Gains Across WHO Dimensions of Function After Robot-Based Therapy in Stroke Subjects

Background Studies examining the effects of therapeutic interventions after stroke often focus on changes in loss of body function/structure (impairment). However, improvements in activities limitations and participation restriction are often higher patient priorities, and the relationship that these measures have with loss of body function/structure is unclear. Objective This study measured gains across WHO International Classification of Function (ICF) dimensions and examined their interrelationships. Methods Subjects were recruited 11 to 26 weeks after hemiparetic stroke. Over a 3-week period, subjects received 12 sessions of intensive robot-based therapy targeting the distal arm. Each subject was assessed at baseline and at 1 month after end of therapy. Results At baseline, subjects (n = 40) were 134.7 ± 32.4 (mean ± SD) days poststroke and had moderate-severe arm motor deficits (arm motor Fugl-Meyer score of 35.6 ± 14.4) that were stable. Subjects averaged 2579 thumb movements and 1298 wrist movements per treatment session. After robot therapy, there was significant improvement in measures of body function/structure (Fugl-Meyer score) and activity limitations (Action Research Arm Test, Barthel Index, and Stroke Impact Scale–Hand), but not participation restriction (Stroke Specific Quality of Life Scale). Furthermore, while the degree of improvement in loss of body function/structure was correlated with improvement in activity limitations, neither improvement in loss of body function/structure nor improvement in activity limitations was correlated with change in participation restriction. Conclusions After a 3-week course of robotic therapy, there was improvement in body function/structure and activity limitations but no reduction in participation restriction

Gains Across WHO Dimensions of Function After Robot-Based Therapy in Stroke Subjects

Background Studies examining the effects of therapeutic interventions after stroke often focus on changes in loss of body function/structure (impairment). However, improvements in activities limitations and participation restriction are often higher patient priorities, and the relationship that these measures have with loss of body function/structure is unclear. Objective This study measured gains across WHO International Classification of Function (ICF) dimensions and examined their interrelationships. Methods Subjects were recruited 11 to 26 weeks after hemiparetic stroke. Over a 3-week period, subjects received 12 sessions of intensive robot-based therapy targeting the distal arm. Each subject was assessed at baseline and at 1 month after end of therapy. Results At baseline, subjects (n = 40) were 134.7 ± 32.4 (mean ± SD) days poststroke and had moderate-severe arm motor deficits (arm motor Fugl-Meyer score of 35.6 ± 14.4) that were stable. Subjects averaged 2579 thumb movements and 1298 wrist movements per treatment session. After robot therapy, there was significant improvement in measures of body function/structure (Fugl-Meyer score) and activity limitations (Action Research Arm Test, Barthel Index, and Stroke Impact Scale–Hand), but not participation restriction (Stroke Specific Quality of Life Scale). Furthermore, while the degree of improvement in loss of body function/structure was correlated with improvement in activity limitations, neither improvement in loss of body function/structure nor improvement in activity limitations was correlated with change in participation restriction. Conclusions After a 3-week course of robotic therapy, there was improvement in body function/structure and activity limitations but no reduction in participation restriction

Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA deletion syndromes

Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM), progressive external ophthalmoplegia (PEO), and Kearns-Sayre syndrome (KSS), to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH) followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients\u27 age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (\u3c6 years old) showed a diffused pattern of deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41). Only 15% (3/20) of the young patients (\u3c6 years old) carry the 5 kb common deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17) exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier onset and more severe disease with multisystem involvement. © 2010 Sadikovic et al

Correction: Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA deletion syndromes (PLoS ONE (2010) 5:12 (e15687) DOI: 10.1371/journal.pone.0015687)

The middle initial of the third author is missing. The third author’s complete name is: Ayman W. El-Hattab. The correct citation is: Sadikovic B, Wang J, El-Hattab AW, Landsverk M, Douglas G, Brundage EK, et al. (2010) Sequence Homology at the Breakpoint and Clinical Phenotype of Mitochondrial DNA Deletion Syndromes. PLoS ONE 5(12): e15687. https://doi.org/10.1371/journal.pone.0015687

Sequence Homology at the Breakpoint and Clinical Phenotype of Mitochondrial DNA Deletion Syndromes

Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM), progressive external ophthalmoplegia (PEO), and Kearns-Sayre syndrome (KSS), to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH) followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (<6 years old) showed a diffused pattern of deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41). Only 15% (3/20) of the young patients (<6 years old) carry the 5 kb common deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17) exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier onset and more severe disease with multisystem involvement

A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms ( SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds ( a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines - in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN