7 research outputs found
Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.
BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden
Thinking About Power and Schooling Through Educational Theorists
Multiethnic practitioner researchers explore issues of power and schooling in relation to curriculum studies in the South. We discuss how the articulation and examination of issues of power and schooling are illuminated in the eleven key texts of prominent educational thinkers (e.g., Bell, 1992; Foucault, 1977; Freire, 1970/1992; Kozol, 1992; Nussbaum, 2010; Palmer, 1998; Saïd, 1994; Schubert, 2009; Takaki, 1993; Watkins, 2011; Zinn, 1980/2003). We particularly explore how the eleven educational thinkers cultivate critical consciousness through counternarratives to explore issues of power and schooling such as race, gender, class, power, and place to contest the official or metanarrative that often portrays disenfranchised individuals and groups as deficient and inferior. The counternarratives in the eleven key texts help tell silenced and neglected stories of repressions, suppressions, and subjugations that challenge stereotypes of Southern women, Blacks, and other disenfranchised individuals and groups and encourage examination of the forces of slavery, racism, sexism, classism, religious repression, and other forms of oppression on the life curriculum in schools, neighborhoods, and communities in the South.There are six specific purposes to the session. One purpose is to understand multiple theories of power. A second purpose is to engage in power analyses and critiques of pedagogical practices. The third purpose is to engage in power analyses and critiques of institutions in contemporary schooling. The fourth purpose is to engage in power analyses and critiques of policies and contexts in contemporary schooling. The fifth purpose is to explore the contradictions and complexities of competing theories of power
Design, Synthesis, and Evaluation of Nonretinoid Retinol Binding Protein 4 Antagonists for the Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease
Accumulation of lipofuscin in the
retina is associated with pathogenesis
of atrophic age-related macular degeneration and Stargardt disease.
Lipofuscin bisretinoids (exemplified by <i>N</i>-retinylidene-<i>N</i>-retinylethanolamine) seem to mediate lipofuscin toxicity.
Synthesis of lipofuscin bisretinoids depends on the influx of retinol
from serum to the retina. Compounds antagonizing the retinol-dependent
interaction of retinol-binding protein 4 (RBP4) with transthyretin
in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid
formation. We recently showed that A1120 (<b>3</b>), a potent
carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin
bisretinoid formation in the retinas of <i>Abca4</i><sup><i>–/–</i></sup> mice. As part of the NIH
Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained
RBP4 antagonists with improved potency and metabolic stability. We
also demonstrate that upon acute and chronic dosing in rats, <b>43</b>, a potent cyclopentyl fused pyrrolidine antagonist, reduced
circulating plasma RBP4 protein levels by approximately 60%
Bicyclic [3.3.0]-Octahydrocyclopenta[<i>c</i>]pyrrolo Antagonists of Retinol Binding Protein 4: Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease
Antagonists of retinol-binding protein
4 (RBP4) impede ocular uptake of serum all-<i>trans</i> retinol
(<b>1</b>) and have been shown to reduce cytotoxic bisretinoid
formation in the retinal pigment epithelium (RPE), which is associated
with the pathogenesis of both dry age-related macular degeneration
(AMD) and Stargardt disease. Thus, these agents show promise as a
potential pharmacotherapy by which to stem further neurodegeneration
and concomitant vision loss associated with geographic atrophy of
the macula. We previously disclosed the discovery of a novel series
of nonretinoid RBP4 antagonists, represented by bicyclic [3.3.0]-octahydrocyclopenta[<i>c</i>]pyrrolo analogue <b>4</b>. We describe herein the
utilization of a pyrimidine-4-carboxylic acid fragment as a suitable
isostere for the anthranilic acid appendage of <b>4</b>, which
led to the discovery of standout antagonist <b>33</b>. Analogue <b>33</b> possesses exquisite <i>in vitro</i> RBP4 binding
affinity and favorable drug-like characteristics and was found to
reduce circulating plasma RBP4 levels <i>in vivo</i> in
a robust manner (>90%)
Tartrazine: physical, thermal and biophysical properties of the most widely employed synthetic yellow food-colouring azo dye
Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries
This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London