53 research outputs found

    Neuropsychological characterization of aggressive behavior in children and adolescents with cd/odd and effects of single doses of medications: The protocol of the matrics_wp6-1 study

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    Aggressive behaviors and disruptive/conduct disorders are some of the commonest reasons for referral to youth mental health services; nevertheless, the efficacy of therapeutic interventions in real-world clinical practice remains unclear. In order to define more appropriate targets for innovative pharmacological therapies for disruptive/conduct disorders, the European Commission within the Seventh Framework Programme (FP7) funded the MATRICS project (Multidisciplinary Approaches to Translational Research in Conduct Syndromes) to identify neural, genetic, and molecular factors underpinning the pathogenesis of aggression/antisocial behavior in preclinical models and clinical samples. Within the program, a multicentre case-control study, followed by a single-blind, placebo-controlled, cross-over, randomized acute single-dose medication challenge, was conducted at two Italian sites. Aggressive children and adolescents with conduct disorder (CD) or oppositional defiant disorder (ODD) were compared to the same age (10–17 y) typically developing controls (TDC) on a neuropsychological tasks battery that included both “cold” (e.g., inhibitory control, decision making) and “hot” executive functions (e.g., moral judgment, emotion processing, risk assessment). Selected autonomic measures (heart rate variability, skin conductance, salivary cortisol) were recorded before/during/after neuropsychological testing sessions. The acute response to different drugs (methylphenidate/atomoxetine, risperidone/aripiprazole, or placebo) was also examined in the ODD/CD cohort in order to identify potential neuropsychological/physiological mechanisms underlying aggression. The paper describes the protocol of the clinical MATRICS WP6-1 study, its rationale, the specific outcome measures, and their implications for a precision medicine approach

    Association between IGF-1 levels ranges and all-cause mortality: A meta-analysis

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    The association between IGF-1 levels and mortality in humans is complex with low levels being associated with both low and high mortality. The present meta-analysis investigates this complex relationship between IGF-1 and all-cause mortality in prospective cohort studies. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, and Cochrane Library up to September 2019. Published studies were eligible for the meta-analysis if they had a prospective cohort design, a hazard ratio (HR) and 95% confidence interval (CI) for two or more categories of IGF-1 and were conducted among adults. A random-effects model with a restricted maximum likelihood heterogeneity variance estimator was used to find combined HRs for all-cause mortality. Nineteen studies involving 30,876 participants were included. Meta-analysis of the 19 eligible studies showed that with respect to the low IGF-1 category, higher IGF-1 was not associated with increased risk of all-cause mortality (HR = 0.84, 95% CI = 0.68–1.05). Dose–response analysis revealed a U-shaped relation between IGF-1 and mortality HR. Pooled results comparing low vs. middle IGF-1 showed a significant increase of all-cause mortality (HR = 1.33, 95% CI = 1.14–1.57), as well as comparing high vs. middle IGF-1 categories (HR = 1.23, 95% CI = 1.06–1.44). Finally, we provide data on the association between IGF-1 levels and the intake of proteins, carbohydrates, certain vitamins/minerals, and specific foods. Both high and low levels of IGF-1 increase mortality risk, with a specific 120–160 ng/ml range being associated with the lowest mortality. These findings can explain the apparent controversy related to the association between IGF-1 levels and mortality

    Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes

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    Type-2 Diabetes (T2D), diabetic complications, and their clinical risk factors harbor a substantial genetic component but the genetic factors contributing to overall diabetes mortality remain unknown. Here, we examined the association between genetic variants at 21 T2D-susceptibility loci and all-cause mortality in an elderly cohort of 542 Italian diabetic patients who were followed for an average of 12.08 years. Univariate Cox regression analyses detected age, waist-to-hip ratio (WHR), glycosylated haemoglobin (HbA1c), diabetes duration, retinopathy, nephropathy, chronic kidney disease (CKD), and anaemia as predictors of all-cause mortality. When Cox proportional hazards multivariate models adjusted for these factors were run, three erythropoietin (EPO) genetic variants in linkage disequilibrium (LD) with each other (rs1617640-T/G, rs507392-T/C and rs551238-A/C) were significantly (False Discovery Rate < 0.1) associated with mortality. Haplotype multivariate analysis revealed that patients carrying the G-C-C haplotype have an increased probability of survival, while an opposite effect was observed among subjects carrying the T-T-A haplotype. Our findings provide evidence that the EPO gene is an independent predictor of mortality in patients with T2D. Thus, understanding the mechanisms by which the genetic variability of EPO affects the mortality of T2D patients may provide potential targets for therapeutic interventions to improve the survival of these patients

    Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes

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    Biometry supporting species identification from underwater images in two Mediterranean Sea urchins

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    The analysis of samples and in-vivo underwater images of two sea urchin species, Cidaris cidaris and Stylocidaris affinis, allowed to collect biometric parameters, such as diameter of the dermal skeleton and length of the primary spines. The ratio between the two measures proved to be a useful tool for the discrimination and specific identification of these two similar species from video analysis

    Mesophotic rocks dominated by Diazona violacea: a Mediterranean codified habitat

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    The football ascidian Diazona violacea was observed in three different sites in the Aeolian Archipelago (Southern Tyrrhenian Sea), from 53 to 116 m depth. A large population of this ascidian was found on rocky habitat, enhancing its three-dimensionality and constituting a peculiar facies. Colonies of D. violacea showed a mean density of 0.87 ± 0.09 colonies m−2 and a maximum of 4 colonies m−2. The number of zooids was used as a proxy of colony size and age (assuming that the higher the number of zooids, the larger and older is the colony), and the population showed a leptokurtic distribution with the dominant presence of colonies with fewer than 100 zooids. Large aggregations of this species proved to play an important role in terms of seabed complexity, influencing the underwater landscape and worth of being recognized as a relevant type of biogenic habitat (although ephemeral) that can characterize mesophotic rocks in the Mediterranean Sea

    Association between NLRP3 rs10754558 and CARD8 rs2043211 Variants and Susceptibility to Chronic Kidney Disease

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    Nod-like receptor protein 3 (NLRP3) is a multi-protein complex belonging to the innate immune system, whose activation by danger stimuli promotes inflammatory cell death. Evidence supports the crucial role of NLRP3 inflammasome activation in the transition of acute kidney injury to Chronic Kidney Disease (CKD), by promoting both inflammation and fibrotic processes. Variants of NLRP3 pathway-related genes, such as NLRP3 itself and CARD8, have been associated with susceptibility to different autoimmune and inflammatory diseases. In this study, we investigated for the first time the association of functional variants of NLRP3 pathway-related genes (NLRP3-rs10754558, CARD8-rs2043211), with a susceptibility to CKD. A cohort of kidney transplant recipients, dialysis and CKD stage 3-5 patients (303 cases) and a cohort of elderly controls (85 subjects) were genotyped for the variants of interest and compared by using logistic regression analyses. Our analysis showed a significantly higher G allele frequency of the NLRP3 variant (67.3%) and T allele of the CARD8 variant (70.8%) among cases, compared with the control sample (35.9 and 31.2%, respectively). Logistic regressions showed significant associations (p < 0.001) between NLRP3 and CARD8 variants and cases. Our results suggest that the NLRP3 rs10754558 and CARD8 rs2043211 variants could be associated with a susceptibility to CKD

    A genetic-demographic approach reveals male-specific association between survival and tumor necrosis factor (A/G)-308 polymorphism

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    The (A/G)-308 polymorphism of the tumor necrosis factor α gene (TNF) is associated with age-related diseases, but its influence on longevity is controversial. We genotyped for this polymorphism 747 Italian volunteers (401 women and 346 men, age 19-110 years). By applying a genetic-demographic (GD) approach we found that, in men, the survival function of allele A carriers is lower than that of noncarriers at all the ages (p = .044). After defining (by exploiting again demographic information) three age classes, we found that the frequency of men carrying the A allele decreases with age (p = .019), thus confirming the GD analysis results. The same analyses gave negative results in women. Therefore, allele A has a detrimental effect on life expectancy, and this effect is specific to men. A haplotype analysis carried out in men by screening the TNFa, TNFc, and TNFe microsatellite polymorphisms (spanning about 20 kb) confirmed the association of the TNF region with life expectancy. Copyright 2008 by The Gerontological Society of America
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