10 research outputs found

    A Case of Acute Disseminated Encephalomyelitis in a MIddle-Aged Adult

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    BACKGROUND Acute disseminated encephalomyelitis (ADEM) is a monophasic inflammatory demyelinating disorder of the white matter that is often preceded by viral infection or recent vaccination. Encephalopathy and focal neurological deficits usually manifest one to three weeks after a prodromal illness with neurologic decline progressing rapidly over days to weeks. Approximately 25% of patients will develop multiple sclerosis (MS) within five years of initial presentation of ADEM but the majority of individuals do not progress beyond three months.4 ADEM is most commonly seen in children and young adults, where prognosis is favorable, but very few cases have been reported of middle-aged or elderly patients. The clinical course of these patients as compared to younger patients with ADEM is unclear. Here we present a case of ADEM in a middle-aged adult that recovered well after treatment with high-dose corticosteroids. Pages: 15-17

    Explaining oscillations and variability in the p53-Mdm2 system

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    <p>Abstract</p> <p>Background</p> <p>In individual living cells p53 has been found to be expressed in a series of discrete pulses after DNA damage. Its negative regulator Mdm2 also demonstrates oscillatory behaviour. Attempts have been made recently to explain this behaviour by mathematical models but these have not addressed explicit molecular mechanisms. We describe two stochastic mechanistic models of the p53/Mdm2 circuit and show that sustained oscillations result directly from the key biological features, without assuming complicated mathematical functions or requiring more than one feedback loop. Each model examines a different mechanism for providing a negative feedback loop which results in p53 activation after DNA damage. The first model (ARF model) looks at the mechanism of p14<sup>ARF </sup>which sequesters Mdm2 and leads to stabilisation of p53. The second model (ATM model) examines the mechanism of ATM activation which leads to phosphorylation of both p53 and Mdm2 and increased degradation of Mdm2, which again results in p53 stabilisation. The models can readily be modified as further information becomes available, and linked to other models of cellular ageing.</p> <p>Results</p> <p>The ARF model is robust to changes in its parameters and predicts undamped oscillations after DNA damage so long as the signal persists. It also predicts that if there is a gradual accumulation of DNA damage, such as may occur in ageing, oscillations break out once a threshold level of damage is acquired. The ATM model requires an additional step for p53 synthesis for sustained oscillations to develop. The ATM model shows much more variability in the oscillatory behaviour and this variability is observed over a wide range of parameter values. This may account for the large variability seen in the experimental data which so far has examined ARF negative cells.</p> <p>Conclusion</p> <p>The models predict more regular oscillations if ARF is present and suggest the need for further experiments in ARF positive cells to test these predictions. Our work illustrates the importance of systems biology approaches to understanding the complex role of p53 in both ageing and cancer.</p

    Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics

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    Decompressive Hemicraniectomy in Acute Neurological Diseases

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    Increased intracranial pressure (ICP) secondary to severe brain injury is common. Increased ICP is commonly encountered in malignant middle cerebral artery ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage. Multiple interventions – both medical and surgical – exist to manage increased ICP. Medical management is used as first-line therapy; however it is not always effective and is associated with significant risks. Decompressive hemicraniectomy is a surgical option to reduce ICP, increase cerebral compliance, and increase cerebral blood perfusion when medical management becomes insufficient. The purpose of this review is to provide an up-to-date summary of the use of decompressive hemicraniectomy for the management of refractory elevated ICP in malignant middle cerebral artery ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage. INTRODUCTION Increased intracranial pressure (ICP) secondary to cerebral edema is common in acute neurological disorders. Severe edema can be seen in malignant middle cerebral artery (MCA) ischemic stroke, traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH). Increased ICP can lead to life-threatening herniation syndromes and is a common cause of death when left untreated. Decompressive hemicraniectomy (DHC) is a surgical option to reduce ICP, increase cerebral compliance, and increase cerebral blood perfusion when medical management becomes insufficient. By removing the skull, the brain is allowed to expand, thereby normalizing ICP and reducing compression and/or midline shift. By reducing ICP, cerebral perfusion pressure and blood flow are restored. This article will summarize current medical literature regarding DHC in intracerebral hemorrhages, subarachnoid hemorrhage, malignant MCA stroke and traumatic brain injury

    Assessing adjustment to aging : A validation study for the Adjustment to Aging Scale (AtAS)

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    Adjustment to aging (AtA) is a multifactor adjustment process with implications on aging well among older adults. The aim of this study was to develop and validate a scale to assess the factors that older adults recognized as indicators of their AtA, with a cross-national comparative perspective towards aging well. Convenience sampling was used to gather questionnaire data, including demographics and the proposed scale. Complete data was available for 1,291 older community-dwelling adults, aged between 75 and 102 years (M = 83.9; SD = 6.68), who represented four different nationalities. Exploratory and confirmatory factor analyses were performed for dimension reduction and exploration of the factorial structure. Data gathered with the 22-items AtA five-factor scale showed overall good psychometric properties (in terms of distributional properties, statistical significant factor weights, factorial, convergent, discriminant criterion and externalrelated validities, as well as reliability). Five factors were selected for the Adjustment to Aging Scale: (a) sense of purpose and ambitions (b) zest and spirituality; (c) body and health; (d) aging in place and stability; and (e) social support. We present a 22-item scale with five factors for AtA estimation in a cross-national elderly population which produced valid and reliable data for elder persons from four different nationalities. Results showed that this scale is an adequate cross-cultural instrument for research, clinical practice and program development in the health care context. These may benefit from clearly understanding AtA as an important component for reducing health disparities and for aging well, across nationalities.Foundation for Science and Technolog

    Tracing environmental markers of autoimmunity: introducing the infectome

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    We recently introduced the concept of the infectome as a means of studying all infectious factors which contribute to the development of autoimmune disease. It forms the infectious part of the exposome, which collates all environmental factors contributing to the development of disease and studies the sum total of burden which leads to the loss of adaptive mechanisms in the body. These studies complement genome-wide association studies, which establish the genetic predisposition to disease. The infectome is a component which spans the whole life and may begin at the earliest stages right up to the time when the first symptoms manifest, and may thus contribute to the understanding of the pathogenesis of autoimmunity at the prodromal/asymptomatic stages. We provide practical examples and research tools as to how we can investigate disease-specific infectomes, using laboratory approaches employed from projects studying the "immunome" and "microbiome". It is envisioned that an understanding of the infectome and the environmental factors that affect it will allow for earlier patient-specific intervention by clinicians, through the possible treatment of infectious agents as well as other compounding factors, and hence slowing or preventing disease development

    Search for New Phenomena in tt̅ Events with Large Missing Transverse Momentum in Proton-Proton Collisions at √s=7  TeV with the ATLAS Detector

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    A search for new phenomena in t &lt;span style="text-decoration: overline"&gt;t&lt;/span&gt; events with large missing transverse momentum in proton-proton collisions at a center-of-mass energy of 7 TeV is presented. The measurement is based on 1.04  fb&lt;sup&gt;-1&lt;/sup&gt; of data collected with the ATLAS detector at the LHC. Contributions to this final state may arise from a number of standard model extensions. The results are interpreted in terms of a model where new top-quark partners are pair produced and each decay to an on-shell top (or antitop) quark and a long-lived undetected neutral particle. The data are found to be consistent with standard model expectations. A limit at 95% confidence level is set excluding a cross section times branching ratio of 1.1 pb for a top-partner mass of 420 GeV and a neutral particle mass less than 10 GeV. In a model of exotic fourth generation quarks, top-partner masses are excluded up to 420 GeV and neutral particle masses up to 140 GeV

    Search for supersymmetry in final states with jets, missing transverse momentum and one isolated lepton in root s=7 TeV pp collisions using 1 fb(-1) of ATLAS data

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    We present an update of a search for supersymmetry in final states containing jets, missing transverse momentum, and one isolated electron or muon, using 1.04 fb(-1) of proton-proton collision data at root s =7 TeV recorded by the ATLAS experiment at the LHC in the first half of 2011. The analysis is carried out in four distinct signal regions with either three or four jets and variations on the (missing) transverse momentum cuts, resulting in optimized limits for various supersymmetry models. No excess above the standard model background expectation is observed. Limits are set on the visible cross section of new physics within the kinematic requirements of the search. The results are interpreted as limits on the parameters of the minimal supergravity framework, limits on cross sections of simplified models with specific squark and gluino decay modes, and limits on parameters of a model with bilinear R-parity violation
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