3.9 angstrom structure of the nucleosome core particle determined by phase-plate cryo-EM

The Volta phase plate is a recently developed electron cryo-microscopy (cryo-EM) device that enables contrast enhancement of biological samples. Here we have evaluated the potential of combining phase-plate imaging and single particle analysis to determine the structure of a small protein-DNA complex. To test the method, we made use of a 200 kDa Nucleosome Core Particle (NCP) reconstituted with 601 DNA for which a high-resolution X-ray crystal structure is known. We find that the phase plate provides a significant contrast enhancement that permits individual NCPs and DNA to be clearly identified in amorphous ice. The refined structure from 26,060 particles has an overall resolution of 3.9 angstrom and the density map exhibits structural features consistent with the estimated resolution, including clear density for amino acid side chains and DNA features such as the phosphate backbone. Our results demonstrate that phase-plate cryo-EM promises to become an important method to determine novel near-atomic resolution structures of small and challenging samples, such as nucleosomes in complex with nucleosome-binding factors

A randomized single blind crossover trial comparing leather and commercial wrist splints for treating chronic wrist pain in adults

<p>Abstract</p> <p>Background</p> <p>To compare the effectiveness of a custom-made leather wrist splint (LS) with a commercially available fabric splint (FS) in adults with chronic wrist pain.</p> <p>Methods</p> <p>Participants (N = 25, mean age = 54) were randomly assigned to treatment order in a 2-phase crossover trial. Splints were worn for 2 weeks, separated by a one-week washout period. Outcomes were assessed at baseline and after each splint phase using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Canadian Occupational Performance Measure (COPM) and Jamar dynamometer by an observer blinded to treatment allocation.</p> <p>Results</p> <p>Both styles of wrist splint significantly reduced pain (effect size LS 0.79, FS 0.43), improved hand function and increased grip strength compared to baseline (all p < 0.05) with no increase in wrist stiffness. There was a consistent trend for the LS to be superior to the FS but this was statistically significant only for patient perceived occupational performance (p = 0.008) and satisfaction (p = 0.015). Lastly, 72% of patients preferred the custom-made leather splint compared to the commercially available splint.</p> <p>Conclusion</p> <p>Leather wrist splints were superior to a commercially available fabric splint for the short-term relief of pain and dysfunction.</p

Joint Protection : enabling change in musculoskeletal conditions

Joint protection includes applying ergonomic principles in daily life, altering working methods, using assistive devices, and modifying environments. It is taught to people with musculoskeletal conditions, such as rheumatoid arthritis (RA), osteoarthritis (OA), and soft tissue rheumatisms. Common principles are to: distribute load over several joints; reduce effort using assistive devices; pace activities; use orthoses; and exercise regularly. Cognitive-behavioral, self-efficacy, and motor-learning approaches are employed. Trials demonstrate that using these approaches is significantly more effective than advice and demonstration alone in changing joint-protection behavior, improving self-efficacy, function, and reducing pain in both early and established RA and hand OA. There is still conflicting evidence for its effectiveness in soft-tissue rheumatisms

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes