577 research outputs found

    Selenium-Binding Protein 1 Indicates Myocardial Stress and Risk for Adverse Outcome in Cardiac Surgery

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    Selenium-binding protein 1 (SELENBP1) is an intracellular protein that has been detected in the circulation in response to myocardial infarction. Hypoxia and cardiac surgery affect selenoprotein expression and selenium (Se) status. For this reason, we decided to analyze circulating SELENBP1 concentrations in patients (n = 75) necessitating cardioplegia and a cardiopulmonary bypass (CPB) during the course of the cardiac surgery. Serum samples were collected at seven time-points spanning the full surgical process. SELENBP1 was quantified by a highly sensitive newly developed immunological assay. Serum concentrations of SELENBP1 increased markedly during the intervention and showed a positive association with the duration of ischemia (ρ = 0.6, p < 0.0001). Elevated serum SELENBP1 concentrations at 1 h after arrival at the intensive care unit (post-surgery) were predictive to identify patients at risk of adverse outcome (death, bradycardia or cerebral ischemia, "endpoint 1"; OR 29.9, CI 3.3-268.8, p = 0.00027). Circulating SELENBP1 during intervention (2 min after reperfusion or 15 min after weaning from the CPB) correlated positively with an established marker of myocardial infarction (CK-MB) measured after the intervention (each with ρ = 0.5, p < 0.0001). We concluded that serum concentrations of SELENBP1 were strongly associated with cardiac arrest and the duration of myocardial ischemia already early during surgery, thereby constituting a novel and promising quantitative marker for myocardial hypoxia, with a high potential to improve diagnostics and prediction in combination with the established clinical parameters

    Constitutional Analogies in the International Legal System

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    This Article explores issues at the frontier of international law and constitutional law. It considers five key structural and systemic challenges that the international legal system now faces: (1) decentralization and disaggregation; (2) normative and institutional hierarchies; (3) compliance and enforcement; (4) exit and escape; and (5) democracy and legitimacy. Each of these issues raises questions of governance, institutional design, and allocation of authority paralleling the questions that domestic legal systems have answered in constitutional terms. For each of these issues, I survey the international legal landscape and consider the salience of potential analogies to domestic constitutions, drawing upon and extending the writings of international legal scholars and international relations theorists. I also offer some preliminary thoughts about why some treaties and institutions, but not others, more readily lend themselves to analysis in constitutional terms. And I distinguish those legal and political issues that may generate useful insights for scholars studying the growing intersections of international and constitutional law from other areas that may be more resistant to constitutional analogies

    Panelists\u27 Comments on the Presentation by Javier Livas and Samuel del Villar

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    Factors Affecting European Farmers’Participation in Biodiversity Policies

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    This article reports the major findings from an interdisciplinary research project that synthesises key insights into farmers’ willingness and ability to co-operate with biodiversity policies. The results of the study are based on an assessment of about 160 publications and research reports from six EU member states and from international comparative research.We developed a conceptual framework to systematically review the existent literature relevant for our purposes. This framework provides a common structure for analysing farmers’ perspectives regarding the introduction into farming practices of measures relevant to biodiversity. The analysis is coupled and contrasted with a survey of experts. The results presented above suggest that it is important to view support for practices oriented towards biodiversity protection not in a static sense – as a situation determined by one or several influencing factors – but rather as a process marked by interaction. Financial compensation and incentives function as a necessary, though clearly not sufficient condition in this process

    Coagulopathy management of multiple injured patients – a comprehensive literature review of the European guideline 2019

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    The European guideline on the management of trauma-induced major bleeding and coagulopathy summarises the most relevant recommendations for trauma coagulopathy management.center dot The management of trauma-induced major bleeding should interdisciplinary follow algorithms which distinguish between life-threatening and non-life-threatening bleeding.center dot Point-of-care viscoelastic methods (VEM) assist target-controlled haemostatic treatment. Neither conventional coagulation assays nor VEM should delay treatment in life-threatening trauma-induced bleeding.center dot Adjustments may be rational due to local circumstances, including the availability of blood products, pharmaceuticals, and employees

    PTEN Depletion Decreases Disease Severity and Modestly Prolongs Survival in a Mouse Model of Spinal Muscular Atrophy.

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    Spinal muscular atrophy (SMA) is the second most common genetic cause of death in childhood. However, no effective treatment is available to halt disease progression. SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene. We previously reported that PTEN depletion leads to an increase in survival of SMN-deficient motor neurons. Here, we aimed to establish the impact of PTEN modulation in an SMA mouse model in vivo. Initial experiments using intramuscular delivery of adeno-associated vector serotype 6 (AAV6) expressing shRNA against PTEN in an established mouse model of severe SMA (SMNΔ7) demonstrated the ability to ameliorate the severity of neuromuscular junction pathology. Subsequently, we developed self-complementary AAV9 expressing siPTEN (scAAV9-siPTEN) to allow evaluation of the effect of systemic suppression of PTEN on the disease course of SMA in vivo. Treatment with a single injection of scAAV9-siPTEN at postnatal day 1 resulted in a modest threefold extension of the lifespan of SMNΔ7 mice, increasing mean survival to 30 days, compared to 10 days in untreated mice. Our data revealed that systemic PTEN depletion is an important disease modifier in SMNΔ7 mice, and therapies aimed at lowering PTEN expression may therefore offer a potential therapeutic strategy for SMA

    Consensus guidelines for lumbar puncture in patients with neurological diseases

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    Introduction Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post-LP headache or back pain. Methods We provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II-2), (2) systematic literature review on LP needle characteristics and post-LP complications (evidence level II-2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and Biomarkers for Multiple Sclerosis consortia (evidence level III). Results Our consensus guidelines address contraindications, as well as patient-related and procedure-related risk factors that can influence the development of post-LP complications. Discussion When an LP is performed correctly, the procedure is well tolerated and accepted with a low complication rate
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