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Malignant pleural mesothelioma (MPM) is an aggressive tumour resistant to treatments. Multimodality treatment is the gold standard therapy at early stage of MPM; however, failure to eradicate in local and/or distant sites is a major concern. It has been postulated that cancer stem cells (CSCs) persist in tumours causing relapse after multimodality treatment. In the present study, a novel miRNA-based therapy approach is proposed. MPM-derived spheroids, which resemble the natural tumours, have been treated with exosome-delivered miR-126 (exo-miR) and evaluated for its anticancer effect. The exo-miR treatment increased MPM stem-cell like stemness and inhibited cell proliferation. However, at prolonged time, the up taken miR-126 was released by the cells themselves through exosomes; the inhibition of exosome release by an exosome release inhibitor GW4869 induced miR-126 intracellular accumulation leading to massive cell death and in vivo tumour growth arrest. Autophagy is involved in these processes; miR-126 accumulation induced a protective autophagy and the inhibition of this process by GW4869 generates a metabolic crisis that promotes necroptosis, which was associated with PARP-1 over-expression and cyt-c and AIF release. In association to the exosome release inhibition, GW4869 showed also a role as inhibitor of autophagy, which is a survival process used by CSCs to evade cancer therapy. Here, for the first time we proposed a therapy against CSCs, a heterogeneous cell population involved in cancer development and relapse.

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.

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.

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 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

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.

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

MnFe

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.

Micro synchrotron radiation X-ray fluorescence (m-SRXRF) is a powerful spectroscopy technique that uses synchrotron radiation to induce X-ray fluorescence in samples and provides exhaustive information on the micron and submicron scale. Among the major advantages of m-SRXRF spectroscopy are its nondestructive nature and that samples can usually be analyzed without pretreatment. At the ESRF (Grenoble, France) ID-21 beamline, we examined PM10 samples collected at two sites in the Province of Trieste, Italy, in order to determine possible correlations among some low- to mid-Z elements (S, Cl, K, Ca, Ti, V, Cr, Mn, and Fe), as well as investigated the possibility of using synchrotron radiation imaging techniques as a way to examine the granulometry of PM10 particles containing the various chemical elements. A consistent significant correlation between Ca and S has been found, which, coupled with the data obtained in a related study, indicates that a major part of the sulfate is present as CaSO4. Granulometry measurement via imaging techniques has shown that some elements such as Fe, Ca, and S are more amenable to this type of analysis than others. Additionally, the spatial homogeneity of a PM2.5 certified reference material (NIST SRM-2783) has been investigated by analyzing four adjacent areas on the certified sample (total area 1mm 2 ). The certified reference material has shown a percentage relative standard deviation less than 7% for Al, Si, P, S, Cl, K, Ca, V, Cr, and Fe, and close to 17% for Ti and Mn. Copyright © 2011 John Wiley & Sons, Ltd.

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.

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.

Objectives: To identify the current state of knowledge, current uncertainties and future needs related to the diagnosis of disorders associated with the use of vibratory hand-held tools. Method: An international workshop was convened with invited experts, medical doctors, scientists and engineers familiar with hand-transmitted vibration and the diagnosis of vascular, neurological and musculoskeletal disorders. This paper records the general conclusions from four panel discussions. Results: For the most common vascular disorder (vibration-induced white finger), the principal symptom and sign involves attacks of well-demarcated finger blanching (Raynaud's phenomenon); low finger systolic blood pressure following cooling is indicative of vibration-induced white finger and zero finger systolic blood pressure can confirm an attack of Raynaud's phenomenon. For neurological disorders, some symptoms can exist without detectable signs and some signs can exist without symptoms; numbness and tingling are commonly reported but neurological changes may be present without these symptoms. The pathogenesis of musculoskeletal disorders in users of vibratory tools is not clear; symptoms may include pain that may not be associated with abnormal results in objective tests. For both neurological and musculoskeletal disorders, a thorough neuromuscular and skeletal examination is required; diagnosis must consider the work history and medical history, the results of physical examination and any objective tests in addition to other factors (e.g. age, smoking, alcohol, systemic disorders, medication and neurotoxic agents) that might have contributed to symptoms, signs and test results. Conclusions: While vibration-induced white finger is caused by vibration, some neurological and musculoskeletal disorders are the result of work with vibratory tools where the separate roles of vibration, repetitive movements, grip and push forces, non-neutral postures and any other ergonomic stressors are often unclear. Such disorders may be more easily identified as being caused by the work rather than by exposure to hand-transmitted vibration per se. A person found to have developed disorders induced by either vibration or the work situation should not be returned to the same vibration exposure or work without any changes expected to lessen the risks.

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.

To evaluate whether residential radon exposure explains the excess mortality for lung cancer in an Italian alpine valley with high natural radioactivity, the authors conducted a population-based case-control study on 138 deceased cases and 291 sex- and year-of-birth-matched controls. Year-long alpha-track measurements of radon were performed in the most recent residence, and information about occupational history and lifetime smoking habits was obtained. The authors adjusted for smoking, and radon was associated with lung cancer risk among men: compared with a radon level of < 40 becquerels (Bq) per cubic meter (m3), the odds ratios for 40-76 Bq/m3, 77-139 Bq/m3, 140-199 Bq/m3, and 200+ Bq/m3 were 2.1, 2.0, 2.7, and 1.4, respectively. The association between radon and lung cancer, as determined with a multiplicative model, was found only among male smokers.

Seamen and marine engineers were formerly exposed to asbestos used in gasket, pipes, valves and machinery. Ship motion and vibration can release asbestos in the surrounding space. Asbestos fibres may also be inhaled by workers involved in maintenance operations of vessels built before 1992 in Italy. History of asbestos exposure has been reported by workers and confirmed by a higher prevalence of pleural abnormalities and a significant excess of mesothelioma with a Standardized Incidence Ratio (SIR) ranging between 1.83 and 4.8 as a function of years of exposure. SIR for lung cancer ranged between 1.10 and 1.62. Mesothelioma in seamen and marine engineers represents about 2.5% of the overall Italian mesothelioma cases with a very long latency period (47.6 +/- 9.6 years). There is no epidemiological evidence for an excess risk of mesothelioma in fishermen.

OBJECTIVES—To investigate the acute effects of the frequency of hand transmitted vibration on finger circulation. A further aim was to investigate whether the frequency weighting assumed in current standards for hand transmitted vibration reflects the haemodynamic changes which occur in the fingers exposed to vibration with different frequencies but with the same frequency weighted acceleration magnitude. METHODS—Finger skin temperature (FST) and finger blood flow (FBF) were measured in the middle fingers of both hands of 10 healthy men. With a static load of 10 N, the right hand was exposed for 15 minutes to the following root mean square (rms) acceleration magnitudes and frequencies of vertical vibration: 5.5 m/s2 at 16 Hz; 11 m/s2 at 31.5 Hz; 22 m/s2 at 63 Hz; 44 m/s2 at 125 Hz; and 88 m/s2 at 250 Hz. These exposures to vibration produce the same frequency weighted acceleration magnitude (5.5 m/s2 rms) according to the frequency weighting included in the international standard ISO 5349. A control condition consisted of exposure to the static load only. Finger circulation was measured before application of the vibration and static load and at fixed intervals during exposure to vibration and a 45 minute recovery period. RESULTS—No significant changes in finger circulation were found with only the static load. The FST did not change significantly during or after acute exposure to vibration. In the vibrated right finger, exposures to vibration with frequencies of 31.5-250 Hz provoked a greater reduction in FBF than did vibration of 16 Hz or the static load only. In the non-vibrated left finger, the FBF measured with vibration at each frequency of 63-250 Hz was significantly lower than that measured with static load only. The reduction in FBF during exposure to vibration with any frequency was stronger in the vibrated finger than in the non-vibrated finger. In both fingers, there was a progressive decrease in FBF after the end of exposure to vibration with frequencies of 31.5-250 Hz. The higher the frequency of vibration, the stronger the decrease in FBF in both fingers during recovery. CONCLUSIONS—Acute exposures to vibration with equal frequency weighted magnitude reduce the FBF in both vibrated and non-vibrated fingers for frequencies between 31.5 and 250 Hz. The extent of digital vasoconstriction after exposure to vibration increases with increasing frequency. The frequency weighting given in current standards tends to overestimate the vasoconstriction associated with acute exposures to vibration frequencies around 16 Hz. Keywords: finger circulation; frequency weighted acceleration magnitude; vibration frequency

It seems evident from a large number of studies that there is a positive relationship between exposure to whole body vibration (WBV) and the occurrence of low back pain. There are existing standards for evaluating the human exposure to WBV, which are based on other factors than the effect of musculoskeletal disorders. Several national and international standards also exist for evaluating human exposure to WBV. The exposure limit values or health guidance caution zones included in some of these standards are not or only to a limited extent based on systematic epidemiological investigations. It has not yet been possible to establish a clear exposure-response relationship. There are many confounding or contributing factors which influence the hazards to workers caused by exposure to WBV. Reliable methods for the detection and prevention of injury due to vibration exposure at work, alone or in combination with other risk factors, need to be implemented. The aim of this paper was to design a protocol and a questionnaire for conducting collaborative studies of WBV and musculoskeletal back disorders. The protocol will be tested in a pilot study before it will be used in multi-center studies. (C) 1998 Academic Press

The aim of this paper is to update the information on the epidemiologic evidence of the adverse health effects of whole-body vibration (WBV) on the spinal system by means of a review of the epidemiologic studies published between 1986 and 1996. In a systematic search of epidemiologic studies of low back pain (LBP) disorders and occupations with exposure to WBV, 37 articles were retrieved. The quality of each study was evaluated according to criteria concerning the assessment of vibration exposure, assessment of health effects, and methodology. The epidemiologic studies reaching an adequate score on each of the above mentioned criteria, were included in the final review. A meta-analysis was also conducted in order to combine the results of independent epidemiologic studies. After applying the selection criteria, 16 articles reporting the occurrence of LBP disorders in 19 WBV-exposed occupational groups, reached a sufficient score. The study design was cross-sectional for 13 occupational groups, longitudinal for 5 groups and of case-control type for one group. The main reasons for the exclusion of studies were insufficient quantitative information on WBV exposure and the lack of control groups. The findings of the selected studies and the results of the meta-analysis of both cross-sectional and cohort studies showed that occupational exposure to WBV is associated with an increased risk of LBP, sciatic pain, and degenerative changes in the spinal system, including lumbar intervertebral disc disorders. Owing to the cross-sectional design of the majority of the reviewed studies, this epidemiologic evidence is not sufficient to outline a clear exposure–response relationship between WBV exposure and LBP disorders. Upon comparing the epidemiological studies included in this review with those conducted before 1986, it is concluded that research design and the quality of exposure and health effect data in the field of WBV have improved in the last decade.

This study investigated the relation between vibration exposure, the prevalence of white fingers, and the cold response of digital arterial vessels in workers using vibrating tools.The change in finger systolic blood pressure (FSBP) at 15 and 10 degrees C as the percentage of the pressure at 30 degrees C (FSBP%) was measured in 455 healthy referents and 822 workers exposed to hand-transmitted vibration. Exposure to hand-transmitted vibration was assessed in terms of 8-hour energy-equivalent frequency-weighted acceleration [A(8)] and total operating time with vibrating tools.The prevalence of white fingers was 1.1% for the referents and ranged from 9.0% to 51.6% for the vibration-exposed groups. The estimated mean value of A(8) ranged between 1.6 (referents) and 8.3 (quarry drillers) m/s2. After adjustment for age, smoking, and drinking habits, the FSBP% was significantly lower in the vibration-exposed groups than in the reference group. Groupwise, the FSBP%(10 degrees) was inversely related to the prevalence of white fingers, the estimated A(8), and total operating time. With FSBP%(10 degrees)70% or60% as the lower normal limit, the sensitivity of the cold test varied from 86% to 100%, with a specificity of 90% to 94%, and a positive predictive value of 68% to 74%.FSBP measurement during cold provocation is a useful laboratory test for white fingers. A quantitative relationship between cold-induced digital arterial hyperresponsiveness and occupational exposure to hand-transmitted vibration was suggested.

This paper provides an overview of the exposure-response relationship for the vascular component of the hand-arm vibration syndrome, called vibration-induced white finger (VWF). Over the past two decades, several epidemiological studies have shown a poor agreement between the risk for VWF observed in various occupational groups and that predicted by models included in annexes to International Standard ISO 5349 (ISO 5349:1986, ISO 5349-1:2001). Either overestimation or underestimation of the occurrence of VWF have been reported by investigators. It has been argued that the current ISO frequency-weighting curve for hand-transmitted vibration, which assumes that vibration-induced adverse health effects are inversely related to the frequency of vibration between 16 and 1250 Hz, may be unsuitable for the assessment of VWF. To investigate this issue, a prospective cohort study was carried out to explore the performance of four alternative frequency weightings for hand-transmitted vibration to predict the incidence of VWF in groups of forestry and stone workers. The findings of this study suggested that measures of vibration exposure which give relatively more weight to intermediate and high frequency vibration produced better predictions of the incidence of VWF than that obtained with the frequency weighting currently recommended in International Standard ISO 5349-1:2001.

Objectives This study investigated whether reductions in finger blood flow (FBF) during and after vibration are similarly dependent on the magnitude and duration of vibration. Methods FBF on the left and right hand was measured every minute during, and for 1 hour following, exposure of the right hand to one of three magnitudes of 125-Hz sinusoidal vibration (0, 22, or 88 ms 2 r.m.s.) for one of two durations (7.5 or 15 minutes). Each session comprised 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 (7.5 or 15 minutes), (iv) 2-N force and no vibration (5 minutes), and (v) no force and no vibration (60 minutes). Results Both magnitudes and durations of vibration reduced FBF in the exposed and unexposed hands, both during and after vibration. With increased magnitude of vibration, there was increased vasoconstriction in all fingers during and after exposure, and longer recovery times after vibration exposure. With increased duration of vibration, there were no changes in vascular responses during exposure but increased vasoconstriction after exposure and prolonged recovery times. With the higher vibration magnitude, the reduction in FBF during exposure was correlated with the time taken to recover after exposure. Conclusions Subjects with greater reduction in blood flow during vibration exposure also have stronger and longer vasoconstriction during subsequent recovery. The correlation between vascular changes during and after vibration exposure suggests similar mechanisms control FBF during and after vibration exposure.