Sociodemographic and clinical predictors of depression in children and adolescents: results of a two-year follow-up study

Depressive disorders are a main cause of disability-adjusted life years already in children and adolescents, in whom the clinical picture somewhat differs from adult-onset depression. Thus, we studied sociodemographic and clinical predictors of depression/dysthymia in a sample of minors. Our baseline sample (N=676) included patients at clinical high-risk for psychosis (CHR-P, n=183), inpatients admitted for non-psychotic, non-affective disorders (n=277), and community participants (n=216) of age 7.0 to 17.9 years (43.8% male). They were assessed by clinical psychologists for mental disorders and symptoms with various clinical interviews including the Mini International Neuropsychiatric Interview for Children and Adolescents, which was also used to assess depression/dysthymia in the CHR-P group at 1- and 2-year-follow up (n=117 and 73, respectively). Analyses followed a stepwise procedure at baseline with stepwise logistic regression analyses to identify the final baseline model that was tested in the follow-up samples. The final cross-sectional model included nationality and 13 clinical variables Mild depressive symptoms in particular played a decisive role here. Variables contributing significantly to the prediction varied over time, indicating that CAD depression/dysthymia may require different predictors depending on the follow-up time. Furthermore, the prospective accuracy of ruling out depression/dysthymia was superior to the accuracy of ruling it in. This lower positive likelihood ratio might be overcome in future by stepwise approaches that further stratify risk in those initially identified as at increased risk of depression/dysthymia

A Metabolomic Analysis of Omega-3 Fatty Acid-Mediated Attenuation of Western Diet-Induced Nonalcoholic Steatohepatitis in LDLR[superscript -/-] Mice

Background: Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n-3) at reversing western diet (WD) induced NASH in LDLR-/- mice. Methods: Using livers from our previous study, we carried out a global non-targeted metabolomic approach to quantify diet-induced changes in hepatic metabolism. Results: Livers from WD + olive oil (WD + O)-fed mice displayed histological and gene expression features consistent with NASH. The metabolomic analysis of 320 metabolites established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation had broad effects on all major metabolic pathways. Livers from WD + O-fed mice were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA), palmitoylsphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of C20-22 n-3 PUFA-containing phosphoglycerolipids, C20-22 n-3 PUFA-derived oxidized lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal detoxification product. WD + DHA was more effective than WD + EPA at attenuating WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA and sphingolipid content were associated with changes in expression of enzymes involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C20-22 PUFA content. Hepatic C20-22 n-3 PUFA content was inversely associated with hepatic α-tocopherol and ascorbate content and positively associated with urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative stress. Conclusion: DHA regulation of hepatic SFA, MUFA, PUFA, sphingomyelin, PUFA-derived oxidized lipids and Slactoylglutathione may explain the protective effects of DHA against WD-induced NASH in LDLR-/- mice

Dietary intake associated with serum versus urinary carboxymethyl-lysine, a major advanced glycation end product, in adults: the Energetics Study

Background/Objectives: Advanced glycation end products (AGEs) are implicated in the pathogenesis of atherosclerosis, diabetes and kidney disease. The objective was to describe dietary intake, the dominant source of exposure to AGEs, with carboxymethyl-lysine (CML), a major AGE, in serum and urine, respectively. Subjects/Methods: Serum and urinary CML were measured in 261 adults, aged 21-69 years, and compared with diet as assessed by six separate 24-h dietary recalls. Results: Median (25th, 75th percentile) serum and urinary CML concentrations were 686 (598, 803) mu g/l and 1023 (812, 1238) mu g/gm creatinine. There was no correlation between serum and urinary CML (r = -0.02, P = 0.78). Serum CML was positively correlated with intake of soy, fruit juice, cold breakfast cereal, non-fat milk, whole grains, fruit, non-starchy vegetables and legumes, and negatively correlated with intake of red meat. Intake of fast food was not significantly correlated with serum CML. Urinary CML was positively correlated with intake of starchy vegetables, whole grains, sweets, nuts/seeds and chicken, and negatively correlated with intake of fast foods. Intake of AGE-rich foods such as fried chicken, French fries, bacon/sausage and crispy snacks were not significantly correlated with serum or urinary CML, except for a significant negative correlation between fried chicken and serum CML. Conclusions: These findings suggest that the high consumption of foods considered high in CML is not a major determinant of either serum or urinary CML. Further work is needed to understand the relationship of AGEs in blood and urine with the metabolism of dietary AGEs.Keywords: Food, 24-h dietary recall, Diet, Carboxymethyl-lysine, Advanced glycation end product

Modulating Activity of Vancomycin and Daptomycin on the Expression of Autolysis Cell-Wall Turnover and Membrane Charge Genes in hVISA and VISA Strains

Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus) infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-Staphylococcus aureus (VISA)], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes) are involved. In addition, reduced susceptibility to vancomycin can influence the development of resistance to daptomycin. Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin cross-resistance are not clearly understood. The aim of our study was to investigate, by real time RT-PCR, the relative quantitative expression of genes involved in autolysis (atl-lytM), cell-wall turnover (sceD), membrane charges (mprF-dltA) and regulatory mechanisms (agr-locus-graRS-walKR), in hVISA and VISA cultured with or without vancomycin and daptomycin, in order to better understand the molecular basis of vancomycin-reduced susceptibility and the modulating activity of vancomycin and daptomycin on the expression of genes implicated in their reduced susceptibility mechanisms. Our results show that hVISA and VISA present common features that distinguish them from Vancomycin-Susceptible Staphylococcus aureus (VSSA), responsible for the intermediate glycopeptide resistance i.e. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality. Indeed, VISA emerges from hVISA when VISA acquires a reduced autolysis caused by a down-regulation of autolysin genes, atl/lytM, and a reduction of the net negative cell-envelope charge via dltA over-expression. Vancomycin and daptomycin, acting in a similar manner in hVISA and VISA, can influence their cross-resistance mechanisms promoting VISA behavior in hVISA and enhancing the cell-wall pathways responsible for the intermediate vancomycin resistance in VISA. Daptomycin can also induce a charge repulsion mechanism both in hVISA and VISA increasing the activity of the mprF

Estimation of metabolite T1 relaxation times using tissue specific analysis, signal averaging and bootstrapping from magnetic resonance spectroscopic imaging data

Object A novel method of estimating metabolite T1 relaxation times using MR spectroscopic imaging (MRSI) is proposed. As opposed to conventional single-voxel metabolite T1 estimation methods, this method investigates regional and gray matter (GM)/white matter (WM) differences in metabolite T1 by taking advantage of the spatial distribution information provided by MRSI