BackgroundThe area of Milazzo-Valle del Mela (Sicily, Italy) is considered at high risk of environmental crisis by regional authorities.ObjectiveTo measure oxidative-stress, DNA repair and detoxification genes in school children living near the industrial area and in age-matched controls.MethodsThe parent study was a biomonitoring investigation evaluating heavy metal urine levels in 226 children aged 12–14 years, living in the high risk area, and in 29 age-matched controls living 45 km far from the industrial site. In the present study 67 exposed adolescents and 29 controls were included. Samples were analyzed for urinary 8-hydroxydeoxyguanosine (8OHdG) levels, and gene expression of OGG1 (DNA repair gene), NQO1, ST13, and MT1A (detoxifying genes).ResultsUrinary cadmium was higher (p = 0.0004) in exposed [geometric mean, 0.46 µg/L; 25th–75th percentile: 0.3–0.56] than in control adolescents [geometric mean, 0.26 µg/L; 25th–75th percentile: 0.2–0.3]. Chromium was also significantly elevated in exposed [geometric mean, 1.52 µg/L; 25th–75th percentile: 1.19–1.93] compared with controls [geometric mean, 1.25 µg/L; 25th–75th percentile: 1.05–1.48; p = 0.02]. Urinary 8-OHdG concentration was greater in exposed than in controls (71.49 vs 61.87 µg/L, p = 0.02), and it was correlated with cadmium levels (r = 0.46, p < 0.0001), and with the combined exposure index (r = 0.43, p < 0.0001). Moreover, cadmium levels showed a robust correlation with OGG1 and MT1A gene expression levels (r = 0.44, p < 0.0001; r = 0.39, p < 0.0001, respectively). Finally, OGG1 and MT1A were over-expressed in adolescents from Milazzo-Valle del Mela area compared with controls (p = 0.0004; p < 0.0001, respectively).ConclusionsContinuous exposure at relatively low concentrations of heavy metals is associated with increased oxidative DNA damage and impaired expression of DNA repair and detoxification genes in adolescents.

This study, for the first time, suggests that increased Cd burden is associated with delayed onset of puberty in male adolescents and impaired testicular growth.

On the basis of our experiences we can infer that it is necessary perform specific further investigations of hypothalamic function in all the children with rapid onset obesity in order to early prevent the catastrophic consequences that may occur in this syndrome.

a) At the time of diagnosis GHD children had a metabolic picture that was not different from non- GHD group; b) in children with severe GHD, the metabolic profile showed a trend towards at improvement after the initiation of replacement therapy with GH, with beneficial effects in terms of total cholesterol, LDL cholesterol and cardiovascular risk indices; c) GHD patients with unfavorable metabolic profile (high BMI and hypercholestorolemia) need a monitoring of glucose metabolism by periodical evaluations of insulin and HOMA - IR.

Vedolizumab (VDZ) is a humanized monoclonal antibody and an antiintegrin molecule which interferes with lymphocytes trafficking in the inflamed gastrointestinal tract, therefore reducing immune cell infiltration and local inflammation. 1 In particular, VDZ is characterized by a gut selectivity thanks to its interaction with a4b7-integrin, which is expressed specifically by a subset of gastrointestinalhoming T lymphocytes. Such a blockade prevents the binding of a4b7-integrin-positive leukocytes to the mucosal addressing cell adhesion molecule-1 (Mad-CAM-1) and their translocation from the blood into the inflamed gastrointestinal submucosa. 1 Integrin antagonists represent a relatively new class of therapy and an attractive option for the treatment of inflammatory bowel disease (IBD) as they target different inflammatory pathways in patients who are refractory or intolerant to tumour necrosis factor (TNF)α inhibitors.In addition, they are reported to show reduced systemic side-effects due to gastrointestinal selectivity. 1 Pivotal phase-3, double-blind, placebo-controlled studies, i.e.GEMINI studies 1 and 2, have shown VDZ to be effective in inducing and maintaining clinical remission in adult ulcerative colitis (UC) and Crohn's disease (CD), respectively. 2,3 Based on these results, VDZ has been approved for the treatment of moderate-to-severe CD and UC in patients of 18 years and older who are refractory or intolerant to either conventional treatments or anti-TNFα agents. [3][4][5] The effectiveness and safety of VDZ has been assessed in several real-world studies, displaying promising results both in adult and paediatric settings. 1 Moreover, beyond clinical remission, VDZ has been shown to induce endoscopic and histologic healing, with higher rates in UC than CD. 4,6 Overall rates of adverse events, serious adverse effects, and serious infections were not different between patients treated with placebo and those who received VDZ. 5,7 AEs reported from pooled data of clinical trials were approximately 30.6%, and mostly minor, including myalgia and arthralgia, followed by nasopharyngitis, infection, and skin infections. 8 The exposure-adjusted incidence rates of infections