Controlling Surface Topology and Functionality of Electrospun Fibers using Amphiphilic Block Copolymers to Direct Mesenchymal Progenitor Cell Adhesion

Surface patterning in three dimensions is of great importance in biomaterials design for controlling cell behavior. A facile one-step functionalization of biodegradable PDLLA fibers using amphiphilic diblock copolymers is demonstrated here, to systematically vary the fiber surface composition. The copolymers comprise a hydrophilic poly[oligo(ethylene glycol) methacrylate] (POEGMA), poly[(2-methacryloyloxy)ethyl phosphorylcholine] (PMPC) or poly[2-(dimethylamino)ethyl methacrylate)] (PDMAEMA) block and a hydrophobic poly(L-lactide) (PLA) block. The block copolymer modified fibers have increased surface hydrophilicity compared to PDLLA fibers. Mixtures of PLA-PMPC and PLA-POEGMA copolymers are utilized to exploit micro-phase separation of the incompatible hydrophilic PMPC and POEGMA blocks at the fiber surface. Conjugation of an RGD cell-adhesive peptide to one hydrophilic block (POEGMA) using thiol-ene chemistry produces fibers with domains of cell-adhesive (POEGMA) and cell-inert (PMPC) sites, mimicking the adhesive properties of the extracellular matrix (ECM). Human mesenchymal progenitor cells (hES-MPs) showed much better adhesion to the fibers with surface adhesive heterogeneity, compared to fibers with only adhesive or only inert surface chemistries

Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population

BACKGROUND: Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs) might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI) in patients. METHODS: We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year. RESULTS: Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95–1.21). However, we found that the relative risk (RR) of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00–1.48). The corresponding RR was 1.34 (95% CI, 1.06–1.70) for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01–1.65). The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47–1.62) with naproxen to 1.38 (95% CI, 1.00–1.90) with diclofenac. CONCLUSION: This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs

The differential hormonal milieu of morning versus evening, may have an impact on muscle hypertrophic potential

Substantial gains in muscle strength and hypertrophy are clearly associated with the routine performance of resistance training. What is less evident is the optimal timing of the resistance training stimulus to elicit these significant functional and structural skeletal muscle changes. Therefore, this investigation determined the impact of a single bout of resistance training performed either in the morning or evening upon acute anabolic signalling (insulin-like growth factor-binding protein-3 (IGFBP-3), myogenic index and differentiation) and catabolic processes (cortisol). Twenty-four male participants (age 21.4±1.9yrs, mass 83.7±13.7kg) with no sustained resistance training experience were allocated to a resistance exercise group (REP). Sixteen of the 24 participants were randomly selected to perform an additional non-exercising control group (CP) protocol. REP performed two bouts of resistance exercise (80% 1RM) in the morning (AM: 0800 hrs) and evening (PM: 1800 hrs), with the sessions separated by a minimum of 72 hours. Venous blood was collected immediately prior to, and 5 min after, each resistance exercise and control sessions. Serum cortisol and IGFBP-3 levels, myogenic index, myotube width, were determined at each sampling period. All data are reported as mean ± SEM, statistical significance was set at P≤0.05. As expected a significant reduction in evening cortisol concentration was observed at pre (AM: 98.4±10.5, PM: 49.8±4.4 ng/ml, P0.05). Timing of resistance training regimen in the evening appears to augment some markers of hypertrophic potential, with elevated IGFBP-3, suppressed cortisol and a superior cellular environment. Further investigation, to further elucidate the time course of peak anabolic signalling in morning vs evening training conditions, are timely

Review for the generalist: evaluation of anterior knee pain

Anterior knee pain is common in children and adolescents. Evaluation and management is challenging and requires a thorough history and physical exam, and understanding of the pediatric skeleton. This article will review common causes of chronic anterior knee pain in the pediatric population with a focus on patellofemoral pain

The BSR-PsA:study protocol for the British Society for Rheumatology psoriatic arthritis register

Acknowledgements We acknowledge contribution of BSR-PsA study staff, under the supervision of KFK: Maureen Heddle, Barry Morris, Jonathan Lock and Jane Brady. We also acknowledge the support from the Centre for Healthcare Randomised Trials (CHaRT) at the University of Aberdeen, especially Mark Forrest and Brian Taylor, for database and IT support. We would like to thank Professor Iain McInnes from the University of Glasgow, and our International Advisory Committee (Professors Merete Hetland, Oliver Fitzgerald and Philip Mease), for their comments when developing the protocol and for advice in harmonising data collection with other international studies, and the staff at the British Society for Rheumatology, in particular Alan Roach, Ross Matthews, Chris Hiley and Debbie MacDonald. Finally, we are indebted to the staff at all participating NHS trusts (details of which are available from www.abdn.ac.uk/bsr-psa) and especially the NIHR Clinical Research Network research nurses for their assistance with participant recruitment and data collection. Funding The BSR-PsA is funded by the BSR as part of its rheumatology registers portfolio and, in turn, receives funding for this from pharmaceutical companies. At the time of publication, only Amgen (previously Celgene) have contributed to the funding of the BSR-PsA. Pharmaceutical companies providing funds to BSR do not participant in the conduct or oversight of the study. However, they do receive advance notice of publications on which they are able to comment. Companies contributing to the funding of the register can request anonymised data on clinically confirmed serious adverse events and some events of special interest (e.g. pregnancy) among participants prescribed the specific bDMARD or tsDMARD agents that they manufacture. Other than this information, they do not have access to any raw data. They may, however, request specific analyses to be performed, for which a pre-specific analysis plan is discussed, and additional funds are provided.Peer reviewedPublisher PD

A pilot randomised controlled trial investigating a mindfulness-based stress reduction (MBSR) intervention in individuals with pulmonary arterial hypertension (PAH): the PATHWAYS study

Background: Pulmonary arterial hypertension (PAH) is an uncommon condition with progressive heart failure and premature death. Treatment costs up to £120,000 per patient per year, and the psychological burden of PAH is substantial. Mindfulness-based stress reduction (MBSR) is an intervention with the potential to reduce this burden, but to date, it has not been applied to people with pulmonary hypertension. We wished to determine whether a trial of MBSR for people with PAH would be feasible. Methods: A customised gentle MBSR programme of eight sessions was developed for people with physical disability due to PAH, and they were randomised to group-based MBSR or treatment as usual. The completeness of outcome measures including Beck Anxiety Index, Beck Depression Inventory and standard physical assessment at 3 months after randomisation were recorded. Health care utilisation was measured. Attendance at the sessions and the costs involved in delivering the intervention were assessed. Semi-structured interviews were conducted to explore the acceptability of the MBSR intervention and when appropriate the reasons for trial non-participation. Results: Fifty-two patients were recruited, but only 34 were randomised due to patients finding it difficult to travel to sessions. Twenty-two completed all questionnaires and attended all clinics, both routine and additional in order to collect outcomes measures. The MSBR sessions were delivered in Bristol, Cardiff and London, costing, on average, between £2234 (Cardiff) and £4128 (London) per patient to deliver. Attendance at each session averaged between two patients in Bristol and Cardiff and three in London. For those receiving treatment as usual, clinician blinding was achievable. Interviews revealed that people who attended MBSR found it interesting and helpful in managing their symptoms and minimising the psychological component of their disease. Conclusions: We found that attendance at group MBSR was poor in people with chronic PAH within the context of a trial. Achieving better MBSR intervention attendance or use of an Internet-based programme might maximise the benefit of MBSR

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT

Background: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. Objective: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? Design: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. Settings: Glasgow, UK, and Melbourne, Australia. Participants: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. Interventions: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. Main outcome measures: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. Results: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference –4.29, 95% confidence interval –7.29 to –1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. Limitations: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. Conclusions: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible

Weight-loss and exercise for communities with arthritis in North Carolina (we-can): design and rationale of a pragmatic, assessor-blinded, randomized controlled trial

Background: Recently, we determined that in a rigorously monitored environment an intensive diet-induced weight loss of 10% combined with exercise was significantly more effective at reducing pain in men and women with symptomatic knee osteoarthritis (OA) than either intervention alone. Compared to previous long-term weight loss and exercise trials of knee OA, our intensive diet-induced weight loss and exercise intervention was twice as effective at reducing pain intensity. Whether these results can be generalized to less intensively monitored cohorts is unknown. Thus, the policy relevant and clinically important question is: Can we adapt this successful solution to a pervasive public health problem in real-world clinical and community settings? This study aims to develop a systematic, practical, cost-effective diet-induced weight loss and exercise intervention implemented in community settings and to determine its effectiveness in reducing pain and improving other clinical outcomes in persons with knee OA. Methods/Design: This is a Phase III, pragmatic, assessor-blinded, randomized controlled trial. Participants will include 820 ambulatory, community-dwelling, overweight and obese (BMI ≥ 27 kg/m2) men and women aged ≥ 50 years who meet the American College of Rheumatology clinical criteria for knee OA. The primary aim is to determine whether a community-based 18-month diet-induced weight loss and exercise intervention based on social cognitive theory and implemented in three North Carolina counties with diverse residential (from urban to rural) and socioeconomic composition significantly decreases knee pain in overweight and obese adults with knee OA relative to a nutrition and health attention control group. Secondary aims will determine whether this intervention improves self-reported function, health-related quality of life, mobility, and is cost-effective. Discussion: Many physicians who treat people with knee OA have no practical means to implement weight loss and exercise treatments as recommended by numerous OA treatment guidelines. This study will establish the effectiveness of a community program that will serve as a blueprint and exemplar for clinicians and public health officials in urban and rural communities to implement a diet-induced weight loss and exercise program designed to reduce knee pain and improve other clinical outcomes in overweight and obese adults with knee OA