841 research outputs found

    Hyperglycemia may alter cytokine production and phagocytosis by means other than hyperosmotic stress

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    In the previous issue of Critical Care, Otto and colleagues used in vitro studies to explore the theory that immunomodulation, by correction of hyperglycemia, may be a contributing factor to the reported efficacy of intensive insulin therapy (IIT) in critically ill patients. They suggested that hyperglycemia via hyperosmolarity at supra-physiological levels potentiates the production of cytokines by peripheral blood mononuclear cells in response to lipopolysaccharide (LPS) stimulation and that it also reduces the responses of phagocytosis and oxidative burst in human granulocytes. The efficacy of IIT, they concluded, may be partially due to the correction of hyperosmolality. Other studies, however, have suggested that immunological responses to LPS in the presence of hyperglycemia are mediated by a mechanism other than hyperosmolality

    The mass of the neutron star in Cyg X-2 (V1341 Cyg)

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    Cygnus X-2 is one of the brightest and longest known X-ray sources. We present high resolution optical spectroscopy of Cyg X-2 obtained over 4 years which gives an improved mass function of 0.69 +/- 0.03 Msun (1 sigma error). In addition, we resolve the rotationally broadened absorption features of the secondary star for the first time, deriving a rotation speed of vsin(i) = 34.2 +/- 2.5 km per s (1 sigma error) which leads to a mass ratio of q = M_c/M_x = 0.34 +/- 0.04 (1 sigma error), assuming a tidally-locked and Roche lobe-filling secondary). Hence with the lack of X-ray eclipses (i.e. i <~ 73 degrees) we can set firm 95% confidence lower limits to the neutron star mass of M_x > 1.27 Msun and to the companion star mass of M_c > 0.39 Msun. However, by additionally requiring that the companion must exceed 0.75 Msun (as required theoretically to produce a steady low-mass X-ray binary), then M_x > 1.88 Msun and i < 61 degrees (95% confidence lower and upper limit, respectively), thereby making Cyg X-2 the highest mass neutron star measured to date. If confirmed this would set significant constraints on the equation of state of nuclear matter.Comment: 16 pages, 4 figures, ApJ Letters, accepted, LaTeX, aasms4.st

    Structure and Mechanism of a Metal-Sensing Regulatory RNA

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    SummaryOrganisms maintain the correct balance of intracellular metals primarily through metal-sensing proteins that control transport and storage of the target ion(s). Here, we reveal the basis of metal sensing and genetic control by a metalloregulatory RNA. Our data demonstrate that a previously uncharacterized orphan riboswitch, renamed the “M-box,” is a divalent metal-sensing RNA involved in Mg2+ homeostasis. A combination of genetic, biochemical, and biophysical techniques demonstrate that Mg2+ induces a compacted tertiary architecture for M-box RNAs that regulates the accessibility of nucleotides involved in genetic control. Molecular details are provided by crystallographic structure determination of a Mg2+-bound M-box RNA. Given the distribution of this RNA element, it may constitute a common mode for bacterial metal ion regulation, and its discovery suggests the possibility of additional RNA-based metal sensors in modern and primordial organisms

    Assessing protocol adherence in a clinical trial with ordered treatment regimens: Quantifying the pragmatic, randomized optimal platelet and plasma ratios (PROPPR) trial experience

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    AbstractBackgroundMedication dispensing errors are common in clinical trials, and have a significant impact on the quality and validity of a trial. Therefore, the definition, calculation and evaluation of such errors are important for supporting a trial’s conclusions. A variety of medication dispensing errors can occur. In this paper, we focus on errors in trials where the intervention includes multiple therapies that must be given in a pre-specified order that varies across treatment arms and varies in duration.MethodsThe Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial was a Phase III multi-site, randomized trial to compare the effectiveness and safety of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with a 1:1:2 ratio. In this trial, these three types of blood products were to be transfused in a pre-defined order that differed by treatment arm. In this paper, we present approaches from the PROPPR trial that we used to define and calculate the occurrence of out of order blood transfusion errors. We applied the proposed method to calculate protocol adherence to the specified order of transfusion in each treatment arm.ResultsUsing our proposed method, protocol adherence was greater in the 1:1:1 group than in the 1:1:2 group (96% vs 93%) (p<0.0001), although out of order transfusion errors in both groups were low. Final transfusion ratios of plasma to platelets to red blood cells for the 1:1:1 ratio group was 0.93:1.32:1, while the transfusion ratio for the 1:1:2 ratio group was 0.48:0.48:1.ConclusionsOverall, PROPPR adherence to blood transfusion order pre-specified in the protocol was high, and the required order of transfusions for the 1:1:2 group was more difficult to achieve. The approaches proposed in this manuscript were useful in evaluating the PROPPR adherence and are potentially useful for other trials where a specific treatment orders with varying durations must be maintained