Search

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers-DNA methylation age (DNAmAge) and telomere length (TL)-in blood leukocytes, nasal cells (NCs), and induced sputum (IS) one year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data from questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male sex, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV ( p < 0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL ( p < 0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes ( p ≤ 0.05) and NCs ( p < 0.001) and were biologically older than COPD patients ( p < 0.05). These findings suggest the need to monitor aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

Healthcare workers (HCWs) represent a population with a significant burden of paucisymptomatic COVID-19, as the general population. We evaluated autonomic nervous system activity by means of heart rate variability (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings were obtained 30 days (IQR 5.25-55.75) after a negative naso-pharyngeal swab for SARS-CoV-2 in 44 cases and compared with ECGs of 44 controls with similar age and sex distribution. Time and frequency domain HRV were evaluated. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded. Frequency domain HRV analysis showed a significantly higher low/high-frequency power ratio (LF/HF) in the case study compared with controls (t = 2.84, p = 0.006). In time domain HRV analysis, mean standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were significantly lower for cases compared with controls (t = -2.64, p = 0.01 and t = -3.27, p = 0.002, respectively). In the post-acute phase of infection, SARS-CoV-2 produces an autonomic imbalance mirrored by a reduction in HRV. These results are consistent with epidemiological data that suggest a higher risk of acute cardiovascular complications in the first 30 days after COVID-19 infection.

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.

Coke production was classified as carcinogenic to humans by the International Agency for Research on Cancer. Besides polycyclic aromatic hydrocarbons, coke oven workers may be exposed to benzene and other volatile organic compounds (VOCs). The aim of this study was to assess the exposure to several VOCs in 49 coke oven workers and 49 individuals living in the same area by determining urinary mercapturic acids. Active tobacco smoking was an exclusion criterion for both groups. Mercapturic acids were investigated by a validated isotopic dilution LC-MS/MS method. Linear models were built to correct for different confounding variables. Urinary levels of N-acetyl-S-phenyl-L-cysteine (SPMA) (metabolite of benzene), N-acetyl-S-(2-hydroxy-1/2-phenylethyl)-L-cysteine (PHEMA) (metabolite of styrene), N-acetyl-S-(2-cyanoethyl)-L-cysteine (CEMA) (metabolite of acrylonitrile), N-acetyl-S-[1-(hydroxymethyl)-2-propen-1-yl)-L-cysteine and N-acetyl-S-(2-hydroxy-3-buten-1-yl)-L-cysteine (MHBMA) (metabolites of 1,3-butadiene) were 2-10 fold higher in workers than in controls ( p < 0.05). For SPMA, in particular, median levels were 0.02 and 0.31 µg/g creatinine in workers and controls, respectively. Among workers, coke makers were more exposed to PHEMA and SPMA than foremen and engine operators. The comparison with biological limit values shows that the exposure of workers was within 20% of the limit values for all biomarkers, moreover three subjects exceeded the restrictive occupational limit value recently proposed by the European Chemicals Agency (ECHA) for SPMA.

DNA methylation (DNAm) is an emerging estimator of biological aging, i.e., the often-defined "epigenetic clock", with a unique accuracy for chronological age estimation (DNAmAge). In this pilot longitudinal study, we examine the hypothesis that intensive relaxing training of 60 days in patients after myocardial infarction and in healthy subjects may influence leucocyte DNAmAge by turning back the epigenetic clock. Moreover, we compare DNAmAge with another mechanism of biological age, leucocyte telomere length (LTL) and telomerase. DNAmAge is reduced after training in healthy subjects ( p = 0.053), but not in patients. LTL is preserved after intervention in healthy subjects, while it continues to decrease in patients ( p = 0.051). The conventional negative correlation between LTL and chronological age becomes positive after training in both patients ( p < 0.01) and healthy subjects ( p < 0.05). In our subjects, DNAmAge is not associated with LTL. Our findings would suggest that intensive relaxing practices influence different aging molecular mechanisms, i.e., DNAmAge and LTL, with a rejuvenating effect. Our study reveals that DNAmAge may represent an accurate tool to measure the effectiveness of lifestyle-based interventions in the prevention of age-related diseases., Competing Interests: The authors declare no conflict of interest.

Introduction: Additional or better markers are needed to guide the clinical monitoring of patients with non-muscle-invasive bladder cancer (NMIBC). Aim: To investigate the influence of occupational exposures and genetic polymorphisms on recurrence and progression of NMIBC. Methods: The study includes 160 NMIBC patients. We collected on questionnaire information on demographic variables, lifetime smoking history, lifetime history of occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons. Genetic polymorphism (glutathione S-transferase M1; T1; P1 (GSTM1; GSTT1; GSTP1); N-acetyltransferase 1; 2 (NAT1; NAT2); cytochrome P450 1B1 (CYP1B1); sulfotransferase 1A1 (SULT1A1); myeloperoxidase (MPO); catechol-O-methyltransferase (COMT); manganese superoxide dismutase (MnSOD); NAD(P)H:quinone oxidoreductase (NQO1); X-ray repair cross-complementing group 1; 3 (XRCC1; XRCC3) and xeroderma pigmentosum complementation group (XPD)) was assessed in peripheral blood lymphocytes. DNA adducts were evaluated by 32P-postlabeling. Predictors of recurrence (histological confirmation of a newly found bladder tumor) and progression (transition of tumor from low-grade to high-grade and/or increase in TNM stage) were identified by multivariate Cox proportional hazard regression with stepwise backward selection of independent variables. Hazard ratios (HR) with 95% confidence interval (95%CI) and two-tail probability of error ( p -value) were estimated. Results: The risk of BC progression decreased with the homozygous genotype "ValVal" of both COMT and MnSOD (HR = 0.195; 95%CI = 0.060 to 0.623; p = 0.006). The results on BC recurrence were of borderline significance. No occupational exposure influenced recurrence or progression. Conclusion: Our results are supported by experimental evidence of a plausible mechanism between cause (ValVal genotype of both MnSOD and COMT) and effect (decreased progression of tumor in NMIBC patients). The genetic polymorphisms associated with better prognosis may be used in clinic to guide selection of treatment for patients initially diagnosed with NMIBC. However, external validation studies are required.

Background : Telomere length (TL) maintenance plays an important role in bladder cancer (BC) and prognosis. However the manifold influence of everyday life exposures and genetic traits on leucocyte TL (LTL), is not fully elucidated. Methods : Within the framework of a hospital-based case ( n = 96)/control ( n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Data on lifetime smoking, alcohol and coffee drinking, dietary habits and occupational exposures, pointing to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) were collected. Structural equation modelling (SEM) analysis appraised this complex relationships. Results : The SEM analysis indicates negative direct links ( p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk ( p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. There was evidence of indirect effects ( p < 0.05) on BC risk, probably via LTL reduction, by age and NAT2 (positive link), MPO and XRCC3 (negative link)., Conclusions: Our study supports evidence that LTL attrition is a critical event in BC. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention., Competing Interests: The authors declare no conflict of interest.