[Temporal analysis of the prevalence of congenital hypospadias in the municipality of Gela]. / Analisi temporale della prevalenza di ipospadia congenita nel comune di Gela.

OBJECTIVES: to evaluate the risk profile of hypospadias in Gela, an Italian National Priority Contaminated Site (NPCS) located in Sicily Region (Southern Italy), characterized by a significant excess of hypospadias in newborn residents compared to data from reference on regional, national, and international basis and, until 2014, by the presence of a petrochemical plant. DESIGN: geographical analyses were conducted by comparing the prevalence of the Gela municipality to prevalence found in Sicily, in a territorial area bordering Gela (ALG), and in the NPCSs of Milazzo and Priolo. The geographical comparisons were conducted for the period 2010-2020, the trend within the Gela NPCS was evaluated by comparing two subperiods (2010-2014 and 2015-2020). SETTING AND PARTICIPANTS: children up to 1 year of age with hypospadias resident in the municipality of Gela in the period 2010-2020. MAIN OUTCOMES MEASURES: crude odds ratios (OR) and respective 95% confidence intervals (95%CI) were used to compare the prevalence observed in Gela and that detected in the comparison areas. RESULTS: excess risk for hypospadias was highlighted in 2010-2020 in Gela vs Sicily (OR 4.45; 95%CI 3.45-5.75), vs ALG (OR 4.29; 95%CI 3.02-6.10), and vs the NPCSs of Milazzo (OR 2.32; 95%CI 1.32-4.07) and Priolo (OR 2.37; 95%CI 1.55-3.62). The between-period comparisons in Gela did not show an important difference between 2010-2014 and 2015-2020 (OR 1.37; 95%CI 0.83-2.24), with a prevalence of 98.9 and 72.4 per 10,000, respectively. CONCLUSIONS: the prevalence of hypospadias in 2015-2020 remains very high, although decreasing when compared to 2010-2014 period. The Gela data, despite the refinery being closed after 2014, suggest a complex situation in which multiple risk factors may play a role.

Extracellular Vesicles and Immunity: At the Crossroads of Cell Communication.

Extracellular vesicles (EVs), comprising exosomes and microvesicles, are small membranous structures secreted by nearly all cell types. They have emerged as crucial mediators in intercellular communication, playing pivotal roles in diverse physiological and pathological processes, notably within the realm of immunity. These roles go beyond mere cellular interactions, as extracellular vesicles stand as versatile and dynamic components of immune regulation, impacting both innate and adaptive immunity. Their multifaceted involvement includes immune cell activation, antigen presentation, and immunomodulation, emphasising their significance in maintaining immune homeostasis and contributing to the pathogenesis of immune-related disorders. Extracellular vesicles participate in immunomodulation by delivering a wide array of bioactive molecules, including proteins, lipids, and nucleic acids, thereby influencing gene expression in target cells. This manuscript presents a comprehensive review that encompasses in vitro and in vivo studies aimed at elucidating the mechanisms through which EVs modulate human immunity. Understanding the intricate interplay between extracellular vesicles and immunity is imperative for unveiling novel therapeutic targets and diagnostic tools applicable to various immunological disorders, including autoimmune diseases, infectious diseases, and cancer. Furthermore, recognising the potential of EVs as versatile drug delivery vehicles holds significant promise for the future of immunotherapies.

Exposure profiles in pregnant women from a birth cohort in a highly contaminated area of southern Italy.

Protecting the health of pregnant women from environmental stressors is crucial for reducing the burden of non-communicable diseases. In industrially contaminated sites, this action is particularly challenging due to the heterogeneous pollutant mixtures in environmental matrices. The aim of this study was to evaluate distribution patterns of mercury, hexachlorobenzene and polychlorobiphenyls in the serum of 161 pregnant women recruited in the framework of the Neonatal Environment and Health Outcomes (NEHO) cohort and living both inside and outside the National Priority Contaminated Site (NPCS) of Priolo. Food macro-categories were determined, and serum levels of contaminants were used to perform k-means cluster analysis and identify the role of food in pollutant transfer from the environment. Two groups of mothers with high and low measured pollutant levels were distinguished. Concentrations in mothers in the high-exposure cluster were at least twofold for all the evaluated pollutants (p < 0.0001) and included mothers living inside and outside NPCS, with a predominance of individuals from the NPCS (p = 0.045). Fish consumption was higher in the high-exposure cluster (p = 0.019). These findings suggest a link between contamination of environmental matrices such as sediment with maternal exposure, through the intake of local food. Such consideration appears poorly investigated in the context of contaminated sites.

The Influence of Sociodemographic Factors, Lifestyle, and Risk Perception on Dietary Patterns in Pregnant Women Living in Highly Contaminated Areas: Data from the NEHO Birth Cohort.

During pregnancy, maternal nutrition and lifestyle play a critical role in influencing fetal development and newborn health outcomes. The aim of this study is to investigate the factors influencing the adherence to dietary patterns in pregnant women living in highly contaminated areas, and whether women with higher environmental risk perception manifest different nutritional behaviors during pregnancy. Food consumption data on 816 pregnant women from the Neonatal Environment and Health Outcomes (NEHO) residential birth cohort were analyzed. Dietary patterns were computed by principal component analysis. A multinomial logistic regression was also applied to identify sociodemographic, lifestyle, and pregnancy-related determinants of adherence to dietary patterns during pregnancy. Three patterns of food consumption-explaining 24.9% of the total variance-were identified as "prudent", "high energy", and "vegetarian" patterns. Results suggest that food choices during pregnancy follow a social gradient and align with other health behaviors during pregnancy: older, better educated, and physically active women with higher risk perception are more likely to follow healthier dietary patterns. Knowledge about what is eaten can contribute to dietary choices. Interventions to improve the prenatal nutrition knowledge of pregnant women are needed, especially concerning younger mothers and those with lower educational levels.

A multipollutant low-grade exposure regulates the expression of miR-30b, Let-7a and miR-223 in maternal sera: Evidence from the NEHO cohort.

There is growing evidence that environmental pollutants can induce epigenetic modifications altering the balance of miRNAs and inducing the onset of pathological conditions in animals. In this study, we measured the serum concentration of a suite of inorganic and organic pollutants (Cu, Zn, Se, Hg, HCB, p,p'-DDE, PCBs) and their association to serum miR-30b, miR-223 and Let-7a microRNA expression in 68 healthy pregnant women from the NEHO birth cohort sited in a highly industrialized area. The effects of the pollutants on the modulation of circulating miRNAs' expression were first investigated using linear continuous regression models with a single-compound approach showing that miR-223 expression was significantly associated with serum concentration of Se and Zn (pSe = 0.0336; pZn = 0.0225) and miR-30b was associated with Hg levels (pHg = 0.019). Furthermore, when contaminants were categorized into tertiles, miR-223 and miR-30b showed a positive association with higher tertiles of Zn, p,p'-DDE (pZn = 0.023; pDDE = 0.041) and Hg (pHg = 0.008), respectively. Moreover, Let-7a expression was exclusively influenced by medium tertiles levels of Se (low vs medium tertiles, p = 0.001). Simultaneous exposure to multi-pollutant mixture was approached by WQS regression model. Statistical analysis shows a driving effect of Zn, Se, Cu, Hg and HCB on significant increased expression of Let-7a (p = 0.045). Mercury and Se significantly amplified the expression for miR-30b (p = 0.038). Differently, the combined effect of p,p'-DDE, Zn and Se decreased miR-223 expression (p = 0.0001). The documented modified expression of circulating miRNAs in the serum of pregnant women, exposed to low-medium dose contaminants mixtures offers innovative early-warning approaches to human health risk assessment.

Association between greenspace and lung function in Italian children-adolescents.

BACKGROUND: Few studies have examined the impact of urban greenspace exposure on lung function in children-adolescents, and the available evidence is still inconsistent. The aim of the current study was to verify the hypothesis that the effects of greenspace exposure vary with differing levels of lung function of children-adolescents. METHODS: Between November 2005 and May 2006, 2150 children-adolescents (age-range: 10-15 years) living in the city of Palermo were enrolled in a cross-sectional survey. Parents were interviewed through a modified version of the Italian Studies on Respiratory Disorders in Children and the Environment (SIDRIA) questionnaire. All children-adolescents performed spirometry and were tested for allergic sensitization. Exposures to greenspace and grey space at the home addresses were measured using the CORINE land-cover classes. Parametric quantile regression models were applied for assessing the association between greenspace exposure and spirometry parameters, accounting for possible confounders and effect modifiers. A p-value lower than 0.05 was considered statistically significant. RESULTS: From the 1st to the 21st percentile, children-adolescents living within greenspace had higher FEV1 than those living within grey space. In particular, the estimated effects were: 1st (ß = 0.238 L, p = 0.01), 5th (ß = 0.140 L, p = 0.01), 10th (ß = 0.097 L, p = 0.015), and 15th (ß = 0.073 L, p = 0.025). Similarly, from the 1st to the 29th percentile, children-adolescents living within greenspace had higher FVC than those living within grey space. In particular, the estimated effects were: 1st (ß = 0.367 L, p = 0.0003), 5th (ß = 0.215 L, p = 0.0003), 10th (ß = 0.150 L, p = 0.0004), and 15th (ß = 0.112 L, p = 0.001). No significant associations were found for FEV1/FVC, FEF25-75 and FEF25-75/FVC. CONCLUSION: Quantile regression techniques may provide new insights into the evaluation of the association between greenspace exposure and lung function in children-adolescents, showing substantially heterogeneous effects from lower to higher quantiles of spirometry parameters. These results may help implementing policies for planning sustainable housing and surrounding greenspaces.

[Application of an algorithm for the validation of congenital anomaly cases using hospital discharge records]. / Applicazione di un algoritmo per la validazione dei casi di malformazione congenita provenienti dal flusso delle schede di dimissione ospedaliera.

OBJECTIVES: to evaluate and validate the adoption of an algorithm for the identification of cases of congenital anomalies (CAs) to improve the performance of the Congenital Malformations Registry of Sicily Region (Southern Italy). DESIGN: an algorithm was used to identify congenital anomalies on a sample of hospital discharge records (SDO) with ICD-9-CM code between 740-759 on any of the diagnoses within the first year of life, together with a sample of healthy births equal to 5% of total births for the same period. The identified cases were evaluated through the clinical record analysis. SETTING AND PARTICIPANTS: the analysed sample was composed of 4,271 cases identified between June 2013 and December 2014 along with 3,993 SDO without any code of MC (5% of the total volume of births in the same period). MAIN OUTCOME MEASURES: positive predictive value (VPP) and negative predictive value (VPN) were computed by means of the comparison between the algorithm outcomes and the clinical record verification. RESULTS: 4,271 potentially malformed records involving 3,381 subjects born in the Sicilian territory have been identified. Among the hospital discharge records that it was possible to verify, the application of the algorithm led to the exclusion of 924 cases: of these, 62 proved to be false negatives (VPN: 93.3). The valid cases were 1,179, while the cases to be evaluated 617: the comparison between algorithm and clinical record analysis led to a VPP of 91.7 and 72.1, respectively, for valid and to be evaluated. CONCLUSIONS: the tested algorithm proved to be a useful tool for identifying SDO potentially related to congenital anomalies. In the overall sample, the algorithm provided an outcome consistent with the clinical record assessment in 87.4% (2,379) of cases.

Measuring Risk Perception in Pregnant Women in Heavily Polluted Areas: A New Methodological Approach from the NEHO Birth Cohort.

Risk perception (RP) evaluation during pregnancy and its relationship with lifestyles are considered useful tools for understanding communities living in high-risk areas and preventing dangerous exposure. It is well known that exposure to pollutants and less-healthy lifestyles may result in increased disease occurrence during life. Our work investigated environmental RP through ad hoc questionnaires administered to 611 mothers within the NEHO birth cohort, recruited in three heavily contaminated areas of Southern Italy. Four different RP indices, an exploratory factorial analysis (EFA), and a latent class analysis were evaluated from questionnaires. The highest values of risk perception index were observed in the Milazzo site (0.64 ± 0.16) and the lowest in the Crotone site (0.5 ± 0.18). EFA revealed four latent factors, including different items describing environmental pollution, and subjects were classified into four latent classes with different RP indices. Significant RP profiles were different among the sites (p < 0.001). Our results did not demonstrate any association between RP and lifestyles during pregnancy. Improving healthy lifestyle behaviours, particularly in polluted areas, would generate co-benefits by preventing further risk factors. As remediation interventions can take a long time, it needs to improve healthy lifestyles in residents until remediation is completed.

PBDEs affect inflammatory and oncosuppressive mechanisms via the EZH2 methyltransferase in airway epithelial cells.

AIMS: We aimed to investigate the effect of PBDEs (47, 99, 209) on cellular events involved in epigenetic modification, inflammation, and epithelial mesenchymal transition (EMT). MATERIALS AND METHODS: We studied: 1) ERK1/2 phosphorylation; 2) Enhancer of Zester Homolog 2 (EZH2); 3) Histone H3 tri-methylated in lysine 27 (H3K27me3); 4) K-RAS; 5) silencing disabled homolog 2-interacting protein gene (DAB2IP), 6) let-7a; 7) Muc5AC/Muc5B, and 8) IL-8 in a 3D in vitro model of epithelium obtained with primary Normal Human Bronchial Epithelial cells (pNHBEs) or A549 cell line, chronically exposed to PBDEs (47, 99, 209). KEY FINDINGS: PBDEs (10 nM, 100 nM and 1 µM) increased ERK1/2 phosphorylation, and EZH2, H3K27me3, and K-RAS protein expression, while decreased DAB2IP and Let-7a transcripts in pNHBEs ALI culture. Furthermore PBDEs (47, 99) (100 nM) increased Muc5AC and Muc5B mRNA, and PBDE 47 (100 nM) IL-8 mRNA via EZH2 in pNHBEs. Finally, PBDEs (100 nM) affected EZH2, H3K27me3, K-RAS protein expression, and DAB2IP, Let-7a transcripts and cell invasion in A549 cells. Gsk343 (methyltransferase EZH2 inhibitor) (1 mM) and U0126 (inhibitor of MEK1/2) (10 µM) were used to show the specific effect of PBDEs. SIGNIFICANCE: PBDE inhalation might promote inflammation/cancer via EZH2 methyltransferase activity and H3K27me3, k-RAS and ERk1/2 involvement, generating adverse health outcomes of the human lung.

Association Between Smoking and SARS-CoV-2 Infection: Cross-sectional Study of the EPICOVID19 Internet-Based Survey.

BACKGROUND: Several studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn. OBJECTIVE: We investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders. METHODS: The nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics. RESULTS: Out of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19-like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked. CONCLUSIONS: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.

The Neonatal Environment and Health Outcomes (NEHO) Birth Cohort Study: Behavioral and Socioeconomic Characteristics and Drop-Out Rate from a Longitudinal Birth Cohort in Three Industrially Contaminated Sites in Southern Italy.

Pregnant women living in industrially contaminated sites (ICSs) are exposed to environmental contaminants through different pathways, and thus children's health may be affected by pollutants. We created the Neonatal Environment and Health Outcomes (NEHO) longitudinal birth cohort in three ICSs in the Mediterranean area of southern Italy, collecting comprehensive information on personal data and lifestyles by questionnaire. Through multiple correspondence analysis, we identified possible clusters of enrolled women, and a neural network classifier analysis (NNCA) was performed to identify variables capable of predicting the attrition rate of the study. NEHO recruited 845 mother-child pairs over two years. The mothers' mean age was 31.1 ± 5.2 SD years. We found significant differences in socioeconomic status (SES) among the three evaluated ICS, and an overall 11.1% prevalence of mothers who actively smoked during pregnancy. Active smoking during pregnancy was strongly associated with the lowest socioeconomic level (p < 0.0001). By means of the NNCA, we found that smoking during pregnancy and the lowest education level characterized the cluster with the highest attrition rate (p < 0.001). Our results demonstrate that reason for public health concern still exists regarding smoking during pregnancy and that SES influences both lifestyles, producing negative pregnancy outcomes and a higher survey attrition rate.

Blastomere removal affects homeostatic control leading to obesity in male mice.

Preimplantation embryos are particularly vulnerable to environmental perturbations, including those related to assisted reproductive technologies. Invasive embryo manipulations, such as blastomere biopsy, are applied worldwide in clinical settings for preimplantation genetic testing. Mouse models have previously shown that blastomere biopsy may be associated with altered phenotypes in adult offspring. The aim of the present study was to investigate the specific contribution of blastomere removal to the physiological, behavioral, and molecular regulators of energy homeostasis, as compared to sham manipulation (re-introducing the blastomere into the embryo after its removal) and in vitro culture. Mice derived from 8-cell embryos subjected to blastomere removal displayed: (i) higher body weight and adiposity, (ii) increased food intake and sucrose preference, (iii) decreased time of immobility in the tail suspension test, and (iv) resistance to weight loss after social isolation or following 3 days of physical exercise - compared to mice derived from sham biopsy or from in vitro-cultured embryos. Mice generated after blastomere removal also had increased circulating leptin and leptin gene expression in adipose tissue, as well as increased ghrelin receptor gene expression in the hypothalamus, compared to control mice. The effects of blastomere biopsy on offspring phenotype were sexually dimorphic, with females not being affected. These results indicate that blastomere deprivation, rather than other perturbations of the blastomere biopsy procedure, programs male embryos to develop physiological, behavioral, and molecular dysregulation of energy homeostasis, leading to postnatal obesity.

Determinants of Allergic Sensitization, Asthma and Lung Function: Results from a Cross-Sectional Study in Italian Schoolchildren.

Prenatal smoking exposure and early-life respiratory infections are major determinants of asthma during childhood. We investigate the factors influencing allergic sensitization (AS), asthma, and lung function in children and the balance between individual and environmental characteristics at different life stages. 1714 children aged 7-16 years and living in southern Italy were investigated using a parental questionnaire, skin prick tests, and spirometry. We found 41.0% AS prevalence: among children without parental history of asthma, male sex, maternal smoking during pregnancy (MatSmoke), and acute respiratory diseases in the first two years of life (ARD2Y) were significant risk factors for AS. MatSmoke was associated (OR = 1.79) with ARD2Y, and this association was influenced by sex. ARD2Y was, in turn, a significant risk factor (OR = 8.53) for childhood current asthma, along with AS (OR up to 3.03) and rhinoconjuctivitis (OR = 3.59). Forced mid-expiratory flow (FEF25-75%) was negatively affected by ARD2Y, with a sex-related effect. Thus, males exposed to MatSmoke had significantly lower FEF25-75% than unexposed males. Despite the difficulty of discriminating among the complex interactions underlying the development of allergic respiratory diseases, ARD2Y appears to strongly influence both asthma and lung function during childhood. In turn, ARD2Y is influenced by prenatal exposure to tobacco smoke with a sex-dependent effect.

Birth Cohorts in Highly Contaminated Sites: A Tool for Monitoring the Relationships Between Environmental Pollutants and Children's Health.

Industrial areas are characterized by the dispersion of environmental stressors that could possibly have long-term detrimental effects on both human health and the environment. Environmental contamination has been indicated to be one of the major risks for reproductive health. In this context, the effects of environmental pollution on pregnant women living in heavily polluted areas is of special interest. In fact, fetal development is a crucial phase due to the dynamic interaction between the maternal/external environments and the developing organs and tissues. Moreover, following Barker's postulate of the intrauterine origin of health and disease, the events occurring in this time window could affect future health. Birth cohorts provide the most suitable design for assessing the association between early-life and possible long-term health outcomes in highly contaminated sites. By providing an assessment of the early life environment throughout the collection of biological samples, birth cohorts offer the opportunity to study in-depth several possible confounders and outcomes by means of questionnaires and follow-ups based on clinical evaluations and bio-specimen samplings. The exposome comprises the totality of exposures from conception onwards; the birth cohort approach allows the integration of the exposures as a whole, including those related to socioeconomic status, with "omics" data from biological samples collected at birth and throughout life. In the characterization of the "fetal exposome," the placenta represents a highly informative and scarcely considered organ. For this purpose, the "Neonatal Environment and Health Outcomes" (NEHO) birth cohort has been established by enrolling pregnant women residing in contaminated sites and in surrounding areas.

Can PBDEs affect the pathophysiologic complex of epithelium in lung diseases?

Brominated flame-retardant (BFRs) exposure promotes multiple adverse health outcomes involved in oxidative stress, inflammation, and tissues damage. We investigated BFR effects, known as polybrominated diphenyl ethers (PBDEs) (47, 99 and 209) in an air-liquid-interface (ALI) airway tissue derived from A549 cell line, and compared with ALI culture of primary human bronchial epithelial cells (pHBEC). The cells, exposed to PBDEs (47, 99 and 209) (0.01-1 µM) for 24 h, were studied for IL-8, Muc5AC and Muc5B (mRNAs and proteins) production, as well as NOX-4 (mRNA) expression. Furthermore, we evaluated tight junction (TJ) integrity by Trans-Epithelial Electrical Resistance (TEER) measurements, and zonula occludens-1 (ZO-1) expression in the cells, and pH variations and rheological properties (elastic G', and viscous G″, moduli) in apical washes of ALI cultures. N-acetylcysteine (NAC) (10 mM) effects were tested in our experimental model of A549 cells. PBDEs (47, 99 and 209) exposure decreased TEER, ZO-1 and pH values, and increased IL-8, Muc5AC, Muc5B (mRNAs and proteins), NOX-4 (mRNA), and rheological parameters (G', G″) in ALI cultures of A549 cell line and pHBEC. NAC inhibited PBDE effects in A549 cells. PBDE inhalation might impairs human health of the lungs inducing oxidative stress, inflammatory response, loss of barrier integrity, unchecked mucus production, as well as altered physicochemical and biological properties of the fluids in airway epithelium. The treatment with anti-oxidants restored the negative effects of PBDEs in epithelial cells.

Three contaminated sites in southern Italy. The Neonatal Environment and Health Outcomes cohort: protocol for a longitudinal birth cohort study.

INTRODUCTION: Exposure to environmental contaminants during pregnancy is one of the determinants of child's future health outcomes. The effect of environmental pollution on pregnant women living in heavily polluted areas is of special interest and, in this context, the Neonatal Environment and Health Outcomes (NEHO) cohort will focus on the investigation of (1) toxicants transferred from the environment to the mother and from the mother to the developing fetus and (2) the influence of toxicants on pregnancy outcomes, fetal development and health status during infancy. Because the human placenta is positioned at the interface between the maternal/external environment and the embryo, it can be considered a highly informative matrix regarding many key pregnancy events that can shape infant's future health. METHODS AND ANALYSIS: The NEHO cohort will enrol an estimated total of 800 pregnant women in three selected National Priority Contaminated Sites in southern Italy. Epidemiological data, concerning maternal health status, lifestyle and pregnancy, are obtained through questionnaires provided to the mother starting from the last 2 months of pregnancy. At delivery, maternal blood, umbilical cord blood and placenta tissue are collected to assess contaminant levels and to clarify how toxicants interact with the placental domain. Furthermore, placental transcriptome is studied in order to explore the interferences of toxicants on the role of the placenta in maternal/fetal interplay. Regular follow-up is planned at 6, 12 and 24 months. ETHICS AND DISSEMINATION: The study has been approved by all the Ethics Committees of the three National Priority Contaminated Sites involved: the Ethics Committee of the University Hospitals of Messina (18 September 2017, n. 9/2017); the Ethics Committee 'Catania 2' (11 July 2017, n. 38/2017/CECT2); the Ethics Committee of the Region of Calabria (20 July 2017, n. 173). Findings will be disseminated in the scientific community and on a regional basis for appropriate policy actions.

Indoor air quality in schools of a highly polluted south Mediterranean area.

This study aimed at surveying lower secondary schools in southern Italy, in a highly polluted area. A community close to an industrial area and three villages in rural areas was investigated. Indoor temperature, relative humidity (RH), gaseous pollutants (CO2 and NO2 ), selected biological pollutants in indoor dust, and the indoor/outdoor mass concentration and elemental composition of PM2.5 were ascertained. Temperature and RH were within, or close to, the comfort range, while CO2 frequently exceeded the threshold of 1000 ppm, indicating inadequate air exchange rate. In all the classrooms, median NO2 levels were above the WHO threshold value. Dermatophagoides p. allergen concentration was below the sensitizing threshold, while high endotoxin levels were detected in the classrooms, suggesting schools may produce significant risks of endotoxin exposure. Concentration and solubility of PM2.5 elements were used to identify the sources of indoor particles. Indoor concentration of most elements was higher than outdoors. Resuspension was responsible for the indoor increase in soil components. For elements from industrial emission (Cd, Co, Ni, Pb, Sb, Tl, V), the indoor concentration depended on penetration from the outside. For these elements, differences in rural vs industrial concentrations were found, suggesting industrial sources may influence indoor air quality nearby schools.

Relationship between domestic smoking and metals and rare earth elements concentration in indoor PM2.5.

Cigarette smoke is the main source of indoor chemical and toxic elements. Cadmium (Cd), Thallium (Tl), Lead (Pb) and Antimony (Sb) are important contributors to smoke-related health risks. Data on the association between Rare Earth Elements (REE) Cerium (Ce) and Lanthanum (La) and domestic smoking are scanty. To evaluate the relationship between cigarette smoke, indoor levels of PM2.5 and heavy metals, 73 children were investigated by parental questionnaire and skin prick tests. The houses of residence of 41 "cases" and 32 "controls" (children with and without respiratory symptoms, respectively) were evaluated by 48-h PM2.5 indoor/outdoor monitoring. PM2.5 mass concentration was determined by gravimetry; the extracted and mineralized fractions of elements (As, Cd, Ce, La, Mn, Pb, Sb, Sr, Tl) were evaluated by ICP-MS. PM2.5 and Ce, La, Cd, and Tl indoor concentrations were higher in smoker dwellings. When corrected for confounding factors, PM2.5, Ce, La, Cd, and Tl were associated with more likely presence of respiratory symptoms in adolescents. We found that: i) indoor smoking is associated with increased levels of PM2.5, Ce, La, Cd, and Tl and ii) the latter with increased presence of respiratory symptoms in children.

Sensitization to dust mite defines different phenotypes of asthma: A multicenter study.

BACKGROUND: Indoor allergens are risk factors for asthma: Thus, the characterization of indoor air quality is important for studying environment-health relationships in children. In particular, Dermatophagoides pteronyssinus is the dominant allergen for asthma. We cross-sectionally investigated the relationships among respiratory symptoms and function, airway inflammation, allergen sensitization, and indoor allergen concentration. METHODS: One hundred and thirty-two children aging 10-14 years and living in a Southern Mediterranean area were evaluated by parental questionnaires. Spirometry, exhaled nitric oxide (FeNO), skin prick tests, total, and specific serum IgE analyses were performed along with the evaluation of home dust samples for the content in Der p 1 allergen. Three clusters were created on the basis of the presence/absence of wheeze in the last 12 months (Wh12m) and Der p 1-specific IgE level. RESULTS: Cluster 1 (Wh12m+/high Der p 1 IgE) presented higher FeNO and poorer pulmonary function (lower FEV1 and FEF25%-75% ), while its symptom score was not different from Cluster 2 (Wh12m+/low Der p 1 IgE). Cluster 3 (Wh12m-/low IgE) showed the lowest FeNO values and pulmonary function similar to Cluster 2. Within Cluster 1, both Der p 1-specific IgE and FeNO were positively correlated with dust Der p 1. CONCLUSIONS: Similar asthma phenotypes may occur in children despite differences in their atopic state. In atopic children, sensitizing allergens in the indoor environment may increase airway inflammation worsening pulmonary function. Moreover, environmental exposures may contribute to the development of asthma-like symptoms also in the absence of atopic sensitization, thus contributing to asthma overdiagnosis.

Pregnancy at Advanced Maternal Age Affects Behavior and Hippocampal Gene Expression in Mouse Offspring.

There is growing evidence that advanced maternal age is a risk factor for neurological and neuropsychiatric disorders in offspring. However, it remains unclear whether the altered brain programming induced by advanced maternal age is mediated by pre- or postnatal factors. Here, a mouse model was used to investigate whether pregnancy at advanced age may provoke behavioral and brain gene expression changes in offspring. Swiss Albino mice conceived by 3-month-old males and either 15-18-month-old (n = 11) or 3-month-old control females (n = 5), were delivered by cesarean section, fostered after birth by 3-month-old dams and subjected to a battery of behavioral tests. Furthermore, genome-wide mRNA expression was analyzed in the hippocampi of 4-month-old males offspring using microarrays. Offspring conceived by old mothers exhibited increased ultrasound vocalization activity during separation from the foster mother, increased anxiety-like behaviors in adult life, and altered patterns of hippocampal gene expression, compared to controls. These effects were not reversed by the postnatal maternal care provided by the young foster mothers, suggesting that the altered brain programming is already established at birth, consistent with prenatal effects related to maternal aging.