Similar plasma lipidomic profile in people living with HIV treated with a darunavir-based or an integrase inhibitor-based antiretroviral therapy

Cardiovascular disease is an important cause of morbidity and mortality in people living with HIV (PLWH), who commonly experience lipid disturbances. The aim of this study was to determine whether the plasma lipidomic profile differs between PLWH receiving a darunavir-based ART and those receiving integrase inhibitor-based ART. This was a cross-sectional study of unselected patients for whom metabolomic analysis was performed using ultra-high-performance liquid chromatography coupled to mass spectrometry. Data for the two subgroups were compared by calculating the log2 of the fold change for each metabolite and then grouping these into the main lipid families. Sixty-two PLWH aged 49.3 +/- 8.6 years (82% men) were included: 12 patients (19.4%) had hypertension, 8 (12.9%) had type 2 diabetes, 25 (41.0%) had dyslipidaemia and 9 (14.5%) were taking statins, without significant differences in all these variables between the two groups. Twenty-five (40.3%) received darunavir-based ART and 37 (59.7%) integrase inhibitor-based ART. Although the differences were not statistically significant, patients treated with darunavir-based ART had higher concentrations of total cholesterol (211 mg/dL vs 194 mg/dL), LDL-cholesterol (132 mg/dL vs 117 mg/dL) and triglycerides (155 mg/dL vs 122 mg/dL), and lower HDL-cholesterol concentration (50 mg/dL vs 52 mg/dL). The main lipid families and metabolites differed slightly between groups (log2-fold change; P-value): ceramides (-0.07; 0.49), phosphatidylinositols (-0.05; 0.63), diacylglycerols (0.10; 0.64), phosphatidylethanolamines (0.03; 0.78), triacylglycerols (0.27; 0.18) and lysophosphatidylethanolamines (0.03; 0.83). In the integrase inhibitor-based group, the use of tenofovir alafenamide fumarate significantly increases the majority of lipid fractions, when compared with tenofovir disoproxil fumarate. The lipidomic profile did not differ between PLWH treated with darunavir-based or integrase inhibitor-based ART. This was especially true for ceramides, which are involved in cardiovascular disease. Further studies are needed to study the impact of ART in lipidomic profile

Natural Orifice Surgery (NOS) Using StomaphyX™ for Repair of Gastric Leaks after Bariatric Revisions

Gastric leaks represent serious complications of bariatric surgery. With the increasing popularity and performance of bariatric procedures, the incidence of leaks and associated complications are expected to increase. Minimally invasive natural orifice surgery represents a novel and promising approach to gastric leak management, especially for morbidly obese patients who are at much higher risk from open or laparoscopic surgical procedures. The present article reports two cases of the safe and successful use of the EndoGastric Solutions StomaphyX™ device to alter the flow of gastric contents and repair gastric leaks resulting from bariatric revision surgery. Both patients were at a high risk and could not undergo another open or laparoscopic surgery to correct the leaks that were not healing. The StomaphyX procedures lasted approximately 30 min, were performed without any complications, and resulted in the resolution of the gastric leaks in both patients

Comparison of design concepts in multi-criteria decision-making using level diagrams

[EN] In this work, we address the evaluation of design concepts and the analysis of multiple Pareto fronts in multi-criteria decision-making using level diagrams. Such analysis is relevant when two (or more) design concepts with different design alternatives lie in the same objective space, but describe different Pareto fronts. Therefore, the problem can be stated as a Pareto front comparison between two (or more) design concepts that only differ in their relative complexity, implementation issues, or the theory applied to solve the problem at hand. Such analysis will help the decision maker obtain a better insight of a conceptual solution and be able to decide if the use of a complex concept is justified instead of a simple concept. The approach is validated in a set of multi-criteria decision making benchmark problems. © 2012 Elsevier Inc. All rights reserved.This work was partially supported by the FPI-2010/19 Grant and Project PAID-06-11 from the Universitat Politecnica de Valencia and by Projects ENE2011-25900, TIN2011-28082 (Spanish Ministry of Science and Innovation) and GV/2012/073, PROMETEO/2012/028 (Generalitat Valenciana).Reynoso Meza, G.; Blasco Ferragud, FX.; Sanchís Saez, J.; Herrero Durá, JM. (2013). Comparison of design concepts in multi-criteria decision-making using level diagrams. INFORMATION SCIENCES. 221(1):124-141. https://doi.org/10.1016/j.ins.2012.09.049S124141221

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Live cell dynamics of production, explosive release and killing activity of phage tail-like weapons for Pseudomonas kin exclusion.

Interference competition among bacteria requires a highly specialized, narrow-spectrum weaponry when targeting closely-related competitors while sparing individuals from the same clonal population. Here we investigated mechanisms by which environmentally important Pseudomonas bacteria with plant-beneficial activity perform kin interference competition. We show that killing between phylogenetically closely-related strains involves contractile phage tail-like devices called R-tailocins that puncture target cell membranes. Using live-cell imaging, we evidence that R-tailocins are produced at the cell center, transported to the cell poles and ejected by explosive cell lysis. This enables their dispersal over several tens of micrometers to reach targeted cells. We visualize R-tailocin-mediated competition dynamics between closely-related Pseudomonas strains at the single-cell level, both in non-induced condition and upon artificial induction. We document the fatal impact of cellular self-sacrifice coupled to deployment of phage tail-like weaponry in the microenvironment of kin bacterial competitors, emphasizing the necessity for microscale assessment of microbial competitions

Prediction of Protein Modification Sites of Pyrrolidone Carboxylic Acid Using mRMR Feature Selection and Analysis

Pyrrolidone carboxylic acid (PCA) is formed during a common post-translational modification (PTM) of extracellular and multi-pass membrane proteins. In this study, we developed a new predictor to predict the modification sites of PCA based on maximum relevance minimum redundancy (mRMR) and incremental feature selection (IFS). We incorporated 727 features that belonged to 7 kinds of protein properties to predict the modification sites, including sequence conservation, residual disorder, amino acid factor, secondary structure and solvent accessibility, gain/loss of amino acid during evolution, propensity of amino acid to be conserved at protein-protein interface and protein surface, and deviation of side chain carbon atom number. Among these 727 features, 244 features were selected by mRMR and IFS as the optimized features for the prediction, with which the prediction model achieved a maximum of MCC of 0.7812. Feature analysis showed that all feature types contributed to the modification process. Further site-specific feature analysis showed that the features derived from PCA's surrounding sites contributed more to the determination of PCA sites than other sites. The detailed feature analysis in this paper might provide important clues for understanding the mechanism of the PCA formation and guide relevant experimental validations

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America

Background & Aims: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. / Methods: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. / Results: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03–1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84–3.58) for Native American race vs European American race. / Conclusions: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment

Brain Changes in Long-Term Zen Meditators Using Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: A Controlled Study

Introduction: This work aimed to determine whether 1H magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are correlated with years of meditation and psychological variables in long-term Zen meditators compared to healthy non-meditator controls. Materials and Methods: Design. Controlled, cross-sectional study. Sample. Meditators were recruited from a Zen Buddhist monastery. The control group was recruited from hospital staff. Meditators were administered questionnaires on anxiety, depression, cognitive impairment and mindfulness. 1H-MRS (1.5 T) of the brain was carried out by exploring four areas: both thalami, both hippocampi, the posterior superior parietal lobule (PSPL) and posterior cingulate gyrus. Predefined areas of the brain were measured for diffusivity (ADC) and fractional anisotropy (FA) by MR-DTI. Results: Myo-inositol (mI) was increased in the posterior cingulate gyrus and Glutamate (Glu), N-acetyl-aspartate (NAA) and N-acetyl-aspartate/Creatine (NAA/Cr) was reduced in the left thalamus in meditators. We found a significant positive correlation between mI in the posterior cingulate and years of meditation (r = 0.518; p = .019). We also found significant negative correlations between Glu (r =20.452; p = .045), NAA (r =20.617; p = .003) and NAA/Cr (r =20.448; P = .047) in the left thalamus and years of meditation. Meditators showed a lower Apparent Diffusion Coefficient (ADC) in the left posterior parietal white matter than did controls, and the ADC was negatively correlated with years of meditation (r =20.4850, p = .0066). Conclusions: The results are consistent with the view that mI, Glu and NAA are the most important altered metabolites. This study provides evidence of subtle abnormalities in neuronal function in regions of the white matter in meditators