Smart working and tele-conferences during the lockdown caused by COVID-19 bring new editorial guidelines.

At the time of writing, the COVID-19 pandemic is assuming a distinct shape as do healthcare systems around the world. Some countries resisted to the tsunami and are now re-opening their industrial and commercial activities while re-organizing to face a possible new wave. Others are still struggling not to be overwhelmed by the most significant public health challenge of the last century. In Italy, after a strict lockdown, almost all activities are re-opening, trying to navigate between Scylla (epidemics and its economic consequences) and Cariddi (economic recession and its adverse health effects) bearing in mind that there is collinearity between the circulation of money and spreading of the virus and that there is a serious risk of a vicious spiral which could affect the society. The prolonged lockdown deemed to prevent the spreading of the virus also reduced the circulation of money, and hence tax revenues, thus it will ultimately result in fewer finances available for social security and Public Health (3). The main political issue will then be the definition of a right point of equilibrium between risks and benefits, between action and precaution. As scientists, we are called to distinguish between what we know and what is unknown, between data and opinions, between facts and beliefs. [...].

Occupational Medicine in the time of COVID-19.

Editorial.

Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats.

BACKGROUND: Non-communicable diseases, intended as the results of a combination of inherited, environmental and biological factors, kill 40 million people each year, equivalent to roughly 70% of all premature deaths globally. The possibility that manufactured nanoparticles (NPs) may affect cardiac performance, has led to recognize NPs-exposure not only as a major Public Health concern, but also as an occupational hazard. In volunteers, NPs-exposure is problematic to quantify. We recently found that inhaled titanium dioxide NPs, one of the most produced engineered nanomaterials, acutely increased cardiac excitability and promoted arrhythmogenesis in normotensive rats by a direct interaction with cardiac cells. We hypothesized that such scenario can be exacerbated by latent cardiovascular disorders such as hypertension. RESULTS: We monitored cardiac electromechanical performance in spontaneously hypertensive rats (SHRs) exposed to titanium dioxide NPs for 6 weeks using a combination of cardiac functional measurements associated with toxicological, immunological, physical and genetic assays. Longitudinal radio-telemetry ECG recordings and multiple-lead epicardial potential mapping revealed that atrial activation times significantly increased as well as proneness to arrhythmia. At the third week of nanoparticles administration, the lung and cardiac tissue encountered a maladaptive irreversible structural remodelling starting with increased pro-inflammatory cytokines levels and lipid peroxidation, resulting in upregulation of the main pro-fibrotic cardiac genes. At the end of the exposure, the majority of spontaneous arrhythmic events terminated, while cardiac hemodynamic deteriorated and a significant accumulation of fibrotic tissue occurred as compared to control untreated SHRs. Titanium dioxide nanoparticles were quantified in the heart tissue although without definite accumulation as revealed by particle-induced X-ray emission and ultrastructural analysis. CONCLUSIONS: The co-morbidity of hypertension and inhaled nanoparticles induces irreversible hemodynamic impairment associated with cardiac structural damage potentially leading to heart failure. The time-dependence of exposure indicates a non-return point that needs to be taken into account in hypertensive subjects daily exposed to nanoparticles.

Higher Number of Night Shifts Associates with Good Perception of Work Capacity and Optimal Lung Function but Correlates with Increased Oxidative Damage and Telomere Attrition.

Sleep deprivation and the consequent circadian clock disruption has become an emergent health question being associated with premature aging and earlier chronic diseases onset. Night-shift work leads to circadian clock misalignment, which is linked to several age-related diseases. However, mechanisms of this association are not well understood. Aim of this study is to explore in night-shift workers early indicators of oxidative stress response and biological aging [oxidized/methylated DNA bases and leukocytes telomere length (LTL)] and late indicators of functional aging [lung function measurements (FEV1 and FVC)] in relation to personal evaluation of work capacity, measured by work ability index (WAI). One hundred fifty-five hospital workers were studied within the framework of a cross-sectional study. We collected physiological, pathological, and occupational history including pack-years, alcohol consumption, physical activity, and night shifts, together with blood and urine samples. Relationships were appraised by univariate and multivariate ordered-logistic regression models. We found that workers with good and excellent WAI present higher FEV1 (p< 0.01) and number of night-work shifts (p<0.05), but they reveal higher urinary levels of 8-oxoGua (p<0.01) and shorter LTL (p<0.05). We confirmed that higher work ability was prevalent among chronological younger workers (p<0.05), who have also a significant reduced number of diseases, particularly chronic (p<0.01) and musculoskeletal diseases (p<0.01). The new findings which stem from our work are that subjects with the highest work ability perception may have more demanding and burdensome tasks; they in fact present the highest number of night-shift work and produce unbalanced oxidative stress response that might induce premature aging.

Non-invasive techniques to assess restrictive lung disease in workers exposed to free crystalline silica.

OBJECTIVES: To compare the reliability of spirometry and body plethysmography in detecting restrictive lung disease in clay excavation workers exposed to free crystalline silica (FCS). The exhaled breath condensate (EBC) biomarkers of oxidative stress were also assessed in order to evaluate early lung damage. METHODS: The study involved 62 workers (58 males and 4 females) at a company that extracts and processes clay. RESULTS: Body plethysmography (total lung capacity below the lower normal limit) and spirometry respectively indicated restrictive pattern prevalence rates of 22.6% and 1.6%. EBC 4-hydroxynonenale levels were not sufficiently sensitive to highlight a restrictive deficit, but did distinguish low and high rates of occupational exposure. There was no correlation between plethysmography values and the intensity or duration of exposure. CONCLUSIONS: Only one out of 14 cases of restrictive deficit diagnosed on the basis of body plethysmography values was also identified by means of spirometry. This finding supports the need to use body plethysmography in the health surveillance of clay workers exposed to FCS.

CYP2D6 genotype can help to predict effectiveness and safety during opioid treatment for chronic low back pain: results from a retrospective study in an Italian cohort.

BACKGROUND: Opioids are widely used for chronic low back pain (CLBP); however, it is still unclear how to predict their effectiveness and safety. Codeine, tramadol and oxycodone are metabolized by CYP/CYP450 2D6 (CYP2D6), a highly polymorphic enzyme linked to allele-specific related differences in metabolic activity. PURPOSE: CYP2D6 genetic polymorphisms could potentially help to predict the effectiveness and safety of opioid-based drugs in clinical practice, especially in the treatment of CLBP. PATIENTS AND METHODS: A cohort of 224 Italian patients with CLBP treated with codeine or oxycodone was retrospectively evaluated to determine whether adverse reactions and effectiveness were related to CYP2D6 single-nucleotide polymorphisms. CYP2D6 genotyping was performed using the xTAG® CYP2D6 Kit v3 (Luminex) to determine CYP2D6 metabolizer phenotype (poor, intermediate, rapid and ultrarapid). Subjects from the cohort were categorized into two groups according to the occurrence of side effects (Case) or benefit (Control) after chronic analgesic treatment. The impact of CYP2D6 polymorphism on treatment outcome was tested at the metabolizer phenotype, diplotype and haplotype levels. RESULTS: CYP2D6 polymorphism was significantly associated with opioid treatment outcome (Omnibus P=0.018, for both global haplotype and diplotype distribution test). CYP2D6*6 and *9 carriers, alleles characterized by a reduced (*9) or absent (*6) enzymatic activity, were significantly (P<0.05) associated with therapeutic failure. CYP2D6 ultrarapid metabolizers (CYP2D6*2N patients) showed an increased risk of side effects, as would be predicted. Despite their low frequency, CYP2D6 *1/*11, *4/*6 and *41/* 2N diplotypes showed significant (P<0.05) associations of efficacy and side effects with chronic opioid treatment. CONCLUSION: Our results showed that reduced CYP2D6 activity is correlated with lack of therapeutic effect. We found that the pharmacogenetic analysis of CYP2D6 could be helpful in foreseeing the safety and effectiveness of codeine or oxycodone treatment in CLBP.

Biomarkers of exposure to stainless steel tungsten inert gas welding fumes and the effect of exposure on exhaled breath condensate.

The respiratory tract is the main target organ of the inhaled hexavalent chromium (Cr-VI) and nickel (Ni) contained in stainless steel (SS) welding fumes (WFs). The aim of this study was to investigate the Cr and Ni content of the exhaled breath condensate (EBC) of SS tungsten inert gas (TIG) welders, and relate their concentrations with oxidative stress and inflammatory biomarkers. EBC and urine from 100 SS TIG welders were collected pre-(T0) and post-shift (T1) on a Friday, and pre-shift (T2) on the following Monday morning. Both EBC and urinary Cr concentrations were higher at T1 (0.08 µg/L and 0.71 µg/g creatinine) and T0 (0.06 µg/L and 0.74 µg/g creatinine) than at T2 (below the limit of detection [LOD] and 0.59 µg/g creatinine), and EBC Ni concentrations generally remained

Reference Intervals for Urinary Cotinine Levels and the Influence of Sampling Time and Other Predictors on Its Excretion Among Italian Schoolchildren.

(1) Background: Environmental Tobacco Smoke (ETS) exposure remains a public health problem worldwide. The aims are to establish urinary (u-) cotinine reference values for healthy Italian children, to evaluate the role of the sampling time and of other factors on children's u-cotinine excretion. (2) Methods: A cross-sectional study was performed on 330 children. Information on participants was gathered by a questionnaire and u-cotinine was determined in two samples for each child, collected during the evening and the next morning. (3) Results: Reference intervals (as the 2.5th and 97.5th percentiles of the distribution) in evening and morning samples were respectively equal to 0.98⁻4.29 and 0.91⁻4.50 µg L-1 (ETS unexposed) and 1.39⁻16.34 and 1.49⁻20.95 µg L-1 (ETS exposed). No statistical differences were recovered between median values found in evening and morning samples, both in ETS unexposed and exposed. Significant predictors of u-cotinine excretions were ponderal status according to body mass index of children (ß = 0.202; p-value = 0.041 for evening samples; ß = 0.169; p-value = 0.039 for morning samples) and paternal educational level (ß = -0.258; p-value = 0.010; for evening samples; ß = -0.013; p-value = 0.003 for morning samples). (4) Conclusions: The results evidenced the need of further studies for assessing the role of confounding factors on ETS exposure, and the necessity of educational interventions on smokers for rising their awareness about ETS.

MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study.

BACKGROUND: The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression. AIMS: To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients. METHODS: miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients. CONCLUSIONS: All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.

Titanium dioxide aggregating nanoparticles induce autophagy and under-expression of microRNA 21 and 30a in A549 cell line: A comparative study with cobalt(II, III) oxide nanoparticles.

The toxicity of TiO2 nanoparticles (NPs) is controversial, while it is widely accepted for Co3O4 NPs. We present a comparative study concerning the uptake of these NPs and their effect on cytoplasmic organelles and autophagy in a human lung carcinoma cell line (A549), including assays on the expression of autophagy-related microRNAs. The NP accumulation caused a fast dose- and time-dependent change of flow cytometry physical parameters particularly after TiO2 NP exposure. The intracellular levels of metals confirmed it, but the Co concentration was ten times higher than that of Ti. Both NPs caused neither necrosis nor apoptosis, but cytotoxicity was mainly evident for Co3O4 NPs in the first 72h. TiO2 NPs caused autophagy, contrarily to Co3O4 NPs. Furthermore, a significant and persistent downregulation of miRNA-21 and miRNA-30a was observed only in TiO2 NPs-treated cultures. The expression of miRNA-155 was similar for both NPs. Oxidative stress was evident only for Co3O4 NPs, while both NPs perturbed endoplasmic reticulum and p-53 expression. In conclusion, the oxidative stress caused by Co3O4 NPs can influence energy homeostasis and hamper the ability to detoxify and to repair the resulting damage, thus preventing the induction of autophagy, while TiO2 NPs elicit autophagy also under sub-toxic conditions.