2,104 research outputs found
International Conference on NeuroRehabilitation 2012
This volume 3, number 2 gathers a set of articles based on the most outstanding research on accessibility and disability issues that was presented in the International Conference on NeuroRehabilitation 2012 (ICNR).The articles’ research present in this number is centred on the analysis and/or rehabilitation of body impairment most due to brain injury and neurological disorders.JACCES thanks the collaboration of the ICNR members and the research authors and reviewers that have collaborated for making possible that issue
alpha-Sarcin catalytic activity is not required for cytotoxicity
<p>Abstract</p> <p>Background</p> <p>α-Sarcin is a protein toxin produced by <it>Aspergillus giganteus</it>. It belongs to a family of cytotoxic ribonucleases that inactivate the ribosome and inhibit protein synthesis. α-Sarcin cleaves a single phosphodiester bond within the RNA backbone of the large ribosomal subunit, which makes the ribosome unrecognizable to elongation factors and, in turn, blocks protein synthesis. Although it is widely held that the protein synthesis inhibition caused by the toxin leads to cell death, it has not been directly shown that catalytically inactive mutants of α-sarcin are non-toxic when expressed directly within the cytoplasm of cells. This is important since recent studies have cast doubt on whether protein synthesis inhibition is sufficient to initiate apoptosis.</p> <p>Results</p> <p>In this report, we assay α-sarcin cytotoxicity and ability to inhibit protein synthesis by direct cytoplasmic expression. We show that mutations in α-sarcin, which impair α-sarcin's ability to inhibit protein synthesis, do not affect its cytotoxicity. The mutants are unable to activate JNK, confirming that the sarcin-ricin loop remains intact and that the α-sarcin mutants are catalytically inactive. In addition, both mutant and wildtype variants of α-sarcin localize to the nucleus and cytoplasm, where they co-localize with ribosomal marker RPS6.</p> <p>Conclusion</p> <p>We conclude that although protein synthesis inhibition likely contributes to cell death, it is not required. Thus, our results suggest that α-sarcin can promote cell death through a previously unappreciated mechanism that is independent of rRNA cleavage and JNK activation.</p
Assessment and training in home-baesd telerehabilitation ofr arm mobility impairment
The aging population and limited healthcare capacities call for a change in how rehabilitation care is provided. There is a need to provide more autonomous and scalable care that can be more easily transferred out of the clinic and into home environments. One important barrier to this objective is achieving reliable assessment of motor performance using low-cost technology. Toward this end, an assessment framework and methodology is proposed. The framework uses 4 sequential games to measure aspects of range of motion, range of force, control of motion, and control of force. Parameters derived from the range of motion task are used to define motion requirements in all subsequent assessment games, while parameters derived from the range of force task are used to define subsequent lifting force requirements. A 12-week usability study was conducted in which 9 patients completed the clinical testing phase and 6 therapists and 7 patients completed the questionnaire. Feedback from the questionnaire shows the system is easy to use and integrates well in the clinical setting. The most commonly requested modifications were the inclusion of more games and the incorporation of hand training. Some initial position and force data are shown for one subject and discussion on implications for mobility assessment using the developed device are provided.Peer Reviewe
Assessment and training in home-based telerehabilitation of arm mobility impairment
In an era where rehabilitation services are diminishing under the weight of the growing demands and fewer therapists, home-based telerehabilitation offers a way of increasing duration and intensity of post-stroke training. Novel systems that guide the therapist and patient in planning, executing, and assessing the training can reduce the burden on the healthcare system while maintaining or improving the quality of care. To achieve this effectively, a unified approach is needed that can address the diverse needs of the users and adequately assess the level of mobility deficits remotely. This document presents a methodology and prototype system for assessment and training adaptation within a telerehabilitation framework targeting home-based rehabilitation of the upper limbs after stroke. The framework uses 4 games for assessment of motor performance based on measures of range and control of movement. Assessment games include range of motion, range of force, control of motion, and control of force. The initial assessment games are used to tune the deficit-specific parameters in each successive game for assessment and training. Games are administered over the web-based TeleREHA platform through a novel arm rehabilitation device called the ArmAssist. An overview of the developments in each project is presented including the basic assessment parameters and a methodology for making patient-specific adaptation to game levels. Preliminary feedback from an ongoing usability evaluation is also presented and discussed
Nonlinear Radiation Pressure and Stochasticity in Ultraintense Laser Fields
The radiation force on a single electron in an ultraintense plane wave () is calculated and shown to be proportional to in the
high- limit for arbitrary waveform and polarization. The cyclotron motion of
an electron in a constant magnetic field and an ultraintense plane wave is
numerically found to be quasiperiodic even in the high- limit if the
magnetic field is not too strong, as suggested by previous analytical work. A
strong magnetic field causes highly chaotic electron motion and the boundary of
the highly chaotic region of parameter space is determined numerically.
Applications to experiments and astrophysics are briefly discussed.Comment: 5 pages, 4 figures; uses RevTex, epsf macros. Corrected, expanded
versio
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Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy.
ObjectiveTo characterize individual and group-level neuroimaging findings in patients at risk for Chronic Traumatic Encephalopathy (CTE).MethodsEleven male patients meeting criteria for Traumatic Encephalopathy Syndrome (TES, median age: 64) underwent neurologic evaluation, 3-Tesla MRI, and PET with [18F]-Flortaucipir (FTP, tau-PET) and [11C]-Pittsburgh compound B (PIB, amyloid-PET). Six patients underwent [18F]-Fluorodeoxyglucose-PET (FDG, glucose metabolism). We assessed imaging findings at the individual patient level, and in group-level comparisons with modality-specific groups of cognitively normal older adults (CN). Tau-PET findings in patients with TES were also compared to a matched group of patients with mild cognitive impairment or dementia due to Alzheimer's disease (AD).ResultsAll patients with TES sustained repetitive head injury participating in impact sports, ten in American football. Three patients met criteria for dementia and eight had mild cognitive impairment. Two patients were amyloid-PET positive and harbored the most severe MRI atrophy, FDG hypometabolism, and FTP-tau PET binding. Among the nine amyloid-negative patients, tau-PET showed either mildly elevated frontotemporal binding, a "dot-like" pattern, or no elevated binding. Medial temporal FTP was mildly elevated in a subset of amyloid-negative patients, but values were considerably lower than in AD. Voxelwise analyses revealed a convergence of imaging abnormalities (higher FTP binding, lower FDG, lower gray matter volumes) in frontotemporal areas in TES compared to controls.ConclusionsMildly elevated tau-PET binding was observed in a subset of amyloid-negative patients at risk for CTE, in a distribution consistent with CTE pathology stages III-IV. FTP-PET may be useful as a biomarker of tau pathology in CTE but is unlikely to be sensitive to early disease stages
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An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery.
Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs
Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms
Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS
Association of traumatic brain injury with subsequent neurological and psychiatric disease: a meta-analysis
Mild traumatic brain injury (TBI) has been proposed as a risk factor for development of Alzheimer’s disease, Parkinson’s disease, depression, and other illnesses. This study’s objective was to determine the association of prior mild TBI with subsequent diagnosis (i.e., at least one year post-injury) of neurologic or psychiatric disease
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