Maternal heterodisomy/isodisomy and paternal supernumerary ring of chromosome 7 in a child with Silver-Russell syndrome

Silver-Russell syndrome (SRS) is clinically variable although most cases have several common signs. Different chromosomes and chromosomal regions have been associated with SRS. Maternal uniparental disomy (UPD) of chromosome 7 is responsible for 5-10% of cases, probably because of an imbalance between maternal and paternal imprinted genes and more recently maternal duplication or epimutations in the 11p15 imprinted region have been described. To date, only two patients with maternal UPD7 and a mosaic condition for a supernumerary ring 7 marker have been reported, and we here report a further case. Standard QFQ banding of lymphocytes as well as fluorescence in-situ hybridization analyses were performed to identify and characterize the supernumerary marker. UPD testing was performed on both the patient's and parents' DNA using chromosome 7 microsatellite markers. The patient demonstrated a ring in about 4% of the analysed cells. On the basis of cytogenetic and molecular results, break points were tentatively identified as 7p11.2 and 7q21. Maternal hetero-/iso-UPD and a paternal origin for the supernumerary ring were demonstrated. Clinical data comparison between our patient who has a SRS phenotype and cases with hetero-/iso-UPD7 mat and mosaicism for a paternally derived chromosome 7 ring and previously reported ring 7 cases suggest that the SRS phenotype is probably because of the UPD rather than to the partial trisomy.     

Role of visfatin, insulin-like growth factor-I and insulin in fetal growth

OBJECTIVE: IGF-I and insulin are the main regulators of intrauterine and postnatal growth. Adipose tissue secreted cytokines are implicated in intrauterine growth. The relevant function of the adipocytokine visfatin is unknown. MATERIALS AND METHODS: Serum visfatin, IGF-I and insulin levels were measured by enzyme immunoassays in 40 singleton full-term fetuses and neonates on postnatal days 1(N1) and 4 (N4). RESULTS: No significant correlations exist between visfatin and IGF-I or insulin. N1 and N4 visfatin positively correlated with customized (adjusted) birth weight centiles (r=0.511, P=0.021, and r=0.597, P=0.005, respectively). Fetal and N1 IGF-I positively correlated with customized centiles (r=0.608, P<0.001 and r=0.485, P=0.006, respectively). Fetal insulin positively correlated with customized centiles (r=0.654, P=0.021). CONCLUSIONS: Potential implication of visfatin in fetal growth is probably not mediated by IGF-I or insulin. Although a more active role cannot be excluded, visfatin may simply represent a marker of fat accumulation.     

The Role of Social Support in Machismo and Acceptance of Violence Among Adolescents in Europe: Lights4Violence Baseline Results

PurposeTo analyze the potential association between social support, experiences of violence, and sociodemographic characteristics of adolescents and the likelihood of acceptance of violence and machismo in different European countries.MethodsCross-sectional design. We recruited 1,555 participants ages 13–16 from secondary schools in Alicante (Spain), Rome (Italy), Iasi (Romania), Matosinhos (Portugal), Poznan (Poland), and Cardiff (UK). We used linear regression models to identify how social support from teachers and parents, experiences of violence—dating violence, bullying, cyberbullying, abuse in childhood—and sociodemographic characteristics were associated with violent thinking, specifically: machismo and acceptance of violence. The analysis was stratified by sex.ResultsAcceptance of violence was higher for those who had lower perceived social support from parents (β_girls = ?154, p < .001; β_boys = ?.114, p = .019) for both sexes. Perpetration of bullying and/or cyberbullying was associated with higher scores for machismo and acceptance of violence for both sexes (β_girls = .067, p = .035; β_boys = .225, p < .001; (β_girls = .118, p < .001; β_boys = .210, p < .001). Being the victim of dating violence, having suffered physical and/or sexual abuse in childhood, and lower perceived social support from teachers were associated with higher scores for both machismo and acceptance of violence. These associations differed between girls and boys.ConclusionsMachismo and acceptance of violence are widely present amongst adolescents in different European countries. Our results suggest the importance of providing educational/psycho-educational interventions with boys and girls to prevent these attitudes and, in turn, prevent interpersonal violence, including bullying and dating violence.     

Systematic review of existing guidelines for NAFLD assessment

Aim: In this systematic review, guidelines on non-alcoholic fatty liver disease (NAFLD) were evaluated, aiming at a guideline synthesis focusing on diagnosis an...     

von Willebrand factor binds to the surface of dendritic cells and modulates peptide presentation of factor VIII

It has been proposed that von Willebrand factor might affect factor VIII immunogenicity by reducing factor VIII uptake by antigen presenting cells. Here we investigate the interaction of recombinant von Willebrand factor with immature monocyte-derived dendritic cells using flow cytometry and confocal microscopy. Surprisingly, von Willebrand factor was not internalized by immature dendritic cells, but remained bound to the cell surface. As von Willebrand factor reduces the uptake of factor VIII, we investigated the repertoire of factor VIII presented peptides when in complex with von Willebrand factor. Interestingly, factor VIII-derived peptides were still abundantly presented on major histocompatibility complex class II molecules, even though a reduction of factor VIII uptake by immature dendritic cells was observed. Inspection of peptide profiles from 5 different donors showed that different core factor VIII peptide sequences were presented upon incubation with factor VIII/von Willebrand factor complex when compared to factor VIII alone. No von Willebrand factor peptides were detected when immature dendritic cells were pulsed with different concentrations of von Willebrand factor, confirming lack of von Willebrand factor endocytosis. Several von Willebrand factor derived peptides were recovered when cells were pulsed with von Willebrand factor/factor VIII complex, suggesting that factor VIII promotes endocytosis of small amounts of von Willebrand factor by immature dendritic cells. Taken together, our results establish that von Willebrand factor is poorly internalized by immature dendritic cells. We also show that von Willebrand factor modulates the internalization and presentation of factor VIII-derived peptides on major histocompatibility complex class II.     

Self-reported influenza vaccination uptake in people with chronic diseases: data from Progressi delle Aziende Sanitarie per la Salute in Italia (PASSI)

BackgroundInfluenza is an important public health problem, with potential severe consequences among people with chronic diseases. The aim of this study was to obtain reliable measures of seasonal influenza vaccine uptake in this population, otherwise not available in Italy.MethodsProgressi delle Aziende Sanitarie per la Salute in Italia (PASSI) is a nationwide surveillance system of health-related behaviours and acceptance of preventive interventions (including influenza immunisation) offered by the Italian National Health Service. Data are collected with telephone interviews at local health unit level for supporting local activities. The survey sample is randomly selected from local health unit lists of adult residents. The trend of annual vaccine coverage since 2008 was estimated for people aged 18–64 years who reported having at least one chronic disease. To obtain a sufficient sample size in subgroups, we analysed the characteristics of vaccinated people in the 2010–13 cumulative dataset. Univariate, multivariate, and logistic regression analyses were undertaken.FindingsIn 2008–13, 13 659 individuals with at least one chronic disease were interviewed. Vaccination coverage fell significantly from 29·7% (95% CI 27·2–32·4) in 2007–08 to 19·9% (18·0–22·1) in 2012–13. During 2010–13, the overall proportion of vaccinated people with a chronic disease was 25·6% (24·5–26·7). Vaccine coverage of people with diabetes (34·3%, 31·7–36·9) or cardiovascular diseases (31·8%, 29·6–34·2) was greater than that of people affected by renal failure, respiratory diseases, tumours, or chronic liver diseases (26·5% [22·5–30·7], 24·9% [23·2–26·7], 22·2% [20·0–24·6], and 20·6% [17·5–24·6], respectively). Vaccination coverage increased with age (from 13·1% [11·0–15·5] in the 18–34 year age group to 33·4% [31·9–35·1] in people aged 50–64 years); it was higher among people with a low educational level than among those with a high educational level, higher in those having economic difficulties than in those with no economic difficulties, and higher among Italian citizens than among non-citizens.InterpretationIn the past few years, prevalence of influenza vaccination in Italian adults with at least one chronic disease was well below the Ministry of Health's goal (75% minimum) and showed a downward trend. A major reason of this evolution is probably the changing public perception of the benefits and risks of vaccines. PASSI is a source of useful data not otherwise available for public health intervention.FundingItalian Ministry of Health.