Predictors of severe hyperbiliruniaemia in HIV-infected patients treated with atazanavir (ATV)

Methods HIV-infected subjects on ATV/ritonavir containing stable HAART regimen were included. ATV plasma concentrations were measured 24 hours after the last dose by HPLC with UV detector. Polymorphism at the uridin-glocoronosyl-transferase 1A1 (UGT1A1) was examined in DNA extracted from blood mononuclear cells, to identify subjects with Gilbert's syndrome. The correlation between bilirubin plasma levels, ATV concentration and polymorphism of UGT1A1 (defined as the presence than at least one TA7 allele) were evaluated by multivariate linear regression (other covariates included: gender, age, CD4 count, months of ATV exposure). Predictors of severe hyperbilirubinemia (>2.5 μmol/l; grade 3) were evaluated by multivariate logistic regression (polymorphism at UGT1A1, Cmin, BMI, age included as covariates)

Predicting and Characterizing Neurodegenerative Subtypes with Multimodal Neurocognitive Signatures of Social and Cognitive Processes

Background: Social cognition is critically compromised across neurodegenerative diseases, including the behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD). However, no previous study has used social cognition and other cognitive tasks to predict diagnoses of these conditions, let alone reporting the brain correlates of prediction outcomes. Objective: We performed a diagnostic classification analysis using social cognition, cognitive screening (CS), and executive function (EF) measures, and explored which anatomical and functional networks were associated with main predictors. Methods: Multiple group discriminant function analyses (MDAs) and ROC analyses of social cognition (facial emotional recognition, theory of mind), CS, and EF were implemented in 223 participants (bvFTD, AD, PD, controls). Gray matter volume and functional connectivity correlates of top discriminant scores were investigated. Results: Although all patient groups revealed deficits in social cognition, CS, and EF, our classification approach provided robust discriminatory characterizations. Regarding controls, probabilistic social cognition outcomes provided the best characterization for bvFTD (together with CS) and PD, but not AD (for which CS alone was the best predictor). Within patient groups, the best MDA probabilities scores yielded high classification rates for bvFTD versus PD (98.3%, social cognition), AD versus PD (98.6%, social cognition+CS), and bvFTD versus AD (71.7%, social cognition+CS). Top MDA scores were associated with specific patterns of atrophy and functional networks across neurodegenerative conditions. Conclusion: Standardized validated measures of social cognition, in combination with CS, can provide a dimensional classification with specific pathophysiological markers of neurodegeneration diagnoses.Fil: Ibanez Barassi, Agustin Mariano. Universidad de San Andrés; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Adolfo Ibañez; Chile. Universidad de Dublin; Irlanda. University of California; Estados UnidosFil: Fittipaldi, Sol. Universidad Nacional de Córdoba; Argentina. Universidad de San Andrés; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trujillo, Catalina. Universidad del Valle; ColombiaFil: Jaramillo, Tania. Universidad del Valle; ColombiaFil: Torres, Alejandra. Universidad del Valle; ColombiaFil: Cardona, Juan F.. Universidad del Valle; ColombiaFil: Rivera, Rodrigo. Universidad de Chile; ChileFil: Slachevsky, Andrea. Universidad de Chile; ChileFil: Garciá, Adolfo. Universidad de San Andrés; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Santiago de Chile; Chile. University of California; Estados UnidosFil: Bertoux, Maxime. Universidad Adolfo Ibañez; ChileFil: Baez, Sandra. Universidad de los Andes; Colombi

Comparison of three strategies for myocardial protection during coronary artery bypass graft surgery based on markers of cardiac damage

Objectives: To evaluate myocardial damage during coronary artery bypass grafting using three different intermittent cardioplegia and then measuring cTnI and CKMBm release. Design and methods: Forty-two patients belonging to the hypothermic crystalloid (n = 16), hypothermic (n = 13), and normothermic blood (n = 13) groups were collected when removing the aortic cross-clamp (t = 0) and after 4, 12, 24 and 48 h. For each patient, cumulative cTnI and CKMBm release was calculated as the five measurement mean. There were no significant preoperative and operative differences in the three groups. Results: In the normothermic group, cTnI mean values at 4, 12, and 24 h were significantly lower than those in both hypothermic groups; moreover, CKMBm mean values were higher at 4, 12, and 24 h in the hypothermic crystalloid group and at 4 and 12 h in the hypothermic blood group than in the normothermic group. In the normothermic group, the area under the curve of the release of both markers was significantly lower than in the hypothermic groups. No significant difference was reported in the release of both markers in hypothermic groups. Conclusions: A strategy of normothermic cardioplegia seems to preserve myocardium better than hypothermic cardioplegia

Evaluation of microalbuminuria in patients with erectile dysfunction

Introduction: The recent sophisticated diagnostic procedures aimed at identifying the exact cause of erectile dysfunction (ED) are often complicated in clinical application, invasive, or highly expensive. Microalbuminuria, a test easy to perform and of low cost, is a marker of extensive endothelial dysfunction, and it has been suggested to be linked to ED. Aim: The aim of this study was to investigate the eventual role of microalbuminuria in differentiating patients with arteriogenic and non arteriogenic ED. Methods: The diagnosis of ED was based on the International Index of Erectile Function 5-questionnaire, and patients were classified as arteriogenic (N = 29) and non-arteriogenic (N = 49) in relation to the results of echo-color-doppler examination of cavernosal arteries in basal conditions and after intracavernous injection of 10 \u3bcg prostaglandin E1. Main Outcome Measures: The microalbuminuria of 78 males without the most common atheriosclerotic risks and with ED was measured. Results: Microalbuminuria, defined as urinary albumin/creatinine ratio, was not significantly (P > 0.05) different between patients of the two groups. Conclusions: Our data show that in ED patients the cavernosal arteries damage, as assessed by dynamic echo-color-doppler, may be independent on or precede extensive endothelial dysfunction, and that microalbuminuria cannot be predictive of penile arteriogenic etiology

Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and L-arginine in patients with arteriogenic and non-arteriogenic erectile dysfunction

The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been linked to endothelial dysfunction. We investigated the relation between ADMA, symmetric dimethylarginine (SDMA) and L-arginine concentrations and erectile dysfunction. We compared plasma levels of ADMA, SDMA and L-arginine in 61 men in good health with erectile dysfunction of arteriogenic and non-arteriogenic origin. Diagnosis of erectile dysfunction was based on the International Index of Erectile Function Score and its aetiology was classified with penile echo-colour-Doppler in basal condition and after intracavernous injection of prostaglandin E1. The ADMA and SDMA concentrations were significantly higher in men with arteriogenic erectile dysfunction compared with those with erectile dysfunction of non-arteriogenic origin (p 0.05) nor between each of the two erectile dysfunction subgroups and controls (p > 0.05). The L-arginine/ADMA and the L-arginine/SDMA ratios in arteriogenic erectile dysfunction subgroups were significantly lower than both in controls (p 0.05). We conclude that ADMA and SDMA concentrations are significantly higher and L-arginine/ADMA ratio lower in patients who have arteriogenic erectile dysfunction compared with both patients with non-arteriogenic erectile dysfunction and controls. The negative correlation between ADMA and severity of erectile dysfunction is present only in patients with arteriogenic erectile dysfunction. This study supports the importance to always distinguish arteriogenic from non-arteriogenic erectile dysfunction patients to study the complicate erectogenic mechanisms that lead to erectile dysfunction and also to provide potential therapeutic agents for patients with arteriogenic erectile dysfunction

Fractional Integration Versus Structural Change: Testing the Convergence of CO2 Emissions

This paper assesses the stochastic convergence of relative CO₂ emissions within 28 OECD countries over the period 1950–2013. Using the local Whittle estimator and some of its variants we assess whether relative per capita CO₂ emissions are long memory processes which, although highly persistent, may revert to their mean/trend in the long run thereby indicating evidence of stochastic convergence. Furthermore, we test whether (possibly) slow convergence or the complete lack of it may be the result of structural changes to the deterministics of each of the relative per-capita emissions series by means of the tests of Berkes et al. (Ann Stat 1140–1165, 2006) and Mayoral (Oxford Bull Econ Stat 74(2):278–305, 2012). Our results show relatively weak support for stochastic convergence of CO₂ emissions, indicating that only between 30 and 40% of the countries converge to the OECD average in a stochastic sense. This weak evidence disappears if we enlarge the sample to include 4 out of the 5 BRICS, indicating that our results are not robust to the inclusion of countries which are experiencing rates of growth which are far larger than those of the OECD members. Our results also decisively indicate that a slow or lack of convergence is not the results of a structural break in the relative CO₂ emissions series

Natural anti-CCR5 antibodies in HIV-infection and -exposure

Natural antibodies constitute a first-line of defence against pathogens; they may also play other roles in immune regulation and homeostasis, through their ability to bind host antigens, surface molecules and receptors. Natural anti-CCR5 antibodies can be decisive in preventing HIV infection in mucosal tissues and offer prompt and effective protection just at major sites of virus entry. Among natural anti-CCR5 antibodies, IgG and IgA to the ECL1 domain have been shown to block HIV effectively and durably without causing harm to the host. Their biological properties and their uncommon generation in subsets of HIV-infected and HIV-exposed individuals (so called ESN) will be introduced and discussed, with the aim at exploiting their potential in therapy and prevention

Phenotype Fingerprinting Suggests the Involvement of Single-Genotype Consortia in Degradation of Aromatic Compounds by Rhodopseudomonas palustris

Anaerobic degradation of complex organic compounds by microorganisms is crucial for development of innovative biotechnologies for bioethanol production and for efficient degradation of environmental pollutants. In natural environments, the degradation is usually accomplished by syntrophic consortia comprised of different bacterial species. This strategy allows consortium organisms to reduce efforts required for maintenance of the redox homeostasis at each syntrophic level. Cellular mechanisms that maintain the redox homeostasis during the degradation of aromatic compounds by one organism are not fully understood. Here we present a hypothesis that the metabolically versatile phototrophic bacterium Rhodopseudomonas palustris forms its own syntrophic consortia, when it grows anaerobically on p-coumarate or benzoate as a sole carbon source. We have revealed the consortia from large-scale measurements of mRNA and protein expressions under p-coumarate, benzoate and succinate degrading conditions using a novel computational approach referred as phenotype fingerprinting. In this approach, marker genes for known R. palustris phenotypes are employed to determine the relative expression levels of genes and proteins in aromatics versus non-aromatics degrading condition. Subpopulations of the consortia are inferred from the expression of phenotypes and known metabolic modes of the R. palustris growth. We find that p-coumarate degrading conditions may lead to at least three R. palustris subpopulations utilizing p-coumarate, benzoate, and CO2 and H2. Benzoate degrading conditions may also produce at least three subpopulations utilizing benzoate, CO2 and H2, and N2 and formate. Communication among syntrophs and inter-syntrophic dynamics in each consortium are indicated by up-regulation of transporters and genes involved in the curli formation and chemotaxis. The N2-fixing subpopulation in the benzoate degrading consortium has preferential activation of the vanadium nitrogenase over the molybdenum nitrogenase. This subpopulation in the consortium was confirmed in an independent experiment by consumption of dissolved nitrogen gas under the benzoate degrading conditions