Occurrence of Fipronil in residential house dust in the presence and absence of pets: a hint for a comprehensive toxicological assessment

The presence of the insecticide Fipronil and its main products of toxicological relevance, namely Sulfone and Desulfinyl, was assessed in 161 residential house dust samples in the absence (N = 101) and presence (N = 60) of cats and dogs in Italy. High-resolution mass spectrometry analysis revealed a significant difference (p < 0.001) in the dust contamination in the presence of pets (median: 467 vs. 24 ng/g dry weight), even if the highest value was found in the absence of pets (82,069 vs. 67,799 ng/g dry weight). Fipronil intake estimates from dust in toddlers, computed according to US-EPA and EU-ECHA guidelines, ranged from 333 to 556 and from 20 to 34 ng/kg per day for acute and chronic scenario, respectively. Dust seemed not able itself to lead to Fipronil overexposure with respect to acute and chronic toxicity health-based guidance values. Kittens were potentially overexposed to Fipronil under both acute (26,076 ng/kg per day) and chronic (1,633 ng/kg per day) scenarios. The mild symptomatology associated with acute intoxication could possibly determine case underreporting within pharmacosurveillance schemes. Its administration was estimated in 7.3\u20139.7 tons per year. Such a range suggests its prudent use under strict veterinary control to prevent pest resistance and ecotoxicological outcomes

Combined esophageal intraluminal impedance, pH and skin conductance monitoring to detect discomfort in GERD infants

BACKGROUND: The clinical significance of weakly acidic reflux in infants is unclear. Skin conductance is a novel not-invasive method to evaluate discomfort. The aim of our study was to evaluate reflux-induced discomfort in infants with gastroesophageal reflux disease using simultaneously combined skin conductance and esophageal multichannel intraluminal impedance and pH monitoring. METHODOLOGY/PRINCIPAL FINDINGS: Infants with gastroesophageal reflux symptoms were investigated for almost 20 hours divided into 120-second intervals. Temporal relationships between refluxes and discomfort were evaluated calculating the symptom association probability. Twelve infants aged 17-45 days were studied. Out of 194.38 hours of adequate artifact-free MII/pH and skin conductance monitoring, 584 reflux events were observed; 35.78% were positive for stress, of which 16.27% were acid and 83.73% weakly acidic. A significant association between refluxes and discomfort (p<0.05) was present in all infants. The intervals with reflux events showed increased skin conductance values compared to reflux-free intervals (p<0.001); SC values were similar for acid and weakly acidic reflux events. CONCLUSION/SIGNFICANCE: Discomfort was significantly associated with reflux events and did not differ between weakly acidic and acid refluxes. Our results may raise concerns about the over-prescription use of antacid drugs in the management of gastroesophageal reflux symptoms in infancy

Perfuorooctane Sulfonate (PFOS), Perfluorooctanoic Acid (PFOA), Brominated Dioxins (PBDDs) and Furans (PBDFs) in Wild and Farmed Organisms at Different Trophic Levels in the Mediterranean Sea

The present study shows the results of perfuorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), brominated dioxins (PBDDs) and furans (PBDFs) measured in several marine fish and seafood of commercial interest at different trophic levels of the food chain. The aims were to investigate the level of the contamination in Mediterranean aquatic wildlife, and in farmed fish, to assess human exposure associated to fishery products consumption. Samples of wild fish were collected during three different sampling campaigns in different Food and Agriculture Organization (FAO) 37 areas of the Mediterranean Sea. In addition, farmed fish (gilthead sea bream and European sea bass) from off-shore cages from different marine aquaculture plants. Results showed contamination values of PFOS and PFOA were lower than those detected in sea basins other than the Mediterranean Sea. Concentration values of PFOS were generally higher than those of PFOA; moreover, levels in farmed fish were lower than in wild samples from the Mediterranean Sea. Intake of PFOS and PFOA through fishery products consumption was estimated to be 2.12 and 0.24 ng/kgBWday, respectively, for high consumers (95th percentile). Results of 2,3,7,8-substituted congeners of PBDDs and PBDFs were almost all below the limit of detection (LOD), making it difficult to establish the contribution of these compounds to the total contamination of dioxin-like compounds in fish and fishery products

Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome.

iskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating the cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative, but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach. We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical scores. Vector integration analyses revealed highly polyclonal and multilineage haematopoiesis resulting from the gene-corrected HSPCs. Lentiviral gene therapy did not induce selection of integrations near oncogenes, and no aberrant clonal expansion was observed after 20 to 32 months. Although extended clinical observation is required to establish long-term safety, lentiviral gene therapy represents a promising treatment for WAS