933 research outputs found

    Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

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    OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

    The SunPy Project: Open Source Development and Status of the Version 1.0 Core Package

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    The goal of the SunPy project is to facilitate and promote the use and development of community-led, free, and open source data analysis software for solar physics based on the scientific Python environment. The project achieves this goal by developing and maintaining the sunpy core package and supporting an ecosystem of affiliated packages. This paper describes the first official stable release (version 1.0) of the core package, as well as the project organization and infrastructure. This paper concludes with a discussion of the future of the SunPy project

    Search for the standard model Higgs boson at LEP

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    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

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    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

    RLIP76, a Glutathione-Conjugate Transporter, Plays a Major Role in the Pathogenesis of Metabolic Syndrome

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    PURPOSE: Characteristic hypoglycemia, hypotriglyceridemia, hypocholesterolemia, lower body mass, and fat as well as pronounced insulin-sensitivity of RLIP76⁻/⁻ mice suggested to us the possibility that elevation of RLIP76 in response to stress could itself elicit metabolic syndrome (MSy). Indeed, if it were required for MSy, drugs used to treat MSy should have no effect on RLIP76⁻/⁻ mice. RESEARCH DESIGN AND METHODS: Blood glucose (BG) and lipid measurements were performed in RLIP76⁺/⁺ and RLIP76⁻/⁻ mice, using Ascensia Elite Glucometer® for glucose and ID Labs kits for cholesterol and triglycerides assays. The ultimate effectors of gluconeogenesis are the three enzymes: PEPCK, F-1,6-BPase, and G6Pase, and their expression is regulated by PPARγ and AMPK. The activity of these enzymes was tested by protocols standardized by us. Expressions of RLIP76, PPARα, PPARγ, HMGCR, pJNK, pAkt, and AMPK were performed by Western-blot and tissue staining. RESULTS: The concomitant activation of AMPK and PPARγ by inhibiting transport activity of RLIP76, despite inhibited activity of key glucocorticoid-regulated hepatic gluconeogenic enzymes like PEPCK, G6Pase and F-1,6-BP in RLIP76⁻/⁻ mice, is a salient finding of our studies. The decrease in RLIP76 protein expression by rosiglitazone and metformin is associated with an up-regulation of PPARγ and AMPK. CONCLUSIONS/SIGNIFICANCE: All four drugs, rosiglitazone, metformin, gemfibrozil and atorvastatin failed to affect glucose and lipid metabolism in RLIP76⁻/⁻ mice. Studies confirmed a model in which RLIP76 plays a central role in the pathogenesis of MSy and RLIP76 loss causes profound and global alterations of MSy signaling functions. RLIP76 is a novel target for single-molecule therapeutics for metabolic syndrome

    Mosquito Infection Responses to Developing Filarial Worms

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    Human lymphatic filariasis is a mosquito-vectored disease caused by the nematode parasites Wuchereria bancrofti, Brugia malayi and Brugia timori. These are relatively large roundworms that can cause considerable damage in compatible mosquito vectors. In order to assess how mosquitoes respond to infection in compatible mosquito-filarial worm associations, microarray analysis was used to evaluate transcriptome changes in Aedes aegypti at various times during B. malayi development. Changes in transcript abundance in response to the different stages of B. malayi infection were diverse. At the early stages of midgut and thoracic muscle cell penetration, a greater number of genes were repressed compared to those that were induced (20 vs. 8). The non-feeding, intracellular first-stage larvae elicited few differences, with 4 transcripts showing an increased and 9 a decreased abundance relative to controls. Several cecropin transcripts increased in abundance after parasites molted to second-stage larvae. However, the greatest number of transcripts changed in abundance after larvae molted to third-stage larvae and migrated to the head and proboscis (120 induced, 38 repressed), including a large number of putative, immunity-related genes (∼13% of genes with predicted functions). To test whether the innate immune system of mosquitoes was capable of modulating permissiveness to the parasite, we activated the Toll and Imd pathway controlled rel family transcription factors Rel1 and Rel2 (by RNA interference knockdown of the pathway's negative regulators Cactus and Caspar) during the early stages of infection with B. malayi. The activation of either of these immune signaling pathways, or knockdown of the Toll pathway, did not affect B. malayi in Ae. aegypti. The possibility of LF parasites evading mosquito immune responses during successful development is discussed

    A review of bronchiolitis obliterans syndrome and therapeutic strategies

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    Lung transplantation is an important treatment option for patients with advanced lung disease. Survival rates for lung transplant recipients have improved; however, the major obstacle limiting better survival is bronchiolitis obliterans syndrome (BOS). In the last decade, survival after lung retransplantation has improved for transplant recipients with BOS. This manuscript reviews BOS along with the current therapeutic strategies, including recent outcomes for lung retransplantation

    Molecular basis of structure and function of the microvillus membrane of intestinal epithelial cells

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    Correlation of molecular structure with biochemical functions of the plasma membrane of the microvilli of intestinal epithelial cells has been investigated by biochemical and electron microscopic procedures. Repeating particles, measuring approximately 60 &#197;in diameter, were found on the surface of the microvilli membrane which had been isolated or purified from rabbit intestinal epithelial cells and negatively stained with phosphotungstic acid. These particles were proved to be inherent components of the microvillus membrane, attached to the outer surface of its trilaminar structure, and were designated as the elementary particles of the microvilli of intestinal epithelial cells. Biochemical and electron microscopic identification of these elementary particles has been carried out by isolation of the elementary particles with papain from the isolated microvillus membrane, followed by purification of the particles by chromatographies on DEAE-cellulose and Sephadex columns. The partially purified particles containing invertase and leucine aminopeptidase are similar in size and structure to those of the elementary particles in the microvillus membrane. Evidence indicates that each of the elementary particles coincide with or include an enzyme molecule such as disaccharidase or peptidase, which carry out the terminal hydrolytic digestion of carbohydrates and proteins, respectively, on the surface of the microvillus membrane. Magnesium ionactivated adenosine triphosphatase and alkaline phosphatase cannot be solubilized with papain but remains in the smooth-surface membrane after the elementary particles have been removed. Cytochemical electron microscopic observation revealed that the active site of magnesium ion-activated adenosine triphosphatase is localized predominantly in the inner surface of the trilaminar structure of the microvillus membrane.</p
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