TRIM25 mutation (p.C168*), coding for an E3 ubiquitin ligase, is a cause of early-onset autosomal dominant dementia with amyloid load and parkinsonism.

INTRODUCTION: Patients with familial early-onset dementia (EOD) pose a unique opportunity for gene identification studies. METHODS: We present the phenotype and whole-exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild-type and mutant protein of the final candidate. RESULTS: Age at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss-of-function mechanism. DISCUSSION: This study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases. HIGHLIGHTS: A TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early-onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease. TRIM25 protein studies support that the mutation exerts its effect through loss of function. TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration. The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research.

Effects of High-Intensity Laser Therapy on Pain Sensitivity and Motor Performance in Patients with Thumb Carpometacarpal Joint Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVE: To examine the effects of high-intensity laser therapy (HILT) on pain sensitivity and motor performance in patients with thumb carpometacarpal (CMC) osteoarthritis (OA). DESIGN: Prospective, triple-blinded, randomized, placebo-controlled trial. SETTING: Private practice, Malaga, Spain. SUBJECTS: Forty-three patients (mean ± SD age = 71 ± 12 years) with a diagnosis of thumb CMC OA grade 1-2 were randomized to the control group (N = 21) or experimental group (N = 22). METHODS: The experimental group (ExpG) received high-intensity laser therapy (HILT), and the control group (ConG) received a placebo treatment. The outcome measures were pain intensity (visual analog scale) and key pinch strength measurements (dynamometer). All outcome measures were collected at baseline, immediately following the intervention, at four weeks, and at 12 weeks following the intervention. RESULTS: Analysis of variance revealed a group × time interaction (F = 40.8, P < 0.001) for pain intensity, with those patients receiving LT experiencing a greater reduction in pain compared with those receiving placebo therapy at the end of the intervention (P < 0.001), as well as at 12 weeks after the intervention. Although mean values in the ExpG were higher than in the ConG for key pinch at assessment, these differences were not statistically significant. CONCLUSIONS: HILT effectively diminishes pain intensity when used as an isolated treatment for patients with thumb CMC OA, but the effect of treatment decreases after 12 weeks.

Class IV laser therapy for trapeziometacarpal joint osteoarthritis: Study protocol for a randomized placebo-controlled trial.

OBJECTIVE: Osteoarthritis (OA) is a chronic and prevalent joint disorder with great impact on quality of life and high economic burden. Although a number of conservative therapies have proven to be effective for the management of hand OA, only modest treatment effects were reported for most individual interventions. The aim of the proposed study is to assess the effect of Class IV laser therapy (LT) on pain and pinch strength in patients with thumb carpometacarpal (TCMC) OA. METHODS: A randomized, controlled, single-centre, double-blind, clinical trial, with 1:1 allocation ratio, will be carried out involving patients presenting TCMC-OA Grades 1-2 (aged >18 years). Both assessor and statistician will remain blinded. Patients with TCMC-OA will be randomly assigned to the experimental group (will receive LT) and control group (will receive a placebo treatment). Outcome measures will be pain scores at the base of the thumb measured with visual analogue scale (0-10: 0, no pain and 10, worst pain) and changes in pinch strength, both collected at baseline, 4, and 12 weeks. Statistical analyses will be based on an intention-to-treat analysis using the last value forward method. A two-tailed independent Student's t test for the continuous variable of age and baseline scores will be used for comparison of baseline characteristics and outcome variables. Paired Student's t tests will be used to determine the level of significance of the differences between the pretreatment and posttreatment measurements of the individual groups. Repeated measures analysis of variance will be used to determine the differences in time as the within-subjects factor and group as the between-subjects factor. DISCUSSION: To our knowledge, the results of this study will provide the first double-blinded evidence for Class IV LT in patients with TCMC-OA.

Treatment of proximal interphalangeal joint flexion contracture: combined static and dynamic orthotic intervention compared with other therapy intervention: a randomized controlled trial.

PURPOSE: To test the effectiveness of static and dynamic orthoses using them as an exclusive treatment for proximal interphalangeal (PIP) joint flexion contracture compared with other hand therapy conservative treatments described in the literature. METHODS: 60 patients who used orthoses were compared with a control group that received other hand therapy treatments. Clinical assessments were measured before the experiment and 3 months after and included active PIP joint extension and function. RESULTS: A significant improvement in the extension active range of motion at the PIP joint in the second measurement was found in both groups, but it was significantly greater in the experimental group. Improvement in function (Disabilities of the Arm, Shoulder, and Hand score) between the first and second assessment was similar in the control and experimental groups. CONCLUSIONS: Using night progressive static and daily dynamic orthoses as an exclusive treatment during the proliferative phase led to significant improvements in the PIP joint active extension, but the improvement did not correlate with increased function as perceived by the patient. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Effect of muscle strength and pain on hand function in patients with trapeziometacarpal osteoarthritis. A cross-sectional study.

OBJECTIVE: To assess the relationship between muscle strength (Jama), and pain (VAS) levels with hand function (DASH) in patients with trapeziometarcapal osteoarthritis. Cross-sectional study. PARTICIPANTS: Sample of 72 patients with osteoarthritis stage 2-3 (Eaton) and trapeziometacarpal osteoarthritis. Patients were recruited when they came to the Hand Surgery Unit. METHOD: Grip strength, pinch, pain and hand function were measured, and correlation and regression coefficients between them were obtained. RESULTS: For function, the most significant model (R(2)=0.83) included pain and strength. But it is tip to tip pinch force which has a stronger relationship with DASH (Standardized B: -57) questionnaire. Pain also influenced strength measured with the dynamometer but it was tip to tip pinch force that was the most affected. CONCLUSIONS: Findings confirm that there is a significant correlation between function referred by the patient and variables that can be measured in the clinic such as grip strength and pinch. The correlation between pain intensity and function was also significant, but tip to tip pinch strength had the greatest impact on the function.