BackgroundOlder people are at risk for health decline and loss of independence. Lifestyle interventions offer potential for reducing such negative outcomes. The aim of this study was to determine the effectiveness and cost-effectiveness of a preventive lifestyle-based occupational therapy intervention, administered in a variety of community-based sites, in improving mental and physical well-being and cognitive functioning in ethnically diverse older people.MethodsA randomised controlled trial was conducted comparing an occupational therapy intervention and a no-treatment control condition over a 6-month experimental phase. Participants included 460 men and women aged 60–95 years (mean age 74.9±7.7 years; 53% <$12 000 annual income) recruited from 21 sites in the greater Los Angeles metropolitan area.ResultsIntervention participants, relative to untreated controls, showed more favourable change scores on indices of bodily pain, vitality, social functioning, mental health, composite mental functioning, life satisfaction and depressive symptomatology (ps<0.05). The intervention group had a significantly greater increment in quality-adjusted life years (p<0.02), which was achieved cost-effectively (US $41 218/UK £24 868 per unit). No intervention effect was found for cognitive functioning outcome measures.ConclusionsA lifestyle-oriented occupational therapy intervention has beneficial effects for ethnically diverse older people recruited from a wide array of community settings. Because the intervention is cost-effective and is applicable on a wide-scale basis, it has the potential to help reduce health decline and promote well-being in older people.Trial Registrationclinicaltrials.gov identifier: NCT0078634.

The activation of mononuclear muscle precursor cells after crush injury to mouse tibialis anterior muscles was monitored in vivo by in situ hybridization with MyoD1 and myogenin probes. These genes are early markers of skeletal muscle differentiation and have been extensively studied in vitro. The role in vivo of these regulatory proteins during myogenesis of mature muscle has not been studied previously. MyoD1 and myogenin mRNA were present in occasional mononuclear cells of uninjured muscle. Increased MyoD1 and myogenin mRNA sequences in mononuclear cells were detected as early as 6 h after injury, peaked between 24 and 48 h, and thereafter declined to pre-injury levels at about 8 days. The mRNAs were detected in mononuclear cells throughout the muscle, with the majority of cells located some distance from the site of crush injury. The presence of MyoD1 and myogenin mRNA at 6 to 48 h indicates that transcription of these genes is occurring at the same time as replication of muscle precursor cells in vivo. At no time were significant levels of mRNA for these genes detected in myotubes. MyoD1 and myogenin provide precise markers for the very early identification and study of mononuclear skeletal muscle precursor cells in muscle regenerating in vivo.

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Regional and age-related differences in the peripapillary and macular RNFL thickness should be considered when diagnosing and monitoring individuals with diseases that affect the RNFL.

Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy against amyloidogenesis is to minimize the populations of toxic oligomers and protofibrils by inhibiting protein aggregation with small molecules or nanoparticles. However, melanin synthesis in nature is realized by accelerated protein fibrillation to circumvent accumulation of toxic intermediates. Accordingly, we designed and demonstrated the use of star-shaped poly(2-hydroxyethyl acrylate) (PHEA) nanostructures for promoting aggregation while ameliorating the toxicity of human islet amyloid polypeptide (IAPP), the peptide involved in glycemic control and the pathology of type 2 diabetes. The binding of PHEA elevated the β-sheet content in IAPP aggregates while rendering a new morphology of “stelliform” amyloids originating from the polymers. Atomistic molecular dynamics simulations revealed that the PHEA arms served as rodlike scaffolds for IAPP binding and subsequently accelerated IAPP aggregation by increased local peptide concentration. The tertiary structure of the star nanoparticles was found to be essential for driving the specific interactions required to impel the accelerated IAPP aggregation. This study sheds new light on the structure–toxicity relationship of IAPP and points to the potential of exploiting star polymers as a new class of therapeutic agents against amyloidogenesis.

Background-Sudden Unexplained Death Syndrome (SUDS) is the leading cause of death in young, healthy, Southeast Asian men. The role of an implantable cardioverter defibrillator (ICD) for mortality reduction in these patients remains unclear. Methods and Results-The Defibrillator Versus ␤-Blockers for Unexplained Death in Thailand (DEBUT) study is a randomized, clinical trial conducted in 2 phases (pilot study followed by the main trial) to compare the annual all-cause mortality rates among SUDS patients treated with ␤-blockers versus that among those treated with an ICD. A total of 86 patients who were SUDS survivors and probable SUDS survivors were randomized to receive an ICD or propranolol (20 patients were in the pilot study and 66 were in the main trial). The primary end point was death from all causes. The secondary end point was recurrent ventricular tachycardia/ventricular fibrillation (VF) or cardiac arrest. During the 3-year follow-up period of the main trial, there were 4 deaths; all occurred in the ␤-blocker group (Pϭ0.02). Seven subjects in the ICD arm had recurrent VF, and all were effectively treated by the ICD. On the basis of the main trial results, the Data Safety Monitoring Board stopped the study. In total (both from the Pilot study and the main trial), there were 7 deaths (18%) in the ␤-blocker group and no deaths in the ICD group, but there were a total of 12 ICD patients receiving ICD discharges due to recurrent VF. Conclusions-ICD treatment provides full protection from death related to primary VF in a SUDS population and is superior to ␤-blockade treatment.

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