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

Silver nanoparticles (AgNPs) are commonly used in antiseptic sprays and mist and can easily come in contact with the mucosa of the upper airways. The intranasal pathway represents the only direct connection between the external environment and the brain structures, which traditionally are considered well protected. Much is known regarding drugs absorption through this route, but toxicological knowledge is scant. The olfactory bundles are surrounded by meningeal sheets in their course from the nasal mucosa to the olfactory bulb. This study investigated in vitro the transmeningeal absorption of 19 nmAgNPs, using excised porcine meninges mounted on Franz diffusion cells. We used two donor solutions: the first containing AgNPs (0.5 g/L) and the second containing only the water-soluble silver species derived from the ultrafiltration of the first one. Each experiment was carried separately for 2 hours. Results showed silver flux permeation through the meninges, with similar values in both experiments (0.78 ± 0.71 ng cm-2 h-1 and 0.73 ± 0.43 ng cm-2 h-1, for AgNPs and Ag ions respectively, mean and SD). Our study demonstrate that the meningeal barrier is permeable to silver and silver ions, when is applied in the nanoparticles form. This could lead to neurotoxic and neurodegenerative effects, which are now emerging in the scientific literature. Metal nanoparticles are commonly encountered in working scenarios, but their behavior in physiological media is different. Therefore the toxicological potential of metal NPs is heterogeneous and requires further efforts to be assessed on a case by case basis.

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

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

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.

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

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

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

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

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

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

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

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

The aim of the study was to evaluate percutaneous penetration of platinum and rhodium nanoparticles (PtNPs: 5.8 ± 0.9 nm, RhNPs: 5.3 ± 1.9 nm) through human skin. Salts compounds of these metals are sensitizers and some also carcinogenic agents. In vitro permeation experiments were performed using Franz diffusion cells with intact and damaged skin. PtNPs and RhNPs, stabilized with polyvinylpyrrolidone, were synthesized by reduction of Na2PtCl6 and RhCl3·3H2O respectively. Suspensions with a concentration of 2.0 g/L of PtNPs and RhNPs were dispersed separately in synthetic sweat at pH 4.5 and applied as donor phases to the outer surface of the skin for 24 h. Measurements of the content of the metals in the receiving solution and in the skin were performed subsequently. Rhodium skin permeation was demonstrated through damaged skin, with a permeation flux of 0.04 ± 0.04 μg cm−2 h−1 and a lag time of 7.9 ± 1.1 h, while no traces of platinum were found in receiving solutions. Platinum and rhodium skin- analysis showed significantly higher concentrations of the metals in damaged skin. Rh and Pt applied as NPs can penetrate the skin barrier and Rh can be found in receiving solutions. These experiments pointed out the need for skin contamination prevention, since even a minor injury to the skin barrier can significantly increase penetration.

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

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

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

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

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

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

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

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

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.

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

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

The aim of this study 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 1997. In a systematic search, using several databases, of epidemiologic studies of low back pain (LBP) disorders and occupations with exposure to WBV, 45 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, 17 articles reporting the occurrence of LBP disorders in 22 WBV-exposed occupational groups reached a sufficient score. The study design was cross-sectional for 13 occupational groups, longitudinal for four groups and of case-control type for one group. Two studies included both cross-sectional and follow-up data on the occurrence of LBP disorders in four occupational groups. 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 for 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. Comparing the epidemiologic 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.

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.

Cobalt nanoparticles (CoNPs) are produced for many applications but there is a lack of data on human absorption. The aim of our study was to evaluate the CoNPs skin absorption. Experiments were performed using Franz cells with human skin. Physiological solution was used as receiving phase and 1.0 mg cm-2 of CoNPs was applied as donor phase for 24 h. Mean Co content of 8.3 ± 1.5 ng cm-2 and 1.87 ± 0.86 ug cm-2 were found in the receiving solutions of cells where the CoNPs suspension was applied on intact skin and on damaged skin respectively. Twenty-four hours Co flux permeation was 76 ± 49 ng cm-2 h-1 in damaged skin with a lag time of 2.8 ± 2.1 hours. Transmission Electron Microscope analysis on skin samples and spectroscopic analysis demonstrated the presence of CoNPs into epidermis. This study showed that CoNPs are able to penetrate the human skin in an in-vitro diffusion cell system., JRC.I.4-Nanobiosciences

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.

BACKGROUND: Cosensitization to nickel, cobalt and chromium occurs in the general population and in some occupational groups. OBJECTIVES: To estimate the isolated and concurrent occurrence of nickel, cobalt and chromium contact sensitization and their association with individual and occupational risk factors. PATIENTS/METHODS: Twelve thousand four hundred and ninety-two patients were patch tested with the European baseline series between 1997 and 2004 in north-eastern Italy. The associations between patch test results and patient characteristics and occupations were investigated by means of multinomial logistic regression analysis. RESULTS: Of the patients, 34.7% (4334 patients) had one or more positive patch test reactions to metals. As compared with those with negative reactions to all three metals, nickel sensitization was significantly higher in females than in males, not only as monosensitization, but also as cosensitization with cobalt, with chromium, or with both metals. Building and related trades workers showed positive reactions to chromium + nickel [odds ratio (OR) 1.99; 95% confidence interval (CI) 1.05-3.76) and chromium + cobalt (OR 2.61; 95% CI 1.46-4.67]. Cleaning workers showed a high prevalence of nickel, chromium, nickel + chromium and nickel + cobalt + chromium cosensitization (ORs 1.29, 1.66, 2.11, and 1.79, respectively). An excess risk for cosensitization to all three metals was found in textile and leather workers (OR 2.19; 95% CI 1.10-4.33), and in bartenders (OR 2.10; 95% CI 1.03-4.26). CONCLUSIONS: Some occupational groups are more likely to develop nickel, cobalt and chromium cosensitization.

Salivary cortisol offers a novel approach to understand the relationship between psychosocial environment and health. This study examines the intra-individual relationships among indicators of the cortisol circadian rhythm and investigates the influence of determinants affecting the day-to-day variability of the cortisol measures. Over three weekdays, 87 healthy subjects (63 females and 24 males) collected saliva samples at seven time points to assess the cortisol awakening response (CAR), and to evaluate the post morning cortisol profile. The generalized estimating equations method was used to explore the relations between repeated cortisol measures and potential determinants (sociodemographic, health, and sampling factors) influencing salivary cortisol levels. Younger age, being smoker, and sampling on a working day were associated with higher at awakening and total cortisol excretion in the morning period. Higher overall cortisol excretion and cortisol increase in the first hour of the day were found for adherents to sampling procedure. Higher educational level was found associated with greater total cortisol excretion in the morning and post morning period, while a flatter diurnal slope was found in smokers. Results are consistent with the knowledge that the circadian cortisol rhythm is differentially determined by situational factors and that results obtained in the early morning hour are of crucial importance corroborating the evidence that the CAR is a highly state-dependent phenomenon. These data indicate that many confounding factors need to be controlled when using salivary cortisol as biomarker of the mind-health interrelationship.

Background. Sensitization to nickel, cobalt and chromium is frequent in patch test populations. The prevalence is affected by geographical and socio-cultural factors. Objectives. To investigate the temporal trend of nickel, cobalt and chromium contact sensitization between 1996 and 2010 in north-eastern Italy. Patients/methods. Nineteen thousand and eighty-eight patients (67.2% women and 32.8% men) with suspected allergic dermatitis underwent patch testing with the European baseline series. The associations between nickel, cobalt and chromium sensitization and patient age (in quintiles) and year of patch testing were investigated by means of multivariate logistic regression analysis. Results. The prevalence of nickel sensitization decreased significantly among younger women (≤26 years), from 38.3% (1996–1998) to 31.9% (2002–2004), 28.3% (2005–2007) and 29.0% (2008–2010), whereas an increase was observed in the 36–45-year and 46–58-year age groups. The overall prevalence of chromium sensitization dropped from 10.2% (1996–1998) to 4.6% (2008–2010) among women, and from 11.3% (1996–1998) to 5.9% (2008–2010) among men. The prevalence of cobalt sensitization increased among younger men (≤26 years), from 2.7% (1996–1998) to 7.3% (1999–2001), 9.6% (2002–2004), and 6.6% (2005–2007). Conclusions. Our study showed a decreasing trend of nickel sensitization (only among younger women) and of chromium sensitization in both sexes.

Objectives Finger blood flow is reduced by hand-transmitted vibration but there has been little study of the peripheral vascular response to repetitive mechanical shocks. This study investigated how reductions in finger blood flow depend on shock repetition rate and the peak and rms magnitude of acceleration. Methods Subjects attended seven sessions: six with repetitive mechanical shocks and a control session with no shocks. Each session comprised five successive 5-min periods: (1) no force and no vibration, (2) force and no vibration, (3) force and vibration, (4) force and no vibration and (5) no force and no vibration. During the second– fourth periods, the palm of the right hand applied 2-N force to a vibrator. During the third period, a 125-Hz mechanical shock was applied with one of four repetition rates (1.3, 5.3, 21 or 83.3/s) and one of three acceleration magnitudes (2.5, 5 or 10 ms-2 rms, unweighted). Finger blood flow was measured every 30 s in the middle and little fingers of the right (exposed) hand and the left (unexposed) hand. Results Different repetition rates (1.3–83.3 s-1) and different peak magnitudes (10–88 ms-2 peak) but the same rms acceleration (10 ms-2 rms) caused similar decreases in blood flow in fingers on exposed and unexposed hands. Shocks with a 83.3 s-1 repetition rate, peak magnitude of 10 ms-2 and rms acceleration of 10 ms-2 provoked greater reduction in finger blood flow than shocks with the same peak magnitude but lower repetition rate (21 or 5.3 s-1) and lower rms acceleration (5 or 2.5 ms-2). Conclusions For shocks similar to those based on 125-Hz oscillations with repetition rates between 1.3 and 83.3 s-1, acute reductions in finger blood flow can be predicted from the rms acceleration.

Human malignant pleural mesothelioma (MPM) is considered a rare tumor, but recent estimations indicate that one-quarter million people will die of this neoplasm in Europe in the next three decades. The mineral asbestos is considered the main causative agent of this neoplasm. MPM is largely unresponsive to conventional chemotherapy/radiotherapy. In addition to asbestos exposure, genetic predisposition to asbestos carcinogenesis and to simian virus (SV)40 infection has also been suggested. SV40 is a DNA tumor virus found in some studies to be associated at high prevalence with MPM. SV40 sequences have also been detected, although at a lower prevalence than in MPM, in blood specimens from healthy donors. However, some studies have failed to reveal SV40 footprints in MPM and its association with this neoplasm. These conflicting results indicate the need for further investigations with new approaches. We report on the presence of antibodies in serum samples from patients affected by MPM that specifically react with two different SV40 mimotopes. The two SV40 peptides used in indirect ELISAs correspond to viral capsid proteins. ELISA with the two SV40 mimotopes gave overlapping results. Our data indicate that in serum samples from MPM-affected patients ( n = 97), the prevalence of antibodies against SV40 viral capsid protein antigens is significantly higher (26%, P = 0.043) than in the control group (15%) represented by healthy subjects ( n = 168) with the same median age (66 y) and sex. Our results suggest that SV40 is associated with a subset of MPM and circulates in humans.

OBJECTIVES--To investigate the occurrence of disorders associated with the hand arm vibration syndrome in a large population of stone workers in Italy. The dose-response relation for vibration induced white finger (VWF) was also studied. METHODS--The study population consisted of 570 quarry drillers and stonecarvers exposed to vibration and 258 control stone workers who performed only manual activity. Each subject was interviewed with health and workplace assessment questionnaires. Sensorineural and VWF disorders were staged according to the Stockholm workshop scales. Vibration was measured on a representative sample of percussive and rotary tools. The 8 h energy equivalent frequency weighted acceleration (A (8)) and lifetime vibration doses were calculated for each of the exposed stone workers. RESULTS--Sensorineural and musculoskeletal symptoms occurred more frequently in the workers exposed to vibration than in the controls, but trend statistics did not show a linear exposure-response relation for these disorders. The prevalence of VWF was found to be 30.2% in the entire group exposed to vibration. Raynaud's phenomenon was discovered in 4.3% of the controls. VWF was strongly associated with exposure to vibration and a monotonic dose-response relation was found. According to the exposure data of this study, the expected percentage of stone workers affected with VWF tends to increase roughly in proportion to the square root of A(8) (for a particular exposure period) or in proportion to the square root of the duration of exposure (for a constant magnitude of vibration). CONCLUSION--Even although limited to a specific work situation, the dose-response relation for VWF estimated in this study suggests a time dependency such that halving the years of exposure allows a doubling of the energy equivalent vibration. According to these findings, the vibration exposure levels currently under discussion within the European Community seem to represent reasonable exposure limits for the protection of workers against the harmful effects of hand transmitted vibration.

In a six year follow up study of the handarm vibration syndrome, 62 stoneworkers operating hand held vibrating tools in 10 travertine quarries and mills were first investigated in 1985 and then in 1991. The frequency weighted acceleration of vibration from the rock drills and stone hammers used by the travertine workers exceeded 20 m/s2, indicating a hazardous work activity according to the proposal of the EC directive for physical agents. A clinical examination and a cold provocation test were repeated with the same procedures as those adopted at the time of the first survey. The stoneworkers were divided into groups according to current work state: active stoneworkers who continued to use powered tools during the follow up (n = 21, median exposure time 22 years), and ex-stoneworkers with retirement vibration free intervals of three years (n = 22, median exposure time 27.5 years) and of six years (n = 19, median exposure time 20 years). In the group of active stoneworkers, a 38% onset a new cases of vibration-induced white finger (VWF) was found during the follow up (p < 0.01). Among the retired stoneworkers affected with VWF (n = 24), one recovered from VWF, one showed improvement, 20 remained stationary, and two deteriorated. The ex-stoneworkers experienced no significant change in sensorineural disturbances and a decrease in musculoskeletal symptoms of the upper limbs. At the cold provocation test, the currently active stoneworkers with VWF showed, on a group basis, a delayed finger rewarming time between the two examinations (p = 0.002). An abnormal response to cold provocation persisted in the fingers of the ex-stoneworkers with VWF, even in those reporting subjective improvement. These findings indicate a tendency towards the irreversibility of sensorineural and VWF symptoms in a group of ex-stoneworkers with prolonged exposure to high vibration levels in the past. The increased occurrence of VWF in the active stone workers after a few extra years of vibrating tool usage argues for an urgent implementation of preventive measures in the stone industry.

Summary Background. p-Phenylenediamine (PPD) is an extreme delayed-type skin sensitizer, and is relevant in both occupational and non-occupational exposures. Objectives. To estimate the prevalence of PPD sensitization in a population of consecutive patients with suspected allergic contact dermatitis who attended units of dermatology or occupational medicine in north-eastern Italy and to investigate the association between their PPD sensitization and occupation. Patients/Materials/Methods. A total of 14 464 patients (67.6% women and 32.4% men) with suspected allergic dermatitis underwent patch testing. The associations between patch test results and occupations were studied by multivariate logistic regression analysis. Results. In both sexes, PPD sensitization was significantly associated with hairdressing and beauty occupation [women, odds ratio (OR) 6.58, 95% confidence interval (CI) 3.76–11.50; men, OR 22.3, 95% CI 4.18–119]. In the female group, PPD sensitization was also significantly higher in professional drivers (OR 5.31, 95% CI 1.76–16.1), barmaids (OR 1.89, 95% CI 1.04–3.44), and cleaners (OR 1.82, 95% CI 1.24–2.68). In the male group, PPD sensitization was significantly higher in bakers and waiters (OR 13.0, 95% CI 1.38–123), household workers (OR 8.46, 95% CI 1.68–42.8), and printers (OR 5.68, 95% CI 1.50–21.5). Conclusions. Our study showed that workers in several occupations may be at higher risk of developing sensitization to PPD. It is of importance to reduce possible exposure to PPD-crossreacting substances in these occupations.

To investigate prospectively the relation between vibration-induced sensory dysfunction and measures of daily exposure to hand-transmitted vibration (HTV). Thermal perception thresholds for warmth and cold (TPT in °C) and vibrotactile perception thresholds (VPT in dB) at 31.5 and 125 Hz were measured at the fingertips of digit II (for the median nerve) and digit V (for the ulnar nerve) of both hands in 27 male controls and 29 naval engine workers exposed to HTV. In the HTV workers, peripheral sensory function was investigated over a follow-up period of 1–3 years. Vibration exposure was expressed in terms of equivalent frequency-weighted acceleration [A h(eq,T) in ms−2 rms], duration of exposure (T in hours), and frequency-weighted acceleration normalised to a period of 8 h [A(8) in ms−2 rms]. At baseline, the HTV workers showed significantly higher TPT for warmth and lower TPT for cold than the controls, while no differences in the VPTs at both frequencies were observed between the two groups. After adjustment for several confounders, data analysis with the generalised estimating equations method and a transition model showed that the changes over time in the TPTs of the HTV workers were significantly related to all measures of daily vibration exposure [A h(eq,T), T, A(8)]. No significant associations were observed for VPTs at either 31.5 or 125 Hz. The findings of this longitudinal study suggest a significant exposure–response relationship between thermal sensory impairment over time and measures of vibration exposure. The measurement of TPT may be a useful testing method to assess vibration-induced neuropathy at an early stage.

The simultaneous detection of oncogenic human papillomavirus (HPV) and BK virus (BKV) has been recently reported in cervical cancers, suggesting that these viruses may act together in the process of cell transformation; host genetic polymorphisms may also influence virus persistence/reactivation. To disclose a possible role of the gene encoding for the mannose-binding lectin, MBL2, in susceptibility to BKV infection, we analyzed functional polymorphisms in the first exon of MBL2 in women stratified for the presence/absence of BKV and affected by different grades of HPV-induced cervical precancerous lesions. All BKV-positive samples were also HPV positive (HPV 16), and all presented with high-grade squamous intraepithelial lesions. The MBL2 A allele was significantly more frequent in BKV-negative patients than in BKV-positive patients. These data indicate a possible role for the A allele in conferring protection to BKV infection in high-risk HPV-positive women (odds ratio 0.40, 95% confidence interval 0.20-0.85, p = 0.01).

A case-control study of lung cancer and occupational exposure was conducted in a coastal area of Northeastern Italy where metallurgical and mechanical industries, docks and shipyards are located. Cases comprised 756 men who died of primary lung cancer in a 5-year period. Controls comprised 756 male subjects dying from other causes during the same period. Occupational exposures to lung carcinogens were assessed according to a job title-based approach, using two separate lists of industries/occupations recognized as being causally associated (list A) or suspected of being causally associated (list B) with lung cancer in humans. Exposure to asbestos was classified as absent, possible, or definite. After adjustment for cigarette smoking and place of residence, a significant association was found between lung cancer and occupations in both list A [relative risk (RR) = 2.25, 95% confidence interval (CI) = 1.68–3.03] and list B (RR = 1.33, 95% CI = 1.03–1.71). A significant excess risk was found for workers with definite exposure to asbestos as compared to those with no exposure to lung carcinogens (RR = 1.98, 95% CI = 1.42–2.75). Among occupations with recognized exposure to lung carcinogens other than asbestos, a significant excess risk for lung cancer was observed in iron and metalware workers. In occupational groups with definite exposure to asbestos, elevated risk estimates were found for shipyard workers, dockworkers, carpenters, and electricians. The combined effect of smoking and asbestos was found to be compatible with that expected under a multiplicative model. The overall population-attributable risk (ARp) for cigarette smoking was found to be 87.5%. The ARp estimate for occupations in list A was 16.0%. The estimate increased to 25.3% (95% CI = 16.2–34.4) when occupations in list B were included. The ARp estimate for possible or definite exposure to asbestos was 20.0% (95% CI = 11.5–28.5). With regard to the histologic types of lung cancer, significant associations were found between definite exposure to asbestos and squamous cell carcinoma (RR = 2.00, 95% CI = 1.28-–3.11), small cell carcinoma (RR = 2.11, 95% CI = 1.31–3.39), and adenocarcinoma (RR = 2.16, 95% CI = 1.32–3.53).

For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products designed to come in direct contact with the skin. In this study we investigated the effects of Ag NPs on skin using the human-derived keratinocyte HaCaT cell line model. Ag NPs caused a concentration- and time-dependent decrease of cell viability, with IC(50) values of 6.8 ± 1.3 μM (MTT assay) and 12 ± 1.2 μM (SRB assay) after 7 days of contact. A 24h treatment, followed by a 6 day recovery period in Ag NPs-free medium, reduced cell viability with almost the same potency (IC(50)s of 15.3 ± 4.6 and 35 ± 20 μM, MTT and SRB assays, respectively). Under these conditions, no evidence of induction of necrotic events (propidium iodide assay) was found. Apocynin, NADPH-oxidase inhibitor, or N(G)-monomethyl-L-argynine, nitric oxide synthase inhibitor, did not prevent NPs-induced reduction of cell viability. TEM analysis of cells exposed to NPs for 24h revealed alteration of nuclear morphology but only a marginal presence of individual NPs inside the cells. These results demonstrate that on HaCaT keratinocytes a relatively short time of contact with Ag NPs causes a long-lasting inhibition of cell growth, not associated with consistent Ag NPs internalization.

OBJECTIVES: To examine the association between two job stress models-the job strain (JDC) and the effort-reward imbalance (ERI) model-and ambulatory blood pressure monitoring in call handler operators. METHODS: Participants included 74 women (age, 34.9 ± 9.9 years) and 26 men (age 36.0 ± 10.8 years) who were monitored on 2 workdays for ambulatory blood pressure. Measures of both job stress models were related to blood pressure by the generalized estimating equations (GEE) method while adjusting for potential confounders (gender, age, cigarette smoking, alcohol consumption, educational level, marital status, time of day, and work schedule). RESULTS: Workshifts were associated with an increase of 3-4 and 14 mmHg in mean arterial pressure (MAP) compared with diurnal activities out of work and sleeping period, respectively (P < 0.001). Ambulatory blood pressure was also significantly related with work schedule preference: unpleasant work schedule was associated with an increase of 2 mmHg in MAP compared with pleasant work schedule (P = 0.013). In the ERI model, subjects scoring high in work stress have higher ambulatory blood pressure at work, at home, and during sleep. Work stress by time interaction was not longer significant when controlling for potential confounders: generalized estimating equations revealed that MAP was influenced by BMI (>25 vs.