Dolores Catelan

Asthma symptoms, lung function, and markers of oxidative stress and inflammation in children exposed to oil refinery pollution.

Objectives. Little is known about the effects of exposure to petroleum refinery emissions on respiratory health in children. We evaluated lung function and markers of inflammation and oxidative stress in children and adolescents with and without asthma or wheezing symptoms living in a petrochemical polluted area (Sarroch, Sardinia) versus a reference area (Burcei). Methods. Parents of 275/300 6- to 14-year-old children living in Sarroch and parents of 214/323 children living in Burcei answered a questionnaire on respiratory symptoms and risk factors. Measurements of forced expiratory volume after 1 second (FEV1) and of forced expiratory flow rates at 25–75% of vital capacity (FEF25–75) were available in 27 and 23 asthma/wheezing-positive subjects and in 7 and 54 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively; for fractional exhaled nitric oxide (FENO) corresponding figures were 27 and 24 and 8 and 55 in Sarroch and in Burcei, respectively. Malondialdehyde–deoxyguanosine (MDA–dG) adduct levels in nasal mucosa were measured in 12- to 14-year-old adolescents (8 and 14 asthma/wheezing-positive and 20 and 28 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively). Air pollutants were assessed during 3 weeks, starting 1 week before lung function, FENO, and MDA–dG measurements. Generalized linear models were used to estimate the effect of the area of residence adjusting for confounders. Results. Weekly average concentrations of sulfur dioxide were 6.9–61.6μg/m3 in Sarroch versus 0.3–7.6μg/m3 in the rural area of Burcei; of nitrogen dioxide, 5.2–28.7μg/m3 versus 1.7–5.3μg/m3; and of benzene, 1.8–9.0μg/m3 versus 1.3–1.5μg/m3, respectively. Children living in Sarroch versus children living in the reference area showed an increase in wheezing symptoms {adjusted prevalence ratio=1.70 [90% confidence interval (CI)=1.01; 2.86]}; a decrease in lung function [variation in FEV1=−10.3% (90% CI=−15.0; −6.0%) and in FEF25–75=−12.9% (90% CI=−20.7; −4.3%)]; an increase in bronchial inflammation [variation in FENO=+35% (90% CI=11.7; 80.1%)]; and an increase in MDA–dG adducts of +83% (90% CI=22.9; 174.1%). Conclusions. Data from this small study are consistent with the role of environmental pollutants on lung function and inflammation.

Nasal cell DNA methylation, inflammation, lung function and wheezing in children with asthma.

AIMS DNA methylation is increasingly proposed as a mechanism for underlying asthma-related inflammation. However, epigenetic studies are constrained by uncertainties on whether samples that can be easily collected in human individuals can provide informative results. METHODS Two nasal cell DNA samples were collected on different days by nasal brushings from 35 asthmatic children aged between 8 and 11 years old. We correlated DNA methylation of IL-6, iNOS, Alu and LINE-1 with fractional exhaled nitric oxide, forced expiratory volume in 1 s and wheezing. RESULTS Fractional exhaled nitric oxide increased in association with lower promoter methylation of both IL-6 (+29.0%; p = 0.004) and iNOS (+41.0%; p = 0.002). Lower IL-6 methylation was nonsignificantly associated with wheezing during the week of the study (odds ratio = 2.3; p = 0.063). CONCLUSION Our findings support the use of nasal cell DNA for human epigenetic studies of asthma.

Canine faecal contamination and parasitic risk in the city of Naples (southern Italy)

BackgroundDogs are associated with more than 60 zoonotic diseases among which, parasitosis and, in particular, helminthosis, can pose serious public-health concerns worldwide. Many canine gastrointestinal parasites eliminate their dispersion elements (eggs, larvae, oocysts) by the faecal route. The quantity of canine faeces deposited on public and private property in cities worldwide is both a perennial nuisance and an important health issue. Public sites such as playgrounds, parks, gardens, public squares and sandpits may be an important source of human infection. The aim of this study was to evaluate the extent of both canine faecal contamination in the city of Naples (southern Italy), and presence of canine parasitic elements, with particular regard to those which are potential agents of zoonosis. A regular grid of sub-areas (1 km × 700 m) was overlaid on the city map using a Geographical Information System (GIS). In each sub-area the straightest 1 km transect was drawn and digitalized on-screen in the GIS. Between February and May 2005 canine faeces were counted along the 1 km transects in 143 sub-areas, and 415 canine faecal samples were collected and submitted to coprological examinations. Negative binomial regression models and Gaussian random effects models were used to analyze the association between faeces count and human population density taking into account for extraPoisson variability. Logistic regression model was used to evaluate the association between positivity to parasitic elements and number of canine faeces.ResultsOut of the 143 studied sub-areas, 141 (98.6%) contained canine faeces. There was a strong spatial gradient with 48% of the total variability accounted by between neighbourhood variability; a positive association between the number of faeces and the human population density was found. Seventy (over 415, 16.9%) canine faecal samples were positive for parasitic elements. There was no association between positivity to parasitic elements and the number of canine faeces. Eggs of Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Trichuris vulpis were found, as well as oocysts of Isospora canis.ConclusionIn conclusion, the results of the present study, conducted using GIS both for planning and sampling and for evaluation and presentation of findings, showed the presence of canine faecal contamination in the city of Naples, and the presence of canine parasitic elements, some of which are potential agents of zoonosis.

Disease mapping in veterinary epidemiology: a Bayesian geostatistical approach

Model-based geostatistics and Bayesian approaches are useful in the context of veterinary epidemiology when point data have been collected by appropriate study design. We take advantage of an example of Epidemiological Surveillance on urban settings where a two-stage sampling design with first stage transects is applied to study the risk of dog parasite infection in the city of Naples, 2004-2005. We specified Bayesian Gaussian spatial exponential models and Bayesian kriging were performed to predict the continuous risk surface of parasite infection on the study region. We compared the results with those obtained by the application of hierarchical Bayesian models on areal data (proportion of positive specimens by transect). The models results were consistent with each other and the Bayesian geostatistical approach proved to be more accurate in identifying areas at risk of zoonotic parasitic diseases. In general, larger risk areas were identified at the city border where wild dogs mixed with domestic dogs and human or urban barriers were less present.

Long-term dietary extra-virgin olive oil rich in polyphenols reverses age-related dysfunctions in motor coordination and contextual memory in mice: role of oxidative stress.

The aim of this study was to evaluate the effects of olive oil phenols on brain aging in mice and to verify whether the antioxidant and antiinflammatory activities of these polyphenols were involved. C57Bl/6J mice were fed from middle age to senescence with extra-virgin olive oil (10% wt/wt dry diet) rich in phenols (total polyphenol dose/day, 6 mg/kg). Behavioral tests were employed to assess cognitive, motor, and emotional behavior after 6 or 12 months of treatment. Parameters of oxidative status and inflammation were measured in different brain areas at the same times and evaluated for correlation with behavioral changes. The treatment with olive oil phenols improved contextual memory in the step-down test to levels similar to young animals and prevented the age-related impairment in motor coordination in the rotarod test. This motor effect was correlated with reduced lipid peroxidation in the cerebellum (p<0.05), whereas the memory effect did not correlate with oxidation or inflammation parameters. In conclusion, this work points out that natural polyphenols contained in extra-virgin olive oil can improve some age-related dysfunctions by differentially affecting different brain areas. Such a modulation can be obtained with an olive oil intake that is normal in the Mediterranean area, provided that the oil has a sufficiently high content of polyphenols.

Air pollution exposure, cause-specific deaths and hospitalizations in a highly polluted Italian region

BACKGROUND The Lombardy region in northern Italy ranks among the most air polluted areas of Europe. Previous studies showed air pollution short-term effects on all-cause mortality. We examine here the effects of particulate matter with aerodynamic diameter ≤10µm (PM10) and nitrogen dioxide (NO2) exposure on deaths and hospitalizations from specific causes, including cardiac, cerebrovascular and respiratory diseases. METHODS We considered air pollution, mortality and hospitalization data for a non-opportunistic sample of 18 highly polluted and most densely populated areas of the region in the years 2003-2006. We obtained area-specific effect estimates for PM10 and NO2 from a Poisson regression model on the daily number of total deaths or cause-specific hospitalizations and then combined them in a Bayesian random-effects meta-analysis. For cause-specific mortality, we applied a case-crossover analysis. Age- and season-specific analyses were also performed. Effect estimates were expressed as percent variation in mortality or hospitalizations associated with a 10µg/m(3) increase in PM10 or NO2 concentration. RESULTS Natural mortality was positively associated with both pollutants (0.30%, 90% Credibility Interval [CrI]: -0.31; 0.78 for PM10; 0.70%, 90%CrI: 0.10; 1.27 for NO2). Cardiovascular deaths showed a higher percent variation in association with NO2 (1.12%, 90% Confidence Interval [CI]: 0.14; 2.11), while the percent variation for respiratory mortality was highest in association with PM10 (1.64%, 90%CI: 0.35; 2.93). The effect of both pollutants was more evident in the summer season. Air pollution was also associated to hospitalizations, the highest variations being 0.77% (90%CrI: 0.22; 1.43) for PM10 and respiratory diseases, and 1.70% (90%CrI: 0.39; 2.84) for NO2 and cerebrovascular diseases. The effect of PM10 on respiratory hospital admissions appeared to increase with age. For both pollutants, effects on cerebrovascular hospitalizations were more evident in subjects aged less than 75 years. CONCLUSIONS Our study provided a sound characterization of air pollution exposure and its potential effects on human health in the most polluted, and also most populated and productive, Italian region, further documenting the need for effective public health policies.

Fetal striatal grafting slows motor and cognitive decline of Huntington's disease

Objective To assess the clinical effect of caudate-putaminal transplantation of fetal striatal tissue in Huntingtons disease (HD). Methods We carried out a follow-up study on 10 HD transplanted patients and 16 HD not-transplanted patients. All patients were evaluated with the Unified HD Rating Scale (UHDRS) whose change in motor, cognitive, behavioural and functional capacity total scores were considered as outcome measures. Grafted patients also received morphological and molecular neuroimaging. Results Patients were followed-up from disease onset for a total of 309.3 person-years (minimum 5.3, median 11.2 years, maximum 21.6 years). UHDRS scores have been available since 2004 (median time of 5.7 years since onset, minimum zero, maximum 17.2 years). Median post-transplantation follow-up was 4.3 years, minimum 2.8, maximum 5.1 years. Adjusted post-transplantation motor score deterioration rate was reduced compared to the pretransplantation period, and to that of not-transplanted patients by 0.9 unit/years (95% CI 0.2 to 1.6). Cognitive score deterioration was reduced of 2.7 unit/years (95% CI 0.1 to 5.3). For grafted patients the 2-year post-transplantation [18F]fluorodeoxyglucose positron emission tomography (PET) showed striatal/cortical metabolic increase compared to the presurgical evaluation; 4-year post-transplantation PET values were slightly decreased, but remained higher than preoperatively. [123I]iodobenzamide single photon emission CT demonstrated an increase in striatal D2-receptor density during postgrafting follow-up. Conclusions Grafted patients experienced a milder clinical course with less pronounced motor/cognitive decline and associated brain metabolism improvement. Life-time follow-up may ultimately clarify whether transplantation permanently modifies the natural course of the disease, allowing longer sojourn time at less severe clinical stage, and improvement of overall survival.

Malondialdehyde-deoxyguanosine and bulky DNA adducts in schoolchildren resident in the proximity of the Sarroch industrial estate on Sardinia Island, Italy.

Air quality is a primary environmental concern in highly industrialised areas, with potential health effects in children residing nearby. The Sarroch industrial estate in Cagliari province, Sardinia Island, Italy, hosts the worlds largest power plant and the second largest European oil refinery and petrochemical park. This industrial estate produces a complex mixture of air pollutants, including benzene, heavy metals and polycyclic aromatic hydrocarbons. Thus, we conducted a cross-sectional study to evaluate the prevalence of malondialdehyde-deoxyguanosine adducts in the nasal epithelium of 75 representative children, aged 6-14 years, attending primary and secondary schools in Sarroch in comparison with 73 rural controls. Additionally, the levels of bulky DNA adducts were analysed in a subset of 62 study children. DNA damage was measured by (32)P-postlabelling methodologies. The air concentrations of benzene and ethyl benzene were measured in the school gardens of Sarroch and a rural village by diffusive samplers. Outdoor measurements were also performed in other Sarroch areas and in the proximity of the industrial estate. The outdoor levels of benzene and ethyl benzene were significantly higher in the school gardens of Sarroch than in the rural village. Higher concentrations were also found in other Sarroch areas and in the vicinity of the industrial park. The mean levels of malondialdehyde-deoxyguanosine adducts per 10(8) normal nucleotides ± standard error (SE) were 74.6±9.1 and 34.1±4.4 in the children from Sarroch and the rural village, respectively. The mean ratio was 2.53, 95% confidence interval (CI): 1.71-2.89, P < 0.001, versus rural controls. Similarly, the levels of bulky DNA adducts per 10(8) normal nucleotides ± SE were 2.9±0.4 and 1.6±0.2 in the schoolchildren from Sarroch and the rural village, respectively. The means ratio was 1.90, 95% CI: 1.25-2.89, P = 0.003 versus rural controls. Our study indicates that children residing near the industrial estate have a significant increment of DNA damage.

Covariate selection in multivariate spatial analysis of ovine parasitic infection.

Gastrointestinal (GI) strongyle and fluke infections remain one of the main constraints on health and productivity in sheep dairy production. A cross-sectional survey was conducted in 2004-2005 on ovine farms in the Campania region of southern Italy in order to evaluate the prevalence of Haemonchus contortus, Fasciola hepatica, Dicrocoelium dendriticum and Calicophoron daubneyi from among other parasitic infections. In the present work, we focused on the role of the ecological characteristics of the pasture environment while accounting for the underlying long range geographical risk pattern. Bayesian multivariate spatial statistical analysis was used. A systematic grid (10 km×10 km) sampling approach was used. Laboratory procedures were based on the FLOTAC technique to detect and count eggs of helminths. A Geographical Information System (GIS) was constructed by using environmental data layers. Data on each of these layers were then extracted for pasturing areas that were previously digitalized aerial images of the ovine farms. Bayesian multivariate statistical analyses, including improper multivariate conditional autoregressive models, were used to select covariates on a multivariate spatially structured risk surface. Out of the 121 tested farms, 109 were positive for H. contortus, 81 for D. dendriticum, 17 for C. daubneyi and 15 for F. hepatica. The statistical analysis highlighted a north-south long range spatially structured pattern. This geographical pattern is treated here as a confounder, because the main interest was in the causal role of ecological covariates at the level of each pasturing area. A high percentage of pasture and impermeable soil were strong predictors of F. hepatica risk and a high percentage of wood was a strong predictor of C. daubneyi. A high percentage of wood, rocks and arable soil with sparse trees explained the spatial distribution of D. dendriticum. Sparse vegetation, river, mixed soil and permeable soil explained the spatial distribution of the H. contortus. Bayesian multivariate spatial analysis of parasitic infections with covariates from remote sensing at a very small geographical level allowed us to identify relevant risk predictors. All the covariates selected are consistent with the life cycles of the helminths investigated. This research showed the utility of appropriate GIS-driven surveillance systems. Moreover, spatial features can be used to tailor sampling design where the sampling fraction can be a function of remote sensing covariables.

A hierarchical Bayesian approach to multiple testing in disease mapping.

We propose a Bayesian approach to multiple testing in disease mapping. This study was motivated by a real example regarding the mortality rate for lung cancer, males, in the Tuscan region (Italy). The data are relative to the period 1995–1999 for 287 municipalities. We develop a tri-level hierarchical Bayesian model to estimate for each area the posterior classification probability that is the posterior probability that the municipality belongs to the set of non-divergent areas. We show also the connections of our model with the false discovery rate approach. Posterior classification probabilities are used to explore areas at divergent risk from the reference while controlling for multiple testing. We consider both the Poisson-Gamma and the Besag, York and Mollié model to account for extra Poisson variability in our Bayesian formulation. Posterior inference on classification probabilities is highly dependent on the choice of the prior. We perform a sensitivity analysis and suggest how to rely on subject-specific information to derive informative a priori distributions. Hierarchical Bayesian models provide a sensible way to model classification probabilities in the context of disease mapping.