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(1) Background : Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with still unknown etiology. Some occupational and environmental risk factors have been suggested, including long-term air pollutant exposure. We carried out a pilot case-control study in order to evaluate ALS risk due to particulate matter with a diameter of ≤10 µm (PM 10 ) as a proxy of vehicular traffic exposure. (2) Methods : We recruited ALS patients and controls referred to the Modena Neurology ALS Care Center between 1994 and 2015. Using a geographical information system, we modeled PM 10 concentrations due to traffic emissions at the geocoded residence address at the date of case diagnosis. We computed the odds ratio (OR) and 95% confidence interval (CI) of ALS according to increasing PM 10 exposure, using an unconditional logistic regression model adjusted for age and sex. (3) Results : For the 132 study participants (52 cases and 80 controls), the average of annual median and maximum PM 10 concentrations were 5.2 and 38.6 µg/m 3 , respectively. Using fixed cutpoints at 5, 10, and 20 of the annual median PM 10 levels, and compared with exposure <5 µg/m 3 , we found no excess ALS risk at 5-10 µg/m 3 (OR 0.87, 95% CI 0.39-1.96), 10-20 µg/m 3 (0.94, 95% CI 0.24-3.70), and ≥20 µg/m 3 (0.87, 95% CI 0.05-15.01). Based on maximum PM 10 concentrations, we found a statistically unstable excess ALS risk for subjects exposed at 10-20 µg/m 3 (OR 4.27, 95% CI 0.69-26.51) compared with those exposed <10 µg/m 3 . However, risk decreased at 20-50 µg/m 3 (OR 1.49, 95% CI 0.39-5.75) and ≥50 µg/m 3 (1.16, 95% CI 0.28-4.82). ALS risk in increasing tertiles of exposure showed a similar null association, while comparison between the highest and the three lowest quartiles lumped together showed little evidence for an excess risk at PM 10 concentrations (OR 1.13, 95% CI 0.50-2.55). After restricting the analysis to subjects with stable residence, we found substantially similar results. (4) Conclusions : In this pilot study, we found limited evidence of an increased ALS risk due to long-term exposure at high PM 10 concentration, though the high statistical imprecision of the risk estimates, due to the small sample size, particularly in some exposure categories, limited our capacity to detect small increases in risk, and further larger studies are needed to assess this relation.

We much appreciate the positive comments and interest concerning our study on the environmental and occupational risk factors of amyotrophic lateral sclerosis (ALS) [...].

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with still unknown etiology. We aimed at investigating the association between environmental and occupational factors with ALS risk. Methods: We performed a population-based case-control study in four Italian provinces (Catania, Modena, Novara, and Reggio Emilia) by administration of tailored questionnaires to ALS cases ( n = 95) and randomly selected population referents ( n = 135). We estimated ALS risk by calculating the odds ratio (OR) with its 95% confidence interval (CI) using an unconditional logistic regression model. Results: We found a positive association with disease risk for history of occupation in the agricultural sector (OR = 2.09, 95% CI 0.79-7.54), especially for longer than 10 years (OR = 2.72, 95% 1.02-7.20). Overall occupational exposure to solvents also suggested a positive association, especially for thinners (OR = 2.27, 95% CI 1.14-4.54) and paint removers (OR = 2.01, 95% CI 0.90-4.48). Both occupational and environmental exposure to electromagnetic fields show a slightly increased risk with OR = 1.69 (95% CI 0.70-4.09) and 2.41 (95% CI 1.13-5.12), respectively. Occupational but not environmental exposure to pesticides (OR = 1.22, 95% CI 0.63-2.37), particularly fungicides, and exposure to metals (OR = 4.20, 95% CI 1.88-9.38), particularly lead, mercury, and selenium, showed an imprecise but positive association. Finally, there was an indication of increased risk for living in proximity to water bodies. Conclusions: Despite the caution that needs to be used due to some study limitations, such as the low number of exposed subjects and the possibility of recall bias, these results suggest the potential role of some environmental and occupational factors in ALS etiology.

Cadmium is a metal that is toxic to humans, and the major source of cadmium exposure in the non-smoking general population is diet. To identify major food sources and lower exposure from diet, an accurate estimate of dietary cadmium intake is needed. Hence, the objectives of this study are to develop a method to assess dietary cadmium intake using a biomarker measurement and to improve the estimation of dietary cadmium intake when using a food frequency questionnaire (FFQ). In a random sample of an Italian population, we collected dietary habits by FFQ and measured cadmium in foods and beverages. These data were used to compute the estimated weekly dietary intake (WDI) of cadmium (µg) by kilogram (kg) of body weight (bw) (WDI FFQ ). We also measured fasting serum cadmium levels by inductively-coupled plasma mass spectrometry. We used these data to develop a model for the estimation of the biomarker-derived dietary cadmium intake (WDI bio ). In the 51 subjects recruited, the median level of serum cadmium was 0.041 µg/L (interquartile range (IQR): 0.030-0.054). The median WDI FFQ and WDI bio were 1.34 µg/kg bw/week (IQR: 0.86-1.70) and 0.72 µg/kg bw/week (IQR: 0.55-1.11), respectively. The correlation between the two estimates was low-to-moderate (r = 0.291). In exploratory analyses, the correlation was slightly higher in women and participants ages <50 years, and markedly higher in participants with body mass index <25 kg/m 2 and smokers. Our approach allows for the dietary contribution to be isolated from the overall cadmium exposure measured with a biomarker; the estimated dietary cadmium intake was roughly similar to that estimated using the FFQ, especially in select subgroups. Future refinements to the biomarker-derived dietary cadmium intake approach should take into consideration additional sources of cadmium exposure, as well as factors affecting its absorption and metabolism.

Background : Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease of the motor neurons. The etiology of ALS remains largely unknown, particularly with reference to the potential environmental determinants. Methods : We performed a population-based case-control study in four provinces from both Northern and Southern Italy in order to assess non-genetic ALS risk factors by collecting through tailored questionnaires information about clinical and lifestyle factors. We estimated ALS risk by calculating odds ratio (OR) with its 95% confidence interval (CI) using unconditional logistic regression models adjusted for sex, age and educational attainment. Results : We recruited 230 participants (95 cases and 135 controls). We found a possible positive association of ALS risk with trauma, particularly head trauma (OR = 2.61, 95% CI 1.19-5.72), electric shock (OR = 2.09, 95% CI 0.62-7.06), and some sports, although at a competitive level only. In addition, our results suggest an increased risk for subjects reporting use of private wells for drinking water (OR = 1.38, 95% CI 0.73-2.27) and for use of herbicides during gardening (OR = 1.95, 95% CI 0.88-2.27). Conversely, there was a suggestion of an inverse association with overall fish consumption (OR = 0.27, 95% CI 0.12-0.60), but with no dose-response relation. Consumption of some dietary supplements, namely those containing amino acids and, in the Southern Italy population, vitamins and minerals such as selenium, seemed associated with a statistically imprecise increased risk. Conclusions : Our results suggest a potential etiologic role a number of clinical and lifestyle factors with ALS risk. However, caution is needed due to some study limitations. These include the small sample size and the low number of exposed subjects, which affect statistical precision of risk estimates, the potential for exposure misclassification, and the uncertainties about mechanisms underpinning the possible association between these factors and disease risk., Competing Interests: The authors declare no conflict of interest.

In Italy, the National Health Service offers specialized evidence-based support to smokers who would like to quit through smoking cessation (SC) services. We conducted a two-year prospective study, involving all 288 subjects treated for smoking cessation at the SC service of Reggio Emilia, to assess the association of referral sources and waiting times with the risk of treatment failure, by following participants up to one year after the quit date. We performed Cox-regression analysis, including demographic and smoking-related characteristics as confounding variables. The treatment failure rate at 12 months was 59.4% (171/288), including only 12 subjects lost to follow-up. The main mode of entry was self-referral (42.4%), followed by 32.6% from general practice, 17.4% from hospital and 7.6% from other sources. Only 27.8% participants were involved in the SC-program within 60 days of the first contact, as the guidelines suggest. The risk of treatment failure at 12 months showed little association with the type of referral source, while it correlated with waiting times &ge; 60 days (hazard ratio = 1.59; 95% confidence interval 1.10⁻2.29). This study provides evidence of long-term high quit rates from a SC service, with few subjects lost to follow-up and biochemical verification of almost all abstinent subjects. Timeliness in care provision could further improve the outcome.