Bone manganese is a sensitive biomarker of ongoing elevated manganese exposure, but does not accumulate across the lifespan.

Studies have established associations between environmental and occupational manganese (Mn) exposure and executive and motor function deficits in children, adolescents, and adults. These health risks from elevated Mn exposure underscore the need for effective exposure biomarkers to improve exposure classification and help detect/diagnose Mn-related impairments. Here, neonate rats were orally exposed to 0, 25, or 50 mg Mn/kg/day during early life (PND 1-21) or lifelong through âˆ¼ PND 500 to determine the relationship between oral Mn exposure and blood, brain, and bone Mn levels over the lifespan, whether Mn accumulates in bone, and whether elevated bone Mn altered the local atomic and mineral structure of bone, or its biomechanical properties. Additionally, we assessed levels of bone Mn compared to bone lead (Pb) in aged humans (age 41-91) living in regions impacted by historic industrial ferromanganese activity. The animal studies show that blood, brain, and bone Mn levels naturally decrease across the lifespan without elevated Mn exposure. With elevated exposure, bone Mn levels were strongly associated with blood Mn levels, bone Mn was more sensitive to elevated exposures than blood or brain Mn, and Mn did not accumulate with lifelong elevated exposure. Elevated early life Mn exposure caused some changes in bone mineral properties, including altered local atomic structure of hydroxyapatite, along with some biomechanical changes in bone stiffness in weanlings or young adult animals. In aged humans, blood Mn ranged from 5.4 to 23.5 ng/mL; bone Mn was universally low, and decreased with age, but did not vary based on sex or female parity history. Unlike Pb, bone Mn showed no evidence of accumulation over the lifespan, and may not be a biomarker of cumulative long-term exposure. Thus, bone may be a useful biomarker of recent ongoing Mn exposure in humans, and may be a relatively minor target of elevated exposure.

Neurocognitive impact of metal exposure and social stressors among schoolchildren in Taranto, Italy.

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 (ß - 0.04; 95% CI -0.06, - 0.01; ß - 0.02; 95% CI -0.05, - 0.001; ß - 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 (ß 2.2; 95% CI 0.3, 3.9) and the reaction time of stop signal task (ß 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 (ß 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 (ß - 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.

Thyroidectomy in dogs with thyroid tumors: Survival analysis in 144 cases (1994-2018).

BACKGROUND: Few studies have assessed predictors of outcome in dogs with thyroid tumors undergoing thyroidectomy. OBJECTIVE: To estimate the survival and identify prognostic factors in dogs with thyroid tumors treated by thyroidectomy. ANIMALS: A total of 144 client-owned dogs with thyroid neoplasia that underwent thyroidectomy. METHODS: Retrospective study. Data for analysis included hospital attended and year of surgery, signalment, thyroxine concentration, thyroid tumor features (lobe involvement, size, invasiveness, histopathological type), thrombosis, metastasis, additional surgery and therapy, administration of adjuvant chemotherapy. The association of predictors with survival (time from surgery to death) were assessed by calculating cause-specific hazard ratios (HRcs ) and 95% confidence intervals (CI). Causes of death were classified as thyroid-related or because of other cause. RESULTS: Overall median survival time was 802 days (CI95% = 723-1015 days); 89 dogs (77.4%) survived >500 days. Metastases were identified at admission in 12 (8.3%) dogs and were associated with higher thyroid cancer-related fatality (HR = 5.83, CI95% = 1.56-21.78; P = .009). Thrombosis occurred in 40 dogs and was associated with increased risk of death because of other cause (HR = 2.73, CI95% = 1.18-6.35; P = .019). Nonfollicular carcinoma (HR = 4.17, CI95% = 1.27-13.69; P = .018) and administration of chemotherapy (HR = 3.45, CI95% = 1.35-8.82; P = .01) were associated with higher risk of thyroid cancer-related death. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with thyroid tumors undergoing thyroidectomy have a long life expectancy. Despite the rare presence of nonfollicular carcinoma and metastases, thyroidectomy should still be considered in some of these dogs.

Inverse association of intellectual function with very low blood lead but not with manganese exposure in Italian 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.

The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior.

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.

Critical windows of susceptibility in the association between manganese and neurocognition in Italian adolescents living near ferro-manganese industry.

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: ß = 0.20 (95 % CI: 0.02, 0.38)] and Block design [ß = 0.21 (0.01, 0.41)] and early postnatal Mn was positively associated with Digits forward [ß = 0.24 (0.09, 0.40)], while childhood Mn was negatively associated with Coding [ß = -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.

Antimicrobial and Fermentation Potential of Himanthalia elongata in Food Applications.

Himanthalia elongata is a brown oceanic seaweed rich in bioactive compounds. It could play an important role in food production because of its antimicrobial and antioxidant properties. Three strains belonging to the Lactobacillus casei group (Lactobacillus casei, Lactobacillus paracasei, and Lactobacillus rhamnosus) and a Bacillus subtilis strain were used for the solid-state fermentation of commercial seaweeds, and bacterial growth was monitored using the plate count method. High-pressure processing (HPP) was also employed (6000 bar, 5 min, 5 °C) before extraction. The antimicrobial activity of the extracts was tested in terms of the main food pathogenic bacteria (Salmonella spp., Listeria monocytogenes, Escherichia coli, Staphylococcus aureus, and Bacillus cereus), and the phenolic content was estimated using the Folin-Ciocalteau method. In addition, targeted UHPLC-MS2 methods were used to unravel the profile of phlorotannins. H. elongata allowed the growth of the L. casei group strains and B. subtilis, showing the fermentability of this substrate. Significant antimicrobial activity toward L. monocytogenes was observed in the extracts obtained from unfermented samples, but neither fermentation nor HPP enhanced the natural antimicrobial activity of this seaweed species. The content in the phenolic compounds decreased because of the fermentation process, and the amount of phenolics in both the unfermented and fermented H. elongata extracts was very low. Despite phlorotannins being related to the natural antimicrobial activity of this brown seaweed, these results did not support this association. Even if fermentation and HPP were not proven to be effective tools for enhancing the useful compounds of H. elongata, the seaweed was shown to be a suitable substrate for L. casei group strains as well as for B. subtilis growth, and its extracts exhibited antimicrobial activity toward foodborne pathogens.

Metal Exposure and SNCA rs356219 Polymorphism Associated With Parkinson Disease and Parkinsonism.

Objective: In the province of Brescia, Italy, historical neurotoxic metal exposure has occurred for several decades. This study aimed to explore the role of metal exposure and genetics on Parkinson's Disease (PD) and Parkinsonism. Methods: Cases were enrolled from four local clinics for movement disorders. Randomly selected controls non-affected by neurological or psychiatric conditions were enrolled from the same health centers keeping a similar gender ratio and age distribution as for cases. Data on sociodemographic variables, clinical onset and life habits were collected besides accurate occupational and residential history. Blood samples were collected from all participants for genotyping of target polymorphisms in genes linked to PD and/or metal transport. Results: A total number of 432 cases and 444 controls were enrolled in the study, with average age of 71 years (72.2 for cases and 70 for controls). The average age at diagnosis was 65.9 years (SD 9.9). Among the potential risk factors, family history of PD or Parkinsonism showed the strongest association with the diseases (OR = 4.2, 95% CI 2.3, 7.6 on PD; OR = 4.3, 95% CI 1.9, 9.5 for Parkinsonism), followed by polymorphism rs356219 in the alpha-synuclein (SNCA) gene (OR = 2.03, 95% CI 1.3, 3.3 for CC vs. TT on PD; OR = 2.5, 95% CI 1.1, 5.3 for CC vs. TT on Parkinsonism), exposure to metals (OR = 2.4;, 95% CI 1.3, 4.2 on PD), being born in a farm (OR = 1.8; 95% CI 1.1, 2.8 on PD; OR = 2.6; 95% CI 1.4, 4.9 on Parkinsonism) and being born in the province of Brescia (OR = 1.7; 95% CI 1.0, 2.9 on PD). Conditional OR of having PD depending by SNCA polymorphism and metal exposure highlights higher risk of PD among CC SNCA carriers and being exposed to metals. However, the interaction term was not statistically significant. Conclusions: Lifetime exposure to metals and genetic variation in SNCA gene are relevant determinants of PD and Parkinsonism in the highly industrialized area of Brescia, Italy. The lack of evidence of statistical interaction between environmental and genetic factors may be due to the low frequencies of subjects representing the exposure categories and the polymorphism variants and does not rule out the biological interaction.

Associations of a Metal Mixture Measured in Multiple Biomarkers with IQ: Evidence from Italian Adolescents Living near Ferroalloy Industry.

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, 0.08µg/g; hair Cu, 9.6µg/g; hair Cr, 0.05µg/g; and blood Pb, 1.3µg/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, 5.4µg/g), higher concentrations (90th percentiles) of the mixture of Mn, Pb, and Cr (0.3µg/g, 2.6µg/dL, and 0.1µg/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.

Analysis of settled dust with X-ray Fluorescence for exposure assessment of metals in the province of Brescia, Italy.

Ferroalloy industries have been active for more than a century in the province of Brescia, Northern Italy. Air emission and water discharge have contaminated the environment in the surroundings of four plants with several metals including manganese. The presence of manganese in this region is especially interesting, because of the observed relationship between manganese exposure and Parkinsonism in a previous epidemiological survey. The aim of this study was represented by an initial screening of metal exposure in this area, using a geographic information system. X-ray fluorescence (XRF) was applied to identify heavy metals in deposited dust samples, collected in representative residential households throughout the province. The results were interpreted through a systematic mapping of all municipal districts of the Brescia province. A more frequent distribution of manganese and other metals was observed in the municipalities where the plants were located and differences in the geochemical and anthropogenic origin of metals were discussed, according to the point sources.

Manganese transporter genetics and sex modify the association between environmental manganese exposure and neurobehavioral outcomes in children.

There is increasing evidence that environmental manganese (Mn) exposure early in life can have negative effects on children's neurodevelopment and increase the risk of behavioral problems, including attention deficit hyperactivity disorder (ADHD). Factors that may contribute to differences in sensitivity to Mn exposure are sex and genetic variation of proteins involved in the regulation of Mn concentrations. Here we investigate if sex and polymorphisms in Mn transporter genes SLC30A10 and SLC39A8 influence the association between Mn exposure and ADHD-related behavioral problems in children. The SNPs rs1776029 and rs12064812 in SLC30A10, and rs13107325 in SLC39A8 were genotyped by TaqMan PCR or pyrosequencing in a population of Italian children (aged 11-14 years; n = 645) with a wide range of environmental Mn exposure. Mn in surface soil was measured in situ using XRF technology or modeled by geospatial analysis. Linear regression models or generalized additive models (GAM) were used for analyzing associations between soil Mn and neurobehavioral problems assessed by the Conners' behavior rating scales (self-, and parent-reported). Gene-environment interactions (Mn transporter genotype x soil Mn) were evaluated using a genetic score in which genotypes for the three SNPs were combined based on their association with blood Mn, as an indication of their influence on Mn regulation. We observed differences in associations between soil Mn and neurobehavior between sexes. For several self-reported Conners' scales, girls showed U-shaped relationships with higher (worse) Conners' scoring at higher soil Mn levels, and several parent-reported scales showed positive linear relationships between increasing soil Mn and higher Conner's scores. For boys, we observed a positive linear relationship with soil Mn for one Conner's outcome only (hyperactivity, parent-reported). We also observed some interactions between soil Mn and the genetic score on Conner's scales in girls and girls with genotypes linked to high blood Mn showed particularly strong positive associations between soil Mn and parent-reported Conners' scales. Our results indicate that sex and polymorphisms in Mn transporter genes contribute to differences in sensitivity to Mn exposure from the environment and that girls that are genetically less efficient at regulating Mn, may be a particularly vulnerable group.

Metabolic Outcomes in Southern Italian Preadolescents Residing Near an Industrial Complex: The Role of Residential Location and Socioeconomic Status.

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.

Polymorphisms in Manganese Transporters SLC30A10 and SLC39A8 Are Associated With Children's Neurodevelopment by Influencing Manganese Homeostasis.

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.

Efficacy of a modified-live virus vaccine in pigs experimentally infected with a highly pathogenic porcine reproductive and respiratory syndrome virus type 1 (HP-PRRSV-1).

PRRS is one of the main viral diseases in pig production, causing huge economic losses to the swine industry worldwide. The virus shows an intrinsic genomic instability and is able to change continuously, with the emergence of new strains, with different pathogenicity patterns. Commercially available vaccines only partially prevent or counteract the disease and the correlated losses. Moreover, the emergence of highly virulent and pathogenetic isolates represents a particular concern for PRRS control and diagnosis. The purpose of this study was to evaluate the efficacy of a modified-live virus (MLV) PRRSV-1 commercial vaccine in reducing the severity of the disease and minimizing losses upon challenge with a highly pathogenic PRRSV-1.1 Italian isolate (PRRSV-1_PR40/2014). Four different groups were compared: C (unvaccinated-uninfected), VAC-C (vaccinated-uninfected), PR40 (unvaccinated-infected) and VAC-PR40 (vaccinated-infected). The tested vaccine provided partial, but statistically significant clinical, virological and pathological protection after challenge under experimental conditions. In particular, vaccinated animals showed reduced viremia in terms of duration and magnitude, reduced respiratory signs and pathological lesions. Vaccination was able to trigger adaptive immunity able to respond efficiently also against the HP PR40 isolate. Vaccinated animals showed higher average daily weight gain, even during the viremic period, compared to non-vaccinated challenged pigs.

Critical assessment of the diagnostic value of feline alpha1-acid glycoprotein for feline infectious peritonitis using the likelihood ratios approach.

Alpha-1-acid glycoprotein (AGP) increases in the blood of cats with feline infectious peritonitis (FIP), a lethal disease caused by feline coronavirus (FCoV). However, the diagnostic potential of AGP might be limited because AGP also increases in pathophysiological conditions other than FIP. In this retrospective study, the diagnostic potential of serum AGP concentration was evaluated on the basis of the pretest probability of disease, according to the Bayesian approach. Serum AGP levels from cats with FIP (group 1; n = 58) and without FIP (group 2; n = 104) were evaluated. Non-FIP cats were further subgrouped as follows: 2a) inflammation (n = 26), 2b) asymptomatic FCoV infection (n = 49), 2c) injection-site sarcoma (n = 19), 2d) postvaccination (n = 7), and 2e) specific pathogen free (n = 3). Standard descriptive analyses by group and empirical receiver-operating characteristic (ROC) curve estimation were performed. Ordinary logistic regression analysis was performed to derive an estimate of the continuous likelihood ratio to produce the posttest probability of disease for any combination of pretest probability and serum AGP value. The comparison of serum AGP levels in the different groups and the analysis of the ROC curve confirmed that serum AGP is a powerful discriminating marker for FIP. The Bayesian approach demonstrated that when the pretest probability of FIP is high, based on history and clinical signs (groups 1 or 2a), moderate serum AGP levels (1.5-2 mg/ml) can discriminate cats with FIP from others, while only high serum AGP levels (>3 mg/ml) can support a diagnosis of FIP in cats with a low pretest probability of disease (groups 2b to 2e).

Phenotypic characterization of a highly pathogenic Italian porcine reproductive and respiratory syndrome virus (PRRSV) type 1 subtype 1 isolate in experimentally infected pigs.

Highly pathogenic (HP) isolates of the PRRS virus started emerging in North America and Asia in the late 1990s. More recently, they have emerged in Europe. These isolates are characterized by high viral loads, severe general clinical signs and high mortality, in sows, weaners and growers. Their genome shows a discontinuous aminoacids deletion in the non-structural protein 2 (NSP2). The present study was aimed at characterizing the clinical, pathological and immunological features of a highly pathogenetic, Italian PRRSV-1 subtype 1 isolate (PRRSV1_PR40/2014), following experimental infection in conventional 4-weeks-old pigs. The PRRSV1_PR40/2014 infected group showed severe clinical signs (high fever and dispnoea). Pathological lesions, including severe lymphocytopenia in bronchial lymph-nodes and thymus were also recorded. Higher serum PRRSV genome copies and lower virus neutralizing antibody titer were observed in the PR40 group, when compared to the group infected with a conventional PRRSV strain. The genetic analysis of the strain, and the phenotypic features observed in the field and reproduced in the experimental study, confirmed the high pathogenicity of the Italian PRRSV-1 subtype 1 PR40 isolate.

Metal contamination of home garden soils and cultivated vegetables in the province of Brescia, Italy: implications for human exposure.

BACKGROUND: For the past century, ferroalloy industries in Brescia province, Italy produced particulate emissions enriched in manganese (Mn), lead (Pb), zinc (Zn), copper (Cu), cadmium (Cd), chromium (Cr), iron (Fe), and aluminum (Al). This study assessed metal concentrations in soil and vegetables of regions with varying ferroalloy industrial activity levels. METHODS: Home gardens (n=63) were selected in three regions of varying ferroalloy plant activity durations in Brescia province. Total soil metal concentration and extractability were measured by X-Ray Fluorescence (XRF), aqua regia extraction, and modified Community Bureau of Reference (BCR) sequential extraction. Unwashed and washed spinach and turnips cultivated in the same gardens were analyzed for metal concentrations by flame atomic absorption spectrometry. RESULTS: Median soil Al, Cd, Fe, Mn, Pb, and Zn concentrations were significantly higher in home gardens near ferroalloy plants compared to reference home gardens. The BCR method yielded the most mobile soil fraction (the sum of extractable metals in Fractions 1 and 2) and all metal concentrations were higher in ferroalloy plant areas. Unwashed spinach showed higher metal concentrations compared to washed spinach. However, some metals in washed spinach were higher in the reference area likely due to history of agricultural product use. Over 60% of spinach samples exceeded the 2- to 4-fold Commission of European Communities and Codex Alimentarius Commission maximum Pb concentrations, and 10% of the same spinach samples exceeded 2- to 3-fold maximum Cd concentrations set by both organizations. Turnip metal concentrations were below maximum standard reference values. CONCLUSIONS: Prolonged industrial emissions increase median metal concentrations and most soluble fractions (BCR F1+F2) in home garden soils near ferroalloy plants. Areas near ferroalloy plant sites had spinach Cd and Pb metal concentrations several-fold above maximum standard references. We recommend thorough washing of vegetables to minimize metal exposure.

Manganese concentrations in soil and settled dust in an area with historic ferroalloy production.

Ferroalloy production can release a number of metals into the environment, of which manganese (Mn) is of major concern. Other elements include lead, iron, zinc, copper, chromium, and cadmium. Mn exposure derived from settled dust and suspended aerosols can cause a variety of adverse neurological effects to chronically exposed individuals. To better estimate the current levels of exposure, this study quantified the metal levels in dust collected inside homes (n=85), outside homes (n=81), in attics (n=6), and in surface soil (n=252) in an area with historic ferroalloy production. Metals contained in indoor and outdoor dust samples were quantified using inductively coupled plasma optical emission spectroscopy, whereas attic and soil measurements were made with a X-ray fluorescence instrument. Mean Mn concentrations in soil (4600 µg/g) and indoor dust (870 µg/g) collected within 0.5 km of a plant exceeded levels previously found in suburban and urban areas, but did decrease outside 1.0 km to the upper end of background concentrations. Mn concentrations in attic dust were ~120 times larger than other indoor dust levels, consistent with historical emissions that yielded high airborne concentrations in the region. Considering the potential health effects that are associated with chronic Mn inhalation and ingestion exposure, remediation of soil near the plants and frequent, on-going hygiene indoors may decrease residential exposure and the likelihood of adverse health effects.

Neurofunctional dopaminergic impairment in elderly after lifetime exposure to manganese.

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.

Concurrent vaccinations against PCV2 and PRRSV: study on the specific immunity and clinical protection in naturally infected pigs.

The present study aims at evaluating the efficacy of the concurrent PCV2 and PRRS vaccinations in comparison with single vaccinations and placebo in pigs exposed to both natural viral infections. Four groups of pigs (200 animals each) at 4 weeks of age were considered. Pigs from group A were concurrently vaccinated with a modified live PRRSV-1-based vaccine and a genotype a-based PCV2 subunit (Cap) vaccine via the intramuscular route. Animals from groups B and C were vaccinated with PRRSV and PCV2 vaccines alone, respectively, and group D was inoculated with the adjuvant alone. Clinical score (morbidity), mortality and average daily weight gain (ADWG) were evaluated. Viraemia, virus-specific ELISA antibodies and cell-mediated immunity (CMI) as IFN-γ secreting cells by ELISpot were detected. The clinical signs associated with PRRSV infection lasted from 8 to 16 weeks while those related to PCV2 infection from 5 months of age. The results showed that the concurrent vaccinations reduced clinical signs and increased the preventive fraction (40.4%) and the ADWG. In concurrently vaccinated pigs, the probability of dying due to infection, especially in association with PCV2 viraemia was reduced 3-fold. PRRSV viraemia was not reduced by vaccination but lower and shorter PCV2 viral load was detected in both concurrently and single PCV2-vaccinated pigs. Despite the presence of maternally derived antibodies, animals showed a prompt seroconversion after vaccination and PCV2 natural infection. Moreover, maternal immunity did not interfere with the development of the specific cellular IFN-γ SC response in single and concurrently vaccinated animals. The study demonstrates that concurrent PRRSV+PCV2 vaccination has no interference with the development of the specific humoral and cell-mediated immunity and it is associated with clinical protection upon natural challenge.