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In the present study we evaluated the relationship between human vibrational comfort and psychophysiological processes. We exposed twenty-one participants to three levels of whole-body vibration at low intensity inside a full-scale mock-up of a ship cabin. Autonomic Nervous System (ANS) activity, mood and well-being state during each level of vibration exposure were measured. We found that a positive affective state determined greater changes in ANS activity in response to vibration variations compared to a negative affective condition. Furthermore, we found that variations of the vibration intensity did not always determine variations of the comfort experience at physiological and psychological level. The relevance of our findings is a challenge for comfort design research showing a gap between guidelines for comfort design and evidence based on psycho-physiological responses to environmental stimulation.

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.

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 Al2O3NPs dispersed in synthetic sweat (20 g/L) using excised human skin on Franz cells. Experiments were performed using intact (experiment 1) and needle-abraded skin (experiment 2). After 24 h traces of Al were detectable in receiving solution of exposed cells (35.0 ± 6.0 ng/cm2 for intact and 88.5 ± 34.2 ng/cm2 for damaged skin, mean and SD) and in blank cells (36.3 ± 7.0 ng/cm2), without statistical significance (p = 0.08, Mann-Whitney test). The average amount of Al into intact and damaged skin samples was 3.96 ± 0.20 μg/cm2 for intact and 4.36 ± 0.47 μg/cm2 for damaged skin (p = 0.08). Al content was similar in epidermal and dermal layers of intact and damaged skin (1.95 ± 0.13 μg/cm2 and 2.31 ± 0.12 μg/cm2 epidermal, 2.01 ± 0.25 μg/cm2 and 2.05 ± 0.35 μg/cm2 dermal). Al is a trace element in human body and the amount found in receiving solutions could be due as background impurity. This data suggest a reassuring transdermal permeation profile for Al2O3NPs.

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.

MnFe2O4 nanoparticles (NPs) are commonly produced in some occupational settings and may reach high concentration in activities such as arc-welding or ferroalloy metallurgy. Manganese is an essential cofactor in enzyme activities but it has been demonstrated that long-term exposure to excessive levels can lead to “manganism”, a neurodegenerative disease resembling Parkinson features. Inhaled NPs deposit partially in pharynx and nasopharynx and may reach the central nervous system through the olfactory nerve, which is completely enveloped by the meningeal membranes throughout its course from the nasal cavity to the olfactory bulb or through the trigeminal nerves. This study investigated in vitro the transmeningeal absorption of 50 nm MnFe2O4NPs, using excised porcine meninges mounted on Franz diffusion cells. We tested two donor solutions: the first containing MnFe2O4NPs (2.0 g/L) and the second obtained by the ultrafiltration of the first one, in order to test only the NPs water soluble fraction. Each experiment was carried separately for 4 h. Results showed that no Mn flux permeation through the meninges occurred, since only trace of the metal was found in receivers solutions of cells exposed to MnFeNPs (5.5 ± 2.2 ng/cm2), ultrafiltered solution (3.5 ± 1.5 ng/cm2) and blank cells. (2.1 ± 0.6 ng/cm2) (mean and SE). Differences did not reach the statistical significance. Our study shows – for the first time - that MnFe2O4NPs penetrate the meningeal membrane in a negligible amount, thus making unlikely the hypothesis of a transcellular and paracellular absorption through the olfactory nerve but not excluding the hypothesis of an active intraneuronal absorption.

We herein report an unusual case of a 40-year-old woman presenting to the emergency department with acute-onset tetraparesis due to inhalation of chemical solvents containing n-hexane. The clinical picture, a mild albumin-cytologic dissociation and the demyelinating features on nerve conduction study initially mimicked the presentation of Guillain-Barré syndrome (GBS), but the patient failed to respond to intravenous immunoglobulin treatment and plasma exchange. Diagnosis of hexane-induced neuropathy was then confirmed by means of sural nerve biopsy, showing axonal enlargement with secondary retraction and thinning of the myelin sheath.

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.

A Síndrome do Dedo Branco Induzida pela Vibração (neste texto referida simplesmente como Síndrome) é uma forma secundária do Fenômeno de Raynaud,causada pela exposição ocupacional às vibrações em mãos e braços, geradas em vários processos de trabalho que utilizam ferramentas de rotação ou de pressão, ou quando peças de trabalho em vibração são seguradas pelas mãos ou dedos.

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.

Silver nanoparticles (AgNPs) can come in contact with human oral mucosa due to their wide use in food industry and hygiene devices. We evaluate transmucosal absorption of 19 nm AgNPs using excised porcine buccal mucosa applied on Franz diffusion cells. Two donor solutions were used: one containing AgNPs (0.5 g/L) and one derived from the ultrafiltration of the former and containing only Ag in its soluble form. Experiments were carried out separately for 4 h. Silver flux permeation was demonstrated through oral mucosa, showing similar values for AgNPs (6.8±4.5 ng cm(-2) h(-1)) and Ag ions (5.2±4.3 ng cm(-2) h(-1)). Our study demonstrates that silver can permeate the oromucosal barrier and that absorption is substantially due to Ag ions, since no permeation difference was found using the two solutions. Mucosal absorption has to be considered in further risk assessment studies.

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.

BACKGROUND Non-Hodgkin lymphoma (NHL), the most common cancer of the lymphatic system, is of unknown etiology. The identification of etiologic factors in the onset of NHL is a key event that could facilitate the prevention and cure of this malignancy. Simian virus 40 (SV40) has been considered an oncogenic agent in the onset/progression of NHL. METHODS In this study, an indirect enzyme-linked immunosorbent assay with 2 synthetic peptides that mimic SV40 antigens of viral capsid proteins 1 to 3 was employed to detect specific antibodies against SV40. Serum samples were taken from 2 distinct cohorts of NHL-affected patients (NHL1 [n = 89] and NHL2 [n = 61]) along with controls represented by oncologic patients affected by breast cancer (BC; n = 78) and undifferentiated nasopharyngeal carcinoma (UNPC; n = 64) and 3 different cohorts of healthy subjects (HSs; HS1 [n = 130], HS2 [n = 83], and HS3 [n = 87]). RESULTS Immunologic data indicated that in serum samples from NHL patients, antibodies against SV40 mimotopes were detectable with a prevalence of 40% in NHL1 patients and with a prevalence of 43% in NHL2 patients. In HSs of the same median age as NHL patients, the prevalence was 16% for the HS1 group (57 years) and 14% for the HS2 group (65 years). The difference was statistically significant (P

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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 Regular exposure to hand-arm vibration can lead to hand-arm vibration (HAVS) and carpal tunnel (CTS) syndromes. EU Directive 2002/44/EC, which aims to improve surveillance and reduce exposure to vibration at work, defines exposure limits for hand-arm-vibration. The aim is to investigate whether the staged implementation of the directive since 2005 has been associated with a change in the incidence of HAVS or CTS in European countries. To model the range of potential outcomes of the intervention, we sought to define an exposure-risk relationship based on the best available prospective longitudinal data for exposed workers. Methods In a series of studies, which have been subject of previous publications, 1,2 forestry and stone workers were monitored at intervals of 1 to 5 years, on 1 to 4 occasions. Health status, annual hours of exposure and magnitude of vibration were recorded. In the present study, a novel analytical approach was applied to define a parametric survival function describing the incidence of HAVS as a function of various exposure metrics. Results Incidence of the vascular condition vibration-induced white finger was well described by a Weibull distribution with an increasing hazard rate. The resulting parametric equation reveals the role of duration of exposure and the vibration magnitude (m s-2) relative to a threshold magnitude. Conclusion The exposure-risk relationship, which differs in some respects from the exposure relationship described in current standards (e.g. ISO 5349-1, 2001), has a simple, mechanistically based form that can be easily applied to simulate the consequences of workplace interventions. References Bovenzi M. Int Arch Occup Environ Health 2008; 81 :401–408. doi:10.1007/s00420-007-0225-9 Bovenzi M. Int Arch Occup Environ Health 2010; 83 :259–272. doi:10.1007/s00420-009-0461-2

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.