1,588 research outputs found
Propofol cardioplegia: A single-center, placebo-controlled, randomized controlled trial
OBJECTIVES: Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is an effective treatment for coronary artery and aortic valve diseases. However, the myocardium sustains reperfusion injury after ischemic cardioplegic arrest. Our objective was to assess the benefits of supplementing cardioplegia solution with the general anesthetic propofol in patients undergoing either coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). METHODS: A single-center, double-blind randomized controlled trial was carried out to compare cardioplegia solution supplemented with propofol (concentration 6 Îźg/mL) versus intralipid (placebo). The primary outcome was cardiac troponin T release over the first 48 hours after surgery. RESULTS: We recruited 101 participants (51 in the propofol group, 50 in the intralipid group); 61 underwent CABG and 40 underwent AVR. All participants were followed to 3 months. Cardiac troponin T release was on average 15% lower with propofol supplementation (geometric mean ratio, 0.85; 95% confidence interval [CI], 0.73-1.01; P = .051). There were no differences for CABG participants but propofol-supplemented participants undergoing AVR had poorer postoperative renal function (geometric mean ratio, 1.071; 95% CI, 1.019-1.125; P = .007), with a trend toward longer intensive care stay (median, 89.5 vs 47.0 hours; hazard ratio, 0.58; 95% CI, 0.31-1.09; P = .09) and fewer with perfect health (based on the EQ-5D health utility index) at 3 months (odds ratio, 0.26; 95% CI, 0.06-1.05; P = .058) compared with the intralipid group. Safety profiles were similar. There were no deaths. CONCLUSIONS: Propofol supplementation in cardioplegia appears to be cardioprotective. Its influence on early clinical outcomes may differ between CABG and AVR surgery. A larger, multicenter study is needed to confirm or refute these suggestions
Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process
Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra; ArgentinaFil: Vranych, Cecilia VerĂłnica. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂŠdica Mercedes y MartĂn Ferreyra; Argentin
Diagnostic classification of childhood cancer using multiscale transcriptomics
The causes of pediatric cancersâ distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types
Mapping Genetically Compensatory Pathways from Synthetic Lethal Interactions in Yeast
Background: Synthetic lethal genetic interaction analysis has been successfully applied to predicting the functions of genes and their pathway identities. In the context of synthetic lethal interaction data alone, the global similarity of synthetic lethal interaction patterns between two genes is used to predict gene function. With physical interaction data, such as proteinprotein interactions, the enrichment of physical interactions within subsets of genes and the enrichment of synthetic lethal interactions between those subsets of genes are used as an indication of compensatory pathways. Result: In this paper, we propose a method of mapping genetically compensatory pathways from synthetic lethal interactions. Our method is designed to discover pairs of gene-sets in which synthetic lethal interactions are depleted among the genes in an individual set and where such gene-set pairs are connected by many synthetic lethal interactions. By its nature, our method could select compensatory pathway pairs that buffer the deleterious effect of the failure of either one, without the need of physical interaction data. By focusing on compensatory pathway pairs where genes in each individual pathway have a highly homogenous cellular function, we show that many cellular functions have genetically compensatory properties. Conclusion: We conclude that synthetic lethal interaction data are a powerful source to map genetically compensatory pathways, especially in systems lacking physical interaction information, and that the cellular function network contain
Panarchy: opportunities and challenges for ecosystem management
Addressing unexpected events and uncertainty represents one of the grand challenges of the Anthropocene, yet ecosystem management is constrained by existing policy and laws that were not formulated to deal with today's accelerating rates of environmental change. In many cases, managing for simple regulatory standards has resulted in adverse outcomes, necessitating innovative approaches for dealing with complex socialâecological problems. We highlight a project in the US Great Plains where panarchy â a conceptual framework that emerged from resilience â was implemented at project onset to address the continued inability to halt largeâscale transition from grassâtoâtree dominance in central North America. We review how panarchy was applied, the initial outcomes and evidence for policy reform, and the opportunities and challenges for which it could serve as a useful model to contrast with traditional ecosystem management approaches
Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo
We use data from the second science run of the LIGO gravitational-wave
detectors to search for the gravitational waves from primordial black hole
(PBH) binary coalescence with component masses in the range 0.2--.
The analysis requires a signal to be found in the data from both LIGO
observatories, according to a set of coincidence criteria. No inspiral signals
were found. Assuming a spherical halo with core radius 5 kpc extending to 50
kpc containing non-spinning black holes with masses in the range 0.2--, we place an observational upper limit on the rate of PBH coalescence
of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
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