms.5 Among all countries, Italy (which was the first European COVID-19 cluster) presents a critical disease pattern as of 8 May 2020, having the third highest number of COVID-19 cases in the world after the USA and Spain, the fourth highest prevalence of the disease after Spain, Belgium and the USA, the third highest total number of deaths attributed to COVID-19 after the USA and the UK, and the third highest prevalence of COVID-19 mortality after Belgium and Spain, despite a current 1% rate of severe/critical disease among active cases, which has been progressively decreasing over time.1 The cross-country discrepancies in the burden of COVID-19 observed so far across the globe cannot be explained only by differences in population age structures.6–8 In fact, Japan has a population double that of Italy, with the proportion of subjects older than 65 being 28.8% in Japan vs 21.7% in Italy.9 10 Nonetheless, as of 8 May 2020, the difference in COVID-19 prevalence between Japan (122 per million) and Italy (3570 per million) is massive.1 Likewise, in Germany the percentage of individuals >65 is reportedly 22.1% (hence slightly higher than Italy), but the prevalence of COVID-19 is currently 2022 per million.1 11 In Iran the proportion of people >65 is 5.5% (hence much younger than the Italian, German and Japanese populations), but the prevalence of COVID-19 is 1246 per million, as of 8 May 2020.1 12 The mortality rate for COVID-19 is reportedly enhanced by 5.6%–10.5% in the presence of any comorbidities (hypertension, diabetes, cardiovascular diseases, cancer and/or chronic respiratory conditions) and becomes significantly and progressively higher after 50 years of age,4 6 although the severe form of the disease increases linearly at any age stage.5 Cold dry weather is a recognised risk factor for respiratory infections, rendering viruses as influenza more stable and individuals more susceptible.13 14 This applies also to SARS-CoV-2, the viability and transmissibility of which reportedly reduce with hot and humid weather conditions.14 Moreover, unfavourable disease progression and clinical outcomes of COVID-19 were found to be associated with cigarette smoking in a systematic review.15 A number of factors may have contributed to enhancing the risk of infection with SARS-CoV-2 in Northern Italy. The universal use of face masks was initially discouraged in Italy in order to preserve the limited supplies of personal protective equipment for professional use in healthcare settings; another argument initially was that face masks are ineffective in protecting against coronavirus infections.17 Further major findings of the relevant literature have been summarised in figure 1. The affected areas in Northern Italy (regions of Lombardy, Emilia-Romagna, Piedmont and Veneto) are characterised by high population density18 and recognised air pollution,19 20 especially from fine particulate matter (PM2.5), which was found to increase the risk of death from COVID-19 in the USA.21 Northern Italy includes several cities which, similarly to Philadelphia (USA) during the Spanish flu pandemic in 1918,22 are historically important and densely populated, where social gatherings as well as business activities are certainly fundamental—the latter being vital to the economy of the entire country. [...]the intense case finding in Italy was preceded by an initial overall underestimation of the COVID-19 threat by the Italian government and subsequently by the general population, who perceived the disease as just some sort of influenza, despite worrying news from the first affected country (China).23 Thereafter SARS-CoV-2 was also going to spread to other European countries, which have also now been heavily affected by the disease.1 Figure 1.

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.

Aging is an emerging worldwide threat to public health, even in the workplace, as it links with risk of illness and death. Bewildered inflammatory responses and stressful conditions associate with age-related disorders. Additionally, circadian rhythm disruption, a critical health issue in night-shift workers, correlates with premature aging. We investigated the hypothesis of a link between altered inflammatory response, detected by plasmatic long pentraxin 3 (PTX3), and biological aging, measured by leukocyte telomere length (LTL), attrition, and possibly induced by night-shift work. Within the framework of a cross-sectional study, such possible relationships were appraised by simultaneous equation model (SEM) technique among day and night-shift hospital workers. PTX3 levels, modulated by several aging conditions [i.e., body mass index (BMI) (beta = -0.22;  = 0.022), C-reactive protein (CRP) (beta = -0.07;  = 0.000), and cardiovascular diseases with hypertension included (CVD) (beta = -0.12;  = 0.000)], positively associate with LTL (coefficient = 0.15;  = 0.033). LTL, in turn is reduced by CVD (beta = -0.15;  = 0.000), binge drinking (beta = -0.10;  = 0.004), and CRP (beta = -0.05;  = 0.026). On the other hand, night-shift work, found to be remarkably free from aging risk factors [i.e., age (beta = -0.13;  = 0.017), BMI (beta = -0.17;  = 0.030), CVD (beta = -0.14;  = 0.000), and binge drinking (beta = -0.13;  = 0.000)], does associate almost significantly with reversed PTX3 (coefficient = -0.09;  = 0.089) and even with CRP (beta = 0.17;  = 0.000). In conclusion, the SEM analysis indicates that PTX3 is positively linked to LTL. The finding suggests a possible new role of this long pentraxin that, by orchestrating an efficient governance of inflammatory processes, may protect telomere from attrition, ensuring therefore the genetic stability of cells. The higher CRP levels among night-shift workers suggest that night-shift work is associated with increased systemic inflammation. This would make nocturnal workers more susceptible to premature aging.

Background Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Discussion Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env -gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder and breast cancer. An amino acid sequence similar to HERV-K-MEL, recognized to cause a significant protective effect against melanoma, is shared by the antigenic determinants expressed by some vaccines such as BCG, vaccinia virus and the yellow fever virus. HERV-K are also reactivated in the majority of human breast cancers. Monoclonal and single-chain antibodies against the HERV-K Env protein recently proved capable of blocking the proliferation of human breast cancer cells in vitro, inhibiting tumor growth in mice bearing xenograft tumors. Summary A recent epidemiological study provided provisional evidence of how melanoma risk could possibly be reduced if the yellow fever virus vaccine (YFV) were received at least 10 years before, possibly preventing tumor initiation rather than culling melanoma cells already compromised. Further research is recommended to confirm the temporal pattern of this protection and eliminate/attenuate the potential role of relevant confounders as socio-economic status and other vaccinations. It appears also appropriate to examine the potential protective effect of YFV against other malignancies expressing high levels of HERV-K antigens, namely breast cancer, sarcoma, lymphoma and bladder cancer. Tumor immune-therapy, as described for the monoclonal antibodies against breast cancer, is indeed considered more complex and less advantageous than immune-prevention. Cellular immunity possibly triggered by vaccines as for YFV might also be involved in anti-cancer response, in addition to humoral immunity.