Targets of the Entamoeba histolytica Transcription Factor URE3-BP

The Entamoeba histolytica transcription factor Upstream Regulatory Element 3-Binding Protein (URE3-BP) is a calcium-responsive regulator of two E. histolytica virulence genes, hgl5 and fdx1. URE3-BP was previously identified by a yeast one-hybrid screen of E. histolytica proteins capable of binding to the sequence TATTCTATT (Upstream Regulatory Element 3 (URE3)) in the promoter regions of hgl5 and fdx1. In this work, precise definition of the consensus URE3 element was performed by electrophoretic mobility shift assays (EMSA) using base-substituted oligonucleotides, and the consensus motif validated using episomal reporter constructs. Transcriptome profiling of a strain induced to produce a dominant-positive URE3-BP was then used to identify additional genes regulated by URE3-BP. Fifty modulated transcripts were identified, and of these the EMSA defined motif T[atg]T[tc][cg]T[at][tgc][tg] was found in over half of the promoters (54% p<0.0001). Fifteen of the URE3-BP regulated genes were potential membrane proteins, suggesting that one function of URE3-BP is to remodel the surface of E. histolytica in response to a calcium signal. Induction of URE3-BP leads to an increase in tranwell migration, suggesting a possible role in the regulation of cellular motility

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Test of lepton universality in beauty-quark decays

The standard model of particle physics currently provides our best description of fundamental particles and their interactions. The theory predicts that the different charged leptons, the electron, muon and tau, have identical electroweak interaction strengths. Previous measurements have shown that a wide range of particle decays are consistent with this principle of lepton universality. This article presents evidence for the breaking of lepton universality in beauty-quark decays, with a significance of 3.1 standard deviations, based on proton–proton collision data collected with the LHCb detector at CERN’s Large Hadron Collider. The measurements are of processes in which a beauty meson transforms into a strange meson with the emission of either an electron and a positron, or a muon and an antimuon. If confirmed by future measurements, this violation of lepton universality would imply physics beyond the standard model, such as a new fundamental interaction between quarks and leptons

Relationship between functional status prior to onset of critical illness and mortality: a prospective multicentre cohort study.

This prospective study aimed to assess the association between prior functional status and hospital mortality for patients admitted to four intensive care units in Spain between 2006 and 2012. Prior functional status was classified into three groups, using a modification of the Glasgow Outcome Scale (GOS), including group 1 with no limitations on activities of daily living; group 2 with some limitations but self-sufficient; and group 3 who were dependent on others for their activities of daily living. Of the 1,757 patients considered (mean Simplified Acute Physiology Score [SAPS] predicted mortality 14.8% and hospital mortality 13.7%), group 1 had the lowest observed hospital mortality (8.3%) compared to the SAPS 3 predicted mortality (11.6%). The observed mortality for group 2 (20.6%) and group 3 (27.4%) were both higher than predicted (19.2% and 21.2% respectively; odds ratio [OR] 1.97, 95% confidence interval [CI] 1.38-2.82 for group 2 and OR 2.90, 95% CI 1.78-4.72 for group 3 compared to group 1). Combining prior functional status and Sequential Organ Failure Assessment (SOFA) score with SAPS 3 further improved the ability of the SAPS 3 scores in predicting hospital mortality (area under the receiver operating characteristic curve 0.85 [95% CI 0.82-0.88] versus 0.84 [95% CI 0.81-0.87] respectively). In summary, patients with limited functional status prior to ICU admission had a higher risk of observed hospital mortality than predicted. Assessing prior functional status using a relatively simple questionnaire, such as a modified GOS, has the potential to improve the accuracy of existing prognostic models

Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.

BACKGROUND: Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment. METHODS: 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797. FINDINGS: Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05). INTERPRETATION: Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear