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Introduction: Understanding the neurodevelopmental effects of manganese (Mn) is complicated due to its essentiality for growth and development. While evidence exists for the harmful effects of excess Mn, pediatric epidemiologic studies have observed inconsistent associations between Mn and child cognition., Objective: We sought to estimate prospective associations between Mn measured in three different early-life time windows with adolescent cognition using deciduous teeth biomarkers., Methods: Deciduous teeth were collected from 195 participants (ages 10-14 years) of the Public Health Impact of Manganese Exposure (PHIME) study in Brescia, Italy. Measurements of tooth Mn represented prenatal (∼14 weeks gestation - birth), early postnatal (birth - 1.5 years) and childhood (∼1.5 - 6 years) time windows. Neuropsychologists administered the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III), to obtain composite IQ and subtest scores. Associations between tooth Mn at each time window and adolescent WISC-III scores were estimated using multivariable linear regression. We tested differences in associations between Mn and outcomes across time windows using multiple informant models. Sex-specific associations were explored in stratified models., Results: Adjusted associations between tooth Mn and composite IQ scores were positive in the prenatal period and negative in the childhood period. Associations were strongest for subtest scores that reflect working memory, problem solving, visuospatial ability and attention: prenatal Mn was positively associated with Digits backward [SD change in score per interquartile range increase in Mn: β = 0.20 (95 % CI: 0.02, 0.38)] and Block design [β = 0.21 (0.01, 0.41)] and early postnatal Mn was positively associated with Digits forward [β = 0.24 (0.09, 0.40)], while childhood Mn was negatively associated with Coding [β = -0.14 (-0.28, -0.001)]. Sex-stratified analyses suggested different Mn-cognition associations for boys and girls and was also dependent on the time window of exposure., Conclusion: Our results suggest that exposure timing is critical when evaluating Mn associations between Mn and cognition. Higher prenatal Mn was beneficial for adolescent cognition; however, these beneficial associations shifted towards harmful effects in later time windows. Cognitive domains most sensitive to Mn across time windows included visuospatial ability, working memory, attention and problem-solving., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency's priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.

Background: Research on the health effects of chemical mixtures has focused mainly on early life rather than adolescence, a potentially important developmental life stage., Objectives: We examined associations of a metal mixture with general cognition in a cross-sectional study of adolescents residing near ferromanganese industry, a source of airborne metals emissions., Methods: We measured manganese (Mn), lead (Pb), copper (Cu), and chromium (Cr) in hair, blood, urine, nails, and saliva from 635 Italian adolescents 10-14 years of age. Full-scale, verbal, and performance intelligence quotient (FSIQ, VIQ, PIQ) scores were assessed using the Wechsler Intelligence Scale for Children-III. Multivariable linear regression and Bayesian kernel machine regression (BKMR) were used to estimate associations of the metal mixture with IQ. In secondary analyses, we used BKMR's hierarchical variable selection option to inform biomarker selection for Mn, Cu, and Cr., Results: Median metal concentrations were as follows: hair Mn, 0.08 μ g / g ; hair Cu, 9.6 μ g / g ; hair Cr, 0.05 μ g / g ; and blood Pb, 1.3 μ g / dL . Adjusted models revealed an inverted U-shaped association between hair Cu and VIQ, consistent with Cu as an essential nutrient that is neurotoxic in excess. At low levels of hair Cu (10th percentile, 5.4 μ g / g ), higher concentrations (90th percentiles) of the mixture of Mn, Pb, and Cr ( 0.3 μ g / g , 2.6 μ g / dL , and 0.1 μ g / g , respectively) were associated with a 2.9 (95% CI: - 5.2 , - 0.5 )-point decrease in VIQ score, compared with median concentrations of the mixture. There was suggestive evidence of interaction between Mn and Cu. In secondary analyses, saliva Mn, hair Cu, and saliva Cr were selected as the biomarkers most strongly associated with VIQ score., Discussion: Higher adolescent levels of Mn, Pb, and Cr were associated with lower IQ scores, especially at low Cu levels. Findings also support further investigation into Cu as both beneficial and toxic for neurobehavioral outcomes. https://doi.org/10.1289/EHP6803.

Background: Metal exposure is a public health hazard due to neurocognitive effects starting in early life. Poor socio-economic status, adverse home and family environment can enhance the neurodevelopmental toxicity due to chemical exposure. Disadvantaged socio-economic conditions are generally higher in environmentally impacted areas although the combined effect of these two factors has not been sufficiently studied., Methods: The effect of co-exposure to neurotoxic metals including arsenic, cadmium, manganese, mercury, lead, selenium, and to socio-economic stressors was assessed in a group of 299 children aged 6-12 years, residing at incremental distance from industrial emissions in Taranto, Italy. Exposure was assessed with biological monitoring and the distance between the home address and the exposure point source. Children's cognitive functions were examined using the Wechsler Intelligence Scale for Children (WISC) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Linear mixed models were chosen to assess the association between metal exposure, socio-economic status and neurocognitive outcomes., Results: Urinary arsenic, cadmium and hair manganese resulted inversely related to the distance from the industrial emission source (β - 0.04; 95% CI -0.06, - 0.01; β - 0.02; 95% CI -0.05, - 0.001; β - 0.02 95% CI -0.05, - 0.003) while the WISC intellectual quotient and its sub-scores (except processing speed index) showed a positive association with distance. Blood lead and urinary cadmium were negatively associated with the IQ total score and all sub-scores, although not reaching the significance level. Hair manganese and blood lead was positively associated with the CANTAB between errors of spatial working memory (β 2.2; 95% CI 0.3, 3.9) and the reaction time of stop signal task (β 0.05; 95% CI 0.02, 0.1) respectively. All the other CANTAB neurocognitive tests did not show to be significantly influenced by metal exposure. The highest socio-economic status showed about five points intellectual quotient more than the lowest level on average (β 4.8; 95% CI 0.3, 9.6); the interaction term between blood lead and the socio-economic status showed a significant negative impact of lead on working memory at the lowest socio-economic status level (β - 4.0; 95% CI -6.9, - 1.1)., Conclusions: Metal exposure and the distance from industrial emission was associated with negative cognitive impacts in these children. Lead exposure had neurocognitive effect even at very low levels of blood lead concentration when socio-economic status is low, and this should further address the importance and prioritize preventive and regulatory interventions.

Evidence suggests that environmental exposures and socioeconomic factors may interact to produce metabolic changes in children. We assessed the influence of residential location and socioeconomic status (SES) on pediatric body mass index (BMI) Z-score and fasting blood glucose (FBG) concentration. Participants included 214 children aged 6-11 years who live near a large industrial complex in Taranto, Italy. Participants were grouped into residential zones based on the distance between their home address and the complex periphery (Zone 1: 0.000-4.999 km, Zone 2: 5.000-9.999 km, Zone 3: 10.000-15.000 km). BMI Z-scores were calculated via World Health Organization (WHO) pediatric reference curves. FBG was obtained via venous blood sampling. Closer residential location to the industrial complex on the order of 5.000 km was significantly associated with worsened metabolic outcomes, particularly in female children. Zone 1 participants had higher BMI-adjusted FBG than Zone 2 and 3 participants ( p < 0.05 versus Zone 2; p < 0.01 versus Zone 3). SES did not significantly influence BMI-adjusted FBG. Moreover, BMI Z-scores indicated high rates of overweight (22.0%) and obesity (22.9%) in the cohort. BMI Z-score was not significantly associated with SES or residential zone but was negatively associated with maternal education level ( p < 0.05). These results offer new evidence that residing near industrial activity may predict adverse effects on child metabolic health.

Background: Manganese (Mn) is an essential element but at excessive levels, it is neurotoxic. Even a moderate increase in Mn has been suggested to interfere with neurodevelopment in children. Genetics influencing Mn concentrations and toxicity is unclear. Objective: We assessed, in a cross-sectional study, whether common single-nucleotide polymorphisms in the Mn transporters SLC39A8 (influx) and SLC30A10 (efflux) are associated with neurodevelopment in children. Design: We genotyped SLC39A8 (rs13107325 C/T) and SLC30A10 (rs1776029 G/A and rs12064812 T/C) in Italian children ( n = 686, ages 11-14). We then used linear regression models to analyze associations between genotype, blood Mn concentrations, and neurodevelopmental outcomes including intelligence, behavior, motor function, and sway. Inferred causal relationships were evaluated using instrumental variables (IV) analysis. Results: For SLC30A10 rs1776029, the minor allele (A) was associated with increased average blood Mn of 41% ( p < 0.001), whereas minor alleles for rs12064812 (C) and rs13107325 (T) were associated with reduced blood Mn of 7% ( p = 0.002) and 15% ( p < 0.001), respectively. For children carrying genotypes associated with high blood Mn, we observed lower performance for certain IQ subtests, increased sway, and increased scores for behavioral problems. High Mn genotypes showed odds ratios of 2-4 (p ≤ 0.01) for high scores in tests assessing ADHD-related behavior. IV analyses suggested that several of the associations were mediated by blood Mn. Conclusions: Our results suggest that common polymorphisms in SLC39A8 and SLC30A10 influence neurodevelopmental outcomes in children via differences in Mn homeostasis.

Purpose: We aimed to evaluate patient self-management activities, patient perceptions of the therapeutic relationship and satisfaction with nurse-led consultations as part of a structured, pilot program transitioning young adults with type 1 diabetes (T1DM) to adult-oriented community-based practices., Design and Methods: A descriptive, cross-sectional study of patients receiving nurse-led consultations. Patients provided sociodemographic/health information, glycated hemoglobin (HbA1c) measures and completed questionnaires assessing self-management (Revised Self-Care Inventory) and the therapeutic relationship (Caring Nurse-Patient Interaction - short scale). HbA1c values were compared to guideline recommendations., Results: Twenty patients participated. HbA1c was ≤7.5% in 3/14 (21%) and 5/14 (36%) exhibited poor glycemic control (≥9.5%). The greatest concordance for self-care was in relation to insulin therapy (4.5±0.5) while patients reported the lowest adherence to diet recommendations (2.9±0.8). Overall satisfaction with nurse-led consultations was high (4±0.5 out of 5). Patients considered diabetes knowledge and technical competence as very important and were most pleased with the humanistic aspects of nursing care. Respect for privacy was deemed the most important (and most frequently observed) nursing attitude/behavior during consultations., Conclusions: Young adults found the nurse-led consultations with therapeutic education to develop T1DM self-care skills are an important complement to medical management during transition., Practice Implications: Patient autonomy and privacy should be respected during this developmental period. Nurses taking a humanistic approach towards accompanying and supporting the patient can enhance the therapeutic relationship during transition and promote continuity of care. Transition nurses can use technical competence and therapeutic education to empower patients for self-management., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Manganese (Mn) is an essential element required for growth and development, but higher body burdens have been associated with neurobehavioral decrements in children., Objectives: We examined whether prenatal or postnatal Mn measured in deciduous teeth was associated with scores on a test of visuospatial learning and memory., Methods: Deciduous teeth were collected from 142 participants (ages 10-14years) residing near varied ferro‑manganese industry in Italy. Mn concentrations were measured in prenatal and postnatal tooth regions by laser ablation inductively coupled plasma mass spectrometry (ICP-MS). The Virtual Radial Arm Maze (VRAM), an animal-human analogue task, was used to assess visuospatial learning and memory. We used generalized additive, linear and zero-inflated Poisson mixed regression models to estimate associations between prenatal or postnatal Mn concentrations and repeated measures of all four VRAM outcomes: time, distance, working and reference memory errors. Effect measure modification by sex was examined in stratified models., Results: U-shaped associations between prenatal Mn and VRAM outcomes were observed among girls only (p GAMM =0.001 to 0.02 in stratified models). Compared to the mid-tertile of prenatal Mn, girls in the highest tertile took 7.7s [95% CI: -6.1, 21.5] longer to complete the task, traveled 2.3 maze units [0.1, 4.4] farther, and committed more working and reference memory errors (β for count ratio=1.33 [1.01, 1.83]; 1.10 [0.98, 1.24], respectively). This association was not observed among boys. In contrast, for postnatal Mn, no significant associations were found, and patterns were similar for boys and girls., Conclusions: The prenatal period may be a critical window for the impact of environmental Mn on visuospatial ability and executive function, especially for females., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Children suffering from rheumatic disease are faced with multidimensional challenges that affect their quality of life and family dynamics. Symptom management and monitoring of the course of the disease over time are important to minimize disability and pain. Poor disease control and anticipation of the need for treatment changes may be prompted by specialist medical follow-up and regular nurse-led consultations with the patient and families, in which information and support is provided. The purpose of this study was to evaluate the impact of a nurse-led telephone intervention or Telenursing (TN) compared to standard care (SC) on satisfaction and health outcomes of children with inflammatory rheumatic diseases and their parents., Methods: A multicentered, randomized, longitudinal, crossover trial was conducted with pediatrics outpatients newly diagnosed with inflammatory rheumatic diseases. Participants were randomly assigned to two groups TN and SC for 12 months and crossed-over for the following 12 months. TN consisted of providing individualized affective support, health information and aid to decision making. Satisfaction (primary outcome) and health outcomes were assessed with the Client Satisfaction Questionnaire-8 and the Juvenile Arthritis Multidimensional Assessment Report, respectively. A mixed effect model, including a group x time interaction, was performed for each outcome., Results: Satisfaction was significantly higher when receiving TN (OR = 7.7, 95% CI: 1.8-33.6). Morning stiffness (OR = 3.2, 95% CI: 0.97-7.15) and pain (OR = 2.64, 95% CI: 0.97-7.15) were lower in the TN group. For both outcomes a carry-over effect was observed with a higher impact of TN during the 12 first months of the study. The other outcomes did not show any significant improvements between groups., Conclusion: TN had a positive impact on satisfaction and on morning stiffness and pain of children with inflammatory rheumatic diseases and their families. This highlights the importance of support by specialist nurses in improving satisfaction and symptom management for children with inflammatory rheumatisms and their families., Trial Registration: ClinicalTrial.gov identifier: NCT01511341 (December 1st, 2012).

Manganese (Mn) is an essential metal that plays a fundamental role for brain development and functioning. Environmental exposure to Mn may lead to accumulation in the basal ganglia and development of Parkinson-like disorders. The most recent research is focusing on early-life overexposure to Mn and the potential vulnerability of younger individuals to Mn toxicity also in regard to cognitive and executive functions through the involvement of the frontal cortex.Neurodevelopmental disturbances are increasing in the society, and understanding the potential role of environmental determinants is a key for prevention. Therefore, assessing the environmental sources of Mn exposure and the mechanisms of developmental neurotoxicity and defining appropriate biomarkers of exposure and early functional alterations represent key issues to improve and address preventive strategies. These themes will be reviewed in this chapter.

Long-term exposure to environmental manganese (Mn) affects not only attention and neuromotor functions but also olfactory functions of a pre-adolescent local population who have spent their whole life span in contaminated areas. In order to investigate the effect of such exposure at the level of the central nervous system we set up a pilot fMRI experiment pointing at differences of brain activities between a non-exposed population (nine subjects) and an exposed one (three subjects). We also measured the volume of the olfactory bulb as well as the identification of standard olfactory stimuli. Our results suggest that young subjects exposed to Mn exhibit a reduction of BOLD signal, subjective odor sensitivity and olfactory bulb volume. Moreover a region of interest SPM analysis showed a specifically reduced response of the limbic system in relation to Mn exposure, suggesting an alteration of the brain network dealing with emotional responses.

Background: Release of ambient metals during ferroalloy production may be an important source of environmental exposure for nearby communities and exposure to these metals has been linked to adverse respiratory outcomes. We sought to characterize the association between personal air levels of metals and respiratory health in Italian adolescents living in communities with historic and current ferroalloy activity., Methods: As part of a study in the industrial province of Brescia, Italy, 410 adolescents aged 11-14 years were recruited. Participants were enrolled from three different communities with varying manganese (Mn) levels: Bagnolo Mella which has current ferroalloy activity, Valcamonica, which has historic ferroalloy activity and Garda Lake which has no history of ferroalloy activity. Particulate matter <10 μm in diameter (PM10) was collected for 24 h in filters using personal sampling. Mn, nickel (Ni), zinc (Zn), chromium (Cr) and iron (Fe) were measured in filters using x-ray fluorescence. Data on respiratory health was collected through questionnaire. Data for 280 adolescents were analyzed using a modified Poisson regression, and risk ratios were calculated for an interquartile (IQR) range increase in each pollutant., Results: In adjusted models including PM10 as a co-pollutant, we found significant associations between concentrations of Mn (RR: 1.09, 95% CI [1.00, 1.18] per 42 ng/m(3) increase), Ni (RR: 1.11, 95% CI [1.03, 1.21] per 4 ng/m(3) increase) and Cr (RR: 1.08, 95% CI [1.06, 1.11] per 9 ng/m(3) increase) and parental report of asthma. We also found significant associations between increased Mn and Ni and increased risk of asthma medication use in the past 12 months (RR: 1.13, 95% CI [1.04, 1.29] and (RR: 1.13, 95 % CI [1.01, 1.27] respectively)., Conclusions: Our findings suggest that exposure to ambient Mn, Ni and Cr may be associated with adverse respiratory outcomes.

Background: Manganese (Mn) is an essential element that can become neurotoxic through various exposure windows over the lifespan. While there is clear evidence of Mn neurotoxicity in pediatric and adult occupational populations, little is known about effects in the elderly who may exhibit enhanced susceptibilities due to compromised physiology compared to younger adults. In the province of Brescia, Italy, the Valcamonica area has been the site of three ferroalloy plants operating from 1902 to 2001. Metal emissions of Mn and to a lesser extent lead (Pb) have impacted the surrounding environment, where a high prevalence of Parkinsonism was previously observed. This study aimed to assess neurocognitive and motor functions in healthy elderly subjects residing for most of their lifetime in Valcamonica or in a reference area unimpacted by ferroalloy plant activity., Methods: Subjects were enrolled for extensive neurobehavioral assessment of motor, cognitive and sensory functions. Exposure was assessed with 24h personal air sampling for PM10 airborne particles, surface soil and tap water measurement at individual households, Mn levels in blood and urine and Pb in blood. Dose-response relationships between exposure indicators and biomarkers and health outcomes were analyzed with generalized (linear and logistic) additive models (GAM)., Results: A total of 255 subjects (55% women) were examined; most (52.9%) were within the 65-70 years age class. Average airborne Mn was 26.41 ng/m(3) (median 18.42) in Valcamonica and 20.96 ng/m(3) (median 17.62) in the reference area. Average Mn in surface soil was 1026 ppm (median 923) in Valcamonica and 421 ppm (median 410) in the reference area. Manganese in drinking water was below the LDL of 1 μg/L. The GAM analysis showed significant association between airborne Mn (p=0.0237) and the motor coordination tests of the Luria Nebraska Neuropsychological Battery. The calculation of the Benchmark Dose using this dose-response relationship yielded a lower level confidence interval of 22.7 ng/m(3) (median 26.4). For the odor identification score of the Sniffin Stick test, an association was observed with soil Mn (p=0.0006) and with a significant interaction with blood Pb (p=0.0856). Significant dose-responses resulted also for the Raven's Colored Progressive Matrices with the distance from exposure point source (p=0.0025) and Mn in soil (p=0.09), and for the Trail Making test, with urinary Mn (p=0.0074). Serum prolactin (PRL) levels were associated with air (p=0.061) and urinary (p=0.003) Mn, and with blood Pb (p=0.0303). In most of these associations age played a significant role as an effect modifier., Conclusion: Lifelong exposure to Mn was significantly associated with changes in odor discrimination, motor coordination, cognitive abilities and serum PRL levels. These effects are consistent with the hypothesis of a specific mechanism of toxicity of Mn on the dopaminergic system. Lead co-exposure, even at very low levels, can further enhance Mn toxicity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The aim of this multicentre retrospective study was to compare reverse total shoulder arthroplasty clinical outcomes with glenospheres of different diameters, designs and materials., Methods: Between 2003 and 2008, 133 patients were divided into three groups: 60 (45%) with 36-mm standard CoCrMo (group A), 21 (16%) with 36-mm eccentric cobalt-chromium-molybdenum (CoCrMo) (group B) and 52 (39%) with 44-mm cross-linked ultra-high molecular weight polyethylene (X-UHMWPE) (group C) glenospheres. Mean (SD) follow-up was 38.7 (17.4) months. Clinical evaluation included Constant score and range of motion. Radiographic analysis included radiolucent lines, instability, loosening and assessment of scapular notching., Results: Mean Constant score significantly increased for all groups (Wilcoxon test, p < 0.001). Group C allowed a higher and stable increase in range of motion. After 12 months and 24 months, groups C and B showed less pain than group A (Mann-Whitney U-test, p < 0.05). Group C had significantly lower scapular notching than group B (Mann-Whitney U-test, p = 0.001) and A (Mann-Whitney U-test, p = 0.009) at 12 months, 24 months and 36 months. Groups A and C presented 5 (8.3%) and 4 (7.6%) early complications, respectively., Conclusions: The present study reported good results for all groups, although groups C and A presented better clinical outcomes, significantly lower notching and instability. A 44-mm X-UHMWPE glenosphere allowed a faster and more stable functional recovery, despite poorest pre-operative conditions. Additional long-term studies are needed to evaluate survivorship.

Results from a meta-analysis of aggregated data provoked a new analysis using individual data on the neuropsychological performance of occupationally exposed workers. Data from eight studies examining 579 exposed and 433 reference participants were included, 28 performance variables analyzed. The performance scores were adjusted for well-known individual-level covariates; the influence of possible, but unknown study-level covariates was attenuated by means of a z-normalization. Associations between performance and exposure were estimated by ANOVAs and ANCOVAs, the latter representing multi-level models. Four cognitive and motor performance variables each indicated significantly lower performances of exposed individuals when confounding was considered; slowed motor performances and deficits in attention and short-term memory were found. Performance on a single test was significantly related to the biomarker manganese in blood. The outcomes on susceptibility were weak. The slowing of responses was the most distinct feature of performances of exposed workers. It remains unclear, whether this result is related to the employed tests or provides important information about early stages of the neurotoxic impairment. More specific cognitive tests need to be employed to answer this question. The lack of dose-response relationships was related to features of the biomarker: it does not reflect the Mn in brain responsible for changes in performances., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose of Review: Manganese (Mn) is an essential element, but can be neurotoxic when exceeding the homeostatic range. We reviewed the most recent human studies (from January 2011 to July 2012) regarding the association between Mn exposure and cognitive, motor and behavioral effects on children., Recent Findings: A total of 10 articles were located; data were collected from five different countries. Six studies showed adverse effect of Mn on cognitive function. The most adopted cognitive test was the Wechsler Intelligence Scale for Children (WISC) or some subtests from it and results suggest an inverse association of higher Mn exposure with lower intellligence quotient. Three studies focused on motor effects of Mn; two of them found a direct association of higher Mn exposure with increased motor impairment. Two studies assessed Mn impact on behavior; one of them showed a correlation between higher Mn in water and both internalizing and externalizing behavioral scores. Potential limitations of these studies included the lack of validated biomarkers and the lack of consideration of mixed co-exposure with other neurotoxic agents., Summary: Despite some potential limitations of the reviewed studies, the adverse effects of manganese exposure on the developing brain is well demonstrated and preventive strategies should be promoted.

Background: Pediatric lead (Pb) exposure impacts cognitive function and behavior and co-exposure to manganese (Mn) may enhance neurotoxicity., Objectives: To assess cognitive and behavioral function in adolescents with environmental exposure to Pb and Mn., Methods: In this cross sectional study, cognitive function and behavior were examined in healthy adolescents with environmental exposure to metals. The Wechsler Intelligence Scale for Children (WISC) and the Conners-Wells' Adolescent Self-Report Scale Long Form (CASS:L) were used to assess cognitive and behavioral function, respectively. ALAD polymorphisms rs1800435 and rs1139488 were measured as potential modifiers., Results: We examined 299 adolescents (49.2% females) aged 11-14 years. Blood lead (BPb) averaged 1.71 μg/dL (median 1.5, range 0.44-10.2), mean Blood Manganese (BMn) was 11.1 μg/dL (median 10.9, range 4.00-24.1). Average total IQ was 106.3 (verbal IQ=102, performance IQ=109.3). According to a multiple regression model considering the effect of other covariates, a reduction of about 2.4 IQ points resulted from a two-fold increase of BPb. The Benchmark Level of BPb associated with a loss of 1 IQ-point (BML01) was 0.19 μg/dL, with a lower 95% confidence limit (BMLL01) of 0.11 μg/dL. A very weak correlation resulted between BPb and the ADHD-like behavior (Kendall's tau rank correlation=0.074, p=0.07). No influence of ALAD genotype was observed on any outcome. Manganese was not associated with cognitive and behavioral outcomes, nor was there any interaction with lead., Conclusions: These findings demonstrate that very low level of lead exposure has a significant negative impact on cognitive function in adolescent children. Being an essential micro-nutrient, manganese may not cause cognitive effects at these low exposure levels., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background and Objective: Increased prevalence of Parkinsonism was observed in Valcamonica, Italy, a region impacted by ferroalloy plants emissions containing manganese and other metals for a century until 2001. The aim of this study was to assess neurobehavioral functions in adolescents from the impacted region and the reference area of Garda Lake., Methods: Adolescents age 11-14 years were recruited through the school system for neuro-behavioral testing. Metals including manganese, lead, iron, zinc, copper were measured in airborne particulate matter collected with 24-h personal samplers, and in soil, tap water, blood, urine and hair. Independent variables included parental education and socio-economic status, children's body mass index, number of siblings, parity order, smoking and drinking habits., Results: A total of 311 subjects (49.2% females), residing in either the exposed (n=154) or the reference (n=157) area participated. Average airborne and soil manganese were respectively 49.5 ng/m(3) (median 31.4, range 1.24-517) and 958 ppm (median 897, range 465-1729) in the impacted area, and 27.4 ng/m(3) (median 24.7, range 5.3-85.9) ng/m(3) and 427 ppm (median 409 range 160-734) in the reference area. Regression models showed significant impairment of motor coordination (Luria-Nebraska test, p=0.0005), hand dexterity (Aiming Pursuit test, p=0.0115) and odor identification (Sniffin' task, p=0.003) associated with soil manganese. Tremor intensity was positively associated with blood (p=0.005) and hair (p=0.01) manganese., Conclusion: Historical environmental exposure to manganese from ferroalloy emission reflected by the concentration in soil and the biomarkers was associated with sub-clinical deficits in olfactory and motor function among adolescents., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: A higher prevalence of individuals affected by Parkinsonism was found in Valcamonica, Italy. This may be related to ferro-alloy smelters in the area, releasing manganese (Mn) in the air, soil and water for about a century. There exists individual susceptibility for Mn neurotoxicity., Aim: To analyse how polymorphism in genes regulating Mn metabolism and toxicity can modify neurophysiological effects of Mn exposure., Materials and Methods: Elderly (N=255) and adolescents (N=311) from Northern Italy were examined for neuromotor and olfactory functions. Exposure to Mn was assessed in blood and urine by atomic absorption spectroscopy and in soil by a portable instrument based on X-Ray fluorescence technology. Polymorphisms in the Parkinson-related gene ATPase type 13A2 (ATP13A2, also called PARK9: rs3738815, rs2076602, rs4920608, rs2871776 and rs2076600), and in the secretory pathway Ca(2+)/Mn(2+) ATPase isoform 1 gene (SPCA1: rs218498, rs3773814 and rs2669858) were analysed by TaqMan probes., Results: For both adolescents and elderly, negative correlations between Mn in soil and motor coordination (R(s)=-0.20, p<0.001; R(s)=-0.13, p=0.05, respectively) were demonstrated. Also among adolescents, negative correlations were seen between Mn in soil with odor identification (R(s)=-0.17, p<0.01). No associations were seen for Mn in blood or urine. ATP13A2 polymorphisms rs4920608 and rs2871776 significantly modified the effects of Mn exposure on impaired motor coordination in elderly (p for interaction=0.029, p=0.041, respectively), also after adjustments for age and gender. The rs2871776 altered a binding site for transcription factor insulinoma-associated 1., Conclusions: ATP13A2 variation may be a risk marker for neurotoxic effects of Mn in humans., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The olfactory function can be affected by occupational and environmental exposure to various neurotoxicants that can be transported through the olfactory pathway. Olfactory impairment is a highly recurrent non-motor dysfunction in Parkinson's disease and is considered an early predictive sign of neurodegeneration. Changes in olfactory perception may be caused by a dopaminergic dysregulation, possibly related to changes at the level of dopamine receptors. Manganese is an essential element that can become neurotoxic in various conditions inducing an overload in the organism. Being actively transported through the olfactory tract, manganese can cause impairment of olfactory function and motor coordination in different age groups like children and elderly. Odor and motor changes are interrelated and may be caused by a Mn-induced dopaminergic dysregulation affecting both functions. Given these findings, further research is imperative on the possible role of manganese exposure as a pathogenetic factor for Parkinsonism., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

In recent years, various international organizations have raised awareness regarding psychosocial risks and work-related stress. European stakeholders have also taken action on these issues by producing important documents, such as position papers and government regulations, which are reviewed in this article. In particular, 4 European models that have been developed for the assessment and management of work-related stress are considered here. Although important advances have been made in the understanding of work-related stress, there are still gaps in the translation of this knowledge into effective practice at the enterprise level. There are additional problems regarding the methodology in the evaluation of work-related stress. The European models described in this article are based on holistic, global and participatory approaches, where the active role of and involvement of workers are always emphasized. The limitations of these models are in the lack of clarity on preventive intervention and, for two of them, the lack of instrument standardization for risk evaluation. The comparison among the European models to approach work-related stress, although with limitations and socio-cultural differences, offers the possibility for the development of a social dialogue that is important in defining the correct and practical methodology for work stress evaluation and prevention.

To assess the risk from exposure to occupational stress and burnout in health care workers (HCW), a cross-sectional study was planned to compare objective data that can represent potential job stressors in hospital wards and subjective symptoms reported by the workers. Medical doctors, nurses and ancillary workers of the Internal Medicine Wards of a large public hospital in Northern Italy participated in the study. Three subjective questionnaires were administered: the Job Content Questionnaire (JCQ), the State-Trait Anxiety Inventory (STAI), the Maslach Burnout Inventory (MBI). In addition, seven objective parameters were collected as average during the 3 months period prior to the study: a) working understaffed; b) ratio number of patients/HCW on service; c) ratio number of HCW on sick leave/ HCW on service; d) number of skipped days off after night shifts; e) days of sick leave; f) number of deceased patients; g) number of accidents at work. A total group of 230 HCW were examined, employed in six different sub-units of the Medical wards. The female workers were 67.8% and the male workers 32.2%, the mean age was 37.4 yr (SD 9.3) in the total group of HCW, 35.1 yr (SD 7.9) in females and 42.3 yr (SD 10.3) in males. The average scores of subjective and objective parameters resulted significantly higher in the same sub-units. The correlation analysis showed that the subjective questionnaires were highly inter-related. The multivariate analysis showed that the days of sick leave were significantly related to the subjective questionnaires, and the subjective subscales of emotional exhaustion (from MBI), job demand and decision latitude (from JCQ) and STAIt were significantly related to some of the objective parameters. These results support the integrated use of multiple subjective and objective assessment as the most appropriate approach for the evaluation of occupational stress.

One of the most relevant aspects in the evaluation of occupational stress is concerned with the survey methodology. Several studies adopted subjective and objective methods of evaluation and the debate about the benefits and limitations of both approaches has continued for several years (Frese et al. 1988, Hurrell et al. 1998). To choose an appropriate, specific and focused-on-context evaluation, it is necessary to identify the sources of risk in the investigated area. Then, it is necessary to choose the methods, subjective and objective, more suitable for stress evaluation. In this study we reviewed the psychosocial risk factors that are specific to the health sector and the instruments, objective and subjective, most used in this context. We considered also the methods for the detection of episodes of violence. Finally, we presented the results of a study conducted in the health care sector, which has adopted and compared objective parameters, as potential stressors, and subjective symptoms. The study revealed statistically significant correlations between objective and subjective indicators, suggesting the importance of integrated methods of evaluation.

To assess the risk from exposure to occupational stress and burnout in health care workers (HCW), a cross-sectional study was planned to compare objective data that can represent potential job stressors in hospital wards and subjective symptoms reported by the workers. Medical doctors, nurses and ancillary workers of the Internal Medicine Wards of a large public hospital in Northern Italy were enrolled in the study. Three subjective questionnaires were administered: the Job Content Questionnaire, the State-Trait Anxiety Inventory, the Maslach Burnout Inventory. In addition, seven objective parameters were collected as average on the 3 months period prior to the study: a) working understaffed; b) number of patients/HCW on service; c) number of HCW on sick leave/on service; d) number of skipped days off after night shifts; e) number of sick leaves; f) number of deceased patients; g) number of accidents at work. A total group of 230 HCW were examined, employed in six different sub-units of the Medical wards. The female workers were 67.8% and the male workers 32.2%, the mean age was 37.4 years (SD 9.3) in the total group, 35.1 years (SD 7.9) in females and 42.3 years (SD 10.3) in males. The average scores of subjective and objective parameters resulted significantly higher in the same sub-units. The correlation analysis showed that the subjective questionnaires were highly inter-related. The multivariate analysis showed that the number of sick leave days was significantly related to the subjective questionnaires, and the subjective subscales of emotional exhaustion, job demand, decision latitude and STAIt were significantly related to some of the objective parameters. Therefore, the best approach to measure occupational stress is an integrated one, which involves the use of multiple subjective and objective assessment modalities.

Background: Manganese exposure can cause neurobehavioral and neurological signs and symptoms. A review of the literature was carried out in order to identify the most sensitive and effective methods to assess these outcomes., Methods: Studies on manganese exposure performed with neuropsychological tests were reviewed using Medline. Test methods, obtained outcomes, and dose-response relationships were considered. Based on the review and additional considerations, a testing battery for adult and children was identified., Results: A total number of 31 studies were reviewed and divided in 18 occupational, 7 environmental, and 6 on children. A large variety of tests exploring motor and cognitive functions and mood were applied. Neurobehavioral effects were dose-dependent in several studies and determined by much lower exposure levels compared to 1 mg Mn/m(3) in total dust which is considered to be the minimum concentration able to induce the classical clinical features of "manganism." Although through a wide variety of tests, the observed outcomes support the knowledge that manganese exposure can cause neurobehavioral effects. Motor functions are mainly affected in adults, and cognitive functions and behavior are more affected in children., Conclusions: Literature on manganese neurobehavioral effect is quite consistent, however, further improvement may be achieved by using better structured and more comparable evaluation methods. Based on the analysis of the existing experiences a test battery including tests of motor functions, response speed, cognitive functions, intellectual abilities, mood, and symptom questionnaires is suggested. We recommend that the tests indicated should always be included in future studies as a core battery., ((c) 2007 Wiley-Liss, Inc.)

Background: Environmental exposure to heavy metals and especially manganese (Mn) took place in Valcamonica, Italy, where a high prevalence of Parkinsonism was observed (age and sex standardized 407/100,000; 95% CI: 393.87-420.12), and the Standardized Morbidity Ratios was associated with environmental Mn levels., Methods: A cross sectional study compared Parkinsonian patients residents in Valcamonica with patients from Brescia, Italy. Age- and sex-matched healthy individuals were recruited as controls. The protocol included information on clinical, occupational, residential history and life habits, neuro-psychological testing, and assessment of genetic polymorphism., Results: The target group included 65 patients and 52 controls from Valcamonica, 28 patients and 14 controls from Brescia. Age at onset of the disease was lower in women from both areas. After adjusting for age and age at onset, patients from Valcamonica showed more severe motor impairment at the UPDRS scale, higher damage of cognitive and motor functions at MMSE, Token and Trial Making tests. Genetic variables showed a different allelic distribution of DRD4 gene between cases and controls, outside Valcamonica, where a less frequent familiarity for parkinsonism was reported., Conclusions: Parkinsonian patients with previous exposure to metals showed a more severe neuropsychological phenotype, without detectable contribution from genetic factors.

To compare data obtained in a pilot study (2002) which evaluated the risk from exposure to stress and burnout in health care workers, the same three subjective questionnaires were administered: the Job Content Questionnaire (JCQ), the State-Trait Anxiety Inventory (STAI), the Maslach Burnout Inventory (MBI). The evaluation considered 294 workers employed in eight units: two of the six previous units were reorganized in four subunits. Preliminary data showed that questionnaires' scores have a concordant trend in the different units, as observed in 2002, confirming the validity of the instruments adopted. Results indicated a decreased level of the perceived stress in all the units, especially in the Third Division. We can hypothesize that the new organization, workers' turnover during the 5 years and the effect due to individual variables could have contribute to the observed variation. No significant associations, compared to 2002, between questionnaires' scores and task were found. Further evaluations, including measurement of objective parameters, will be carried out to complete the follow-up study and to determine which variables could have a role in the variation of the levels of stress and burnout's subjective perception.

Aiming to register workplace violence in health care workers, we adopted two evaluation methods: direct and indirect. The direct method is represented by the Violent Incident Form (VIF), a 16 items checklist, which resumes the key aspects of violence events, identifying spatial and temporal circumstances, aggressor, type of violence and consequences. Indirect method is constituted by the observation of injury reports, through three sources: the Prevention and Protection Service (SPP), the Public Relation Office and the Police Position of the First Aid Unit. Although the instruments adopted, thus not comparable each other, pointed out a rather high number of violence events suffered by health care workers (direct method: 34 reports in the period 2002-2006; indirect method: 25 subjects, 8.5% of total); in most cases, the events were perpetrated by a patient, and directed against female of nurses. The most reported types of violence were: kicking, beating, hitting (indirect method) and verbal assault/threats (direct method). The study pointed out that workplace violence is an important risk factor, and therefore it is necessary to consider it for preventive intervention.

Our Institute has been following for 20 years a group of workers of a ferroalloy industry in order to evaluate neurobehavioral effects due to manganese exposure. Five years after the last study we have planned another one, to evaluate differences in neuromotor e cognitive functions between exposed and controls and to perform a longitudinal evaluation of the results. Environmental and biological sampling were collected, liver and kidney functionality, haemochrome, iron metabolism and sieric prolactine were evaluated. Several tests were administered: postural evaluation, tremor, four tests of the SPES battery, Pursuing Aiming, five tests of the Luria Nebraska Motor Battery, Raven Progressive Matrices, Trail Making Test, Mood Scale, Brief Symptoms Inventory, neuropsychological symptoms questionnaire. Personal habits and working, living and clinical histories were collected. We evaluated 43 exposed workers and 40 controls. Exposure indicators resulted all significantly higher in exposed workers. Neuropsychological examination showed differences in Raven Progressive Matrices and Pursuit Aiming, higher tremor values and differences in postural evaluation between exposed and controls.