61 research outputs found
Maintained hand function and forearm bone health 14 months after an in-home virtual-reality videogame hand telerehabilitation intervention in an adolescent with hemiplegic cerebral palsy
Virtual reality videogames can be used to motivate rehabilitation, and telerehabilitation can be used to improve access to rehabilitation. These uses of technology to improve health outcomes are a burgeoning area of rehabilitation research. So far, there is a lack of reports of long-term outcomes of these types of interventions. The authors report a 15-year-old boy with hemiplegic cerebral palsy and epilepsy because of presumed perinatal stroke who improved his plegic hand function and increased his plegic forearm bone health during a 14-month virtual reality videogame hand telerehabilitation intervention. A total of 14 months after the intervention ended, repeat evaluation demonstrated maintenance of both increased hand function and forearm bone health. The implications of this work for the future of rehabilitation in children with neurological disabilities are discussed in this article
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Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.
Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Transcriptome-pathology correlation identified casein kinase 1ε (CSNK1E) mRNA as tightly correlated to levels of pTDP-43 in sALS patients. Enhanced crosslinking and immunoprecipitation in human sALS patient- and healthy control-derived frontal cortex, revealed that TDP-43 binds directly to and regulates the expression of CSNK1E mRNA. Additionally, we were able to show that pTDP-43 itself binds RNA. CK1E, the protein product of CSNK1E, in turn interacts with TDP-43 and promotes cytoplasmic accumulation of pTDP-43 in human stem-cell-derived MNs. Pathological TDP-43 phosphorylation is therefore, reciprocally regulated by CK1E activity and TDP-43 RNA binding. Our framework of transcriptome-pathology correlations identifies candidate genes with relevance to novel mechanisms of neurodegeneration
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell–matrix adhesion biology
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive weakness from loss of motor neurons. The fundamental pathogenic mechanisms are unknown and recent evidence is implicating a significant role for abnormal exon splicing and RNA processing. Using new comprehensive genomic technologies, we studied exon splicing directly in 12 sporadic ALS and 10 control lumbar spinal cords acquired by a rapid autopsy system that processed nervous systems specifically for genomic studies. ALS patients had rostral onset and caudally advancing disease and abundant residual motor neurons in this region. We created two RNA pools, one from motor neurons collected by laser capture microdissection and one from the surrounding anterior horns. From each, we isolated RNA, amplified mRNA, profiled whole-genome exon splicing, and applied advanced bioinformatics. We employed rigorous quality control measures at all steps and validated findings by qPCR. In the motor neuron enriched mRNA pool, we found two distinct cohorts of mRNA signals, most of which were up-regulated: 148 differentially expressed genes (P ≤ 10−3) and 411 aberrantly spliced genes (P ≤ 10−5). The aberrantly spliced genes were highly enriched in cell adhesion (P ≤ 10−57), especially cell–matrix as opposed to cell–cell adhesion. Most of the enriching genes encode transmembrane or secreted as opposed to nuclear or cytoplasmic proteins. The differentially expressed genes were not biologically enriched. In the anterior horn enriched mRNA pool, we could not clearly identify mRNA signals or biological enrichment. These findings, perturbed and up-regulated cell–matrix adhesion, suggest possible mechanisms for the contiguously progressive nature of motor neuron degeneration. Data deposition: GeneChip raw data (CEL-files) have been deposited for public access in the Gene Expression Omnibus (GEO), www.ncbi.nlm.nih.gov/geo, accession number GSE18920
On-line Randomized Controlled Trial of an Internet Based Psychologically Enhanced Intervention for People with Hazardous Alcohol Consumption
Background: Interventions delivered via the Internet have the potential to address the problem of hazardous alcohol consumption at minimal incremental cost, with potentially major public health implications. It was hypothesised that providing access to a psychologically enhanced website would result in greater reductions in drinking and related problems than giving access to a typical alcohol website simply providing information on potential harms of alcohol. DYD-RCT Trial registration: ISRCTN 31070347.Methodology/Principal Findings: A two-arm randomised controlled trial was conducted entirely on-line through the Down Your Drink (DYD) website. A total of 7935 individuals who screened positive for hazardous alcohol consumption were recruited and randomized. At entry to the trial, the geometric mean reported past week alcohol consumption was 46.0 (SD 31.2) units. Consumption levels reduced substantially in both groups at the principal 3 month assessment point to an average of 26.0 (SD 22.3) units. Similar changes were reported at 1 month and 12 months. There were no significant differences between the groups for either alcohol consumption at 3 months (intervention: control ratio of geometric means 1.03, 95% CI 0.97 to 1.10) or for this outcome and the main secondary outcomes at any of the assessments. The results were not materially changed following imputation of missing values, nor was there any evidence that the impact of the intervention varied with baseline measures or level of exposure to the intervention.Conclusions/Significance: Findings did not provide support for the hypothesis that access to a psychologically enhanced website confers additional benefit over standard practice and indicate the need for further research to optimise the effectiveness of Internet-based behavioural interventions. The trial demonstrates a widespread and potentially sustainable demand for Internet based interventions for people with hazardous alcohol consumption, which could be delivered internationally
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