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Background: Work-related fatalities represent an important global public health threat, accounting for over 300,000 deaths annually. Despite preventive strategies, fatalities persist, necessitating comprehensive investigations. Autoptic investigations, when ordered, offer comprehensive data on fatal accidents, in particular with detailed information about the type of accident, lesions, and type of work, enabling a thorough analysis of various factors contributing to workplace deaths. This study investigates work-related fatalities in Milan and Monza Brianza, Lombardy, analyzing patterns, industries, and factors leading to death among workers., Methods: This retrospective study analyzed all fatal work accident data from the Autopsy Database of the Legal Medicine Institute of Milan from January 2000 to December 2022. We also estimated the risk of fatal accidents per 1.00.000 workers using ISTAT data for the different work sectors., Results: Of the 17,841 violent deaths in Milan and Monza Brianza, 308 resulted from work-related accidents. The majority were male (95.1%). The secondary sector showed the higher estimated risk (27 /106 vs. 19/106 in primary and 2.3/106 in tertiary sector) accounted for 78.5% of fatalities, with specialized workers (35.1%) and construction workers (25%) being the most affected. Falls from above were the leading cause of death (36.7%). A decreasing trend in fatal accidents over the study period was observed, with July having the greatest frequency. The most common causes of death were polytrauma (36.4%) and head injuries (19.2%). Non-Italian workers constitute a noteworthy percentage of fatal cases (24%)., Conclusions: The secondary sector has the most fatal accidents at work despite a decrease in accidents over the observed time period. There is a need for rigorous analysis and interventions, using forensic autopsy case data to help understand causes, and collaboration between institutions is encouraged to develop effective preventive policies.

The article discusses a recent study on mortality attributable to COVID-19 in Italy and the need for further analysis. The study used a reliable methodology to estimate excess deaths due to the pandemic. However, there are still questions about the specific effects of COVID-19 compared to other factors, such as delayed or missing access to treatment for other illnesses. Analyzing the time course of excess deaths could reveal such effects. There are also open questions about how COVID-19 deaths are classified and reported, which could lead to over or under-diagnosing cases. The article notes that occupational physicians have played an important role in preventing the spread of COVID-19 among workers. A recent study found that personal protective equipment (PPE), particularly masks, effectively reduced the risk of infection among healthcare workers. However, it is still unclear whether Occupational Medicine should incorporate infectious diseases as a major concern or return to its historically agnostic attitude toward communicable diseases. More data on mortality from specific diseases will be needed for further analysis and understanding of the pandemic's effects on mortality rates in Italy.

Background and Purpose: Cerebral vein thrombosis (CVT) incidence is estimated to be >10 per 1 000 000 per year. Few population-based studies investigating case-fatality rates (CFRs) and pyogenic/nonpyogenic CVT incidence are available. We assessed trends in CVT incidence between 2002 and 2012, as well as adjusted in-hospital CFRs and incidence of hospital admissions for pyogenic/nonpyogenic CVT in a large Northwestern Italian epidemiological study., Methods: Primary and secondary discharge diagnoses of pyogenic/nonpyogenic CVT were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes 325, 671.5, and 437.6. Age, sex, vital status at discharge, length of hospital stay, and up to 5 secondary discharge diagnoses were collected. Concomitant presence of intracerebral hemorrhage (ICH) was registered, and comorbidities were assessed through the Charlson comorbidity index., Results: A total of 1718 patients were hospitalized for CVT (1147 females—66.8%; 810 pyogenic and 908 nonpyogenic CVT, 47.1% and 52.9%, respectively), with 134 patients (7.8%) experiencing a concomitant ICH. The overall incidence rate for CVT was 11.6 per 1 000 000 inhabitants with a sex-specific rate of 15.1 and 7.8 per 1 000 000 in females and males, respectively. CVT incidence significantly increased in women during time of observation (P=0.007), with the highest incidence being at 40 to 44 years (27.0 cases per 1 000 000). In-hospital CFR was 3%, with no difference between pyogenic/nonpyogenic CVT. Patients with concomitant ICH had a higher in-hospital CFR compared with patients without ICH (7.5% versus 2.7%; odds ratio, 2.96 [95% CI, 1.45–6.04]). In-hospital CFR progressively increased with increasing Charlson comorbidity index (P=0.003). Age (odds ratio, 1.03 [95% CI, 1.02–1.05]), Charlson comorbidity index ≥4 (odds ratio, 4.33 [95% CI, 1.29–14.52]), and ICH (odds ratio, 3.05 [95% CI, 1.40–6.62]) were independent predictors of in-hospital mortality., Conclusions: In a large epidemiological study, CVT incidence was found to be comparable to the one registered in population-based studies reported after the year 2000. CVT incidence increased among women over time. In-hospital CFR was low, but not negligible, in patients with concomitant ICH. Age, ICH, and a high number of comorbidities were independent predictors of in-hospital mortality. Pyogenic CVT was not a predictor of in-hospital CFR, although its high proportion was not confirmed by internal validation.

Aims: Air pollution and climate change are intrinsically linked to emerging hazards for global health. High air particulate matter (PM) levels may trigger out-of-hospital cardiac arrest (OHCA). High temperature could act synergistically with PM in determining OHCA. The aim of the present study was to investigate the effect of PM exposure alone, and in combination with temperature, on the risk of OHCA, in a large European metropolitan area with population >4 million., Methods: We evaluated the association between short-term PM exposure, temperature, and the risk of OHCA over a two-year study period, allowing us to investigate 5761 events using a time-stratified case-crossover design combined with a distributed lag non-linear model., Results: Higher risk of OHCA was associated with short-term exposure to PM 10 . The strongest association was experienced three days before the cardiac event where the estimated change in risk was 1.70% (0.48-2.93%) per 10 µg/m 3 of PM. The cumulative exposure risk over the lags 0-6 was 8.5% (0.0-17.9%). We observed a joint effect of PM and temperature in triggering cardiac arrests, with a maximum effect of 14.9% (10.0-20.0%) increase, for high levels of PM before the cardiac event, in the presence of high temperature., Conclusion: The present study helps to clarify the controversial role of PM as OHCA determinant. It also highlights the role of increased temperature as a key factor in triggering cardiac events. This evidence suggests that tackling both air pollution and climate change might have a relevant impact in terms of public health.

Background: Oil refinery workers are exposed to several well-established carcinogens and working in this type of industry has been classified by IARC as probable carcinogen to humans (Group 2A)., Objectives: To examine the mortality experience of workers employed in four Italian oil refineries., Methods: The cohort included 5112 male workers ever employed between 1949 and 2011. The average follow-up period was 49 years. Standardized mortality ratios (SMR) and 95% Confidence Intervals (CI) were calculated using as reference age-gender-calendar specific regional rates. Analyses by duration of employment and latency were performed., Results: In the whole cohort, pleural cancer (6 deaths, SMR 1.59; 95% CI 0.71-3.53), brain cancer (14 deaths, SMR 1.47; 95% CI 0.87-2.49) and lymphatic leukemia (LL) (8 deaths, SMR 1.81; 95% CI 0.91-3.62) showed increased risks. All pleural cancers occurred after 10 years of latency and the highest risk was observed among workers with duration ≥20 years; the brain cancer excess was confined in the shortest duration and latency. The LL (and chronic lymphatic leukemia in particular) excess regarded workers with latency and duration longer than 20 years. Four deaths from acute myeloid leukemia (AML) were observed and all occurred after 20 years of latency (SMR 1.55, 95% CI 0.58-4.12); a two-fold-increased risk was observed in the longest duration. No increased risk for skin cancer has been observed in our study population., Conclusion: Our findings are consistent with recent evidence of an increased mortality from pleural and hematopoietic malignancies (AML and LL) among oil refinery workers. However, the lack of individual quantitative exposure data and the small number of observed events prevent the identification of the possible causal role of individual chemicals, including benzene, especially at the current very low exposure levels.

Respiratory syncytial virus (RSV) is the primary cause of acute lower respiratory infections in children, bronchiolitis in particular. Airborne particulate matter (PM) may influence the children's immune system and foster the spread of RSV infection. We aimed to verify whether PM10 exposure is associated with hospitalization due to RSV bronchiolitis. We selected hospital discharge records (HRD) with ICD-9-CM code 466.11 of infants < 1 year of age, occurring in the epidemic seasons of two years (2012-2013) in Lombardy, Italy. Cases were assigned daily PM10 and apparent temperature levels of the capital city of their residential province. Different exposure windows were considered: single days preceding hospitalization (lag 0 to 30), their average estimates (lag 0-1 to 0-30), and the four weeks preceding hospitalization (week 1 to 4). Negative binomial regression models adjusted for apparent temperature and season were applied to the daily counts of hospitalizations in each province. Results were expressed as incidence rate ratios (IRR) and 95% confidence intervals (95%CI) per 10 µg/m 3 increase in PM10 concentration. Random effects meta-analyses of province-specific IRR were performed to obtain regional estimates. 2814 HRD met our inclusion criteria; males represented about 55% of the cases. A 6% increased risk of hospitalization (95%CI: 1.03-1.10) was found at lag 0 and an almost overlapping 7% increase at lag 1. IRR ranged from 1.03 to 1.05 between lags 2 and 11. No increased risk was observed from lag 12. When considering averaged daily lags, risk estimates gradually increased in the two weeks preceding hospitalization from 1.08 (1.04-1.12) at lag 0-1 to 1.15 (1.08-1.23) between lags 0-11 and 0-13. Analyses on weekly lags showed a risk increase of 6% (1.01-1.12) during week 1 and of 7% (1.02-1.13) during week 2. Our study found a clear association between short- and medium-term PM10 exposures and increased risk of hospitalization due to RSV bronchiolitis among infants., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Longitudinal studies have linked stress at work with a higher incidence of musculoskeletal pain. We aimed to explore the extent to which musculoskeletal pain is a cause as opposed to a consequence of perceived occupational stress., Methods: As part of the international cultural and psychosocial influences on disability study, we collected information from 305 Italian nurses, at baseline and again after 12 months, about pain during the past month in the low-back and neck/shoulder, and about effort-reward imbalance (ERI) (assessed by Siegrist's ERI questionnaire). Poisson regression was used to assess the RR of ERI >1 at follow-up according to the report of pain and of ERI >1 at baseline., Results: Among nurses with ERI ≤1 at baseline, ERI >1 at follow-up was associated with baseline report of pain in the low-back (RR 2.7, 95 % CI 1.4-5.0) and neck/shoulder (RR 2.6, 95 % CI 1.3-5.1). However, there was no corresponding association with persistence of ERI in nurses who already had ERI >1 at baseline. Associations of ERI at baseline with pain at follow-up were weak., Conclusion: Our results suggest that the well-documented association between job stress and musculoskeletal pain is not explained entirely by an effect of stress on reporting of pain. It appears also that workers who report musculoskeletal pain are more likely to develop subsequent perceptions of stress. This may be because pain renders people less tolerant of the psychological demands of work. Another possibility is that reports of pain and stress are both manifestations of a general tendency to be aware of and complain about symptoms and difficulties.

Background: Cutaneous carcinomas are tumors with a potential occupational etiology due to exposure to established carcinogens such as polycyclic aromatic hydrocarbons (PAH), ionizing radiation, ultraviolet (UV) radiation and arsenic. The occupational origin of such neoplasms is hugely underestimated in Italy., Objectives: To asses the proportion of Squamous Cell Carcinomas (SCC) cases with a previous occupational exposure to carcinogens., Methods: We systematically evaluated occupational exposure in a series of consecutive cases, discharged in the period 2010-11 from the Dermatology Unit of Varese Hospital, Italy, with a histological diagnosis of SCC. Through a structured telephone interview we identified patients with a potential exposure to skin carcinogens. As a second-level step, an extensive evaluation by an occupational physician was performed to assess the occupational etiology in those selected cases., Results: 105 patients were identified (65 men). 15 male cases out of a total of 85 patients who did the telephone interview, revealed a potential occupational exposure; 7 cases were confirmed as occupational cancers after second-level evaluation (proportion of male occupational cases = 13.2%). UV radiation and PAH were recognized as major causal agents. Applying those results to the national incidence data, we estimated a number of 700 annual occupational cases, 100-fold more than the cases currently evaluated by the Italian National Workers Compensation Authority., Conclusions: Our results revealed that occupational SCC is still at present a substantially "lost disease" in Italy. Greater attention and enhanced collaboration between specialists is thus needed to overcome this tendency.

As part of the international CUPID investigation, we compared physical and psychosocial risk factors for musculoskeletal disorders among nurses in Brazil and Italy. Using questionnaires, we collected information on musculoskeletal disorders and potential risk factors from 751 nurses employed in public hospitals. By fitting countryspecific multiple logistic regression models, we investigated the association of stressful physical activities and psychosocial characteristics with site-specific and multisite pain, and associated sickness absence. We found no clear relationship between low back pain and occupational lifting, but neck and shoulder pain were more common among nurses who reported prolonged work with the arms in an elevated position. After adjustment for potential confounding variables, pain in the low back, neck and shoulder, multisite pain, and sickness absence were all associated with somatizing tendency in both countries. Our findings support a role of somatizing tendency in predisposition to musculoskeletal disorders, acting as an important mediator of the individual response to triggering exposures, such as workload.

Unbiased estimates of incidence rates of accidents with blood contaminations (ABC) and time trends is the milieu for assessing the effectiveness of preventive interventions. A standardised procedure for registration and follow-up of ABC was et up in a North Italian hospital since 2002. Accurate estimates of rate denominator, as full-time equivalent (FTE) person-years, was calculated, for exposed workers only and excluding periods of prolonged absence. In the observation period (2004-2011), training courses for head nurses on security procedures were repeatedly carried out as well as the progressive introduction of vacuum blood collection systems (since 2009). 1287 ABC have been reported, corresponding to an overall annual crude incidence rate of 4.73 per 100 FTE. Temporal trends, calculated on the biennial incidence, resulted in a reductions over the time period considered, in particular for needlestick injuries. Our results support the notions on the efficacy of the adopted prevention measures.

Sino-nasal cancer (SNC) are rare tumours with an elevated occupational etiological fraction, due both to well-established risk factors (wood and leather) and to more rare carcinogens. We evaluated the assessment for workers' compensation performed by the Italian Authority (INAL) in a case-series of occupational SNC (N = 45). We observed an elevated proportion of cases that were recognised as occupational, overall (36 on 39) and for any histotype. INAIL tended to recognize as professional not only patients with exposure to wood and leather but also cases with a documented exposure to formaldehyde, metal, polycyclic hydrocarbons. Significant differences across Italian macro-regions appeared, when the amount of worker compensation was investigated.

Background: We compared rates and case fatality from a population-based stroke register in Northern Italy between 1998 and 2004 to assess changes over time and to evaluate changes in case diagnosis and management., Methods: The WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease criteria were used to identify suspected fatal or nonfatal events occurring among residents 35-74 years of age. Data on in-hospital treatments, symptoms and diagnostic tools were extracted. Out-of-hospital deaths were also investigated. The annual average relative change (ARC) in death rate, attack rate and case fatality were derived from Poisson models., Results: Death rates due to ischemic stroke (IS) decreased [men: ARC -12.7, 95% confidence interval (CI) -21.3 to -3.2; women: ARC -14.0, 95% CI -23.3 to -3.5]. These reductions are attributable to decreases in case fatality; attack rates of nonfatal IS increased (men: ARC 3.6, 95% CI 0.5-6.7; women: ARC 4.1, 95% CI 0.0-8.2). IS patients showed a higher prevalence of dyslipidemia and hypertension and underwent MRI more frequently in 2004. Both findings may explain the increased proportions of less severe cases. Case fatality and attack rates for hemorrhagic strokes (HS) were stable, with an observed increased prevalence of patients under anticoagulant/antiplatelet treatments., Conclusions: In this low-IS-incidence population, death rates decreased substantially during the investigated period. More accurate diagnostic tools increase the probability of detecting less severe cases. HS remains a frequently fatal disease with a stable incidence., (Copyright © 2012 S. Karger AG, Basel.)

Objectives: We investigated the contribution of major coronary heart disease (CHD) risk factors and job strain to occupational class differences in CHD incidence in a pooled-cohort prospective study in northern Italy., Methods: 2964 men aged 25-74 from four northern Italian population-based cohorts were investigated at baseline and followed for first fatal or non-fatal CHD event (171 events). Standardised procedures were used for baseline risk factor measurements, follow-up and validation of CHD events. Four occupational classes were derived from the Erikson-Goldthorpe-Portocarero social class scheme: higher and lower professionals and administrators, non-manual workers, skilled and unskilled manual workers, and the self-employed. HRs were estimated with Cox models., Results: Among CHD-free subjects, with non-manual workers as the reference group, age-adjusted excess risks were found for professionals and administrators (+84%, p=0.02), the self-employed (+72%, p=0.04) and manual workers (+63%, p=0.04). The relationship was consistent across different CHD diagnostic categories. Adjusting for major risk factors only slightly reduced the reported excess risks. In a sub-sample of currently employed subjects, adjusting for major risk factors, sport physical activity and job strain reduced the excess risk for manual workers (relative change = -71.4%) but did not substantially modify the excess risks of professionals and administrators and the self-employed., Conclusions: In our study, we found higher CHD incidence rates for manual workers, professionals and administrators, and the self-employed, compared to non-manual workers. When the entire spectrum of job categories is considered, the job strain model helped explain the CHD excess risk for manual workers but not for other occupational classes.

Background: The relationship between asbestos exposure and peritoneal mesothelioma (PEM) is under investigation. Some authors suggest that the association could be weaker than that observed for pleural mesothelioma (PLM)., Objective: To compare individual, clinical and exposure characteristics of peritoneal and pleural mesothelioma cases that occurred in the Lombardy Region (Italy)., Methods: Cases were drawn from the regional mesothelioma registry (base population > 9 million). We selected all PEM cases diagnosed between 2000 and 2007 (N = 110) and all PLM cases that occurred between 2000 and 2001 (N = 515). Asbestos exposure data (occupational, environmental/familial, or both) were collected by a standardized and validated questionnaire administered to each case or case's relative. Based on available chest CT scans, we also investigated the concomitant presence of asbestosis and/or pleural plaques as markers of asbestos exposure., Results: PEM and PLM cases had similar proportions of occupational (around 60%) and environmental/familial (7%) asbestos exposure. The proportion of PEM subjects with co-existent occupational and environmental/familial exposures was, however, twice as high as PLM cases (6.1% vs 3.1%). Asbestosis and pleural plaques were more frequent in PEM than in PLM cases (7.7% and 20.9% vs 0.4% and 12.1%, respectively). No differences were detected for duration of exposure and latency among occupationally exposed cases., Conclusion: Our findings from a population-based Registry suggest that high cumulative asbestos exposures are the main risk factors not only for pleural but also for peritoneal mesothelioma.

Exposure to ambient air particles matter (PM) has been associated with increased risk of lung cancer. Aberrant tumor suppressor gene promoter methylation has emerged as a promising biomarker for cancers, including lung cancer. Whether exposure to PM is associated with peripheral blood leukocyte (PBL) DNA methylation in tumor suppressor genes has not been evaluated. In 63 male healthy steel workers with well-characterized exposure to metal-rich particles nearby Brescia, Italy, we evaluated whether exposure to PM and metal components was associated with PBL DNA methylation in 4 tumor suppressor genes (i.e., APC, p16, p53 and RASSF1A). Blood samples were obtained on the 1st (baseline) and 4th day (post-exposure) of the same work week and DNA methylation was measured using pyrosequencing. A linear mixed model was used to examine the correlations of the exposure with promoter methylation levels. Mean promoter DNA methylation levels of APC or p16 were significantly higher in post-exposure samples compared to that in baseline samples (p-values = 0.005 for APC, and p-value = 0.006 for p16). By contrast, the mean levels of p53 or RASSF1A promoter methylation was decreased in post-exposure samples compared to that in baseline samples (p-value = 0.015 for p53; and p-value < 0.001 for RASSF1A). In post-exposure samples, APC methylation was positively associated with PM10 (β = 0.27, 95% CI: 0.13-0.40), and PM1 (β = 0.23, 95% CI: 0.09-0.38). In summary, ambient PM exposure was associated with PBL DNA methylation levels of tumor suppressor genes of APC, p16, p53 and RASSF1A, suggesting that such methylation alterations may reflect processes related to PM-induced lung carcinogenesis.

Background: Epidemiology investigations have linked exposure to ambient and occupational air particulate matter (PM) with increased risk of lung cancer. PM contains carcinogenic and toxic metals, including arsenic and nickel, which have been shown in in vitro studies to induce histone modifications that activate gene expression by inducing open-chromatin states. Whether inhalation of metal components of PM induces histone modifications in human subjects is undetermined., Objectives: We investigated whether the metal components of PM determined activating histone modifications in 63 steel workers with well-characterized exposure to metal-rich PM., Methods: We determined histone 3 lysine 4 dimethylation (H3K4me2) and histone 3 lysine 9 acetylation (H3K9ac) on histones from blood leukocytes. Exposure to inhalable metal components (aluminum, manganese, nickel, zinc, arsenic, lead, iron) and to total PM was estimated for each study subject., Results: Both H3K4me2 and H3K9ac increased in association with years of employment in the plant (p-trend = 0.04 and 0.006, respectively). H3K4me2 increased in association with air levels of nickel [β = 0.16; 95% confidence interval (CI), 0.03-0.3], arsenic (β = 0.16; 95% CI, 0.02-0.3), and iron (β = 0.14; 95% CI, 0.01-0.26). H3K9ac showed nonsignificant positive associations with air levels of nickel (β = 0.24; 95% CI, -0.02 to 0.51), arsenic (β = 0.21; 95% CI, -0.06 to 0.48), and iron (β = 0.22; 95% CI, -0.03 to 0.47). Cumulative exposures to nickel and arsenic, defined as the product of years of employment by metal air levels, were positively correlated with both H3K4me2 (nickel: β = 0.16; 95% CI, 0.01-0.3; arsenic: β = 0.16; 95% CI, 0.03-0.29) and H3K9ac (nickel: β = 0.27; 95% CI, 0.01-0.54; arsenic: β = 0.28; 95% CI, 0.04-0.51)., Conclusions: Our results indicate histone modifications as a novel epigenetic mechanism induced in human subjects by long-term exposure to inhalable nickel and arsenic.

Unlabelled: Oxidative stress generation is a primary mechanism mediating the effects of Particulate Matter (PM) on human health. Although mitochondria are both the major intracellular source and target of oxidative stress, the effect of PM on mitochondria has never been evaluated in exposed individuals., Methods: In 63 male healthy steel workers from Brescia, Italy, studied between April and May 2006, we evaluated whether exposure to PM was associated with increased mitochondrial DNA copy number (MtDNAcn), an established marker of mitochondria damage and malfunctioning. Relative MtDNAcn (RMtDNAcn) was determined by real-time PCR in blood DNA obtained on the 1st (time 1) and 4th day (time 2) of the same work week. Individual exposures to PM10, PM1, coarse particles (PM10-PM1) and airborne metal components of PM10 (chromium, lead, arsenic, nickel, manganese) were estimated based on measurements in the 11 work areas and time spent by the study subjects in each area., Results: RMtDNAcn was higher on the 4th day (mean = 1.31; 95%CI = 1.22 to 1.40) than on the 1st day of the work week (mean = 1.09; 95%CI = 1.00 to 1.17). PM exposure was positively associated with RMtDNAcn on either the 4th (PM10: beta = 0.06, 95%CI = -0.06 to 0.17; PM1: beta = 0.08, 95%CI = -0.08 to 0.23; coarse: beta = 0.06, 95%CI = -0.06 to 0.17) or the 1st day (PM10: beta = 0.18, 95%CI = 0.09 to 0.26; PM1: beta = 0.23, 95%CI = 0.11 to 0.35; coarse: beta = 0.17, 95%CI = 0.09 to 0.26). Metal concentrations were not associated with RMtDNAcn., Conclusions: PM exposure is associated with damaged mitochondria, as reflected in increased MtDNAcn. Damaged mitochondria may intensify oxidative-stress production and effects.

Background: Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs that regulate the expression of broad gene networks at the posttranscriptional level., Objectives: We evaluated the effects of exposure to PM and PM metal components on candidate miRNAs (miR-222, miR-21, and miR-146a) related with oxidative stress and inflammatory processes in 63 workers at an electric-furnace steel plant., Methods: We measured miR-222, miR-21, and miR-146a expression in blood leukocyte RNA on the first day of a workweek (baseline) and after 3 days of work (postexposure). Relative expression of miRNAs was measured by real-time polymerase chain reaction. We measured blood oxidative stress (8-hydroxyguanine) and estimated individual exposures to PM1 (< 1 microm in aerodynamic diameter), PM10 (< 10 microm in aerodynamic diameter), coarse PM (PM10 minus PM1), and PM metal components (chromium, lead, cadmium, arsenic, nickel, manganese) between the baseline and postexposure measurements., Results: Expression of miR-222 and miR-21 (using the 2-DeltaDeltaCT method) was significantly increased in postexposure samples (miR-222: baseline = 0.68 +/- 3.41, postexposure = 2.16 +/- 2.25, p = 0.002; miR-21: baseline = 4.10 +/- 3.04, postexposure = 4.66 +/- 2.63, p = 0.05). In postexposure samples, miR-222 expression was positively correlated with lead exposure (beta = 0.41, p = 0.02), whereas miR-21 expression was associated with blood 8-hydroxyguanine (beta = 0.11, p = 0.03) but not with individual PM size fractions or metal components. Postexposure expression of miR-146a was not significantly different from baseline (baseline = 0.61 +/- 2.42, postexposure = 1.90 +/- 3.94, p = 0.19) but was negatively correlated with exposure to lead (beta = -0.51, p = 0.011) and cadmium (beta = -0.42, p = 0.04)., Conclusions: Changes in miRNA expression may represent a novel mechanism mediating responses to PM and its metal components.

Background: Particulate matter (PM) exposure has been linked to increased risk of cardiovascular disease, possibly resulting from hypercoagulability and thrombosis. Lung and systemic inflammation resulting from PM inhalation may activate blood coagulation, but mechanisms for PM-related hypercoagulability are still largely unknown., Objectives: To identify coagulation mechanisms activated by PM in a population with well-characterized exposure., Methods: We measured prothrombin time (PT), activated partial thromboplastin time, endogenous thrombin potentials (ETPs) with/without exogenous triggers and with/without soluble thrombomodulin, tissue-type plasminogen activator (t-PA) antigen, D-dimer and C-reactive protein (CRP) in 37 workers in a steel production plant with well-characterized exposure to PM with aerodynamic diameter of < 1 mum (PM(1)) and coarse PM (PM(10) - PM(1)). Blood samples were collected from each subject on the first (baseline) and last (postexposure) day of a 4-day work week. We analyzed differences between baseline and postexposure levels using a paired Student's t-test. We fitted multivariate mixed-regression models to estimate the associations of interquartile range PM(1) and coarse PM exposure with parameter levels., Results: None of the parameters showed any significant changes from baseline in postexposure samples. However, exposure levels were associated with shorter PT (beta[PM(1)] = -0.33 s, P = 0.08; beta[PM(coarse)] = - 0.33 s, P = 0.01), and higher ETP without exogenous triggers and with thrombomodulin (beta[PM(1)] = + 99 nm min, P = 0.02; beta[PM(coarse)] = + 66 nm min, P = 0.05), t-PA (beta[PM(1)] = + 0.72 ng mL(-1), P = 0.01; beta[PM(coarse)] = + 0.88 ng mL(-1), P = 0.04), and CRP (beta[PM(1)] = + 0.59 mg L(-1), P = 0.03; beta[PM(coarse)] = + 0.48 mg L(-1), P = 0.01)., Conclusions: PM exposure did not show any short-term effect within the week of the study. The association of PM exposure with PT, ETP and CRP provides some evidence of long-term effects on inflammation and coagulation.

Objectives: Substance abuse is nowadays a recurrent theme in the daily practice of occupational physicians (OP), mainly owing to recent legislation prescribing mandatory assessments for workers performing job tasks involving danger to third parties. While some degree of bureaucracy is inevitable and legislation seems to be inclined towards deterrence, it is recommended to take advantage of the opportunities offered for practical interventions which, in accordance with science and ethics, the OP can carry out in the workplace. Risk assessment, health surveillance, fitness for work, health promotion and cooperation in management issues are the areas of intervention required for the OP to fully accomplish his role in the practice of modern occupational health., Conclusions: We propose specific activities for the OP so as to highlight roles and obligations, based on available scientific evidence and established codes of ethics. Lastly, we wish to emphasize the overall role of the OP in taking on responsibilities shared jointly with all the parties and in the approach to the substance abuse problem in all workplaces with the ultimate goal of acting for the benefit of workers, enterprises and society in general.

Background: Consistent evidence has indicated that air pollution increases the risk of cardiovascular diseases. The underlying mechanisms linking air pollutants to increased cardiovascular risk are unclear., Objectives: We investigated the association between the pollution levels and changes in such global coagulation tests as the prothrombin time (PT) and the activated partial thromboplastin time (APTT) in 1218 normal subjects from the Lombardia Region, Italy. Plasma fibrinogen and naturally occurring anticoagulant proteins were also evaluated., Methods: Hourly concentrations of particulate (PM10) and gaseous pollutants (CO, NO2, SO2, and O3) were obtained from 53 monitoring sites covering the study area. Generalized additive models were applied to compute standardized regression coefficients controlled for age, gender, body mass index, smoking, alcohol, hormone use, temperature, day of the year, and long-term trends., Results: The PT became shorter with higher ambient air concentrations at the time of the study of PM10 (coefficient = -0.06; P < 0.05), CO (coefficient = -0.11; P < 0.001) and NO2 (coefficient =-0.06; P < 0.05). In the 30 days before blood sampling, the PT was also negatively associated with the average PM(10) (coefficient = -0.08; P < 0.05) and NO2 (coefficient = -0.08; P < 0.05). No association was found between the APTT and air pollutant levels. In addition, no consistent relations with air pollution were found for fibrinogen, antithrombin, protein C and protein S., Conclusions: This investigation shows that air pollution is associated with changes in the global coagulation function, suggesting a tendency towards hypercoagulability after short-term exposure to air pollution. Whether these changes contribute to trigger cardiovascular events remains to be established.

Background: In 1992, the International Agency for Research on Cancer (IARC) classified sulphuric acid mists as human carcinogen, based primarily on human data showing increased risk for larynx cancer. Uncertainties still exist about other respiratory cancers., Objectives: We carried out a historical mortality study among workers ofa plant producing sulphuric acid in Tuscany, Italy., Methods: We reconstructed a cohort of 1372 male and 37female workers with at least one year of employment at the plant in the period 1962-97; 46% ofthe workers had previously been working in pyrite mines in the area where rocks have a high silica content. Environmental measurements of sulphuric acid and sulphur dioxide from the 1970's were generally below the TLVs. Mortality was investigated as of August 2000; Standardized Mortality Ratios (SMR) were calculated using Tuscany reference rates., Results: Overall mortality was below expectation (SMR 77). In labourers, larynx cancer deaths were 4 vs 3.1 expected (SMR 130, 95% CI 35-333), while mortality from lung cancer was below expectation (27/32.8, SMR 82, 95% CI 54-120). An excess of myeloid leukaemia was observed mainly in workers without previous experience in mines (3/0.6, SMR 523, 95% CI 108-1527). Mortality from silicosis, but not from lung cancer, was remarkably high among workers with previous employment in mines., Conclusions: Among workers employed in sulphuric acid production, with or without previous experience in mines, we did not observe increased mortality from larynx or lung cancer. The increased mortality from myeloid leukaemia cannot be attributed to any of the exposures documented in the study plant and requires further investigation.

S-Phenylmercapturic acid (S-PMA), is a urinary metabolite of benzene, thought to be derived from the condensation product of benzene oxide with glutathione. S-PMA may be determined by GC, HPLC (UV or fluorescence detection), GC-MS, LC-MS/MS or immunoassays. The limit of sensitivities of most of these techniques is 1 microg/l urine or below. It has been suggested that S-PMA may have value as a biomarker for low level human exposure to benzene, in view of the facts that urinary excretion of S-PMA has been found to be related to airborne benzene in occupationally exposed workers, and that only low background levels of S-PMA have been found in control subjects. We have evaluated the use of S-PMA as a biomarker, using a commercially available analytical service, in a multicentre European study of populations exposed to varying levels of benzene, in Italy (Milan, Genoa) and in Bulgaria (Sofia). These were filling station attendants, urban policemen, bus drivers, petrochemical workers and referents (a total of 623 subjects). S-PMA was measured at the end of the work shift by an immunoassay procedure. Urinary benzene (in Milan only) and the benzene metabolite trans,trans-muconic acid (t,t-MA) were measured before and after the work shift. Air-borne benzene was measured as a monitor of exposure. Urinary benzene was the most discriminatory biomarker and showed a relationship with airborne benzene at all levels of exposure studied (including groups exposed to <0.1 ppm benzene), whereas t,t-MA and S-PMA, as determined by immunoassay, were suitable only in the highest exposed workers (petrochemical industry, geometric mean 1765 microg/m3 (0.55 ppm) benzene). All three biomarkers were positively correlated with smoking as measured by urinary cotinine).

The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible long-term consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.