Metabolomic Investigation of β-Thalassemia in Chorionic Villi Samples

Beta-thalassemias are blood disorders characterized by poorly understood clinical phenotypes ranging from asymptomatic to severe anemia. Metabolic composition of the human placenta could be affected by the presence of pathological states such as β-thalassemia. The aim of our study was to describe metabolic changes in chorionic villi samples of fetuses affected by β-thalassemia compared to a control group by applying a metabolomics approach

High Specificity of Quantitative Methylation-Specific PCR Analysis for MGMT Promoter Hypermethylation Detection in Gliomas

Normal brain tissue from 28 individuals and 50 glioma samples were analyzed by real-time Quantitative Methylation-Specific PCR (QMSP). Data from this analysis were compared with results obtained on the same samples by MSP. QMSP analysis demonstrated a statistically significant difference in both methylation level (P = .000009 Mann Whitney Test) and frequencies (P = .0000007, Z-test) in tumour samples as compared with normal brain tissues. Although QMSP and MSP showed similar sensitivity, the specificity of QMSP analysis was significantly higher (93%; CI95%: 84%–100%) as compared with MSP (64%; 95%CI: 46%–82%). Our results suggest that QMSP analysis may represent a powerful tool to identify glioma patients that will benefit from alkylating agents chemotherapy

Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase

MUTYH-associated polyposis (MAP), the syndrome implicating base excision repair in inherited predisposition to colorectal tumors

In 2002, Al-Tassan and co-workers described for the first time a recessive form of inherited polyposis associated with germline mutations of MUTYH, a gene encoding a base excision repair (BER) protein that counteracts the DNA damage induced by the oxidative stress. MUTYH-associated polyposis (MAP) is now a well-defined cancer susceptibility syndrome, showing peculiar molecular features that characterize disease progression. However, some aspects of MAP, including diagnostic criteria, genotype-phenotype correlations, pathogenicity of variants, as well as relationships between BER and other DNA repair pathways, are still poorly understood. A deeper knowledge of the MUTYH expression pattern is likely to refine our understanding of the protein role and, finally, to improve guidances for identifying and handling MAP patients

Seismic Behaviour of a Full-Scale RC Frame Repaired Using CFRP Laminates

The opportunities provided by the use of Carbon Fiber Reinforced Polymer (CFRP) composites for the seismic repair of reinforced concrete (RC) structures were assessed on a full-scale dual system subjected to pseudodynamic tests in the ELSA laboratory. The aim of the CFRP repair was to recover the structural properties that the frame had before the seismic actions by providing both columns and joints with more deformation capacity. The repair was characterized by a selection of different fiber textures depending on the main mechanism controlling each component. The driving principles in the design of the CFRP repair and the outcomes of the experimental tests are presented in the paper. Comparisons between original and repaired structures are discussed in terms of global and local performance. In addition to the validation of the proposed technique, the experimental results will represent a reference database for the development of design criteria for the seismic repair of RC frames using composite materials.JRC.G.5-European laboratory for structural assessmen

Seismic Behaviour of a Full-Scale RC Frame Repaired Using CFRP Laminates.

Abstract not availableJRC.G-Institute for the Protection and the Security of the Citizen (Ispra

Measurement of external shame: An inside view

The aims of this study were to investigate the construct validity of the Other as Shamer scale (OAS) using confirmatory factor analysis (CFA) and to examine the psychometric properties of its Italian version in a sample of 687 nonclinical individuals. The CFA results indicated that the hypothesized hierarchical model (with 1 higher order factor and 3 first-order factors) was the best fitting solution. Cronbach's alpha indexes, as well as test–retest stability, provided satisfactory results. Correlations of the OAS total score and its subscales with the Beck Depression Inventory–II (rs = .30–.48) and the Teate Depression Inventory (rs = .32–.45) were both substantial and significant (p < .01). Receiver operating characteristic curves were constructed to indicate sensitivity and specificity of the OAS and its subscales when determining those nonclinical subjects who met clinical thresholds for depression symptoms. A series of cutoff scores for the OAS scale and its subscales was developed, with sensitivity values between .70 and .62, and specificity values between .71 and .62, indicating good to fair discrimination between the 2 groups (depressed vs. nondepressed). The theoretical and practical implications of these results were discussed.N/

Colorectal Adenomatous Polyposis: Heterogeneity of Susceptibility Gene Mutations and Phenotypes in a Cohort of Italian Patients

Aims: Colorectal adenomatous polyposis entailing cancer predisposition is caused by constitutional mutations in different genes. APC is associated with the familial adenomatous polyposis (FAP/AFAP) and MUTYH with the MUTYH-associated polyposis (MAP), while POLE and POLD1 mutations cause the polymerase proofreading-associated polyposis (PPAP). Methods: We screened for mutations in patients with multiple adenomas/FAP: 121 patients were analyzed for APC and MUTYH mutations, and 36 patients were also evaluated for POLE and POLD1 gene mutations. Results: We found 20 FAP/AFAP, 15MAP, and no PPAP subjects: pathogenic mutations proved to be heterogeneous, and included 5 APC and 1 MUTYH novel mutations. The mutation detection rate was significantly different between patients with 5-100 polyps and those with >100 polyps (p = 8.154 x 10(-7)), with APC mutations being associated with an aggressive phenotype (p = 1.279 x 10(-9)). Mean age at diagnosis was lower in FAP/AFAP compared to MAP (p = 3.055 x 10(-4)). Mutation-negative probands showed a mean age at diagnosis that was significantly higher than FAP/AFAP (p = 3.46986 x 10(-7)) and included 45.3% of patientswith <30 polyps and 70.9% of patients with no family history. Conclusions: This study enlarges the APC and MUTYH mutational spectra, and also evaluated variants of uncertain significance, including the MUTYH p.Gln338His mutation. Moreover this study underscores the phenotypic heterogeneity and genotype-phenotype correlations in a cohort of Italian patients

HYDROZOAN PLANULAE MAY HAVE AN ANTERIOR MOUTH, A PERIORAL NEURAL PLEXUS, AND INGEST FOOD PARTICLES: PRODROMES OF BILATERIAN CEPHALIZATION?

The presumptive "simple" nervous system of cnidarians has been recently demonstrated in the hydrozoan diploblastic planula of Clava multicornis to achieve a surprisingly high level of histological, cytological, biochemical and functional complexity, with characteristic localization of sensory neurons concentrated in the anterior ectoderm and a prominent anterior neural plexus (PIRAINO et al., 2011). These morphological features are reminiscent of those already present in early bilaterian animals, and they have been interpreted as pre-requisites for the forward-directed crawling behavior of the benthic larva of C. multicornis. In addition, circumferential GLWamide-immunoreactive neurite bundles of the anterior neural plexus are distributed around a frontal gap in the ectoderm and mesoglea, where the endoderm bulges out in contact with the external environment. Opposite to the pole where the polyp mouth will open at metamorphosis, such histological discontinuity has been interpreted as a functional anterior larval orifice, allowing effective communication between the inner planula cavity and the outer environment. To further investigate the features and the functionality of such a mouth-like anterior discontinuity, both TEM ultrastructural analysis and functional experiments with labeled dyes and particles were carried out. Transverse sections were made at the anteriormost part of the planulae and observed under TEM, clearly confirming the occurrence of a mesogleal interruption of the ectodermal layer at the anterior larval pole, i.e. a true anterior orifice, where endodermal cells are in contact with the direct environment. At the level of this orifice, a big mucous aggregate containing several bacteria was documented, surrounded by cytoplasmic protrusions of ectodermal support cells, as in the act of being engulfed into the planula inner cavity. In vivo experiments allowed to documenting the passage of labeled fluids and particles from the outer environment towards the inner planula cavity, through loose intercellular spaces in the anteriormost ectodermal layer, lacking cell-cell septate junctions. Taken together, these findings (neural anterior concentration, anterior orifice surrounded by sensory cells and circumferential plexus) corroborate the hypothesis that a certain degree of ancestral cephalization and a bilateral bauplan organization was already achieved at the dawn of metazoans

Metabolic characterization of amniotic fluids of fetuses with enlarged nuchal translucency

In prenatal diagnosis, a thickened nuchal translucency (NT) is one of the most sensitive and specific markers for several defects but it may also be found in 5% of healthy fetuses. The pathophysiological causes that lead to an increase in NT are not yet fully understood. Metabolomics represents a new promising approach, useful for studying different metabolites in biological organisms in response to environmental stressors. The aim of our study was to investigate the metabolomic profile of the amniotic fluid samples (AFS) of euploid fetuses with enlarged nuchal translucency (ENT) compared to a control group (C group). This study was carried out on a group of women who underwent second-trimester amniocentesis for advanced maternal age (C group) or for NT ≥95 th percentile (ENT group) found during first-trimester aneuploidy screening. AFS were analyzed with proton nuclear magnetic resonance ( 1 H-NMR) and high-performance liquid chromatography (HPLC), and subsequent multivariate and univariate statistical analyses were conducted, followed by pathway analysis. In total, 67 AFS from the C group and 23 from the ENT group were analyzed. Partial least square discriminate analysis was carried out (R 2 X=0.784, R 2 Y=0.658, Q 2 =0.622, P&lt;0.0001). A different metabolic profile was observed in the ENT group compared with the C group, suggesting an energetic shift to a glycolytic phenotype in an oxidative environment in the ENT group compared to the C group. Metabolomic studies enable the identification of metabolic alterations occurring in fetuses with ENT. These findings may provide a new basis for better understanding the pathophysiological mechanisms in this prenatal phenomenon