Outgroup, alignment and modelling improvements indicate that two TNFSF13-like genes existed in the vertebrate ancestor

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Characterisation of the TNF superfamily members CD40L and BAFF in the small-spotted catshark (Scyliorhinus canicula)

The tumour necrosis factor superfamily (TNFSF) members CD40L and BAFF play critical roles in mammalian B cell survival, proliferation and maturation, however little is known about these key cytokines in the oldest jawed vertebrates, the cartilaginous fishes. Here we report the cloning of CD40L and BAFF orthologues (designated ScCD40L and ScBAFF) in the small-spotted catshark (Scyliorhinus canicula). As predicted both proteins are type II membrane-bound proteins with a TNF homology domain in their extracellular region and both are highly expressed in shark immune tissues. ScCD40L transcript levels correlate with those of TCRα and transcription of both genes is modulated in peripheral blood leukocytes following in vitro stimulation. Although a putative CD40L orthologue was identified in the elephant shark genome the work herein is the first molecular characterisation and transcriptional analysis of CD40L in a cartilaginous fish. ScBAFF was also cloned and its transcription characterised in an attempt to resolve the discrepancies observed between spiny dogfish BAFF and bamboo shark BAFF in previously published studies

Organized B cell sites in cartilaginous fishes reveal the evolutionary foundation of germinal centers

The absence of germinal centers (GCs) in cartilaginous fishes lies at odds with data showing that nurse sharks can produce robust antigen-specific responses and affinity mature their B cell repertoires. To investigate this apparent incongruity, we performed RNA sequencing on single nuclei, allowing us to characterize the cell types present in the nurse shark spleen, and RNAscope to provide in situ cellular resolution of key marker gene expression following immunization with R-phycoerythrin (PE). We tracked PE to the splenic follicles where it co-localizes with CXCR5high centrocyte-like B cells and a population of putative T follicular helper (Tfh) cells, surrounded by a peripheral ring of Ki67+ AID+ CXCR4+ centroblast-like B cells. Further, we reveal selection of mutations in B cell clones dissected from these follicles. We propose that the B cell sites iden tified here represent the evolutionary foundation of GCs, dating back to the jawed vertebrate ancestor

Normative values for the Foot Posture Index

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Training the next generation of clinical researchers: Evaluation of a graduate podiatrist research internship in rheumatology

Background: The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors. Methods: Nine new graduates completed the internship programme (July 2006-June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes. Results: Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent 'Jewel in the Crown' award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees. Seven important themes arose from the qualitative phases: perceptions of the internship pre-application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme. Conclusions: The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales

A survey of foot orthoses prescription habits amongst podiatrists in the UK, Australia and New Zealand

Background: Foot orthoses are frequently used but little is known about which types are used in contemporary practice. This study aimed to explore the types of foot orthoses currently used by podiatrists and the prescription variations in a range of conditions. Methods: A web-based, cross-sectional survey was distributed through professional bodies in the United Kingdom (UK), Australia, and New Zealand. Questions focussed on foot orthosis prescription habits in relation to 26 conditions affecting the back and lower limb. Results: Two hundred and sixty-four podiatrists practising in 19 different countries completed the survey; the majority practised in the UK (47%, n=124), Australia (30%, n=79) and New Zealand (12%, n=32). Respondents qualified between 1968 and 2016, and 147 (56%) were female. Respondents worked in different healthcare sectors and this varied between countries: 42 (34%) respondents in the UK worked solely in the public sector, compared to 3 (4%) in Australia and 2 (6%) in New Zealand. Forty-four (35%) respondents in the UK worked solely in private practice, compared to 64 (81%) in Australia and 14 (44%) in New Zealand. UK respondents prescribed more prefabricated orthoses per week (mean 5.5 pairs) than simple insole-type devices (±2.7) and customised devices (±2.9). Similarly, respondents in New Zealand prescribed more prefabricated orthoses per week (±7.7) than simple (±1.4) and customised (±2.8) devices. In contrast, those in Australia prescribed more customised orthoses per week (±4.4) than simple (±0.8) and prefabricated (±1.9) orthoses. Differences in the types of orthoses prescribed were observed between country of practice, working sector, and the condition targeted. Generally, prefabricated orthoses were commonly prescribed for the 26 highlighted conditions in the UK and New Zealand. Australian podiatrists prescribed far fewer devices overall, but when they did prescribe, they were more likely to prescribe custom devices. Respondents in all three countries were more likely to prescribe customised orthoses for people with diabetes complicated by peripheral neuropathy than for diabetes without this complication. Conclusions: Foot orthosis prescription habits vary between countries. Prefabricated orthoses were frequently prescribed in the UK and New Zealand, and customised orthoses in Australia. Prescriptions for people with diabetes differed depending on the presence of neuropathy, despite a lack of robust evidence supporting these decisions. This study provides new insight into contemporary practice

Foot orthoses in the treatment of symptomatic midfoot osteoarthritis using clinical and biomechanical outcomes: a randomised feasibility study.

Objectives: This randomised feasibility study aimed to examine the clinical and biomechanical effects of functional foot orthoses (FFO) in the treatment of midfoot osteoarthritis (OA) and the feasibility of conducting a full randomised-controlled trial. Methods: Participants with painful, radiographically confirmed midfoot OA were recruited and randomised to receive either FFO or a sham control orthosis. Feasibility measures included recruitment and attrition rates, practicality of blinding and adherence rates. Clinical outcome measures were change from baseline to 12 weeks for severity of pain (numerical rating scale), foot function (Manchester Foot Pain and Disability Index) and patient global impression of change scale. To investigate the biomechanical effect of foot orthoses, in-shoe foot kinematics and plantar pressures were evaluated at 12 weeks. Results: Of the 119 participants screened, 37 were randomised and 33 completed the study (FFO=18, sham=15). Compliance with foot orthoses and blinding of the intervention was achieved in three-quarters of the group. Both groups reported improvements in pain, function and global impression of change; the FFO group reporting greater improvements compared to the sham group. The biomechanical outcomes indicated the FFO group inverted the hindfoot and increased midfoot maximum plantar force compared to the sham group. Conclusions: The present findings suggest FFOs worn over 12 weeks may provide detectable clinical and biomechanical benefits compared to sham orthoses. This feasibility study provides useful clinical, biomechanical and statistical information for the design and implementation of a definitive randomised-controlled trial to evaluate the effectiveness of FFO in treating painful midfoot OA

Medial longitudinal arch development of school children : The College of Podiatry Annual Conference 2015: meeting abstracts

Background Foot structure is often classified into flat foot, neutral and high arch type based on the variability of the Medial Longitudinal Arch (MLA). To date, the literature provided contrasting evidence on the age when MLA development stabilises in children. The influence of footwear on MLA development is also unknown. Aim This study aims to (i) clarify whether the MLA is still changing in children from age 7 to 9 years old and (ii) explore the relationship between footwear usage and MLA development, using a longitudinal approach. Methods We evaluated the MLA of 111 healthy school children [age = 6.9 (0.3) years] using three parameters [arch index (AI), midfoot peak pressure (PP) and maximum force (MF: % of body weight)] extracted from dynamic foot loading measurements at baseline, 10-month and 22-month follow-up. Information on the type of footwear worn was collected using survey question. Linear mixed modelling was used to test for differences in the MLA over time. Results Insignificant changes in all MLA parameters were observed over time [AI: P = .15; PP: P = .84; MF: P = .91]. When gender was considered, the AI of boys decreased with age [P = .02]. Boys also displayed a flatter MLA than girls at age 6.9 years [AI: mean difference = 0.02 (0.01, 0.04); P = .02]. At baseline, subjects who wore close-toe shoes displayed the lowest MLA overall [AI/PP/MF: P < .05]. Subjects who used slippers when commencing footwear use experienced higher PP than those who wore sandals [mean difference = 31.60 (1.44, 61.75) kPa; post-hoc P = .04]. Discussion and conclusion Our findings suggested that the MLA of children remained stable from 7 to 9 years old, while gender and the type of footwear worn during childhood may influence MLA development. Clinicians may choose to commence therapy when a child presents with painful flexible flat foot at age 7 years, and may discourage younger children from wearing slippers when they commence using footwear

Interpreting outcome following foot surgery in people with rheumatoid arthritis

BACKGROUND: Foot surgery is common in RA but the current lack of understanding of how patients interpret outcomes inhibits evaluation of procedures in clinical and research settings. This study aimed to explore which factors are important to people with RA when they evaluate the outcome of foot and ankle surgery. METHODS AND RESULTS: Semi structured interviews with 11 RA participants who had mixed experiences of foot surgery were conducted and analysed using thematic analysis. Responses showed that while participants interpreted surgical outcome in respect to a multitude of factors, five major themes emerged: functional ability, participation, appearance of feet and footwear, surgeons' opinion, and pain. Participants interpreted levels of physical function in light of other aspects of their disease, reflecting on relative change from their preoperative state more than absolute levels of ability. Appearance was important to almost all participants: physical appearance, foot shape, and footwear were closely interlinked, yet participants saw these as distinct concepts and frequently entered into a defensive repertoire, feeling the need to justify that their perception of outcome was not about cosmesis. Surgeons' post-operative evaluation of the procedure was highly influential and made a lasting impression, irrespective of how the outcome compared to the participants' initial goals. Whilst pain was important to almost all participants, it had the greatest impact upon them when it interfered with their ability to undertake valued activities. CONCLUSIONS: People with RA interpret the outcome of foot surgery using multiple interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than anticipated. These factors can help clinicians in discussing surgical options in patients