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 yrs 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-hour 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/m3 (median 31.4, range 1.24–517) and 958 ppm (median 897, range 465–1729) in the impacted area, and 27.4 ng/m3 (median 24.7, range 5.3–85.9) ng/m3 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 subclinical deficits in olfactory and motor function among adolescents.

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.

, et al.. One dose of a porcine circovirus 2 subunit vaccine induces humoral and cell-mediated immunity and protects against porcine circovirus-associated disease under field conditions. Veterinary Microbiology, Elsevier, 2011, 149 (3-4) Please cite this article as: Martelli, P., Ferrari, L., Morganti, M., De Angelis, E., Bonilauri, P., Guazzetti, S., Caleffi, A., Borghetti, P., One dose of a porcine circovirus 2 subunit vaccine induces humoral and cell-mediated immunity and protects against porcine circovirus-associated disease under field conditions, Veterinary Microbiology (2010Microbiology ( ), doi:10.1016Microbiology ( /j.vetmic.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 This study investigated the efficacy of a one-dose porcine circovirus 2 (PCV2) subunit 22 vaccine based on the PCV2 Cap protein expressed in a baculovirus system on two different farms at 23 which a history of porcine circovirus-associated disease (PCVD) was present. Morbidity, mortality, 24 average daily weight gain, carcass weight, PCV2 load in serum and vaccine immunogenicity were 25 assessed. Serology to porcine reproductive and respiratory syndrome virus (PRRSV) and 26Mycoplasma hyopneumoniae was performed. A double-blind, randomised, and controlled field trial 27 was performed distributing 818 piglets between two treatment groups. At inclusion (weaning at 21 28 ± 3 days of age), 408 animals (group B) received a 2-mL intramuscular dose of Porcilis PCV between 12 and 26 weeks of age when viremia and the specific disease occurred) as well as carcass 38 weight at slaughter age (+4.5 kg). These effects were associated with virologic and clinical 39 protection from the immunogenicity of the vaccine measured as activation of both a humoral and a 40 cellular immune response. 41 42

Adolescents living in communities with ferromanganese alloy plant activity have been shown to exhibit deficits in olfactory and fine motor function. Household dust may serve as an important manganese (Mn) exposure pathway to children, though dust Mn concentrations have not previously been measured to assess household contamination from ferromanganese alloy plant emissions. Here we determined the association between dust concentrations and surface loadings of Mn and other metals (Al, Cd, Cr, Cu, Fe, Pb, and Zn) in indoor and outdoor household dust from three Italian communities that differ by history of ferromanganese alloy plant activity: Bagnolo Mella, with an active ferromanganese alloy plant (n=178 households); Valcamonica, with historically active plants (n=166); and Garda Lake, with no history of ferromanganese plant activity (n=99). We also evaluated Mn levels in other environmental (soil, airborne particulates) and candidate biomarker (blood, hair, saliva, fingernails) samples from children within the households. Household dust Mn concentrations and surface loadings were significantly different between the three sites, with levels highest in Bagnolo Mella (outdoor median Mn concentration = 4620, range 487 – 183,000 µg/g), intermediate in Valcamonica (median = 876, range 407 – 8240 µg/g), and lowest in Garda Lake (median = 407, range 258 – 7240 µg/g). Outdoor dust Mn concentrations in Bagnolo Mella, but not the other communities, were significantly inversely related with distance from the plant (R2=0.6630, P<0.0001). Moreover, outdoor dust Mn concentrations and loadings were highly predictive of but significantly higher than indoor dust Mn concentrations and loadings by ~2 to ~7-fold (Mn concentrations) and ~7 to ~20-fold (Mn loadings). Finally, both indoor and outdoor dust Mn concentrations and outdoor dust Mn loading values were highly significantly correlated with both soil and air Mn concentrations, and with children’s hair and fingernail Mn concentrations, but weakly or not associated with saliva or blood Mn levels. Given the evidence associating elevated Mn exposure with neurological impairments in children, these data support that dust Mn levels should be reduced in contaminated environments to protect the health of resident children.

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 24hour 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/m3 (median 18.42) in Valcamonica and 20.96 ng/m3 (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/m3 (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.