Assessing the safety of physical rehabilitation in critically ill patients: a Delphi study.

BACKGROUND: Physical rehabilitation of critically ill patients is implemented to improve physical outcomes from an intensive care stay. However, before rehabilitation is implemented, a risk assessment is essential, based on robust safety data. To develop this information, a uniform definition of relevant adverse events is required. The assessment of cardiovascular stability is particularly relevant before physical activity as there is uncertainty over when it is safe to start rehabilitation with patients receiving vasoactive drugs. METHODS: A three-stage Delphi study was carried out to (a) define adverse events for a general ICU cohort, and (b) to define which risks should be assessed before physical rehabilitation of patients receiving vasoactive drugs. An international group of intensive care clinicians and clinician researchers took part. Former ICU patients and their family members/carers were involved in generating consensus for the definition of adverse events. Round one was an open round where participants gave their suggestions of what to include. In round two, participants rated their agreements with these suggestions using a five-point Likert scale; a 70% consensus agreement threshold was used. Round three was used to re-rate suggestions that had not reached consensus, whilst viewing anonymous feedback of participant ratings from round two. RESULTS: Twenty-four multi-professional ICU clinicians and clinician researchers from 10 countries across five continents were recruited. Average duration of ICU experience was 18 years (standard deviation 8) and 61% had publications related to ICU rehabilitation. For the adverse event definition, five former ICU patients and one patient relative were recruited. The Delphi process had a 97% response rate. Firstly, 54 adverse events reached consensus; an adverse event tool was created and informed by these events. Secondly, 50 risk factors requiring assessment before physical rehabilitation of patients receiving vasoactive drugs reached consensus. A second tool was created, informed by these suggestions. CONCLUSIONS: The adverse event tool can be used in studies of physical rehabilitation to ensure uniform measurement of safety. The risk assessment tool can be used to inform clinical practise when risk assessing when to start rehabilitation with patients receiving vasoactive drugs. Trial registration This study protocol was retrospectively registered on https://www.researchregistry.com/ (researchregistry2991).

Dietary lipid is largely deposited in skin and rapidly affects insulating properties.

Skin has been shown to be a regulatory hub for energy expenditure and metabolism: mutations of skin lipid metabolism enzymes can change the rate of thermogenesis and susceptibility to diet-induced obesity. However, little is known about the physiological basis for this function. Here we show that the thermal properties of skin are highly reactive to diet: within three days, a high fat diet reduces heat transfer through skin. In contrast, a dietary manipulation that prevents obesity accelerates energy loss through skins. We found that skin was the largest target in a mouse body for dietary fat delivery, and that fat was assimilated both by epidermis and by dermal white adipose tissue. Dietary triglyceride acyl groups persist in skin for weeks after feeding. Using multi-modal lipid profiling, we have implicated both keratinocytes and sebocytes in the altered lipids which correlate with thermal function. In response to high fat feeding, wax diesters and ceramides accumulate, and triglycerides become more saturated. In contrast, in response to the dramatic loss of adipose tissue that accompanies restriction of the branched chain amino acid isoleucine, skin becomes highly heat-permeable: skins shows limited uptake of dietary lipids and editing of wax esters, and acquires a signature of depleted signaling lipids, which include the acyl carnitines and lipid ethers. We propose that skin should be routinely included in physiological studies of lipid metabolism, given the size of the skin lipid reservoir and its adaptable functionality.

Patient and Public Involvement in Technology-Related Dementia Research: Scoping Review.

BACKGROUND: Technology-related research on people with dementia and their carers often aims to enable people to remain living at home for longer and prevent unnecessary hospital admissions. To develop person-centered, effective, and ethical research, patient and public involvement (PPI) is necessary, although it may be perceived as more difficult with this cohort. With recent and rapid expansions in health and care-related technology, this review explored how and with what impact collaborations between researchers and stakeholders such as people with dementia and their carers have taken place. OBJECTIVE: This review aims to describe approaches to PPI used to date in technology-related dementia research, along with the barriers and facilitators and impact of PPI in this area. METHODS: A scoping review of literature related to dementia, technology, and PPI was conducted using MEDLINE, PsycINFO, Embase, and CINAHL. Papers were screened for inclusion by 2 authors. Data were then extracted using a predesigned data extraction table by the same 2 authors. A third author supported the resolution of any conflicts at each stage. Barriers to and facilitators of undertaking PPI were then examined and themed. RESULTS: The search yielded 1694 papers, with 31 (1.83%) being analyzed after screening. Most (21/31, 68%) did not make clear distinctions between activities undertaken as PPI and those undertaken by research participants, and as such, their involvement did not fit easily into the National Institute for Health and Care Research definition of PPI. Most of this mixed involvement focused on reviewing or evaluating technology prototypes. A range of approaches were described, most typically using focus groups or co-design workshops. In total, 29% (9/31) described involvement at multiple stages throughout the research cycle, sometimes with evidence of sharing decision-making power. Some (23/31, 74%) commented on barriers to or facilitators of effective PPI. The challenges identified often regarded issues of working with people with significant cognitive impairments and pressures on time and resources. Where reported, the impact of PPI was largely reported as positive, including the experiences for patient and public partners, the impact on research quality, and the learning experience it provided for researchers. Only 4 (13%) papers used formal methods for evaluating impact. CONCLUSIONS: Researchers often involve people with dementia and other stakeholders in technology research. At present, involvement is often limited in scope despite aspirations for high levels of involvement and partnership working. Involving people with dementia, their carers, and other stakeholders can have a positive impact on research, patient and public partners, and researchers. Wider reporting of methods and facilitative strategies along with more formalized methods for recording and reporting on meaningful impact would be helpful so that all those involved-researchers, patients, and other stakeholders-can learn how we can best conduct research together.

Are Clinical Prediction Rules Used in Spinal Cord Injury Care? A Survey of Practice.

Background: Accurate outcome prediction is desirable post spinal cord injury (SCI), reducing uncertainty for patients and supporting personalized treatments. Numerous attempts have been made to create clinical prediction rules that identify patients who are likely to recover function. It is unknown to what extent these rules are routinely used in clinical practice. Objectives: To better understand knowledge of, and attitudes toward, clinical prediction rules amongst SCI clinicians in the United Kingdom. Methods: An online survey was distributed via mailing lists of clinical special interest groups and relevant National Health Service Trusts. Respondents answered questions about their knowledge of existing clinical prediction rules and their general attitudes to using them. They also provided information about their level of experience with SCI patients. Results: One hundred SCI clinicians completed the survey. The majority (71%) were unaware of clinical prediction rules for SCI; only 8% reported using them in clinical practice. Less experienced clinicians were less likely to be aware. Lack of familiarity with prediction rules was reported as being a barrier to their use. The importance of clinical expertise when making prognostic decisions was emphasized. All respondents reported interest in using clinical prediction rules in the future. Conclusion: The results show widespread lack of awareness of clinical prediction rules amongst SCI clinicians in the United Kingdom. However, clinicians were positive about the potential for clinical prediction rules to support decision-making. More focus should be directed toward refining current rules and improving dissemination within the SCI community.

Clinical evaluation of post-surgical scar hyperaesthesia: a longitudinal observational pilot study.

Introduction: The mechanisms underlying persistent scar pain are not fully elucidated and evidence for the clinical evaluation of scar pain is limited. This pilot observational study investigated participation data and sought to identify objective clinical scar evaluation measures for future trials. Methods: With ethical approval and consent, adults undergoing planned hand surgery were enrolled from one NHS hospital. At 1- and 4-months post-surgery scar thermal and mechanical pain thresholds were evaluated with quantitative sensory testing; peri-scar inflammation with infrared thermometry and pliability with durometry. Participation data were analysed with descriptive statistics; the association of clinical measures with patient reported scar pain was analysed. Results: Twenty-one participants (22% eligible patients) enrolled before study closure due to the COVID-19 pandemic; 13 completed follow up. No adverse events or dropouts resulted from clinical scar evaluation. Seventy percent of participants reported undertaking topical, nonprescription scar treatment independently. Neuropathic Pain Symptom Inventory (NPSI) scores were dispersed across the score range, capturing variability in participant-reported scar symptoms. Scar morphology, pliability and inflammation were not associated with scar pain. Differences between scar and contralateral skin in thermal and mechanical pain sensitivity were identified. Conclusion: People with acute hand scars participate in clinical research and independently initiate scar treatment. Clinical testing of acute post-surgical hand scars is well tolerated. The NPSI demonstrates utility for exploring scar pain symptoms and may support the elucidation of mechanisms of persistent scar pain. Clinical tests of thermal and mechanical and sensitivity are promising candidate clinical measures of scar pain for future trials. Lay Summary: Background: it is unknown why some scars remain painful long-term. We do not know if scar flexibility, inflammation or sensitivity to temperature or pressure relate to scar pain. We investigated if patients would enrol in scar research, if scar testing was tolerated and if clinical tests are useful for future scar studies. Study conduct: with ethical approval and consent, adult hand surgery patients were enrolled from one NHS hospital. Scar pain, inflammation and response to thermal, sharp and pressure tests were assessed at 1- and 4-months after surgery. Statistically, we analysed study participation, tolerance for clinical scar tests and if the scar tests related to scar pain. Findings: 21 participants (22% eligible patients) enrolled before study closure due to the COVID-19 pandemic; 13 completed follow up. No participants were injured due to scar testing. 70% of participants reported treating their scar independently. Neuropathic Pain Symptom Inventory (NPSI) allows participants to give a broad range of answers about their scar symptoms. Scores for clinical tests of scar flexibility and inflammation did not relate to participant-reported scar pain. Scars were more sensitive to tests of pin prick and cold than unaffected skin. What we learned: people with new hand scars participate in research and independently initiate scar treatment. Clinical testing of post-surgical hand scars is well tolerated. The NPSI is useful for exploring scar pain symptoms and may help us to learn about persistent scar pain. Pinprick and cold clinical tests may be useful objective pain tests for future scar research.

The voice and swallowing profile of adults with laryngotracheal stenosis before and after reconstructive surgery: A prospective, descriptive observational study.

OBJECTIVES: Airway reconstruction for laryngo tracheal stenosis (LTS) improves dyspnoea. There is little evidence relating to impact upon voice and swallowing. We explored voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. DESIGN: Outcome measures were collected pre-reconstructive surgery, two-weeks post-surgery and up to 4-6 months post-surgery. SETTING: Tertiary referral centre. PARTICIPANTS: With ethical approval, twenty consecutive adult (≥18 years) LTS patients undergoing airway reconstruction were prospectively recruited. MAIN OUTCOME MEASURES: These included physiological values (maximum phonation time (MPT) and fundamental frequency; penetration aspiration score, residue score), clinician-reported (GRBAS, functional oral intake score, 100ml Water Swallow Test) and patient-reported outcomes (Voice Handicap Index-10, Reflux Symptoms Index, Eating Assessment Tool, Dysphagia Handicap Index). RESULTS: The observational study identified patient-reported and clinician-reported voice and swallow difficulties pre- and post-surgery; median and interquartile range are reported at each time point: Voice Handicap Index-10 23 (8-31); 20.5 (9-33.5), 24.5 (12.5-29); Dysphagia Handicap Index 9 (0-37); 13 (7-44); 15 (4-34); GRBAS grade 1(1-2); 2 (1-2.5); 2(1-2); 100ml Water Swallow Test volume score 16.7 (11.1-20); 14.3 (12.5-16.7); 16.7 (14.3-20.0); 100ml Water Swallow Test capacity score 16.3 ± 9.0; 11.0 ± 4.1; 12.5 ± 2.6. CONCLUSIONS: We present the first prospective data on voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. The variability of the outcomes was higher than expected but importantly, for many the voice and swallow outcomes were not within normal limits before surgery. The clinical value of the study demonstrates the need for individual assessment and management of LTS patients' voice and swallowing.

Clinician and patient perspectives on the barriers and facilitators to physical rehabilitation in intensive care: a qualitative interview study.

OBJECTIVES: The objective of this study is to explore patient, relative/carer and clinician perceptions of barriers to early physical rehabilitation in intensive care units (ICUs) within an associated group of hospitals in the UK and how they can be overcome. DESIGN: Qualitative study using semi-structured interviews and thematic framework analysis. SETTING: Four ICUs over three hospital sites in London, UK. PARTICIPANTS: Former ICU patients or their relatives/carers with personal experience of ICU rehabilitation. ICU clinicians, including doctors, nurses, physiotherapists and occupational therapists, involved in the delivery of physical rehabilitation or decisions over its initiation. PRIMARY AND SECONDARY OUTCOMES MEASURES: Views and experiences on the barriers and facilitators to ICU physical rehabilitation. RESULTS: Interviews were carried out with 11 former patients, 3 family members and 16 clinicians. The themes generated related to: safety and physiological concerns, patient participation and engagement, clinician experience and knowledge, teamwork, equipment and environment and risks and benefits of rehabilitation in intensive care. The overarching theme for overcoming barriers was a change in working model from ICU clinicians having separate responsibilities (a multidisciplinary approach) to one where all parties have a shared aim of providing patient-centred ICU physical rehabilitation (an interdisciplinary approach). CONCLUSIONS: The results have revealed barriers that can be modified to improve rehabilitation delivery in an ICU. Interdisciplinary working could overcome many of these barriers to optimise recovery from critical illness.

The citrate transporters SLC13A5 and SLC25A1 elicit different metabolic responses and phenotypes in the mouse.

Cytosolic citrate is imported from the mitochondria by SLC25A1, and from the extracellular milieu by SLC13A5. In the cytosol, citrate is used by ACLY to generate acetyl-CoA, which can then be exported to the endoplasmic reticulum (ER) by SLC33A1. Here, we report the generation of mice with systemic overexpression (sTg) of SLC25A1 or SLC13A5. Both animals displayed increased cytosolic levels of citrate and acetyl-CoA; however, SLC13A5 sTg mice developed a progeria-like phenotype with premature death, while SLC25A1 sTg mice did not. Analysis of the metabolic profile revealed widespread differences. Furthermore, SLC13A5 sTg mice displayed increased engagement of the ER acetylation machinery through SLC33A1, while SLC25A1 sTg mice did not. In conclusion, our findings point to different biological responses to SLC13A5- or SLC25A1-mediated import of citrate and suggest that the directionality of the citrate/acetyl-CoA pathway can transduce different signals.

Development of a framework and research impact capture tool for nursing, midwifery, allied health professions, healthcare science, pharmacy and psychology (NMAHPPs).

BACKGROUND: There is an ambitious target to create a UK clinical academic workforce representing 1% of clinicians from nursing, midwifery, the allied health professions, healthcare science, pharmacy and psychology (NMAHPPs). Understanding and recording the impact that clinical academics make across healthcare services is crucial if we are to grow, value and support this highly skilled workforce group. However, it is currently difficult to systematically record, collate and report the impacts associated with NMAHPP research activity. The aims of this project were to i) develop a framework outlining the impacts that were important for key stakeholder groups, and ii) create and pilot a research impact capture tool to record these impacts. METHODS: The framework was developed from the existing literature. It was refined, remodelled and approved by multidisciplinary stakeholder involvement, including patient and public representatives, healthcare managers and research-active clinicians. The framework was converted into a series of questions to create an electronic research impact capture tool, which was also refined through feedback from these stakeholder groups. The impact capture tool was piloted with research-active clinicians across a large NHS Trust and its associated organisations. RESULTS: The impact framework contained eight elements: clinical background, research and service improvement activities, research capacity building, research into practice, patients and service users, research dissemination, economics and research funding, and collaborations. Thirty individuals provided data for the research impact capture tool pilot (55% response rate). Respondents reported a range of positive impacts representing all elements of the framework. Importantly, research-activity appeared to be a key driver for recruitment and retention in the sample population. CONCLUSIONS: The impact capture tool is a feasible method of recording the breadth of impacts associated with NMAHPP research activity. We encourage other organisations to collaboratively use and refine our impact capture tool, with the aim of standardising reporting, and facilitating discussions about research activity within clinical appraisal. Pooling and comparing data will also allow comparison between organisations, and assessment of change over time or after implementation of interventions aimed at supporting and increasing research activity.

Regulation of metabolic health by dietary histidine in mice.

Low-protein (LP) diets are associated with a decreased risk of diabetes in humans, and promote leanness and glycaemic control in both rodents and humans. While the effects of an LP diet on glycaemic control are mediated by reduced levels of the branched-chain amino acids, we have observed that reducing dietary levels of the other six essential amino acids leads to changes in body composition. Here, we find that dietary histidine plays a key role in the response to an LP diet in male C57BL/6J mice. Specifically reducing dietary levels of histidine by 67% reduces the weight gain of young, lean male mice, reducing both adipose and lean mass without altering glucose metabolism, and rapidly reverses diet-induced obesity and hepatic steatosis in diet-induced obese male mice, increasing insulin sensitivity. This normalization of metabolic health was associated not with caloric restriction or increased activity, but with increased energy expenditure. Surprisingly, the effects of histidine restriction do not require the energy balance hormone Fgf21. Histidine restriction that was started in midlife promoted leanness and glucose tolerance in aged males but not females, but did not affect frailty or lifespan in either sex. Finally, we demonstrate that variation in dietary histidine levels helps to explain body mass index differences in humans. Overall, our findings demonstrate that dietary histidine is a key regulator of weight and body composition in male mice and in humans, and suggest that reducing dietary histidine may be a translatable option for the treatment of obesity. KEY POINTS: Protein restriction (PR) promotes metabolic health in rodents and humans and extends rodent lifespan. Restriction of specific individual essential amino acids can recapitulate the benefits of PR. Reduced histidine promotes leanness and increased energy expenditure in male mice. Reduced histidine does not extend the lifespan of mice when begun in midlife. Dietary levels of histidine are positively associated with body mass index in humans.

"Humanizing" mouse environments: Humidity, diurnal cycles and thermoneutrality.

Thermoneutral housing has been shown to promote more accurate and robust development of several pathologies in mice. Raising animal housing temperatures a few degrees may create a relatively straightforward opportunity to improve translatability of mouse models. In this commentary, we discuss the changes of physiology induced in mice housed at thermoneutrality, and review techniques for measuring systemic thermogenesis, specifically those affecting storage and mobilization of lipids in adipose depots. Environmental cues are a component of the information integrated by the brain to calculate food consumption and calorie deposition. We show that relative humidity is one of those cues, inducing a rapid sensory response that is converted to a more chronic susceptibility to obesity. Given high inter-institutional variability in the regulation of relative humidity, study reproducibility may be improved by consideration of this factor. We evaluate a "humanized" environmental cycling protocol, where mice sleep in warm temperature housing, and are cool during the wake cycle. We show that this protocol suppresses adaptation to cool exposure, with consequence for adipose-associated lipid storage. To evaluate systemic cues in mice housed at thermoneutral temperatures, we characterized the circulating lipidome, and show that sera are highly depleted in some HDL-associated phospholipids, specifically phospholipids containing the essential fatty acid, 18:2 linoleic acid, and its derivative, arachidonic acid (20:4) and related ether-phospholipids. Given the role of these fatty acids in inflammatory responses, we propose they may underlie the differences in disease progression observed at thermoneutrality.

'Is there something wrong with your voice?' A qualitative study of the voice concerns of people with laryngotracheal stenosis.

BACKGROUND: Acquired laryngotracheal stenosis (LTS) is a rare condition that causes breathlessness and dyspnoea. Patients have reconstructive airway surgery to improve their breathing difficulties, but both LTS and the surgery can cause voice difficulties. The existing evidence base for management of voice difficulties for adults with LTS focuses on symptoms. There is limited information to provide clinical guidance for speech and language therapists (SLTs) and a limited understanding of the impact of voice changes on adults with LTS. AIM: To investigate the lived experience of adults with laryngotracheal stenosis (LTS), who have had reconstructive surgery; here focussing on voice concerns with the aim of guiding clinical care for SLTs. METHODS AND PROCEDURES: A phenomenological, qualitative study design was used. Focus groups and semi-structured interviews were completed with adults living with LTS who had had reconstructive surgery. Audio recordings were transcribed and inductive thematic analysis was used by the research team to identify themes and sub-themes. OUTCOMES AND RESULTS: A total of 24 participants (five focus groups and two interviews) took part in the study before thematic saturation was identified in analysis. Three main themes were identified specific to the experience of living with LTS: the Medical, Physical and Emotional journey. All participants referenced voice difficulties as they related to each of these overall themes. Sub-themes directly related to voice included experience of surgery, information provision, staff expertise/complacency, symptoms, symptom management, identity, support networks, impact on life and living with a chronic condition. CONCLUSIONS AND IMPLICATIONS: In this qualitative study participants have described the integral part voice difficulties play in their lived experience of LTS and reconstructive surgery. This is considered in the context of their clinical care and the need for individualised management and information provision throughout the course of their condition. The broader research literature relating to voice difficulties is explored with links made to people with LTS and recommendations made for future research into people living with LTS and dysphonia. WHAT THIS PAPER ADDS: What is already known on this subject Adults with laryngotracheal stenosis (LTS) experience voice changes as a result of their condition, and the surgeries necessary as a treatment. These changes can lead to altered pitch, vocal fatigue, loss of pitch range and loss of volume control. Although there are known psychosocial implications both to living with a chronic condition and voice difficulties there has been no research exploring this in adults with LTS, and there is minimal clinical guidance for speech and language therapists (SLTs) working with these patients. What this paper adds to existing knowledge This research is the first study to explore the lived experience of adults with LTS who undergo reconstructive surgery, focusing on their voice concerns. This study demonstrates the multifactorial impacts of voice changes on all aspects of the lives of adults with LTS and the need for individualised information provision and clinical care to help support them. What are the potential or actual clinical implications of this work? Adults with LTS want expert SLTs to facilitate their care and support them throughout their LTS journey alongside other support networks. They want to be carefully prepared for reconstructive surgery and given clear information about symptoms and management of their voice difficulties. This has led to the reorganisation of the care pathway at our centre, and the introduction of a patient-led pretreatment session.

Reflections on contributing to health research: A qualitative interview study with research participants and patient advisors.

OBJECTIVES: The aims of this study were to explore individuals' experiences of contributing to health research and to identify the types of impact that are perceived as important by participants or patient and public advisors. Specifically, research led by NMAHPP clinicians (Nursing, Midwifery, Allied health professions, Healthcare science, Psychology and Pharmacy). METHODS: Semi-structured one-to-one interviews were conducted with health research participants and patient or public advisors. Interviewees were recruited from five UK sites and via social media. Interview transcripts were analysed using Thematic Analysis to identify key themes and areas of disagreement. RESULTS: Twenty-one interviews were completed, and four main themes were identified. The first, optimising research experiences, included personal reflections and broader recommendations to improve participant experiences. The second, connecting health research with healthcare, described research as key for the continued development of healthcare, but illustrated that communication between research teams, participants, and clinicians could be improved. The third theme explored the personal impacts of contributing to research, with interviewees recalling common positive experiences. The final theme discussed capturing research impacts. Interviewees highlighted potential priorities for different stakeholders, but emphasised that financial impacts should not be the sole factor. CONCLUSION: Individuals who were involved in NMAHPP health research recalled positive experiences and reported good relationships with their research teams. They felt that their contributions were valued. Suggested strategies to optimise the research experience focused on simplifying documentation, clear signposting of the research activities involved, and feedback on the research findings. Routine sharing of relevant research data with clinicians was also recommended. Personal impacts included a deeper understanding of their health condition or health more broadly, and increased confidence interacting with healthcare and other professionals. These findings will be used to inform development of a framework to capture the impact of NMAHPP research.

Enhanced Ribonucleoprotein Immunoprecipitation (RIP) Technique for the Identification of mRNA Species in Ribonucleoprotein Complexes.

RNA binding proteins (RBPs) are critical regulators of cellular phenotypes, and dysregulated RBP expression is implicated in various diseases including cancer. A single RBP can bind to and regulate the expression of many RNA molecules via a variety of mechanisms, including translational suppression, prevention of RNA degradation, and alteration in subcellular localization. To elucidate the role of a specific RBP within a given cellular context, it is essential to first identify the group of RNA molecules to which it binds. This has traditionally been achieved using cross-linking-based assays in which cells are first exposed to agents that cross-link RBPs to nucleic acids and then lysed to extract and purify the RBP-nucleic acid complexes. The nucleic acids within the mixture are then released and analyzed via conventional means (e.g., microarray analysis, qRT-PCR, RNA sequencing, or Northern blot). While cross-linking-based ribonucleoprotein immunoprecipitation (RIP) has proven its utility within some contexts, it is technically challenging, inefficient, and suboptimal given the amount of time and resources (e.g., cells and antibodies) required. Additionally, these types of studies often require the use of over-expressed versions of proteins, which can introduce artifacts. Here, we describe a streamlined version of RIP that utilizes exclusion-based purification technologies. This approach requires significantly less starting material and resources compared to traditional RIP approaches, takes less time, which is tantamount given the labile nature of RNA, and can be used with endogenously expressed proteins. The method described here can be used to study RNA-protein interactions in a variety of cellular contexts. Graphical abstract.

An investigation of the control of quadriceps in people who are hypermobile; a case control design. Do the results impact our choice of exercise for people with symptomatic hypermobility?

BACKGROUND: People with symptomatic hypermobility have altered proprioception however, the origin of this is unclear and needs further investigation to target rehabilitation appropriately. The objective of this investigation was to explore the corticospinal and reflex control of quadriceps and see if it differed between three groups of people: those who have symptomatic hypermobility, asymptomatic hypermobility and normal flexibility. METHODS: Using Transcranial Magnetic Stimulation (TMS) and electrical stimulation of peripheral nerves, motor evoked potentials (MEPs) and Hoffman (H) reflexes of quadriceps were evoked in the three groups of people. The threshold and latency of MEPs and the slope of the input-output curves and the amplitude of MEPs and H reflexes were compared across the groups. RESULTS: The slope of the input-output curve created from MEPs as a result of TMS was steeper in people with symptomatic hypermobility when compared to asymptomatic and normally flexible people (p = 0.04). There were no other differences between the groups. CONCLUSION: Corticospinal excitability and the excitability at the motoneurone pool are not likely candidates for the origin of proprioceptive loss in people with symptomatic hypermobility. This is discussed in the light of other work to suggest the receptor sitting in hypermobile connective tissue is a likely candidate. This suggests that treatment aimed at improving receptor responsiveness through increasing muscle tone, may be an effective rehabilitation strategy.

Enhanced immunoprecipitation techniques for the identification of RNA-binding protein partners: IGF2BP1 interactions in mammary epithelial cells.

RNA-binding proteins (RBPs) regulate the expression of large cohorts of RNA species to produce programmatic changes in cellular phenotypes. To describe the function of RBPs within a cell, it is key to identify their mRNA-binding partners. This is often done by crosslinking nucleic acids to RBPs, followed by chemical release of the nucleic acid fragments for analysis. However, this methodology is lengthy, which involves complex processing with attendant sample losses, thus large amounts of starting materials and prone to artifacts. To evaluate potential alternative technologies, we tested "exclusion-based" purification of immunoprecipitates (IFAST or SLIDE) and report here that these methods can efficiently, rapidly, and specifically isolate RBP-RNA complexes. The analysis requires less than 1% of the starting material required for techniques that include crosslinking. Depending on the antibody used, 50% to 100% starting protein can be retrieved, facilitating the assay of endogenous levels of RBPs; the isolated ribonucleoproteins are subsequently analyzed using standard techniques, to provide a comprehensive portrait of RBP complexes. Using exclusion-based techniques, we show that the mRNA-binding partners for RBP IGF2BP1 in cultured mammary epithelial cells are enriched in mRNAs important for detoxifying superoxides (specifically glutathione peroxidase [GPX]-1 and GPX-2) and mRNAs encoding mitochondrial proteins. We show that these interactions are functionally significant, as loss of function of IGF2BP1 leads to destabilization of GPX mRNAs and reduces mitochondrial membrane potential and oxygen consumption. We speculate that this underlies a consistent requirement for IGF2BP1 for the expression of clonogenic activity in vitro.

What is a clinical academic? Qualitative interviews with healthcare managers, research-active nurses and other research-active healthcare professionals outside medicine.

AIMS AND OBJECTIVES: To explore the concept of "clinical academic" from the perspectives of healthcare managers and research-active healthcare professionals outside medicine. BACKGROUND: Clinical academics are understood to be healthcare professionals who combine clinical and research responsibilities within their role. However, there is no agreed definition for this term either within or across nursing, midwifery and the other healthcare professions outside medicine. DESIGN: Qualitative service evaluation, reported using the COREQ checklist. METHODS: Semi-structured qualitative interviews were conducted with a purposive sample of eight healthcare managers and 12 research-active clinicians within a UK hospital group. Interviews were audio recorded, transcribed verbatim and analysed using the Framework method. RESULTS: Clinical academics were described in four themes. Two themes explored the components of the role and the contribution of these individuals to their profession: combining clinical practice, research and education; and pushing boundaries. The third theme identified the clinical academic label as: a title that doesn't fit. The final theme examined a characteristic mindset of research-active clinicians. There were no clear differences in the perceptions of managers and research-active clinicians. CONCLUSIONS: Clinical academics were perceived as valuable members of their team and were able to push the boundaries to move their profession forward. Some research-active clinicians did not identify with the term "clinical academic" and for some managers and research-active clinicians, the term was viewed as jargonistic. A clear and accepted definition would aid development of clinical academic career pathways and identities. It would also assist in evaluating the impact of these roles. RELEVANCE TO PRACTICE: As clinical academic roles and opportunities are being developed across the professions outside medicine, it is important to have a shared common understanding of "clinical academic" to support the creation of career pathways and curricula, and to enable the evaluation of these roles.

Not Just Dyspnoea: Swallowing as a Concern for Adults with Laryngotracheal Stenosis Undergoing Airway Reconstruction.

Acquired laryngotracheal stenosis (LTS) is a rare condition causing dyspnea and stridor. Patients often require multiple surgical procedures with no guarantee of a definitive outcome. Difficulty swallowing is a recognised problem associated with LTS and the reconstructive surgeries required to manage the condition. The breathlessness patient's experience impacts on swallowing, and the vulnerable structures of the larynx are implicated during complex surgeries. This leads to dysphagia post-surgery, with some patients experiencing more chronic symptoms depending on the biomechanical impact of the surgery, or a pre-existing dysphagia. Despite this there is limited observational research about the dysphagia associated with LTS, with no exploration of the patient experience. Our aim was to investigate patient experience of living with LTS focussing on dysphagia in order to guide clinical practice. A qualitative study was completed using focus groups and semi-structured interviews with 24 patients who have had reconstructive surgery for LTS. Thematic analysis was used to identify three over-arching themes: The Physical Journey, The Emotional Journey and The Medical Journey. Key sub-themes included the importance of self-management and control, presence of symptoms, benefits of therapy, living with a life-long condition, fear and anxiety, autonomy, medicalisation of normal processes and the dichotomy between staff expertise and complacency. Swallowing was connected to all themes. The results are reviewed with consideration of the wider literature of lived experience particularly in relation to other chronic conditions and those that carry a high symptom burden such as head and neck cancer. Future clinical and research recommendations have been made. Akin to other clinical groups, adults with LTS are keen that management of their swallowing is person-centred and holistic.

"A Major Quality of Life Issue": A Survey-Based Analysis of the Experiences of Adults With Laryngotracheal Stenosis with Mucus and Cough.

OBJECTIVES: To investigate how the symptoms of mucus and cough impact adults living with laryngotracheal stenosis, and to use this information to guide future research and treatment plans. METHODS: A survey was developed with the support of patient advisors and distributed to people suffering with laryngotracheal stenosis. The survey comprised 15 closed and open questions relating to mucus and cough and included the Leicester Cough Questionnaire (LCQ). Descriptive statistics, X2 and thematic analyses were completed. RESULTS: In total, 641 participants completed the survey, with 83.62% (n = 536) reporting problems with mucus; 79% having daily issues of varying severity that led to difficulties with cough (46.18%) and breathing (20.90%). Mucus affected voice and swallowing to a lesser degree. Respondents described a range of triggers; they identified smoky air as the worst environmental trigger. Strategies to manage mucus varied widely with drinking water (72.26%), increasing liquid intake in general (49.35%) and avoiding or reducing dairy (45.32%) the most common approaches to control symptoms. The LCQ showed a median total score of 14 (interquartile range 11-17) indicative of cough negatively affecting quality of life. Thematic analysis of free text responses identified 4 key themes-the Mucus Cycle, Social impact, Psychological impact, and Physical impact. CONCLUSION: This study shows the relevance of research focusing on mucus and cough and its negative impact on quality of life, among adults with laryngotracheal stenosis. It demonstrates the inconsistent advice and management strategies provided by clinicians for this issue. Further research is required to identify clearer treatment options and pathways.

Would you like to be contacted about future research?

Many research participants are willing to be contacted about future research opportunities, however this question is not always asked. Furthermore, if participants do consent for contact about future research, this information is not always accessible to other research teams. We discuss our experience of recruiting individuals who have previously taken part in healthcare research and suggest potential strategies to support this process and enable greater research participation.