48 research outputs found

    Peer support for patients with type 2 diabetes: cluster randomised controlled trial

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    Objective To test the effectiveness of peer support for patients with type 2 diabetes

    Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow

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    Vascular endothelium is a potential target for therapeutic intervention in diverse pathological processes, including inflammation, atherosclerosis, and thrombosis. By virtue of their intravascular topography, endothelial cells are exposed to dynamically changing mechanical forces that are generated by blood flow. In the present study, we investigated the interactions of negatively charged 2.7 nm and 4.7 nm CdTe quantum dots and 50 nm silica particles with cultured endothelial cells under regulated shear stress (SS) conditions. Cultured cells within the engineered microfluidic channels were exposed to nanoparticles under static condition or under low, medium, and high SS rates (0.05, 0.1, and 0.5 Pa, respectively). Vascular inflammation and associated endothelial damage were simulated by treatment with tumor necrosis factor-α (TNF-α) or by compromising the cell membrane with the use of low Triton X-100 concentration. Our results demonstrate that SS is critical for nanoparticle uptake by endothelial cells. Maximal uptake was registered at the SS rate of 0.05 Pa. By contrast, endothelial exposure to mild detergents or TNF-α treatment had no significant effect on nanoparticle uptake. Atomic force microscopy demonstrated the increased formation of actin-based cytoskeletal structures, including stress fibers and membrane ruffles, which have been associated with nanoparticle endocytosis. In conclusion, the combinatorial effects of SS rates, vascular endothelial conditions, and nanoparticle physical and chemical properties must be taken into account for the successful design of nanoparticle–drug conjugates intended for parenteral delivery

    The effects of 12 weeks’ resistance training on psychological parameters and quality of life in adults with Facioscapulohumeral, Becker, and Limb–girdle dystrophies

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    Purpose Investigate the impact of 12-weeks’ moderate-intensity resistance training on psychological parameters in ambulatory adults with Facioscapulohumeral, Becker, and Limb–girdle muscular dystrophy. Methods Seventeen adults with Facioscapulohumeral (n = 6), Limb–girdle (n = 6; types 2A, 2B, 2L, and 2I), or Becker (n = 5) muscular dystrophy took part. Participants were tested at baseline (PRE), after a 12-week control period (PRE2), and after a 12-week supervised resistance training programme (POST). Training included multi-joint and single-joint resistance exercises. Outcomes from self-report questionnaires were health-related quality of life, depressive symptoms, trait anxiety, self-esteem, and physical self-worth. Results No difference in outcome measures, except depressive symptoms, was found in the control period (PRE to PRE2). Symptoms of depression were reduced by 9% from PRE to PRE2 (p < 0.05) and by a further 19% from PRE2 to POST (p < 0.05). Other changes from PRE2 to POST were that trait anxiety reduced by 10%, self-esteem increased by 10%, physical self-worth increased by 20%, and quality of life improved in 8 domains (p < 0.05). Conclusion These findings demonstrate the positive impact of moderate-intensity resistance training on psychological health and quality of life in adults with Facioscapulohumeral, Becker, and Limb–girdle muscular dystrophies. Implications for rehabilitation Resistance training can have a positive impact on psychological health and quality of life in adults with Facioscapulohumeral, Becker, and Limb–girdle muscular dystrophy. Healthcare professionals should consider including moderate-intensity resistance training within the management and treatment programmes of adults with Facioscapulohumeral, Becker, and Limb–girdle muscular dystrophy

    Experimental study and multiscale modelling of the high temperature deformation of tempered martensite under multiaxial loading

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    peer-reviewedThe microstructural deformation of ex-service 9Cr-1Mo steel, with a tempered martensitic microstructure, has been examined in this study, through the combined use of electron backscatter diffraction (EBSD) and multiscale modelling techniques. Both the experimental and predicted deformation of the material at a notch root on a range of scales from the specimen level down to the microstructural block level are compared. A tension loaded notch specimen of the material which was extracted from an ex-service power plant pipe was used for this analysis. The deformation at the specimen level was quantified by analysis of the load displacement curves and notch opening displacement, which showed excellent agreement with the predicted results from the experimentally calibrated elastic-plastic finite-element model of the specimen geometry. The microstructural deformation was experimentally measured through the use of EBSD carried out at the notch root before and after high temperature mechanical testing. The initial orientation of the microstructure as well as the displacement around the boundary of the area of interest in the macroscale model were applied to a representative volume element (RVE) and a slip based crystal plasticity modelling framework was implemented to model the in-elastic deformation of the material under high temperature loading

    Response to the editorial by Dr Geraghty

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    This article is written in response to the linked editorial by Dr Geraghty about the adaptive Pacing, graded Activity and Cognitive behaviour therapy; a randomised Evaluation (PACE) trial, which we led, implemented and published. The PACE trial compared four treatments for people diagnosed with chronic fatigue syndrome. All participants in the trial received specialist medical care. The trial found that adding cognitive behaviour therapy or graded exercise therapy to specialist medical care was as safe as, and more effective than, adding adaptive pacing therapy or specialist medical care alone. Dr Geraghty has challenged these findings. In this article, we suggest that Dr Geraghty’s views are based on misunderstandings and misrepresentations of the PACE trial; these are corrected

    Daily functioning and self-management in patients with chronic low back pain after an intensive cognitive behavioral programme for pain management

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    Chronic low back pain (CLBP) is associated with persistent or recurrent disability which results in high costs for society. Cognitive behavioral treatments produce clinically relevant benefits for patients with CLBP. Nevertheless, no clear evidence for the most appropriate intervention is yet available. The purpose of this study is to evaluate the mid-term effects of treatment in a cohort of patients with CLBP participating in an intensive pain management programme. The programme provided by RealHealth-Netherlands is based on cognitive behavioral principles and executed in collaboration with orthopedic surgeons. Main outcome parameters were daily functioning (Roland and Morris Disability Questionnaire and Oswestry Disability Questionnaire), self-efficacy (Pain Self-Efficacy Questionnaire) and quality of life (Short Form 36 Physical Component Score). All parameters were measured at baseline, last day of residential programme and at 1 and 12 months follow-up. Repeated measures analysis was applied to examine changes over time. Clinical relevance was examined using minimal clinical important differences (MCID) estimates for main outcomes. To compare results with literature effect sizes (Cohen’s d) and Standardized Morbidity Ratios (SMR) were determined. 107 patients with CLBP participated in this programme. Mean scores on outcome measures showed a similar pattern: improvement after residential programme and maintenance of results over time. Effect sizes were 0.9 for functioning, 0.8 for self-efficacy and 1.3 for physical functioning related quality of life. Clinical relevancy: 79% reached MCID on functioning, 53% on self-efficacy and 80% on quality of life. Study results on functioning were found to be 36% better and 2% worse when related to previous research on, respectively, rehabilitation programmes and spinal surgery for similar conditions (SMR 136 and 98%, respectively). The participants of this evidence-based programme learned to manage CLBP, improved in daily functioning and quality of life. The study results are meaningful and comparable with results of spinal surgery and even better than results from less intensive rehabilitation programmes

    CD1a promotes systemic manifestations of skin inflammation

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    Inflammatory skin conditions are increasingly recognised as being associated with systemic inflammation. The mechanisms connecting the cutaneous and systemic disease are not well understood. CD1a is a virtually monomorphic major histocompatibility complex (MHC) class I-like molecule, highly expressed by skin and mucosal Langerhans cells, and presents lipid antigens to T-cells. Here we show an important role for CD1a in linking cutaneous and systemic inflammation in two experimental disease models. In human CD1a transgenic mice, the toll-like receptor (TLR)7 agonist imiquimod induces more pronounced splenomegaly, expansion of the peripheral blood and spleen T cell compartments, and enhanced neutrophil and eosinophil responses compared to the wild-type, accompanied by elevated skin and plasma cytokine levels, including IL-23, IL-1α, IL-1β, MCP-1 and IL-17A. Similar systemic escalation is shown in MC903-induced skin inflammation. The exacerbated inflammation could be counter-acted by CD1a-blocking antibodies, developed and screened in our laboratories. The beneficial effect is epitope dependent, and we further characterise the five best-performing antibodies for their capacity to modulate CD1a-expressing cells and ameliorate CD1a-dependent systemic inflammatory responses. In summary, we show that a therapeutically targetable CD1a-dependent pathway may play a role in the systemic spread of cutaneous inflammation
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