Efficacy and safety of methylprednisolone sodium succinate in acute spinal cord injury: a systematic review

Study Design: Systematic review and meta-analysis. Objective: The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI). Methods: A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies ere critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated and evaluated using the Assessment of Multiple Systematic Reviews scoring system. Results: The search yielded 723 citations, 13 of which satisfied inclusion criteria. Among these, 6 were primary research articles and 7 were previous systematic reviews. Based on the included research articles, there was moderate evidence that the 24-hour NASCIS II (National Acute Spinal Cord Injury Studies) MPSS regimen has no impact on long-term neurological recovery when all postinjury time points are considered. However, there is also moderate evidence that subjects receiving the same MPSS regimen within 8 hours of injury achieve an additional 3.2 points (95% confidence interval = 0.10 to 6.33; P = .04) of motor recovery compared with patients receiving placebo or no treatment. Conclusion: Although safe to administer, a 24-hour NASCIS II MPSS regimen, when all postinjury time points are considered, has no impact on indices of long-term neurological recovery. When commenced within 8 hours of injury, however, a high-dose 24-hour regimen of MPSS confers a small positive benefit on long-term motor recovery and should be considered a treatment option for patients with SCI

Guidelines for the Management of Severe Traumatic Brain Injury: 2020 Update of the Decompressive Craniectomy Recommendations

© Congress of Neurological Surgeons 2020. When the fourth edition of the Brain Trauma Foundation\u27s Guidelines for the Management of Severe Traumatic Brain Injury were finalized in late 2016, it was known that the results of the RESCUEicp (Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension) randomized controlled trial of decompressive craniectomy would be public after the guidelines were released. The guideline authors decided to proceed with publication but to update the decompressive craniectomy recommendations later in the spirit of living guidelines, whereby topics are updated more frequently, and between new editions, when important new evidence is published. The update to the decompressive craniectomy chapter presented here integrates the findings of the RESCUEicp study as well as the recently published 12-mo outcome data from the DECRA (Decompressive Craniectomy in Patients With Severe Traumatic Brain Injury) trial. Incorporation of these publications into the body of evidence led to the generation of 3 new level-IIA recommendations; a fourth previously presented level-IIA recommendation remains valid and has been restated. To increase the utility of the recommendations, we added a new section entitled Incorporating the Evidence into Practice. This summary of expert opinion provides important context and addresses key issues for practitioners, which are intended to help the clinician utilize the available evidence and these recommendations. The full guideline can be found at: https://braintrauma.org/guidelines/guidelines-for-the-management-of-severe-tbi-4th-ed#/

Plasmas and Controlled Nuclear Fusion

Contains reports on five research projects.U. S. Atomic Energy Commission (Contract AT(30-1)-3980

Plasmas and Controlled Nuclear Fusion

Contains research objectives and reports on six research projects.U. S. Atomic Energy Commission (Contract AT(30-1)-3980

A clinical practice guideline for the management of acute spinal cord injury: introduction, rationale, and scope

Acute spinal cord injury (SCI) is a traumatic event that results in disturbances to normal sensory, motor, or autonomic function and ultimately affects a patient's physical, psychological, and social well-being. The management of patients with SCI has drastically evolved over the past century as a result of increasing knowledge on injury mechanisms, disease pathophysiology, and the role of surgery. There still, however, remain controversial areas surrounding available management strategies for the treatment of SCI, including the use of corticosteroids such as methylprednisolone sodium succinate, the optimal timing of surgical intervention, the type and timing of anticoagulation prophylaxis, the role of magnetic resonance imaging, and the type and timing of rehabilitation. This lack of consensus has prevented the standardization of care across treatment centers and among the various disciplines that encounter patients with SCI. The objective of this guideline is to form evidence-based recommendations for these areas of controversy and outline how to best manage patients with SCI. The ultimate goal of these guidelines is to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care and encouraging clinicians to make evidence-informed decisions

Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors

ABSTRACT Lipopolysaccharide (LPS)-activated monocytes and macrophages produce large quantities of pro-interleukin (IL)-1␤ but externalize little mature cytokine. Efficient post-translational processing of the procytokine occurs in vitro when these cells encounter a secretion stimulus such as ATP, cytolytic T cells, or hypotonic stress. Each of these stimuli promotes rapid conversion of 31-kDa pro-IL-1␤ to its mature 17-kDa species and release of the 17-kDa cytokine. In this study, two novel pharmacological agents, CP-424,174 and CP-412,245, are identified as potent inhibitors of stimulus-coupled IL-1␤ post-translational processing. These agents, both diarylsulfonylureas, block formation of mature IL-1␤ without increasing the amount of procytokine that is released extracellularly, and they inhibit independently of the secretion stimulus used. Conditioned medium derived from LPS-activated/ATP-treated human monocytes maintained in the absence and presence of CP-424,174 contained comparable quantities of IL-6, tumor necrosis factor-␣ (TNF␣), and IL-1RA, but 30-fold less IL-1␤ was generated in the test agent's presence. As a result of this decrease, monocyte conditioned medium prepared in the presence of CP-424,174 demonstrated a greatly diminished capacity to promote an IL-1-dependent response (induction of serum amyloid A synthesis by Hep3B cells). Oral administration of CP-424,174 to mice resulted in inhibition of IL-1 in the absence of an effect on IL-6 and TNF␣. These novel agents, therefore, act as selective cytokine release inhibitors and define a new therapeutic approach for controlling IL-1 production in inflammatory diseases

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

The structure of the scaffold nucleoporin Nup120 reveals a new and unexpected domain architecture

Nucleocytoplasmic transport is mediated by nuclear pore complexes (NPCs), enormous protein assemblies residing in circular openings in the nuclear envelope. The NPC is modular, with transient and stable components. The stable core is essentially built from two multiprotein complexes, the Y-shaped heptameric Nup84 complex and the Nic96 complex, arranged around an eightfold axis. We present the crystal structure of Nup120[subscript 1-757], one of the two short arms of the Y-shaped Nup84 complex. The protein adopts a compact oval shape built around a novel bipartite α-helical domain intimately integrated with a β-propeller domain. The domain arrangement is substantially different from the Nup85•Seh1 complex, which forms the other short arm of the Y. With the data presented here, we establish that all three branches of the Y-shaped Nup84 complex are tightly connected by helical interactions and that the β-propellers likely form interaction site(s) to neighboring complexes.National Institutes of Health (U.S.) (Grant GM77537)Pew Charitable Trusts (Scholar Award

Submicron Structures Fabrication and Research

Contains reports on thirteen research projects.Joint Services Electronics Program (Contract DAAG29-83-K-0003)U.S. Navy - Office of Naval Research (Contract N00014-79-C-0908)National Science Foundation (Grant ECS82-05701)I.B.M. (PO No. 90305-QPSA-559)U.S. Department of Energy (Contract DE-AC02-82-ER13019)Lawrence Livermore Laboratory (Contract 2069209

Submicron Structures Fabrication and Research

Contains reports on twelve research projects.Lawrence Livermore Laboratory (Subcontract 2069209)Joint Services Electronics Program (Contract DAAG29-C-0104)U.S. Navy - Office of Naval Research (Contract N00014-79-C-0908)Joint Services Electronics Program (Contract DAAG29-80-C-0104)Harkness FoundationI.B.M.U.S. Department of Energy (Contract DE-ACO2-80-E10179)National Science Foundation (Grant ECS80-17705