Strengthening and stretching for rheumatoid arthritis of the hand (SARAH). A randomised controlled trial and economic evaluation

Study registration: Current Controlled Trials ISRCTN 89936343.Background - The effectiveness of exercise for improving hand and wrist function in people with rheumatoid arthritis (RA) is uncertain. Objectives - The study aims were (1) to estimate the clinical effectiveness and cost-effectiveness of adding an optimised exercise programme for hands and upper limbs to standard care for patients with RA; and (2) to qualitatively describe the experience of participants in the trial with a particular emphasis on acceptability of the intervention, exercise behaviours and reasons for adherence/non-adherence.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 19. See the NIHR Journals Library website for further project information. This report has been developed in association with the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford and the NIHR Biomedical Research Unit Funding Scheme. This project benefited from facilities funded through Birmingham Science City Translational Medicine Clinical Research and Infrastructure Trials Platform, with support from Advantage West Midlands

Flotillin microdomains interact with the cortical cytoskeleton to control uropod formation and neutrophil recruitment

The association between flotillin microdomains and the cortical cytoskeleton controls myosin IIa activation and neutrophil chemotaxis

Flotillins Interact with PSGL-1 in Neutrophils and, upon Stimulation, Rapidly Organize into Membrane Domains Subsequently Accumulating in the Uropod

BACKGROUND: Neutrophils polarize and migrate in response to chemokines. Different types of membrane microdomains (rafts) have been postulated to be present in rear and front of polarized leukocytes and disruption of rafts by cholesterol sequestration prevents leukocyte polarization. Reggie/flotillin-1 and -2 are two highly homologous proteins that are ubiquitously enriched in detergent resistant membranes and are thought to shape membrane microdomains by forming homo- and hetero-oligomers. It was the goal of this study to investigate dynamic membrane microdomain reorganization during neutrophil activation. METHODOLOGY/PRINCIPAL FINDINGS: We show now, using immunofluorescence staining and co-immunoprecipitation, that endogenous flotillin-1 and -2 colocalize and associate in resting spherical and polarized primary neutrophils. Flotillins redistribute very early after chemoattractant stimulation, and form distinct caps in more than 90% of the neutrophils. At later time points flotillins accumulate in the uropod of polarized cells. Chemotactic peptide-induced redistribution and capping of flotillins requires integrity and dynamics of the actin cytoskeleton, but does not involve Rho-kinase dependent signaling related to formation of the uropod. Both flotillin isoforms are involved in the formation of this membrane domain, as uropod location of exogenously expressed flotillins is dramatically enhanced by co-overexpression of tagged flotillin-1 and -2 in differentiated HL-60 cells as compared to cells expressing only one tagged isoform. Flotillin-1 and -2 associate with P-selectin glycoprotein ligand 1 (PSGL-1) in resting and in stimulated neutrophils as shown by colocalization and co-immunoprecipitation. Neutrophils isolated from PSGL-1-deficient mice exhibit flotillin caps to the same extent as cells isolated from wild type animals, implying that PSGL-1 is not required for the formation of the flotillin caps. Finally we show that stimulus-dependent redistribution of other uropod-located proteins, CD43 and ezrin/radixin/moesin, occurs much slower than that of flotillins and PSGL-1. CONCLUSIONS/SIGNIFICANCE: These results suggest that flotillin-rich actin-dependent membrane microdomains are importantly involved in neutrophil uropod formation and/or stabilization and organize uropod localization of PSGL-1

Caffeine taste signaling in drosophila larvae

The Drosophila larva has a simple peripheral nervous system with a comparably small number of sensory neurons located externally at the head or internally along the pharynx to assess its chemical environment. It is assumed that larval taste coding occurs mainly via external organs (the dorsal, terminal, and ventral organ). However, the contribution of the internal pharyngeal sensory organs has not been explored. Here we find that larvae require a single pharyngeal gustatory receptor neuron pair called D1, which is located in the dorsal pharyngeal sensilla, in order to avoid caffeine and to associate an odor with caffeine punishment. In contrast, caffeine-driven reduction in feeding in non-choice situations does not require D1. Hence, this work provides data on taste coding via different receptor neurons, depending on the behavioral context. Furthermore, we show that the larval pharyngeal system is involved in bitter tasting. Using ectopic expressions, we show that the caffeine receptor in neuron D1 requires the function of at least four receptor genes: the putative co-receptors Gr33a, Gr66a, the putative caffeine-specific receptor Gr93a, and yet unknown additional molecular component(s). This suggests that larval taste perception is more complex than previously assumed already at the sensory level. Taste information from different sensory organs located outside at the head or inside along the pharynx of the larva is assembled to trigger taste guided behaviors

Strengthening and stretching for rheumatoid arthritis of the hand (SARAH):Design of a randomised controlled trial of a hand and upper limb exercise intervention-ISRCTN89936343

Background: Rheumatoid Arthritis (RA) commonly affects the hands and wrists with inflammation, deformity, pain, weakness and restricted mobility leading to reduced function. The effectiveness of exercise for RA hands is uncertain, although evidence from small scale studies is promising. The Strengthening And Stretching for Rheumatoid Arthritis of the Hand (SARAH) trial is a pragmatic, multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of adding an optimised exercise programme for hands and upper limbs to best practice usual care for patients with RA.Methods/design: 480 participants with problematic RA hands will be recruited through 17 NHS trusts. Treatments will be provided by physiotherapists and occupational therapists. Participants will be individually randomised to receive either best practice usual care (joint protection advice, general exercise advice, functional splinting and assistive devices) or best practice usual care supplemented with an individualised exercise programme of strengthening and stretching exercises. The study assessors will be blinded to treatment allocation and will follow participants up at four and 12 months. The primary outcome measure is the Hand function subscale of the Michigan Hand Outcome Questionnaire, and secondary outcomes include hand and wrist impairment measures, quality of life, and resource use. Economic and qualitative studies will also be carried out in parallel.Discussion: This paper describes the design and development of a trial protocol of a complex intervention study based in therapy out-patient departments. The findings will provide evidence to support or refute the use of an optimised exercise programme for RA of the hand in addition to best practice usual care.Trial registration: Current Controlled Trials ISRCTN89936343Keywords: Randomised controlled trial, Rheumatoid arthritis, Exercise, Hand, Rehabilitatio

In-vitro Wear Analysis of 3-Dimensionally Printed Splint Material

Objective: While many manufacturing methods exist, information lacks regarding 3D printed occlusal splint materials. The purpose of this study is to compare 2 body wear properties of 3D printed splint resins. Two commercially available splint resins and a conventional polypropylene material (control) were subject to wear in a chewing simulator. Methods: The 3D printed resins, KEY (KeyPrint® KeySplint Hard®; Keystone Industries) and VERI (VeriSPLINT OS 3D; WhipMix), were printed according to manufacturing criteria and the polypropylene thermoform, FORM (PRO-FORM; Keystone Industries), was excised from a square sample into 10 mm diameter discs with 5 mm height. The discs were embedded in an aluminum housing using an auto-mixed two-part methacrylate ester (Integrity; Dentsply). A total of 18 specimens were prepared (n=6) and subjected to artificial aging in a chewing simulator (CS-4.2/SD Mechatronic/Germany) for 120,000 cycles at 25 °C under a 50 N load with a round, steel tipped 1 mm diameter antagonist. All samples were mapped with a laser scanner (E4D; 3Shape) before and after mechanical aging. Volumetric wear data was quantified using Geomagic 2023.1 (3D Systems) and analyzed using single factor ANOVA with Tukey post-hoc tests (����꞊0.05). The null hypothesis is that all materials exhibit the same wear. Results: VERI presented with the lowest average volumetric loss due to wear (​​0.5736 ±0.33 mm3) followed by FORM (0.9473 ±0.18 mm3) and then KEY (1.838 ±0.42 mm3). Single factor ANOVA yielded a p-value=0.00002 with Tukey HSD determining no statistically significant difference between VERI and FORM. Among the commercially available 3D printed resins tested in this study, the data suggests VERI had significantly lower wear patterns. Conclusion: The null hypothesis was rejected because the VeriSPLINT OS 3D and the PRO-FORM splint material exhibited statistically significant lower volumetric wear than the KeySplint Hard

Student Community Outreach for Public Education: A Year in Review

As former leaders of SCOPE (Student Community Outreach for Public Education) we would like to take time to highlight our positive impact and the extent of our outreach in the Bay Area over the last two years. Our goal is to reflect on and illustrate major challenges returning to ‘normal’ in-person community outreach events following the height of Covid-19. Furthermore, we would like to recapitulate all of the events we accomplished for the term we served as leaders of this student organization. Our main objective is to capture the breadth of communities that we reached last year through a diverse range of ages, cultures, backgrounds, living circumstances, and abilities. As students, finding the time and means in our schedules to dedicate to community outreach has become increasingly difficult. We hope that by presenting on SCOPE’s wide range of accomplishments we can help revitalize the support surrounding student outreach and the impact of oral health education in our surrounding communities. We think that presenting to our peers and faculty during Excellence Day is an important part of maintaining SCOPE’s presence at the school as we look to graduation, and leave the club for students to come. We would like to acknowledge and thank Professor Miller for her mentorship and guidance throughout the term of our leadership and beyond