The 2nd United Kingdom Extracellular Vesicle Forum Meeting Abstracts

The UK Extracellular Vesicles (UKEV) Forum meetings were born of the realization that there were a number of UK laboratories studying extracellular vesicle biology and using similar techniques but without a regular national meeting dedicated to EVs at which to share their findings. This was compounded by the fact that many of these labs were working in different fields and thus networking and sharing of ideas and best practice was sometimes difficult. The first workshop was organized in 2013 by Dr Charlotte Lawson, under the auspices of the Society for Endocrinology, led to the founding of the UKEV Forum and the organization of a British Heart Foundation sponsored 1-day conference held in London in December 2014. Although growing in size every year, the central aims of these workshops have remained the same: to provide a forum for discussion and exchange of ideas, to allow young scientists to present their data in the form of short talks and poster presentations and to discuss their work with more established scientists in the field. Here we include the presented abstracts for the 2015 1-day conference hosted by Cardiff University. This meeting was attended by approximately 130 delegates throughout the United Kingdom, but also attended by delegates from Belgium, Netherlands, France, Ireland and other nations. The day composed of plenary presentations from Prof Matthias Belting, Lund University, Sweden and Dr Guillaume van Niel, Institut Curie, Paris together with 10 short presentations from submitted abstracts. The topics covered were broad, with sessions on Mechanisms of EV production, EVs in Infection, EVs in Cancer and in Blood and Characterizing EVs in Biological fluids. This hopefully gives a reflection of the range of EV-related studies being conducted currently in the UK. There were also 33 poster presentations equally broad in subject matter. The organizers are grateful to the Life Science Research Network Wales – a Welsh government-funding scheme that part-sponsored the conference. We are also grateful to commercial sponsors, and 3 paid-presentations are included in the abstracts. The UK EV Forum is expected to become an established annual event held at different Universities across the UK and continue to attract increasing delegate numbers and abstract submissions. We look forward to the next planned conference, which will be hosted by David Carter and his colleagues at Oxford Brookes University on 13th December 2016

Microvesicles and exosomes: new players in metabolic and cardiovascular disease

The past decade has witnessed an exponential increase in the number of publications referring to extracellular vesicles (EVs). For many years considered to be extracellular debris, EVs are now seen as novel mediators of endocrine signalling via cell-to-cell communication. With the capability of transferring proteins and nucleic acids from one cell to another, they have become an attractive focus of research for different pathological settings and are now regarded as both mediators and biomarkers of disease including cardio-metabolic disease. They also offer therapeutic potential as signalling agents capable of targeting tissues or cells with specific peptides or miRNAs. In this review, we focus on the role that microvesicles (MVs) and exosomes, the two most studied classes of EV, have in diabetes, cardiovascular disease, endothelial dysfunction, coagulopathies, and polycystic ovary syndrome. We also provide an overview of current developments in MV/exosome isolation techniques from plasma and other fluids, comparing different available commercial and non-commercial methods. We describe different techniques for their optical/biochemical characterization and quantitation. We also review the signalling pathways that exosomes and MVs activate in target cells and provide some insight into their use as biomarkers or potential therapeutic agents. In summary, we give an updated focus on the role that these exciting novel nanoparticles offer for the endocrine community

Equine-assisted psychotherapy in New Zealand : a phenomenological investigation : presented in fulfilment of the requirements for the degree of Masters of Arts in Psychology at Massey University, Albany Campus, New Zealand

This study explores the experiences of two New Zealanders who have undertaken a course of equine-assisted psychotherapy in New Zealand. Using the method of Interpretative Phenomenological Analysis, two participants were interviewed. It was concluded that through the therapy, the participants experienced a process of transformation into a new self, a theme composed of transformation, and a new way of thinking and being. The experienced the therapy as fundamentally different from, but complementary to, traditional therapy. Their experiences were grounded in the real world and real experience, a theme that was made up of the natural environment facilitating different conversations; the experiences with the horses making the therapy real and meaningful; and hands-on, in-the-moment activity. The participants experiences with the horses, and of therapy, was spiritual and beyond explanation, a theme that showed their experiences were spiritual and meaningful, beyond explanation, and that the horses embodied symbolic representations. One participant became a convert and an advocate and this theme was composed of overcoming negative preconceptions, a positive experience, and becoming an advocate for its use. These themes and experiences were supported by the literature and provide insight into how and why equine-assisted psychotherapy is an effective therapeutic intervention

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Declines in violence and police arrest among female sex workers in Karnataka state, south India, following a comprehensive HIV prevention programme.

INTRODUCTION: Female sex workers (FSWs) frequently experience violence, harassment and arrest by the police or their clients, but there is little evidence as to the impact that such factors may have on HIV risk or whether community interventions could mitigate this impact. METHODS: As part of the evaluation of the Avahan programme in Karnataka, serial integrated behavioural and biological assessment (IBBA) surveys (four districts) (2005 to 2011) and anonymous polling booth surveys (PBS) (16 districts) (2007 to 2011) were conducted with random samples of FSWs. Logistic regression analysis was used to assess 1) changes in reported violence and arrests over time and 2) associations between violence by non-partners and police arrest and HIV/STI risk and prevalence. Mediation analysis was used to identify mediating factors. RESULTS: 5,792 FSWs participated in the IBBAs and 15,813 participated in the PBS. Over time, there were significant reductions in the percentages of FSWs reporting being raped in the past year (PBS) (30.0% in 2007, 10.0% in 2011, p<0.001), being arrested in the past year [adjusted odds ratio (AOR) 0.57 (0.35, 0.93), p=0.025] and being beaten in the past six months by a non-partner (clients, police, pimps, strangers, rowdies) [AOR 0.69 (0.49, 0.95), p=0.024)] (IBBA). The proportion drinking alcohol (during the past week) also fell significantly (32.5% in 2005, 24.9% in 2008, 16.8% in 2011; p<0.001). Violence by non-partners (being raped in the past year and/or beaten in the past six months) and being arrested in the past year were both strongly associated with HIV infection [AOR 1.59 (1.18, 2.15), p=0.002; AOR 1.91 (1.17, 3.12), p=0.01, respectively]. They were also associated with drinking alcohol (during the past week) [AOR 1.98 (1.54, 2.53), p<0.001; AOR 2.79 (1.93, 4.04), p<0.001, respectively], reduced condom self-efficacy with clients [AOR 0.36 (0.27, 0.47), p<0.001; AOR 0.62 (0.39, 0.98), p=0.039, respectively], symptomatic STI (during the past year) [AOR 2.62 (2.07, 3.30), p<0.001; AOR 2.17 (1.51, 3.13), p<0.001, respectively], gonorrhoea infection [AOR 2.79 (1.51, 5.15), p=0.001; AOR 2.69 (0.96, 7.56), p=0.060, respectively] and syphilis infection [AOR 1.86 (1.04, 3.31), p=0.036; AOR 3.35 (1.78, 6.28), p<0.001, respectively], but not with exposure to peer education, community mobilization or HIV testing uptake. Mediation analysis suggests that alcohol use and STIs may partially mediate the association between violence or arrests and HIV prevalence. DISCUSSION: Violence by non-partners and arrest are both strongly associated with HIV infection among FSWs. Large-scale, comprehensive HIV prevention programming can reduce violence, arrests and HIV/STI infection among FSWs

Allergen specificity of early peanut consumption and effect on development of allergic disease in the Learning Early About Peanut Allergy study cohort

BACKGROUND: Early introduction of dietary peanut in high-risk infants with severe eczema, egg allergy, or both prevented peanut allergy at 5 years of age in the Learning Early About Peanut Allergy (LEAP) study. The protective effect persisted after 12 months of avoiding peanuts in the 12-month extension of the LEAP study (LEAP-On). It is unclear whether this benefit is allergen and allergic disease specific. Objective: We sought to assess the effect of early introduction of peanut on the development of allergic disease, food sensitization, and aeroallergen sensitization. METHODS: Asthma, eczema, and rhinoconjunctivitis were diagnosed based on clinical assessment. Reported allergic reactions and consumption of tree nuts and sesame were recorded by questionnaire. Sensitization to food allergens and aeroallergens was determined by means of skin prick testing and specific IgE measurement. RESULTS: A high and increasing burden of food allergen and aeroallergen sensitization and allergic disease was noted across study time points; 76% of LEAP participants had at least 1 allergic disease at 60 months of age. There were no differences in allergic disease between LEAP groups. There were small differences in sensitization and reported allergic reactions for select tree nuts, with levels being higher in the LEAP consumption group. Significant resolution of eczema and sensitization to egg and milk occurred in LEAP participants and was not affected by peanut consumption. CONCLUSION: Early consumption of peanut in infants at high risk of peanut allergy is allergen specific and does not prevent the development of other allergic disease, sensitization to other food allergens and aeroallergens, or reported allergic reactions to tree nuts and sesame. Furthermore, peanut consumption does not hasten the resolution of eczema or egg allergy

Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes.

The natriuretic peptides, Atrial-, B-type and C-type natriuretric peptides (ANP, BNP, CNP), are regulators of many endocrine tissues and exert their effects predominantly through the activation of their specific guanylyl cyclase receptors (GC-A and GC-B) to generate cGMP. Whereas cGMP-independent signalling has been reported in response to natriuretic peptides, this is mediated via either the clearance receptor (Npr-C) or a renal-specific NPR-Bi isoform, which both lack intrinsic guanylyl cyclase activity. Here, we report evidence of GC-B-dependent cGMP-independent signalling in pituitary GH3 cells. Stimulation of GH3 cells with CNP resulted in a rapid and sustained enhancement of ERK1/2 phosphorylation (P-ERK1/2), an effect that was not mimicked by dibutryl-cGMP. Furthermore, CNP-stimulated P-ERK1/2 occurred at concentrations below that required for cGMP accumulation. The effect of CNP on P-ERK1/2 was sensitive to pharmacological blockade of MEK (U0126) and Src kinases (PP2). Silencing of the GC-B1 and GC-B2 splice variants of the GC-B receptor by using targeted short interfering RNAs completely blocked the CNP effects on P-ERK1/2. CNP failed to alter GH3 cell proliferation or cell cycle distribution but caused a concentration-dependent increase in the activity of the human glycoprotein α-subunit promoter (αGSU) in a MEK-dependent manner. Finally, CNP also activated the p38 and JNK MAPK pathways in GH3 cells. These findings reveal an additional mechanism of GC-B signalling and suggest additional biological roles for CNP in its target tissues

‘We have so much to offer’: Community members’ perspectives on autism research

Autism research is on the cusp of significant change. There are mounting calls from Autistic self-advocates, researchers, and other scientists for a paradigm shift in autism research. Yet little is known about what non-academic members of the Autistic and autism communities think about autism research. We – a team of Autistic and non-autistic researchers – addressed this gap by conducting a secondary analysis of data collected as part of an in-depth research priority-setting exercise in Australia. Specifically, we asked: what are community members’ views and experiences of autism research? In immersive online text-based focus-group discussions held over 10 days, 55 community members, including Autistic people, family members, and professionals, shared their perspectives and experiences of autism research. We analysed the data using reflexive thematic analysis, adopting an inductive approach. Respondents resoundingly agreed that autism research could play a powerful role in helping to shape good Autistic lives, yet they felt that to do that effectively, major changes were needed. These included a shift away from overly narrow, deficits-based views of Autistic people to a greater focus on contextual factors, and more community-led decisions in what is researched and how. These findings highlight new possibilities for research processes, findings, and translation

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