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MiR-126 has been shown to suppress malignant mesothelioma (MM) by targeting cancer-related genes without inducing toxicity or histopathological changes. Exosomes provide the opportunity to deliver therapeutic cargo to cancer stroma. Here, a tumour stromal model composed of endothelial cells (HUVECs), fibroblasts (IMR-90 cells), non-malignant mesothelial cells (Met-5A cells) and MM cells (H28 and MM-B1 cells) was used. The cells were treated with exosomes from HUVECs carrying endogenous (exo-HUVEC) and enriched miR-126 (exo-HUVECmiR−126), and the uptake/turnover of exosomes; miR-126 distribution within the stroma; and effect of miR-126 on cell signalling, angiogenesis and cell proliferation were evaluated. Based on the sensitivity of MM cells to exo-HUVEC miR-126 treatment, miR-126 was distributed differently across stromal cells. The reduced miR-126 content in fibroblasts in favour of endothelial cells reduced angiogenesis and suppressed cell growth in an miR-126-sensitive environment. Conversely, the accumulation of miR-126 in fibroblasts and the reduced level of miR-126 in endothelial cells induced tube formation in an miR-126-resistant environment via VEGF/EGFL7 upregulation and IRS1-mediated cell proliferation. These findings suggest that transfer of miR-126 via HUVEC-derived exosomes represents a novel strategy to inhibit angiogenesis and cell growth in MM.

The stratum corneum protects the body against external agents, such as metals, chemicals, and toxics. Although it is considered poorly permeable to them, comprising the major barrier to the permeation of such substances, it may become a relevant gate of entry for such molecules. Cerium (Ce) is a lanthanide that is widely used in catalytic, energy, biological and medicinal applications, owing to its intrinsic structural and unique redox properties. Cerium salts used to produce cerium oxide (CeO2) nanostructures can potentially come into contact with the skin and be absorbed following dermal exposure. The objective of this study was to investigate the percutaneous absorption of three inorganic Ce salts: cerium (III) chloride (CeCl3); cerium (III) nitrate (Ce(NO3)3) and ammonium cerium (IV) nitrate (Ce(NH4)2(NO3)6), which are commonly adopted for the synthesis of CeO2 using in vitro - ex vivo technique in Franz diffusion cells. The present work shows that Ce salts cannot permeate intact human skin, but they can penetrate significantly in the epidermis (up to 0.29μg/cm2) and, to a lesser extent in dermis (up to 0.11μg/cm2). Further studies are required to evaluate the potential effects of long-term exposure to Ce.

Objective The aim of this study was to compare the performance of alternative measures of cumulative lifetime vibration dose to predict the occurrence of low-back pain (LBP) outcomes in a cohort of 537 professional drivers investigated at baseline and over a two-year follow up period. Methods The exposure data obtained in the EU VIBRISKS project were used to calculate alternative measures of either acceleration- (external) or force- (internal) based lifetime vibration doses. Vibration was measured in representative samples of machines and vehicles used by the drivers. Internal lumbar forces were calculated by means of anatomy-, posture-, and anthropometry-based finite element models. The relations of LBP outcomes to alternative measures of lifetime vibration doses were assessed by the generalized estimating equations method. Results Metrics of cumulative vibration exposure constructed with either acceleration- or force-based methods were significantly associated with the occurrence of LBP outcomes. A measure of model fitting suggested that force-based doses were better predictors of LBP outcomes than acceleration-based doses. Models with force root-mean-square doses provided a better fit to LBP outcomes than those with force-peak doses. Conclusions Measures of internal lumbar forces were better predictors of LBP outcomes than measures of external vibration acceleration although the exposure metrics constructed with the acceleration-based method have the advantage of greater simplicity compared to the force-based method. The differences between the models with force-based doses suggest that the cumulative health effects on the lumbar spine might depend on the integrated resulting total force over the entire exposure time rather than primarily on the force peaks.

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Introduction: Oral mucositis (OM) is a severe side effect in patients undergoing anticancer therapies, which negatively impacts on their quality of life often leading to either the interruption of the therapy. Photobiomodulation (PBM) is emerging as an effective strategy allowing a faster wound healing. Objectives: This pilot study aims at verifying whether PBM modulates the inflammatory response in patients and its effect on the oral microbiome composition. Materials and methods: Buccal swabs were collected from four patients affected by OM, both on ulcerated and clinically healthy areas, before and on the last day of PBM therapy, as well as on the first day after treatment discontinuation. The concentration of 38 cytokines and the composition of oral microbiome were measured. Results: Most of the pro-inflammatory cytokines were reduced, whereas anti-inflammatory cytokines resulted up-regulated by PBM. In addition, PBM influenced the composition of oral microbiome, by decreasing the amount of pathogenic species and promoting the growth of commensal bacteria. These changes were even more evident when separately analysing patients who clinically responded to PBM and the only patient who did not respond. Conclusions: PBM reduces inflammatory burden in patients affected by OM and positively influences the composition of the oral microbiome.

Recent studies have shown that comfort can be influenced more by psychological processes than from the characteristics of environmental stimulation. This is relevant for different industrial sectors, where comfort is defined only as a function of the intensity of external stimuli. In the present study, we measured physiological and psychological comfort during the exposure to four levels of acoustic noise [from 45 to 55 dB(A)] corresponding to different comfort classes inside a full-scale mock-up of a cruise ship cabin. We found an increase of psychological and physiological discomfort for higher noise intensities, but not for all the intensities defining the comfort classes. Furthermore, we found that negative psychological states determine a lower physiological sensitivity to acoustic noise variations compared to positive states. Our results show that, at normal/low intensities, psychological processes have a greater role in determining acoustic comfort when compared to the stimulus intensity. Practitioner Summary: This study shows that psychological factors can be more relevant in determining acoustic comfort inside a ship cabin than the intensity of acoustic stimulus itself. This finding suggests that the cruise industry should consider not only the engineering measurements when evaluating comfort on board, but also the passenger’ psychological state. Abbreviations: AIC: akaike information criterion; CCT: colour correlated temperature; cd/m2: candela/square meters; df: degrees of freedom; F-test: Fisher's test; HF: high frequency; HR: heart rate; HRV: heart rate variability; HSV: hue saturation value; K: kelvin; LF: low frequency; LF/HF: low frequency to high frequency ratio; lme: linear mixed effects; ms: milliseconds; nu: normalized unit; p: p value; pNN50: percentage of adjacent pairs of normal to normal RR intervals differing by more than 50 milliseconds; r2: coefficient of determination; rc: concordance correlation coefficient; RMSSD: square root of the mean normal to normal RR interval; SD: standard deviation; SDNN: standard deviation of normal to normal RR intervals; SEM: standard error of the mean; t-test: student's tests; χ2: chi-square test

Purpose: In the 30 years since the Stockholm Workshop Scale (SWS) was published, the scientific literature on hand-arm vibration syndrome (HAVS) has grown and experience has been gained in its practical application. This research was undertaken to develop an up-to-date evidence-based classification for HAVS by seeking consensus between experts in the field. Methods: Seven occupational physicians who are clinically active and have had work published on HAVS in the last 10 years were asked to independently take part in a three-round iterative Delphi process. Consensus was taken when 5/7 (72%) agreed with a particular statement. Experts were asked to provide evidence from the literature or data from their own research to support their views. Results: Consensus was achieved for most of the questions that were used to develop an updated staging system for HAVS. The vascular and neurological components from the SWS are retained, but ambiguous descriptors and tests without adequately developed methodology such as tactile discrimination, or discriminating power such as grip strength, are not included in the new staging system. A blanching score taken from photographs of the hands during vasospastic episodes is recommended in place of self-recall and frequency of attacks to stage vascular HAVS. Methods with the best evidence base are described for assessing sensory perception and dexterity. Conclusions: A new classification has been developed with three stages for the clinical classification of vascular and neurological HAVS based on international consensus. We recommend it replaces the SWS for clinical and research purposes.

Cerium oxide (CeO2) nanoparticles (NPs) are used in polishing products and absorbents, as promoters in wound healing, and as organopesticide decontaminants. While systemic bioaccumulation and organ toxicity has been described after inhalation, data on CeO2 NPs&rsquo, transdermal permeation are lacking. Our study was an in vitro investigation of the permeation of 17-nm CeO2 NPs dispersed in synthetic sweat (1 g L&minus, 1) using excised human skin on Franz cells. Experiments were performed using intact and needle-abraded skin, separately. The average amount of Ce into intact and damaged skin samples was 3.64 &plusmn, 0.15 and 7.07 &plusmn, 0.78 &micro, g cm&minus, 2, respectively (mean &plusmn, SD, p = 0.04). Ce concentration in the receiving solution was 2.0 &plusmn, 0.4 and 3.3 &plusmn, 0.7 ng cm&minus, 2 after 24 h (p = 0.008). The Ce content was higher in dermal layers of damaged skin compared to intact skin (2.93 &plusmn, 0.71 &micro, 2 and 0.39 &plusmn, 0.16 &micro, 2, respectively, p = 0.004). Our data showed a very low dermal absorption and transdermal permeation of cerium, providing a first indication of Ce skin uptake due to contact with CeO2.

Recently, a supplementary methodology to improve the assessment of occupational exposures to hand-transmitted vibration (HTV) and a revision of the clinical staging of the hand-arm vibration syndrome (HAVS) have been proposed. The Technical Report ISO/TR 18570:2017 provides guidance on a supplementary method to that defined in ISO 5349-1:2001 for measuring and reporting HTV exposures; the method provides an improved assessment methodology for evaluating vascular hand-arm vibration risks (vibration induced white finger). On using a Delphi procedure, an international panel of experts has achieved consensus to develop an updated staging system for the vascular and neurological disorders of the HAVS, previously defined in the Stockholm Workshop Scale (1986); a new classification has been proposed with three stages for vibration related vascular and neurological effects. This paper provides details on the new international criteria for the assessment of vibration induced vascular risk and for the clinical staging of the vascular and neurological components of the HAVS.Recentemente sono state proposte metodologie supplementari per la valutazione dell’esposizione a vibrazioni trasmesse al sistema mano-braccio e revisioni della stadiazione clinica dei sintomi vascolari e neurosensitivi della sindrome da vibrazioni mano-braccio. In particolare, (i) nel Technical Report ISO/TR 18570:2017 viene proposto un metodo supplementare per la predizione del rischio vascolare (fenomeno di Raynaud secondario) da vibrazioni manobraccio, ad integrazione della metodologia definita nello standard ISO 5349-1:2001; (ii) le esperienze accumulate in campo clinico e di laboratorio da parte di un panel internazionale di clinici del lavoro, appartenenti a istituzioni europee e nord-americane e attivi nei settori accademici e assistenziali per la diagnostica della sindrome da vibrazioni mano-braccio, hanno suggerito l’opportunità di procedere ad una revisione della stadiazione dei sintomi vascolari e neurosensitivi da vibrazioni mano-braccio precedentemente classificati nelle scale dello Stockholm Workshop 1986. In questo lavoro vengono riportati i nuovi criteri internazionali per la valutazione del rischio vascolare da vibrazioni mano-braccio e la stadiazione clinica della sindrome da vibrazioni mano-braccio.

Purpose: to investigate to which extent occupational status (employed, unemployed, retired, economically inactive), and job titles in employed, were associated with types of hospitalizations and psychiatric diagnoses among inpatients of Friuli Venezia Giulia (FVG) Region, Italy. Methods: Observational study based on 10-years register data (2008 - 2017) on 2929 subjects hospitalized in General Hospital Psychiatric Units. Odds ratios (OR) of hospitalizations and psychiatric diagnoses for occupational status and job titles were calculated by logistic regression analysis. Results: Employed were at lower risk of urgent and involuntary hospitalization. The risk of urgent hospitalization was higher for affective, organic or other psychiatric disorders, while all psychiatric diagnoses were at lower risk of involuntary hospitalization than psychotic disorders. Using white collars as reference category in employed, police and military forces showed a significant higher risk for urgent hospitalization (OR = 2.3) and affective disorders (OR = 1.9). A higher risk for affective disorders was also found in managers (OR=2.0). Blue collars were at higher risk for alcohol and substance abuse (OR = 1.7). A decreasing number of ordinary and in involuntary hospitalizations was observed during the study period. Conclusions: Employment was protective for urgent and involuntary hospitalizations, and for severe diagnoses, as psychosis. Among employed, hospitalization for affective disorders was more likely in managers, army, as well as for substances abuse in blue collars. More research is needed to assess the association between specific occupational groups and involuntary hospitalization. Future research would benefit to distinct between temporary and permanent job position.

Background: Altered miRNA expression is an early event upon exposure to occupational/environmental carcinogens; thus, identification of a novel asbestos-related profile of miRNAs able to distinguish asbestos-induced cancer from cancer with different etiology can be useful for diagnosis. We therefore performed a study to identify miRNAs associated with asbestos-induced malignancies. Methods: Four groups of patients were included in the study, including patients with asbestos-related (NSCLCAsb) and asbestos-unrelated non–small cell lung cancer (NSCLC) or with malignant pleural mesothelioma (MPM), and disease-free subjects (CTRL). The selected miRNAs were evaluated in asbestos-exposed population. Results: Four serum miRNAs, that is miR-126, miR-205, miR-222, and miR-520g, were found to be implicated in asbestos-related malignant diseases. Notably, increased expression of miR-126 and miR-222 were found in asbestos-exposed subjects, and both miRNAs are involved in major pathways linked to cancer development. Epigenetic changes and cancer-stroma cross-talk could induce repression of miR-126 to facilitate tumor formation, angiogenesis, and invasion. Conclusions: This study indicates that miRNAs are potentially involved in asbestos-related malignancies, and their expression outlines mechanism(s) whereby miRNAs may be involved in an asbestos-induced pathogenesis. Impact: The discovery of a miRNA panel for asbestos-related malignancies would impact on occupational compensation and may be utilized for screening asbestos-exposed populations.

BACKGROUND: Mechanics are at higher risk to develop occupational skin diseases from exposure to irritants, oils, greases, preservatives, and metals. AIMS: The aim of the study was to investigate contact dermatitis in mechanics who underwent patch test in Northeastern Italy and compare them with white-collar workers (WCW). SUBJECTS AND METHODS: From 1996 to 2016, 27,381 patients with suspected allergic contact dermatitis were patch tested in Northeastern Italy; in this group, 1270 mechanics were studied. Odds ratios (ORs) and 95% confidence interval (CI), adjusted by age and sex, were calculated assuming WCW as the reference category (n = 6933). RESULTS: Mechanics represented 4.6% of the population tested. Their mean ± SD age was 36.1 ± 11.2 years. Compared with WCW, they were found to have an increased risk of occupational dermatitis (OR = 14.4; 95% CI = 11.6-18) and hand/forearm dermatitis (OR = 2.5; 95% CI = 2.3-2.9). They presented an increased risk of sensitization to epoxy resin (OR = 2.7; 95% CI = 1.5-4.8), to thiurams (OR = 2.4; 95% CI = 1.5-3.8), to 2-mercaptobenzothiazole (OR = 1.9; 95% CI = 1.1-3.4), and to diaminodiphenylmethane (OR = 1.7; 95% CI = 1.1-2.5). CONCLUSIONS: Compared to WCW, mechanics were found to be at higher risk to develop occupational contact dermatitis, associated mainly to sensitization to epoxy resin and rubber accelerators.

Background The serum level of dehydroepiandrosterone sulphate (DHEA-S) has been suggested as a biological marker of stress. Aims To assess the association between serum DHEA-S, psychosocial factors and musculoskeletal (MS) pain in university workers. Methods The study population included voluntary workers at the scientific departments of the University of Trieste (Italy) who underwent periodical health surveillance from January 2011 to June 2012. DHEA-S level was analysed in serum. The assessment tools included the General Health Questionnaire (GHQ) and a modified Nordic musculoskeletal symptoms questionnaire. The relation between DHEA-S, individual characteristics, pain perception and psychological factors was assessed by means of multivariable linear regression analysis. Results There were 189 study participants. The study population was characterized by high reward and low effort. Pain perception in the neck, shoulder, upper limbs, upper back and lower back was reported by 42, 32, 19, 29 and 43% of people, respectively. In multivariable regression analysis, gender, age and pain perception in the shoulder and upper limbs were significantly related to serum DHEA-S. Effort and overcommitment were related to shoulder and neck pain but not to DHEA-S. The GHQ score was associated with pain perception in different body sites and inversely to DHEA-S but significance was lost in multivariable regression analysis. Conclusions DHEA-S was associated with age, gender and perception of MS pain, while effort-reward imbalance dimensions and GHQ score failed to reach the statistical significance in multivariable regression analysis.

// Ilaria Bononi 1, * , Manola Comar 2, * , Andrea Puozzo 1, * , Mariarita Stendardo 3 , Piera Boschetto 3 , Sara Orecchia 4 , Roberta Libener 4 , Roberto Guaschino 5 , Silvia Pietrobon 1 , Manuela Ferracin 6 , Massimo Negrini 1, 7 , Fernanda Martini 1 , Massimo Bovenzi 8 , Mauro Tognon 1 1 Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, Ferrara, Italy 2 Institute for Maternal and Child Health - IRCCS “Burlo-Garofolo”– Trieste, University of Trieste, Trieste, Italy 3 Department of Medical Sciences, School of Medicine, University of Ferrara, Ferrara, Italy 4 Mesothelioma BioBank, Pathology Unit and City Hospital, Alessandria, Italy 5 Transfusion Medicine, City Hospital, Alessandria, Italy 6 Department of Experimental, Diagnostic and Specialty Medicine – DIMES, University of Bologna, Bologna, Italy 7 Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Ferrara, Italy 8 Clinical Unit of Occupational Medicine, Department of Medical Sciences, School of Medicine, University of Trieste, Trieste, Italy * These authors have contributed equally to this work Correspondence to: Mauro Tognon, email: tgm@unife.it Fernanda Martini, email: mrf@unife.it Keywords: microRNA, mesothelioma, biomarker, asbestos, worker Received: June 07, 2016 Accepted: September 16, 2016 Published: October 03, 2016 ABSTRACT Malignant pleural mesothelioma (MPM), a fatal cancer, is an occupational disease mostly affecting workers ex-exposed to asbestos fibers. The asbestos, a cancerogenic mineral of different chemical composition, was widely employed in western Countries in industrial manufactures of different types. MPM may arise after a long latency period, up to five decades. MPM is resistant to conventional chemo- and radio-therapies. Altogether, these data indicate that the identification of new and specific markers are of a paramount importance for an early diagnosis and treatment of MPM. In recent years, microRNAs expression was found dysregulated in patients, both in cancer cells and sera, affected by tumors of different histotypes, including MPM. Cell and circulanting microRNAs, found to be dysregulated in this neoplasia, were proposed as new biomarkers. It has been reported that circulating microRNAs are stable in biological fluids and could be employed as potential MPM biomarkers. In this investigation, circulating microRNAs (miR) from serum samples of MPM patients and workers ex-exposed to asbestos fibers (WEA) and healthy subjects (HS) were comparatively analyzed by microarray and RT-qPCR technologies. Our results allowed (i) to select MiR-3665, an endogenous stable microRNA, as the internal control to quantify in our analyses circulating miRNAs; to detect (ii) miR-197-3p, miR-1281 and miR 32-3p up-regulated in MPM compared to HS; (iii) miR-197-3p and miR-32-3p up-regulated in MPM compared to WEA; (iv) miR-1281 up-regulated in both MPM and WEA compared to HS. In conclusion, three circulating up-regulated microRNAs, i.e. miR-197-3p, miR-1281 and miR-32-3p are proposed as potential new MPM biomarkers.

Nickel nanoparticles (NiNPs) represent a new type of occupational exposure because, due to the small size/high surface, they can release more Ni ions compared to bulk material. It has been reported a case of a worker who developed sensitization while handling nickel nanopowder without precautions. Therefore there is the need to assess whether the skin absorption of NiNPs is higher compared to bulk nickel. Two independent in vitro experiments were performed using Franz diffusion cells. Eight cells for each experiment were fitted using intact and needle-abraded human skin. The donor phase was a suspension of NiNPs with mean size of 77.7 ± 24.1 nm in synthetic sweat. Ni permeated both types of skin, reaching higher levels up to two orders of magnitude in the damaged skin compared to intact skin (5.2 ± 2.0 vs 0.032 ± 0.010 μg cm(-2), p = 0.006) at 24 h. Total Ni amount into the skin was 29.2 ± 11.2 μg cm(-2) in damaged skin and 9.67 ± 2.70 μg cm(-2) in intact skin (mean and SD, p = 0.006). Skin abrasions lead to doubling the Ni amount in the epidermis and to an increase of ten times in the dermis. This study demonstrated that NiNPs applied on skin surface cause an increase of nickel content into the skin and a significant permeation flux through the skin, higher when a damaged skin protocol was used. Preventive measures are needed when NiNPs are produced and used due to their higher potential to enter in our body compared to bulk nickel.

PURPOSE: To provide an updated epidemiological validation for a supplementary method for assessing the risk of vascular disorders from hand-transmitted vibration. METHODS: The occurrence of vibration-induced white finger (VWF) in the vibration-exposed workers of the Italian cohort of the EU VIBRISKS study was related to measures of daily vibration exposure expressed in terms of r.m.s. acceleration magnitude normalised to an 8-h day, frequency weighted according to either the frequency weighting Wh defined in international standard ISO 5349-1:2001 [Ah(8) in ms- 2] or the hand-arm vascular frequency weighting Wp proposed in the ISO technical report (TR) 18570:2017 [Ap(8) in ms- 2]. To estimate a threshold value for vascular hand-arm vibration risk, the Wp-weighted vibration exposure value Ep,d (in ms- 1.5) was calculated according to the ISO/TR document. The difference in the predictions of VWF between the exposure measures calculated with the frequency weightings Wh or Wp was investigated by means of logistic modelling. RESULTS: Measures of daily vibration exposure constructed with the frequency weighting Wp [Ap(8) and Ep,d], which gives more importance to intermediate- and high-frequency vibration, were better predictors of the occurrence of VWF in the vibration-exposed workers than the metric derived from the conventional ISO frequency weighting Wh [Ah(8)]. There was some epidemiological evidence for a threshold value of Ep,d for the onset of VWF in the vibration-exposed workers. CONCLUSIONS: Measures of daily vibration exposure evaluated with the vascular weighting Wp performed better for the predictions of VWF than those obtained with the frequency weighting Wh recommended in ISO 5349-1.

Dermal exposure to Aluminium nanoparticles (AlNPs) can occur in occupationally- and non occupationally exposed- population, due to the use of Al salts-based antiperspirants. No AlNPs transdermal permeation data exists. Our study investigated in vitro the permeation of 30-60 nm Al

The use of palladium (Pd) has grown in the last decades, commonly used in automotive catalytic converters, jewellery and dental restorations sectors. Both general and working population can be exposed to this metal, which may act as skin sensitizer. This study investigated in vitro palladium powders permeation through excised intact and damaged human skin using the Franz diffusion cell method and the effect of rapid skin decontamination using sodium laureth-sulphate. 1 mL of a 10 min sonicated suspension made of 2.5 g of Pd powder in 50 mL synthetic sweat at pH 4.5 and room temperature was applied to the outer surface of the skin membranes for 24 h. Pd permeation, assessed by ICP-MS, was higher when damaged skin was used (p = 0.03). Final flux permeation values and lag times were 0.02 ± 0.01 μg cm−2 h−1 and 6.00 ± 3.95 h for intact, and 0.10 ± 0.02 μg cm−2 h−1 and 2.05 ± 1.49 h for damaged skin samples, respectively. Damaged skin protocol enhances Pd skin penetration inside dermal layer (p = 0.04), thus making the metal available for systemic uptake. Pd penetration (p = 0.02) and permeation (p = 0.012) through intact skin decreased significantly when a cleaning procedure was applied. This study demonstrates that after skin exposure to Pd powders a small permeation of the metal happen both through intact and damaged skin and that an early decontamination with a common cleanser can significantly decrease the final amount of metal available forsystemic uptake.

Background Colophonium is a natural substance derived from Pineaceae trees. It is used in a wide range of consumer and occupational products because of its tackiness, and is a known sensitizer. Objectives To analyse the temporal trend of contact allergy to colophonium in north-eastern Italy, and to evaluate the associations with occupations in our geographical area. Methodology From 1996 to 2016, 27 381 patients with suspected allergic contact dermatitis were patch tested in north-eastern Italy. Individual characteristics were documented by use of a standardized questionnaire in 6 departments of dermatology or occupational medicine. Results The overall prevalence of colophonium sensitization was 1.67%; the prevalence was significantly higher in women (1.75%) than in men (1.49%). No significant differences among departments were observed. We found significant associations between colophonium sensitization and being a student (odds ratio [OR] 4.64; 95% confidence interval [CI]: 1.04-20.6), being a farmer or fishermen (OR 3.63; 95%CI: 1.21-10.84), being a housekeeper (OR 2.02; 95%CI: 1.08-3.77), and being retired (OR 2.06; 95%CI: 1.08-3.92). Conclusion Our study showed that contact allergy to colophonium is still relevant in north-eastern Italy. The frequency of sensitization has dropped significantly over a period of 10 years, but students and farmers/fishermen still have sensitization prevalences above 3.5%. Our results are in line with European data.

Objectives. To compare a local cohort of 2,488 men occupationally exposed to asbestos and enrolled in a public health surveillance program with the 1995 – 2009 cancer incidence of the general population of Friuli Venezia Giulia (FVG) region, Northeast Italy, we conducted a historical cohort study. Methods. Standardized incidence ratios (SIRs), with 95% confidence interval (95%CI), for specific cancer sites were estimated in the cohort and in subgroups of workers employed in shipbuilding between 1974-1994. For internal comparisons, we estimated incidence rate ratios (IRRs) for all cancers, lung cancer and mesothelioma, by level of exposure to asbestos and sector of employment adjusted for smoking habits and age at start of follow-up. Results. Among cohort members the SIR was 8.82 (95%CI 5.95-12.61) for mesothelioma and 1.61 (95%CI 1.26-2.04) for lung cancer. In subgroup analyses, the SIR for lung cancer in subjects hired in shipbuilding between 1974-1984 was 2.09 (95%CI 1.32-3.13). In the overall cohort, a borderline increased incidence was also found for stomach cancer (SIR=1.53 95%CI 0.96-2.31). Internal comparisons within the cohort show that among men with high asbestos exposure level the relative risk was almost three-fold for lung cancer (IRR=2.94 95%CI 1.01-8.57). Conclusions. This cohort experienced an excess in the incidence of both mesothelioma and lung cancer, showing increasing incidence rates at higher level of asbestos exposure. For lung cancer, the relative incidence was highest among workers hired in shipbuilding between 1974-1984.

Background Intestinal-type sinonasal adenocarcinomas (ITACs) are aggressive malignancies related to wood dust and leather exposure. ITACs are generally associated with advanced stage at presentation due to the insidious growth pattern and non-specific symptoms. Therefore, biomarkers that can detect the switch from the benign disease to malignancy are needed. Essential for tumour growth, angiogenesis is an important step in tumour development and progression. This process is strictly regulated, and MiR-126 considered its master modulator. Methods We have investigated MiR-126 levels in ITACs and compared them to benign sinonasal lesions, such as sinonasal-inverted papillomas (SIPs) and inflammatory polyps (NIPs). The tumour-suppressive functions of MiR-126 were also evaluated. Results We found that MiR-126 can significantly distinguish malignancy from benign nasal forms. The low levels of MiR-126 in ITACs point to its role in tumour progression. In this context, restoration of MiR-126 induced metabolic changes, and inhibited cell growth and the tumorigenic potential of MNSC cells. Conclusions We report that MiR-126 delivered via exosomes from endothelial cells promotes anti-tumour responses. This paracrine transfer of MiRs may represent a new approach towards MiR-based therapy.

Titanium dioxide nanoparticles (TiO2NPs) suspensions (concentration 1.0 g/L) in synthetic sweat solution were applied on Franz cells for 24 h using intact and needle-abraded human skin. Titanium content into skin and receiving phases was determined. Cytotoxicity (MTT, AlamarBlue® and propidium iodide, PI, uptake assays) was evaluated on HaCat keratinocytes after 24 h, 48 h, and seven days of exposure. After 24 h of exposure, no titanium was detectable in receiving solutions for both intact and damaged skin. Titanium was found in the epidermal layer after 24 h of exposure (0.47 ± 0.33 ?g/cm2) while in the dermal layer, the concentration was below the limit of detection. Damaged skin, in its whole, has shown a similar concentration (0.53 ± 0.26 ?g/cm2). Cytotoxicity studies on HaCaT cells demonstrated that TiO2NPs induced cytotoxic effects only at very high concentrations, reducing cell viability after seven days of exposure with EC50s of 8.8 × 10-4 M (MTT assay), 3.8 × 10-5 M (AlamarBlue® assay), and 7.6 × 10-4 M (PI uptake, index of a necrotic cell death). Our study demonstrated that TiO2NPs cannot permeate intact and damaged skin and can be found only in the stratum corneum and epidermis. Moreover, the low cytotoxic effect observed on human HaCaT keratinocytes suggests that these nano-compounds have a potential toxic effect at the skin level only after long-term exposure. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

Skin absorption and toxicity on keratinocytes of cobalt oxide nanoparticles (Co3O4NPs) have been investigated. Co3O4NPs are commonly used in industrial products and biomedicine. There is evidence that these nanoparticles can cause membrane damage and genotoxicity in vitro, but no data are available on their skin absorption and cytotoxicity on keratinocytes. Two independent 24 h in vitro experiments were performed using Franz diffusion cells, using intact (experiment 1) and needle-abraded human skin (experiment 2). Co3O4NPs at a concentration of 1000 mg/L in physiological solution were used as donor phase. Cobalt content was evaluated by Inductively Coupled–Mass Spectroscopy. Co permeation through the skin was demonstrated after 24 h only when damaged skin protocol was used (57 ± 38 ng·cm−2), while no significant differences were shown between blank cells (0.92 ± 0.03 ng cm−2) and those with intact skin (1.08 ± 0.20 ng·cm−2). To further investigate Co3O4NPs toxicity, human-derived HaCaT keratinocytes were exposed to Co3O4NPs and cytotoxicity evaluated by MTT, Alamarblue® and propidium iodide (PI) uptake assays. The results indicate that a long exposure time (i.e., seven days) was necessary to induce a concentration-dependent cell viability reduction (EC50 values: 1.3 × 10−4 M, 95% CL = 0.8–1.9 × 10−4 M, MTT essay, 3.7 × 10−5 M, 95% CI = 2.2–6.1 × 10−5 M, AlamarBlue® assay) that seems to be associated to necrotic events (EC50 value: 1.3 × 10−4 M, 95% CL = 0.9–1.9 × 10−4 M, PI assay). This study demonstrated that Co3O4NPs can penetrate only damaged skin and is cytotoxic for HaCat cells after long term exposure.

Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.

In this study, the daily exposure action values (EAV) and the daily exposure limit values (ELV) for hand-transmitted vibration (HTV) and whole-body vibration (WBV), established by the EU Directive 2002/44/EC and the Italian Decree 81/2008, and expressed in terms of 8-hr frequency weighted r.m.s. acceleration magnitude, are discussed upon consideration of the findings of experimental and epidemiological studies.There is some epidemiological support for the EAV A(8) of 2.5 ms-2 r.m.s. and the ELV A(8) of 5 ms-2 r.m.s. for HTV, at least for the vascular component (secondary Raynaud's phenomenon) of the hand-arm vibration syndrome.There is some experimental evidence for the EAV A(8) of 0.5 ms-2 r.m.s. for WBV, while there is neither biodynamic nor epidemiological validation for the ELV A(8) of 1.15 ms-2 r.m.s. for WBV, this latter lowered to 1 ms-2 r.m.s. in the Italian legislation.In questo studio vengono discussi i valori giornalieri di azione (VA) e i valori limite di esposizione giornaliera (VL) per le vibrazioni trasmesse al sistema mano-braccio e le vibrazioni trasmesse al corpo intero, stabiliti dalla Direttiva EU 2002/44/CE e recepiti dal D.Lgs. 81/2008, ed espressi in termini di valore efficace (r.m.s) dell’accelerazione ponderata in frequenza normalizzata a 8 ore di lavoro (A(8)). I dati della letteratura epidemiologica tendono a supportare il VA A(8) di 2.5 ms-2 r.m.s. e il VL A(8) di 5 ms-2 r.m.s. per le vibrazioni mano-braccio almeno per la componente vascolare (fenomeno di Raynaud secondario) della sindrome da vibrazioni mano-braccio. Vi è qualche evidenza sperimentale per il VA A(8) di 0.5 ms-2 r.m.s. per le vibrazioni al corpo intero, mentre non vi sono elementi di validazione biodinamica o epidemiologica per il VL A(8) di 1.15 ms-2 r.m.s., opportunamente abbassato a 1 ms-2 r.m.s. nella legislazione italiana.

Background Occupational skin diseases are often responsible for sick leave or job changes, affect mostly young subjects, are costly to society and have been reported as significant predictor of unemployment. Objectives To assess, over time, the course of occupational hand dermatitis (OHD) after a specific training, by means of follow-up visits and TEWL measurement, to evaluate skin barrier integrity and if preventive measures for hand skin care provided may influence the course of the disease. Methods Workers with a diagnosis of OHD from January 2011 to December 2013 were contacted by telephone, filled in a questionnaire (NOSQ-2002) and were invited to a training course on prevention of skin dermatitis, and to a new clinical evaluation with TEWL measurement. Workers who joined the training programme were asked to undergo a new evaluation after 3 months. A total of 65 subjects without contact dermatitis were recruited as control group. Results One hundred and one subjects from 143 workers, who were contacted, filled in the questionnaire. Sixty-five of them followed the training course and underwent a new clinical evaluation withTEWL measurements. Ongoing symptoms of subjects decreased from 60.0% to 42.3% 3 months after the training, and the subgroup which strictly adhered to the recommendations given achieved better results (61.9% of symptoms improvement when compared to 29.0% obtained in subjects with partial adhesion to the protocol). TEWL values changed from 21.3 ± 9.6 to 18.6 ± 7.2 g/m²/h (P = 0.001) on the hands and from 16.6 ± 9.0 to 10.5 ± 4.6 g/m²/h (P = 0.001) on the forearm, confirming the skin barrier improvement. Conclusions Our secondary prevention intervention was effective, leading to a reduction in clinical signs of dermatitis. TEWL measurement is a useful tool to evaluate skin integrity, mostly in apparently healthy skin, which may have a compromised barrier function, resulting in an exacerbation of the dermatitis.

The incidence of mesothelioma in Italy shows wide geographical variation, with the highest incidence rates in Genoa and Friuli Venezia Giulia (FVG). For mesothelioma, national standard incidence rates are not available prior to the calendar year 2006.To estimate the Standardized Incidence rate Ratio (SIR) of mesothelioma in a cohort of former workers undergoing health surveillance because of previous asbestos exposure, when sex-, age-, and calendar year-specific rates of the national standard are not available and the number of expected cases calculated from the regional rates is biased by the size of the study cohort.We conducted a sensitivity analysis in a cohort of 2,488 men. We considered every Italian cancer registry available with complete data in the period 1995-2007 (N=14). We calculated, for each year and age group, the corresponding weighted mean rate of 10 registries of North-Italy (Mean W10), the weighted mean rate of all 14 registries available (Mean W14) and considered FVG standard rate.During the period 1995-2007, we observed 25 incident cases of mesothelioma with expected cases that varied between 2.00 (Mean W14) and 2.56 (FVG standard rate), with a SIR of 12.49 (CI95% 8.08-18.48) and 9.76 (CI95% 6.32-14.45) respectively.Our results show that the use of FVG rates as standard does not lead to significant distortions in the calculation of the expected cases. However, distortion is remarkable in the SIRs estimation. Using a weighted mean standard incidence rate may be a valid alternative for SIR estimate when national standard rates are not available.

Background 4,4′-Diaminodiphenylmethane (DDM) is an aromatic amine used as a hardener, insulator and anticorrosive. Exposure implies risk of being sensitized and developing contact dermatitis. Objective The aim of this study was to determine the occurrence of contact sensitization to DDM among patients with contact dermatitis and the role of occupational exposure. Patients and Methods From 1996 to 2012, 24 056 consecutive patients with suspected allergic contact dermatitis were patch tested in north-eastern Italy. Individual characteristics were collected through a standardized questionnaire in eight departments of dermatology and occupational medicine. Results The overall prevalence of DDM sensitization was 2.5% (n = 599) with a decreasing trend in considered years. Trieste area had the higher prevalence of sensitization (3.2%). Mechanics and chemical industry workers had a significant higher risk of being sensitized to DDM. Conclusion DDM sensitization is decreasing in years and is associated with some occupational exposures.

Objective: To explore to what extent and under which diagnoses individuals who committed suicide had received psychiatric in-patient care, and how many had previously committed non-lethal self-harm. To investigate the antidepressant treatment received by these individuals. Methods: Case–control study based on a health register. Results: Psychiatric hospitalisation was found in 31.2% of the cases and 2.3% of the controls, and was a strong predictor for suicide with an odds ratio (OR) = 19.5. This did not differ significantly between diagnostic categories (except anxiety disorders with OR = 5.3). Nonlethal self-harm in the study period was committed by 14.3% of the cases and 0.14% of the controls, and was twice as common in female cases than in male cases. Previous self-harm was a very strong independent predictor for suicide with OR = 53.1 when a single episode of self-harm had occurred, and OR = 98.0 for repeated episodes (adjusted for age, gender and hospitalisation). Only 16.1% of the cases were currently on antidepressant medication at the time of suicide. Conclusions: Few of the suicides had previously been psychiatric in-patients. Even fewer had current prescriptions for antidepressants. This suggests that better diagnosis and treatment of psychiatric patients is an important suicide preventive intervention.

Objectives: Immune mediators are likely to be relevant for the biological response to asbestos exposure. The aim of this study was to investigate the association between immune mediators involved in inflammation, cell survival and angiogenesis, and asbestos-related diseases in workers from a coastal area of North-East Italy with a high incidence of pleural malignant mesothelioma (PMM). Materials and methods: A selected custom set of 12 soluble mediators was evaluated with a Luminex platform in sera, pleural fluid and mesothelioma biopsies from 123 asbestos-exposed workers (38 free from pleural-pulmonary disorders, 46 with non-malignant asbestos diseases, 39 with PMM) and in sera from 33 healthy controls from the same territorial area. Results: Increased immune mediator concentrations were observed in the sera of the asbestos-exposed workers compared to controls for human fibroblast growth factor (FGF-b), vascular endothelial growth factor (VEGF), CCL5 (RANTES), CXCL10 (IP-10), CLEC11A (SCGF-b), CCL27 (CTACK), CCL11 (EOTAXIN), IL-5 and IL-6 (p < 0.001). The chemokines IP-10 and RANTES were associated with the severity of asbestosrelated diseases. In the workers with PMM, the immune proteins secreted by mesothelioma biopsies showed detectable levels of RANTES, VEGF, and IP-10. In the same workers with PMM, a significant relationship between serum and pleural fluid concentrations was found for RANTES alone. Conclusions: Occupational exposure to asbestos seems to drive the production of specific growth factors dually involved in the early inflammatory response and in pro-tumoral activity before clinical evidence of related disorders, suggesting that their over-expression may precede the onset of asbestos-related diseases. These findings suggest that some chemokines may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by non-malignant asbestos-related diseases.

Objective The aim of this study was to investigate the performance of four frequency weightings for hand-transmitted vibration to predict the incidence of vibration-induced white finger (VWF). Methods In a longitudinal study of vibration-exposed forestry and stone workers (N=206), the incidence of VWF was related to measures of vibration exposure expressed in terms of 8-hour frequency-weighted energy-equivalent root-mean-square (rms) acceleration magnitude [A(8)] and years of follow-up. To calculate A(8), the rms acceleration magnitudes of vibration were weighted by means of four frequency weightings: (i) W(subscript h) (the frequency weighting specified in ISO 5349-1:2001); (ii) W(subscript h-bl) (the band-limiting component of W(subscript h)); (iii) W(subscript hf) (a frequency weighting based on finger vibration power absorption); and (iv) W(subscript hT) (a frequency weighting based on a Japanese study of VWF prevalence). The relations of VWF to alternative measures of vibration exposure were assessed by the generalized estimating equations (GEE) method to account for the within-subject dependency of the observations over time. Results Data analysis with a GEE logistic model and a measure of statistical fit suggested that calculating A(8) by weighting the tool rms accelerations with W(subscript h-bl) gave better predictions of the cumulative incidence of VWF than the other alternative measures of daily vibration exposure. Values of A(8) derived from the currently recommended ISO frequency weighting W(subscript h) produced poorer predictions of the incidence of VWF than those obtained with frequency weightings W(subscript hf) or W(subscript hT). Conclusions This prospective cohort study suggests that measures of daily vibration exposure which give relatively more weight to intermediate and high frequency vibration are more appropriate for assessing the probability of VWF.

Gold nanoparticles (AuNPs) are produced for many applications but there is a lack of available data on their skin absorption. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. A physiological solution was used as receiving phase and 0.5 mL (1st exp) and 1.5 mL (2nd exp) of a solution containing 100 mg L⁻¹ of AuNPs (15 and 45 μg cm⁻², respectively) was applied as donor phase to the outer surface of the skin for 24 h. Skin absorption was dose dependent. Mean gold content of 214.0 ± 43.7 ng cm⁻² and 187.7 ± 50.2 ng cm⁻² were found in the receiving solutions of cells where the AuNPs solution was applied in higher concentration on intact skin (8 Franz cells) and on damaged skin (8 Franz cells), respectively. Twenty-four hours gold flux permeation was 7.8 ± 2.0 ng cm⁻² h⁻¹ and 7.1 ± 2.5 ng cm⁻² h⁻¹ in intact and damaged skin, respectively, with a lag time less than 1 hour. Transmission Electron Microscope analysis on skin samples and chemical analysis using Inductively Coupled Plasma-Mass Spectrometry demonstrated the presence of AuNPs into epidermis and dermis. This study showed that AuNPs are able to penetrate the human skin in an in vitro diffusion cell system.

Background: Exposure to nickel, cobalt and chromate are important causes of occupational contact dermatitis. Objectives: To estimate the prevalence of nickel, cobalt and chromate allergy in a population of consecutive patients and to investigate the possible association with individual and occupational risk factors. Patients/Methods: A total of 14 464 patients (67.6% women and 32.4% men) with suspected allergic dermatitis underwent patch tests. The associations between patch test results and occupations were studied by multivariate logistic regression analysis. Results: About 24.6% of the patients reacted positively to nickel sulphate, 10.2% to cobalt chloride and 8.7% to potassium dichromate. Nickel sensitization was higher in women aged 26–35 years in comparison with the youngest group (15–25 years) and the older group (> 45 years). In women, the prevalence of positive reactions to nickel was positively associated with metal and mechanical work (OR 1.54; 95%, CI 1.16–2.05). Chromate sensitization was more prevalent in building trade workers for both women (OR 1.58; 95% CI 1.00–2.49) and men (OR 2.24; 95% CI 1.55–3.22). Cobalt sensitization was associated with textile and leather work in women (OR 1.52; 95% CI 1.09–2.12) and with cleaning work in men (OR 1.86; 95% CI 1.18–2.93). Conclusions: Our study showed interesting associations between some occupations and nickel, chromate and cobalt allergy.

The objective of this study was to investigate the relation between alternative measures of exposure to whole-body vibration (WBV) and low back pain (LBP) in professional drivers.The incidence of 12-month LBP, high pain intensity (numerical rating scale score5), and disability in the lower back (Roland and Morris disability scale scoreor=12) was investigated in a cohort of 537 drivers over a 2-year follow-up period. LBP outcomes, individual characteristics, and work-related risk factors were investigated by direct interview using a structured questionnaire. Daily vibration exposure was expressed in terms of either equivalent acceleration over an 8-h reference period [A(8), root-mean-square (r.m.s.) method] or vibration dose value [VDV, root-mean-quad (r.m.q.) method]. From the vibration magnitudes measured on vehicles and total exposure duration, seven alternative measures of cumulative vibration exposure were calculated for each driver, using expressions of the form Sigma a (i)(m)t(i), where a (i) is the frequency-weighted r.m.s. or r.m.q. acceleration magnitude on vehicle i(a(ws) or a (wq), respectively), t(i) is the lifetime exposure duration for vehicle i, and m = 0, 1, 2, or 4.In the drivers' cohort, the cumulative incidence of LBP outcomes were 36.3% for 12-month LBP, 24.6% for high pain intensity, and 19.2% for disability in the lower back. A transition model, which takes into account the temporal sequence of cause and effect and captures the longitudinal part of the relationship, showed that VDV performed better than A(8) for the prediction of LBP outcomes. After adjusting for potential confounders, test for trends suggested an increased risk for developing high pain intensity and disability over time (and, to a lesser extent, 12-month LBP) with the increases of cumulative vibration doses computed from lifetime exposure duration and r.m.q. vibration magnitude (i.e. Sigma[a (wqi)(m)t(i)]). Measures of exposure duration, either daily or lifetime, also provided good indications of risk for LBP outcomes over time. Physical work load, but not psychosocial environment, was significantly associated with the occurrence of LBP outcomes over time.Measures of vibration exposure derived from exposure duration (daily or lifetime) and r.m.q. acceleration magnitude (VDV, Sigma[a(wqi)(m)t(i)]) were better predictors of LBP outcomes over time than measures of vibration exposure including r.m.s. acceleration (A(8), summation operator[a(wsi)(m)t(i)]). Patterns of exposure-response relationship were more evident for the outcomes high pain intensity or disability in the lower back than for the binary response 12-month LBP.

Objectives To assess the usefulness of color charts for the diagnosis of finger whiteness in vibration-exposed workers. Methods A group of 146 forestry and stone workers exposed to hand-transmitted vibration (HTV) were examined twice over 1 year follow up period. The anamnestic diagnosis of finger whiteness was made on the basis of (a) a medical history alone, and (b) the administration color charts which showed changes in the skin color of fingers and hands. The cold response of digital arteries was assessed by measuring the change in finger systolic blood pressure (FSBP) after local cooling from 30 to 10C (FSBP%10). Results Assuming the administration of color charts as the gold standard, the sensitivity and specificity of the medical history alone to diagnose finger whiteness was 88.2 and 93.8%, respectively, at the initial cross-sectional study and 94.4 and 97.7% at the end of the follow-up. Random-intercept linear regression analysis of follow up data showed that after adjustment for several covariates, FSBP%10 was significantly associated with finger whiteness assessed by either medical history alone (P\0.005) or the color charts (P\0.001). However, a statistical measure of overall fit of regression models (Bayesian Information Criterion) suggested that the color chart method performed better than medical history alone for the prediction of the cold response of digital arteries. Conclusion The administration of color charts seems to reduce the proportion of false positive responses for finger whiteness in a population of vibration-exposed workers. The color chart method was a more significant predictor of digital arterial hyperresponsiveness to cold than medical history alone. These findings suggest that the use of color charts in clinical and epidemiological studies may be of help to assist in the diagnosis of finger whiteness in vibration-exposed workers.

Objectives To investigate the relation between manipulative dexterity and vibration exposure, ergonomic risk factors, and upper limb disorders in a group of workers exposed to hand-transmitted vibration (HTV). Methods Manipulative dexterity was investigated on 115 HTV workers (82 forestry workers and 33 stone workers) and 64 control men over 1-year follow-up period. The Purdue pegboard method was used to test manipulative dexterity which was scored for the dominant hand, nondominant hand, and both hands. Information about individual, work and health history was obtained by means of a standardised questionnaire. Vibration exposure was assessed in terms of tool vibration magnitudes, daily and total exposure duration, and cumulative vibration dose. Results On the cross-sectional investigation, Purdue pegboard scores were significantly lower in the HTV workers than in the controls (0.001 \ P \ 0.05). Over 1-year follow-up period, Purdue pegboard scores were found to be inversely related to age, smoking and use of vibratory tools (0.001 \ P \ 0.05). Moreover, deterioration of some measures of manipulative dexterity was significantly associated with sensorineural and vascular symptoms in the fingers of the HTV workers. Randomintercept linear regression analysis showed that Purdue pegboard scores decreased with the increase of vibration exposure. The reduction of assembly score (i.e. number of pins, collars, and washers assembled in a 60-s period) was significantly associated with the increase in vibration exposure and ergonomic stress (neck-upper arm posture, hand-intensive work, and total ergonomic score). Purdue pegboard scores tended to improve over the follow-up period in both the controls and the HTV workers, suggesting a possible learning effect over time. Conclusion The findings of this longitudinal study suggest an association between deterioration of manipulative dexterity and neurovascular symptoms in the fingers of HTV workers. There was evidence for a significant relation between loss of precise manipulation and exposures to hand-transmitted vibration and ergonomic risk factors.

Occupational exposures to vibration come in many guises, and they are very common at a population level. It follows that an important minority of working-aged patients seen by medical services will have been exposed to this hazard of employment. Vibration can cause human health effects, which may manifest in the patients that rheumatologists see. In this chapter, we identify the health effects of relevance to them, and review their epidemiology, pathophysiology, clinical presentation, differential diagnosis and vocational and clinical management. On either side of this, we describe the nature and assessment of the hazard, the scale and common patterns of exposure to vibration in the community and the legal basis for controlling health risks, and we comment on the role of health surveillance in detecting early adverse effects and what can be done to prevent the rheumatic effects of vibration at work.

OBJECTIVE: This cohort study aims to compare the performance of alternative frequency weightings of hand-transmitted vibration (HTV) for the assessment of the exposure–response relationships for neurosensory disorders and reduced work ability among HTV-exposed workers. METHODS: In a 3-year follow up study, the occurrence of neurosensory symptoms and reduced work ability, and the response to quantitative sensory testing (grip force, manipulative dexterity, touch sensation) were investigated in 249 HTV-exposed workers and 138 healthy controls. Among the HTV-exposed workers, the sensory outcomes were related to measures of daily vibration exposure expressed in terms of 8-hour energy-equivalent frequency-weighted acceleration magnitude [A(8)]. To calculate A(8), the acceleration magnitudes of vibration were weighted by means of four alternative frequency weightings of HTV. RESULTS: The occurrence of neurosensory symptoms, reduced work ability, and abnormalities of sensory tests was greater among the HTV-exposed workers than the controls. Among the HTV-exposed workers, the deterioration of neurosensory outcomes and the reduction of work ability increased on par with the measures of vibration exposure. Exposure–response models revealed that the four alternative frequency weightings of HTV provided the same predictions for the probability of finger numbness among the exposed workers (observed 36% versus predicted 32%). CONCLUSIONS: The findings of this study revealed significant dose–response relationships between measures of vibration exposure, sensory disorders, and reduced work ability among the HTV-exposed workers. There were no differences in the prediction of finger numbness between measures of vibration exposure calculated with alternative frequency weightings of HTV.

In a prospective cohort study of 537 male professional drivers, the occurrence of sciatic pain showed stronger associations with measures of internal lumbar load expressed in terms of daily compressive dose, S(ed) (MPa), and risk factor, R (non-dimensional), according to ISO/WD 2631-5 (2013), than with measures of daily vibration exposure calculated as either 8-h energy-equivalent frequency-weighted acceleration (ms(-2) r.m.s.) or vibration dose value (ms(-1.75)) according to the EU Directive on mechanical vibration (2002). Herniated lumbar disc, previous lumbar trauma and physical work load were also powerful predictors of the occurrence of sciatic pain over time. Psychosocial work environment was poorly associated with sciatic pain. The boundary values of risk factor (R) for low and high probabilities of adverse health effects on the lumbar spine, as proposed by international standard ISO/WD 2631-5 (2013), tend to underestimate the health risk in professional drivers.In a prospective cohort study of professional drivers, measures of internal spinal load were better predictors of the occurrence of sciatic pain than the measures of daily vibration exposure established by the EU Directive (2002). Herniated lumbar disc, lumbar trauma and physical work load were also associated with sciatic pain.

Background Many somatic disorders are complicated by depression and increase the risk of suicide. Little is known about whether antidepressants might reduce the suicidal risk in patients with somatic disorders. Methods Data on diagnoses and antidepressant prescriptions were derived from the Social and Health Information System of the Friuli Venezia Giulia Region. Cases were all suicides that occurred in the region during the years 2003–2013 and were sex- and age-matched to controls from the general population. Conditional logistic regression analysis was used to assess the association between suicide and somatic disorders. Results The suicide rate in Friuli Venezia Giulia decreased from 11.3 to 10.7 per 100,000 inhabitants during the years 2003–2013, however patients with somatic disorder had a three times increased risk of suicide. Elderly somatic patients' suicide risk was twice as high as younger patients. The risk increased from 2.6 to 9.8 times as the number of comorbid disorders increased from 1 to 4 and over. Although no significant risk of suicide in patients with somatic disorders was found when patients were adherent to antidepressants, only 11.5% of the suicides was adherent in the year prior to death. Conclusions Medical illnesses and underlying depressive symptoms may have a synergy effect on the risk of suicide, particularly in older patients and in patients with multiple morbidities. Since medically ill subjects adherent to antidepressants did not show a significant risk of suicide, early identification and adequate treatment of depression in somatic patients should be considered in order to prevent suicide.

Objectives Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as ‘soluble mesothelin-related proteins’ (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage. Materials and methods A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the ‘3-biomarker classifier’ was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated. Results and conclusion The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.

Introduction Epidemiological studies have provided strong evidence for an association between neck pain and awkward working postures [1]. There is also evidence for a causal relationship between highly repetitive work and neck and shoulder pain (NSP), and between neck disorders and forceful movements [1]. At present, epidemiological data are insufficient to provide support for a relationship of whole-body vibration (WBV) to NSP. Some studies have suggested that psychosocial factors at work and individual psychological distress may play a role in the development of NSP. The aims of this cohort study were to investigate the occurrence of NSP and the relation between NSP and individual- and work-related factors (WBV, physical load, psychosocial environment) in Italian professional drivers recruited in the EU VIBRISKS project [2]. Methods The study population included 537 male professional drivers of earth-moving machines, fork-lift trucks, and public utility vehicles. They were investigated over a two-year follow up period (2003-2006). Personal, occupational, and health histories were collected by means of the VIBRISKS questionnaire. NSP outcomes in the previous 12 months were treated as ordinal variables with four levels and assessed in terms of number of episodes (0, 1-5, 6-10, >10), duration (0, 1-6, 7-30, >30 days), and pain intensity (numerical rating scale (NRS) score: 0, 1-3, 4-5, 6-10). Cumulative WBV exposure was expressed as (awsi2ti) in m2s-4h, where awsi is the r.m.s. value of the vibration total value of the frequency-weighted accelerations measured on vehicle i driven for time ti in hours (hours/day  days/year  years). The following physical load factors were investigated: lifting (> 15 kg) with trunk bent or twisted, work with hands above shoulder level, driving with trunk bent or twisted. Psychosocial risk factors were expressed in terms of job decision, job support and job satisfaction. Psychological distress and psychosomatic symptoms were also investigated. The associations between NSP (ordinal) outcomes and individual- and work-related risk factors were expressed as proportional odds ratios estimated by random-intercept ordered logistic regression using time-lag models (i.e. NSP for subject i at time t (Yit) was related to predictor variable(s) k at time t – 1 (Xikt-1), i.e. the values of the predictors at one measurement earlier). Results At the initial survey, in the entire population of professional drivers the point prevalence of neck pain was 43.4%, and that of shoulder pain was 19.9%. The cumulative incidence rates for neck and shoulder pain over the follow-up period were 31.9 and 21.4%, respectively (Table 1). The incidence of high pain intensity (NRS score > 5) was 15.7% for the neck and 10.4% for the shoulder. At some points of the follow-up period there were cases of neck or shoulder pain who reported recovery from symptoms. As a result, the occurrence of persistent neck and shoulder pain in the study population (calculated over period prevalence) was 78.8 and 65.3%, respectively. After adjustment for potential confounders, cumulative WBV exposure was significantly associated with NSP outcomes (episodes, duration, intensity) over the follow-up period (Table 2). Frequent awkward postures while driving were significantly related to the frequency and severity of neck pain, while lifting with trunk bent or twisted > 45 min/day was associated with the duration of neck pain. Tasks involving prolonged exposures to lifting with awkward postures (>45 min/day) and work with hands above shoulder level (>1 h/day) were strongly associated with nearly all shoulder outcomes. Limited job decision and job dissatisfaction were significant predictors of episodes of neck pain over time, and low social support was related to pain intensity in the neck. Perceived psychosocial work factors were not significantly associated with shoulder outcomes even though there was some evidence for a positive trend. Psychological distress was strongly related to all NSP outcomes over the follow-up period. There were no significant interactions between work-related risk factors when appropriate product terms were included in multivariate data analysis. Conclusions The findings of this prospective cohort study tend to confirm that neck and shoulder outcomes are of multifactorial origin in a population of professional drivers. Cumulative WBV exposure, physical load factors and adverse psychosocial environment seem to contribute independently of each other to the development of neck and shoulder disorders in driving occupations. References [1] NIOSH. Musculoskeletal disorders and workplace factors – a critical review of epidemiologic evidence for work-related musculoskeletal disorders of the neck, upper extremity, and low back. DHHS (NIOSH) Publication No. 97-141. Cincinnati, OH, 1997. [2] VIBRISKS. Final Technical Report. (www.vibrisks.soton.ac.uk).

To investigate whether prior exposure to hand-transmitted vibration on the day of a cold provocation test affects the cold response of digital arteries.Each of ten healthy men attended two experimental sessions in which their right hands were exposed for 60 min to either contact force alone (5 N) or a combination of contact force (5 N) and 125-Hz vertical vibration with an acceleration magnitude of 64 m s(-2) r.m.s. (unweighted). Finger systolic blood pressure (FSBP) during local cooling to 10 degrees C was measured in the second right finger (exposed hand) and the second left finger (unexposed hand) before exposure and at 30 and 70 min after the end of both exposure conditions.Analysis of repeated measures of FSBP during local cooling by means of an autoregressive model revealed no significant difference in cold-induced vasoconstriction of the digital arteries between exposure to contact force alone and combined exposure to contact force and vibration. There were no significant changes in the cold response of digital arteries over time in either the right or the left hand after exposure of the right hand to either the contact force alone or the combined contact force and vibration.The results of this experimental study of the influence of prior vibration exposure on the cold test results suggest that in healthy men recent exposure to contact force and moderate levels of hand-transmitted vibration does not affect the response of finger circulation to cold provocation. These findings may be of practical importance for the definition of test conditions in the field, especially the length of time required between the last occupational exposure to tool vibration and the commencement of objective vascular testing.

Nanoparticles (NPs) skin absorption is a wide issue, which needs to be better understood. The attempt of this review is to summarize the scientific evidence concerning open questions, i.e.: the role of NPs intrinsic characteristics (size, shape, charge, surface properties), the penetration of NPs through the intact or impaired skin barrier, the penetration pathways which should be considered and the role of NPs interaction in physiological media. The outcomes suggest that one main difference should be made between metal and non-metal NPs. Both kinds have a secondary NPs size which is given after interaction in physiological media, and allows a size-dependent skin penetration: NPs 6 4 nm can penetrate and permeate intact skin, NPs size between 4 and 20 nm can potentially permeate intact and damaged skin, NPs size between 21 and 45 nm can penetrate and permeate only damaged skin, NPs size > 45 nm cannot penetrate nor permeate the skin. Other aspects play an important role, mostly for metal NPs, i.e., dissolution in physiological media, which can cause local and systemic effects, the sensitizing or toxic potential and the tendency to create aggregates. This paper suggests a decision tree to evaluate the potential risk for consumers and workers exposed to NPs.

Objectives: To investigate the prevalence of vascular, neurological and musculoskeletal disorders of the upper limb in a group of female workers performing either mechanical or hand sanding in the furniture industry (n=100) and in a control group of female office workers (n=100). A further aim was to study the possible adverse effects of exposure to a combination of vibration and ergonomic risk factors in female workers. Methods: All female workers underwent a medical interview and a complete physical investigation. The clinical diagnoses of Raynaud’s phenomenon and carpal tunnel syndrome (CTS) were made according to international consensus criteria. Hand-transmitted vibration from orbital sanders was measured according to International Organization for Standardization (ISO) recommendations. Daily vibration exposure was assessed in terms of 8-h energy-equivalent frequency-weighted acceleration [A(8)] according to the European Directive on physical agents. Ergonomic load on the upper limbs was estimated by means of strain index methodology. Results: There was no significant difference in the prevalence of Raynaud’s phenomenon between the furniture workers (4%) and the controls (8%). The prevalence of CTS, peripheral sensorineural disturbances (after exclusion of CTS cases) and upper-limb musculoskeletal complaints was significantly greater in the furniture workers than in the controls. CTS was clinically diagnosed in 19% of the furniture workers and 8% of the controls. A log-binomial regression analysis showed that the occurrence of soft-tissue disorders of the upper limb increased significantly with the increase of both daily vibration exposure and the strain index score. It was estimated that the risk for CTS increased by a factor of 1.30 (95% CI 1.11–1.53) for each unit of increase in A(8) (ms−2), and by 1.09 (95% CI 1.02–1.15) for each unit of increase in the strain index score. Conclusions: Even though the cross-sectional design of this epidemiological study does not allow aetiological considerations, our findings suggest a significant association between occupational use of vibratory tools and soft-tissue disorders in the upper limbs of female workers. Quantitative estimation of vibration exposure and ergonomic stress showed that these physical risk factors seem to contribute in a multiplicative way to the occurrence of chronic nerve and musculoskeletal disorders in female workers operating hand-held vibrating tools in the furniture industry.

To compare the acute response of finger circulation to continuous and intermittent vibration having the same total duration of vibration exposure and the same energy-equivalent acceleration magnitude.Finger blood flow (FBF) was measured in the middle and little fingers of both hands of ten healthy men. Finger skin temperature (FST) was measured in the middle right finger. With a static load of 10 N, the middle finger of the right hand was exposed to 125 Hz at 44 m s(-2) root mean square (r.m.s.) in five conditions: (1). 30 min continuous exposure, (2). two periods of 15 min, separated by a 15 min period with no vibration, (3). four periods of 7.5 min, separated by 7.5 min periods with no vibration, (4). eight periods of 3.75 min, separated by 3.75 min periods with no vibration, (5). 16 periods of 1.88 min, separated by 1.88 min periods with no vibration. All five exposures correspond to an 8 h energy-equivalent frequency-weighted acceleration magnitude of 1.4 m s(-2) r.m.s. according to International Standard ISO 5349-1 (2001). Finger circulation was measured in all four digits before the application of vibration and at fixed intervals during vibration exposure and during a 45 min recovery period.The FST did not change during vibration exposure, whereas all vibration conditions produced significant reductions in FBF of the vibrated finger when compared with the pre-exposure FBF. During vibration exposure, the vibration caused a similar degree of vasoconstriction in the vibrated finger without evidence of cumulative effects during intermittent exposure. After the end of exposure to 30 min of continuous vibration there was a progressive decrease in the FBF, whereas there was no statistically significant reduction following exposure to intermittent vibration.For the vibration stimuli investigated (exposure durations varying from 1.88 min to 30 min, with rest periods varying from 1.88 min to 15 min), the reduction of FBF during exposure was the same for continuous and intermittent vibration. The after effect of vibration was greater following the continuous vibration exposure. Although some evidence from this study is consistent with the notion that intermittent vibration has a less severe effect than continuous vibration, this evidence is not yet conclusive.

The present study aimed to (1) employ the method for evaluation of vibration containing multiple shocks according to ISO/CD 2631-5:2014 (Model 1) and DIN SPEC 45697:2012 in a cohort of 537 professional drivers, (2) deliver the results for a re-analysis of epidemiological data obtained in the VIBRISKS study, (3) clarify the extent to which vibration acceleration and individual variables influence risk values, such as the daily compressive dose S(ed) and the risk factor R, and (4) compare the results with in vivo measurements and those obtained in previous studies with similar models. The risk factor R was influenced by the acceleration, lifetime exposure duration, sitting posture, age at the start of exposure and body mass/body mass index in order of decreasing effect. Age and annual and daily exposure duration had only a marginal effect. The daily compressive dose S(ed) and the risk factor R showed weak linear association with the daily vibration exposure A(8) and the vibration dose value VDV. The study revealed high shear forces in the lumbar spine.In a re-analysis of an epidemiological study of professional drivers, a software tool available with standards DIN SPEC 45697:2012 and ISO/CD 2631–5:2014 Model 1 was used to calculate the risk to the lumbar spine in terms of daily compressive dose S(ed) and risk factor R. The tool was found to be suitable for risk assessment in a large cohort.

Objectives This study investigated the effect of hand elevation on reductions in finger blood flow (FBF) induced by hand-transmitted vibration. Methods Fourteen males attended six sessions on six separate days, with a control sessions and a vibration session (125-Hz vibration at 44 ms 2 r.m.s.) with the right hand supported at each of three elevations: 20 cm below heart level (HL), at HL, and 20 cm above HL. Finger blood flow on the left and right hand was measured every 30 s during each 25-minute session comprised of five periods: (i) no force and no vibration (5 minutes), (ii) 2-N force and no vibration (5 minutes), (iii) 2-N force and vibration (5 minutes), (iv) 2-N force and no vibration (5 minutes), and (v) no force and no vibration (5 minutes). Results Without vibration, FBF decreased with increasing elevation of the hand. During vibration of the right hand, FBF reduced on both hands. With elevation of the right hand, the percentage reduction in FBF due to vibration (relative to FBF on the same finger at the same elevation before exposure to vibration) was similar on the middle and little fingers of both hands. After cessation of vibration, there was delayed return of FBF with all three hand heights. Conclusions Vibration of one hand reduces finger blood flow on both exposed and unexposed hands, with the reduction dependent on the elevation of the hand. The mechanisms responsible for vibration-induced reductions in FBF seem to reduce blood flow as a percentage of the blood flow without vibration. Tasks requiring the elevation of the hands will be associated with lower FBF, and the FBF will be reduced further if there is exposure to hand-transmitted vibration.

Purpose – To investigate the relationships between low back symptoms and alternative measures of external dose and internal spinal dose in professional drivers exposed to whole body vibration (WBV). Methods – The occurrence of low back symptoms were investigated in a cohort of 537 drivers over a two-year follow up period. Low back pain (LBP), individual characteristics, and work-related risk factors were investigated with a structured questionnaire. Exposure to WBV was evaluated by means of measures of external dose (daily vibration exposure in terms of either equivalent continuous acceleration over an eight-hour period (A(8)) or vibration dose value according to the EU Directive on mechanical vibration) and measures of internal lumbar load (daily compressive dose Sed and risk factor R according to ISO/CD 2631-5 2014). Results – In the drivers’ cohort, the cumulative incidence of 12-month low back outcomes was 16.8% for LBP, 9.3% for chronic LBP, and 21.8% for sciatic pain. The measures of internal spinal load were better predictors of the occurrence of low back symptoms than the measures of daily vibration exposure. A two-fold increase in the risk estimates for low back outcomes was found in the upper quartile of the R factor (0.41-0.72 units) compared to the lower one (0.07-0.19 units). Conclusions – In this prospective cohort study, measures of internal spinal dose performed better than measures of daily vibration exposure (external dose) for the prediction of low back outcomes in professional drivers. The ISO boundary values of the risk factor R for low and high probabilities of adverse health effects on the lumbar spine tend to underestimate the health risk in professional drivers.

Glioblastoma multiforme (GBM) is the most severe form of cancer among gliomas. Indeed, GBM is a World Health Organization grade IV tumor of the CNS, with a mean survival time of 0.5 years.1 Its incidence is ∼1/100 000, which represents 30% of all CNS malignancies.2 According to the recent Eurocare 3 report,3 the mean age of patients affected by glioblastoma is 66 years. The extremely grim prognosis of GBM patients probably explains why such a rare tumor accounts for 2% of all cancer-related deaths in both Europe and the United States.4 GBM is characterized by high genotypic and phenotypic heterogeneities, but it is invariably and homogeneously resistant to conventional chemo/radiotherapy.1 The vast majority (95%) of GBM is represented by primary de novo glioblastomas.5 GBM is considered, like other tumors, a genetic disease of the somatic cell due to an impressive series of alterations of the cellular genome, such as point mutations, gene amplifications, translocations, and deletions, as well as epigenetic modifications, including methylation of specific genes. A limited percentage (5%) of GBM is linked to genetic predispositions, which are mainly associated with rare hereditary syndromes, such as Li–Fraumeni syndrome, Turcot syndrome, Peutz–Jegher syndrome, and neurofibromatosis 1 and 2.2 Exposure to chemical and physical carcinogenic agents, the genetic predisposition, and/or infections by oncogenic viruses, including simian virus 40 (SV40), have been repeatedly advocated in the literature.6,7 SV40 is a nonenveloped small DNA virus of ∼5.2 kb in size. SV40 was recognized in the 1960s as a contaminant of both inactivated (Salk) and live attenuated (Sabin) antipoliomyelitis vaccines. As a consequence, SV40 was inadvertently administered to human populations worldwide mainly by antipoliomyelitis vaccines, produced in SV40 naturally infected monkey kidney cells. Soon after its isolation, SV40 was characterized as a transforming and tumorigenic viral agent.6,7 Cell transformation and tumorigenesis by SV40 is induced by 2 oncoproteins, the large T antigen (Tag) and the small t antigen (tag), which target key cellular proteins, such as the tumor suppressor p53 and retinoblastoma family proteins, inactivating their functions.6,8 This small DNA tumor virus was found to be associated with some human cancers, including GBM. SV40 footprints were detected at high prevalence in GBM specimens, but SV40 sequences have also been revealed, although at lower prevalence, in blood specimens from healthy donors.9–11 In this context it is worth recalling that other investigations did not find SV40 footprints in human brain tumor specimens12,13 or higher SV40 antibodies in serum samples from brain tumor patients than in normal individuals.14 It has been reported that SV40-negative data on human tumor samples obtained by some groups were affected by technical flaws that invalidate the conclusions.15–17 A considerable debate, because of these contrasting reports, has developed in the scientific community.6,7 SV40 antibody detection had been performed in most cases using serologic methods with SV40 virus-like particles, but due to the high protein homology among the 3 main polyomaviruses—SV40, BKV, and JCV—final results were always influenced by some cross-reactivity.18–24 Altogether these reports prompted us to use an indirect ELISA with synthetic peptides employed as specific mimotopes, mimicking SV40 viral capsid antigens. Indeed, recent investigations have reported on the development of a specific and sensitive serologic test for SV40. The test is based on an indirect ELISA employing synthetic peptides as mimotopes/antigens of SV40 viral capsid proteins (VPs), without cross-reactivity with other closely related human polyomaviruses, such as BKV and JCV.25–28 This immunologic assay was used to detect specific serum antibodies against SV40 VPs in normal individuals of different ages and oncologic patients affected by malignant pleural mesothelioma and breast cancer (BC).25–28 In this investigation, serum samples from GBM patients were comparatively analyzed for the presence and titer of antibodies against SV40 infection, with serum samples from healthy individuals and from other reliable controls. No other slow virus infections were investigated.