ABSTRACT
BACKGROUND: Low balance confidence is a prevalent yet overlooked issue among people who use lower limb prostheses (LLP) that can diminish community integration and quality of life. There is a critical need to develop rehabilitation programs that specifically target balance confidence in people who use LLP. Previous research has shown that multicomponent interventions including cognitive-behavioral therapy (CBT) techniques and exercise are feasible and effective for improving balance confidence in older adults. Therefore, a cognitive behavioral-physical therapy (CBPT) intervention was developed to target balance confidence and increase community integration in people who use LLP. METHODS/DESIGN: This randomized control trial will recruit 60 people who use LLP with low balance confidence. Participants will be randomized to the CBPT intervention condition or control condition. DISCUSSION: The trial is designed to test the effects of the CBPT intervention on balance confidence and functional mobility in lower limb prosthesis users by examining self-reported and objective measures of community integration and quality of life. The trial will also examine the relationship between changes in balance confidence and changes in community integration following participation in CBPT intervention. Additionally, through participant feedback, researchers will identify opportunities to improve intervention efficacy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03411148. Registration date: January 26, 2018.
Subject(s)
Amputation, Surgical/rehabilitation , Artificial Limbs , Cognitive Behavioral Therapy/methods , Community Participation , Exercise Therapy/methods , Lower Extremity/surgery , Postural Balance , Self Concept , Adolescent , Adult , Aged , Aged, 80 and over , Exercise , Female , Follow-Up Studies , Health Surveys , Humans , Male , Middle Aged , Quality of Life , Veterans , Video Games , Virtual Reality , Young AdultABSTRACT
Aristaless-related homeobox gene (ARX) is an important paired-type homeobox gene involved in the development of human brain. The ARX gene mutations are a significant contributor to various forms of X-chromosome-linked mental retardation with and without additional features including epilepsy, lissencephaly with abnormal genitalia, hand dystonia or autism. Here we demonstrate that the human ARX protein is a potent transcriptional repressor, which binds to Groucho/transducin-like enhancer of split (TLE) co-factor proteins and the TLE1 in particular through its octapeptide (Engrailed homology repressor domain (eh-1) homology) domain. We show that the transcription repression activity of ARX is modulated by two strong repression domains, one located within the octapeptide domain and the second in the region of the polyalanine tract 4, and one activator domain, the aristaless domain. Importantly, we show that the transcription repression activity of ARX is affected by various naturally occurring mutations. The introduction of the c.98T>C (p.L33P) mutation results in the lack of binding to TLE1 protein and relaxed transcription repression. The introduction of the two most frequent ARX polyalanine tract expansion mutations increases the repression activity in a manner dependent on the number of extra alanines. Interestingly, deletions of alanine residues within polyalanine tracts 1 and 2 show low or no effect. In summary we demonstrate that the ARX protein is a strong transcription repressor, we identify novel ARX interacting proteins (TLE) and offer an explanation of a molecular pathogenesis of some ARX mutations, including the most frequent ARX mutations, the polyalanine tract expansion mutations, c.304ins(GCG)7 and c.428_451dup.
Subject(s)
Enhancer Elements, Genetic/physiology , Homeodomain Proteins/genetics , Mutation , Repressor Proteins/metabolism , Transcription Factors/genetics , Transcription, Genetic/physiology , Age Factors , Alanine/genetics , Animals , Brain/cytology , Cells, Cultured , Embryo, Mammalian , Gene Expression Regulation, Developmental/physiology , Humans , Immunoprecipitation/methods , In Situ Hybridization/methods , Mice , Neurons/metabolism , Transducin/metabolism , Transfection/methodsABSTRACT
There is increasing evidence of psychiatric side-effects following long-term alpha-interferon treatment, but no previous reports of psychosis as a side-effect. There is little evidence to suggest the best treatment of interferonrelated psychiatric illness. A case of manic psychosis developing after longterm alpha-interferon treatment is reported in a woman with no previous psychiatric history. The patient did not respond to termination of alphainterferon therapy. She responded partially to olanzapine but completely recovered after sodium valproate was added, with no deleterious effects. Psychiatric side-effects, including psychosis, are appreciable problems of alpha-interferon. This is the first case report of psychosis developing after long-term treatment. It supports suggestions that the pathological mechanisms of the early and late side-effects are different. Sodium valproate proved to be a safe and effective treatment. (Int J Psych Clin Pract 2000; 4:161-162).
