A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia.

Glial cells have been proposed as a source of neural progenitors, but the mechanisms underpinning the neurogenic potential of adult glia are not known. Using single cell transcriptomic profiling, we show that enteric glial cells represent a cell state attained by autonomic neural crest cells as they transition along a linear differentiation trajectory that allows them to retain neurogenic potential while acquiring mature glial functions. Key neurogenic loci in early enteric nervous system progenitors remain in open chromatin configuration in mature enteric glia, thus facilitating neuronal differentiation under appropriate conditions. Molecular profiling and gene targeting of enteric glial cells in a cell culture model of enteric neurogenesis and a gut injury model demonstrate that neuronal differentiation of glia is driven by transcriptional programs employed in vivo by early progenitors. Our work provides mechanistic insight into the regulatory landscape underpinning the development of intestinal neural circuits and generates a platform for advancing glial cells as therapeutic agents for the treatment of neural deficits.

Exploring the delivery of remote physiotherapy during the COVID-19 pandemic: UK wide service evaluation.

INTRODUCTION: During the Coronavirus (Covid-19) pandemic, physiotherapists changed rapidly to working remotely. Research demonstrates the benefits of remote physiotherapy, but little is known about its implementation in practice. PURPOSE: Explore the take-up and delivery of remote physiotherapy during the pandemic in the United Kingdom. METHODS: Sequential mixed methods evaluation with physiotherapists leading remote physiotherapy delivery. Two-stage approach included online survey (2020) and semi-structured interviews with documentary/data analysis (2021). RESULTS: There were 1620 physiotherapists who completed the survey. The most used devices were telephone (n = 942,71.0%) and the AttendAnywhere platform (n = 511, 38.5%). Remote consultations were frequently used for initial assessment (n = 1105, 83%), screening/triage (n = 882, 67%), or to review, monitor, and progress treatment (n = 982-1004, 74%-76%). Qualitative survey responses reflected respondents' response to COVID-19 and delivery of remote physiotherapy. Twelve remote physiotherapy leads were then purposively sampled across clinical areas. Three main themes emerged from interviews: response to Covid-19, delivery of remote physiotherapy, and future of remote physiotherapy. CONCLUSION: Remote physiotherapy was safe, feasible, and acceptable for those who accessed it. There were patients for which it was deemed unsuitable across clinical areas. In practice, it should be combined with in-person consultation based on patients' needs/preferences. Further research should explore post-pandemic maintenance of remote delivery.

Longitudinal realist evaluation of the Dementia PersonAlised Care Team (D-PACT) intervention: protocol.

BACKGROUND: Different dementia support roles exist but evidence is lacking on which aspects are best, for whom, and in what circumstances, and on their associated costs and benefits. Phase 1 of the Dementia PersonAlised Care Team programme (D-PACT) developed a post-diagnostic primary care-based intervention for people with dementia and their carers and assessed the feasibility of a trial. AIM: Phase 2 of the programme aims to 1) refine the programme theory on how, when, and for whom the intervention works; and 2) evaluate its value and impact. DESIGN & SETTING: A realist longitudinal mixed-methods evaluation will be conducted in urban, rural, and coastal areas across South West and North West England where low-income or ethnic minority populations (for example, South Asian) are represented. Design was informed by patient, public, and professional stakeholder input and phase 1 findings. METHOD: High-volume qualitative and quantitative data will be collected longitudinally from people with dementia, carers, and practitioners. Analyses will comprise the following: 1) realist longitudinal case studies; 2) conversation analysis of recorded interactions; 3) statistical analyses of outcome and experience questionnaires; 4a) health economic analysis examining costs of delivery; and 4b) realist economic analysis of high-cost events and 'near misses'. All findings will be synthesised using a joint display table, evidence appraisal tool, triangulation, and stakeholder co-analysis. CONCLUSION: The realist evaluation will describe how, why, and for whom the intervention does or does not lead to change over time. It will also demonstrate how a non-randomised design can be more appropriate for complex interventions with similar questions or populations.

A systematic review and meta-analysis of the measurement properties of concerns-about-falling instruments in older people and people at increased risk of falls.

BACKGROUND: The 16-item Falls Efficacy Scale International (FES-I) is widely used to assess concerns-about-falling. Variants include 7-item Short FES-I, 30-item Iconographical Falls Efficacy Scale (Icon FES) and 10-item short Icon FES. No comprehensive systematic review and meta-analysis has been conducted to synthesise evidence regarding the measurement properties of these tools. OBJECTIVES: To conduct a systematic review and meta-analysis of the measurement properties of four FES-I variants. METHODS: MEDLINE, Embase, CINAHL Plus, PsycINFO and Web of Science were searched systematically and articles were assessed for eligibility independently. The methodological quality of eligible studies was assessed using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist. The quality of measurement properties was assessed using COSMIN criteria for good measurement properties. Where possible, meta-analysis was conducted; otherwise, narrative synthesis was performed. Overall certainty of evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation system approach. RESULTS: The review included 58 studies investigating measurement properties of the four instruments. There was high-quality evidence to support internal consistency, reliability and construct validity of all instruments. Moderate- to high-certainty evidence suggests one-factor structure of FES-I with two underlying dimensions, one-factor structure of Short FES-I and two-factor structure of Icon FES. There was high-certainty evidence to support the responsiveness of FES-I, with further research needed for the other instruments. CONCLUSION: There is evidence for excellent measurement properties of all four instruments. We recommend the use of these tools with healthy older people and people at a greater risk of falls due to conditions that might affect mobility and balance.

Establishing evidence to inform culturally competent mental health services: A mixed methods study protocol.

BACKGROUND: COVID-19 has exacerbated the significant and longstanding mental health inequalities for ethnic minorities, who were less likely to access mental health support in primary care but more likely to end up in crisis care compared to the majority ethnic group. Services were poorly offered and accessed to respond to the increased mental health challenges. AIM: To 1) establish evidence on which changes to mental health services provided in response to COVID-19 are beneficial for ethnic minorities who experience mental health difficulties in the North of England, and 2) to inform what and how culturally competent mental health services should be routinely provided. METHODS: A mixed methods approach comprising 1) a rapid review to map services and models of care designed or adjusted for mental health during the pandemic, 2) an observational study of retrospective routine data to assess changes to mental health services and associated outcomes, 3) qualitative interviews to understand experiences of seeking care and factors associated with high-quality service provision, and 4) a Delphi study to establish consensus on key features of culturally competent services. From the selected areas in the North of England, adults from ethnic minorities who experience mental health difficulties will be identified from the primary, community and secondary care services and local ethnic minority communities. DISCUSSION: This study will identify ways to tackle health inequalities and contribute to mental health service recovery post pandemic by providing practice recommendations on equitable and effective services to ensure culturally competent and high-quality care. A list of services and features on what and how mental health services will be provided. Working with study collaborators and public and patient involvement partners, the study findings will be widely disseminated through presentations, conferences and publications and will inform the subsequent funding application for intervention development and evaluation.

A scoping review of the feasibility, acceptability, and effects of physiotherapy delivered remotely.

PURPOSE: To review the feasibility, acceptability, and effects of physiotherapy when delivered remotely. MATERIALS AND METHODS: CINAHL, MEDLINE, EBM Reviews, and Cochrane Library databases (January 2015-February 2022) were searched and screened for papers (of any design) investigating remote physiotherapy. Data were extracted by two independent raters. Methodological quality of the identified papers was not assessed. Thematic content analysis drew out the key issues. RESULTS: Forty-one papers (including nine systemic reviews and six with meta-analyses) were selected involving musculoskeletal, stroke and neurological, pulmonary, and cardiac conditions. The most commonly delivered intervention was remote exercise provision, usually following assessment which was completed in-person. All studies, which assessed it, found that remote physiotherapy was comparably effective to in-person delivery at lower cost. Patient satisfaction was high, they found remote physiotherapy to be more accessible and convenient. It boosted confidence and motivation by reminding patients when and how to exercise but adherence was mixed. No adverse events were reported. Barriers related to access to the technology; technical problems and concerns about therapists' workload. CONCLUSIONS: Remote physiotherapy is safe, feasible, and acceptable to patients. Its effects are comparable with traditional care at lower cost.IMPLICATIONS FOR REHABILITATIONRemote physiotherapy is safe, feasible, and acceptable to patients with comparable effects to in-person care.Remote delivery increases access to physiotherapy especially for those who cannot travel to a treatment facility whether due to distance or disability.Remote physiotherapy may increase adherence to exercise by reminding patients when and how to exercise.Remote physiotherapy does not suit everyone, thus a hybrid system with both in-person and remote delivery may be most effective.

Molecular profiling of enteric nervous system cell lineages.

The enteric nervous system (ENS) is an extensive network of enteric neurons and glial cells that is intrinsic to the gut wall and regulates almost all aspects of intestinal physiology. While considerable advancement has been made in understanding the genetic programs regulating ENS development, there is limited understanding of the molecular pathways that control ENS function in adult stages. One of the limitations in advancing the molecular characterization of the adult ENS relates to technical difficulties in purifying healthy neurons and glia from adult intestinal tissues. To overcome this, we developed novel methods for performing transcriptomic analysis of enteric neurons and glia, which are based on the isolation of fluorescently labeled nuclei. Here we provide a step-by-step protocol for the labeling of adult mouse enteric neuronal nuclei using adeno-associated-virus-mediated gene transfer, isolation of the labeled nuclei by fluorimetric analysis, RNA purification and nuclear RNA sequencing. This protocol has also been adapted for the isolation of enteric neuron and glia nuclei from myenteric plexus preparations from adult zebrafish intestine. Finally, we describe a method for visualization and quantification of RNA in myenteric ganglia: Spatial Integration of Granular Nuclear Signals (SIGNS). By following this protocol, it takes ~3 d to generate RNA and create cDNA libraries for nuclear RNA sequencing and 4 d to carry out high-resolution RNA expression analysis on ENS tissues.

Developing a Management Guide (the DemPower App) for Couples Where One Partner Has Dementia: Nonrandomized Feasibility Study.

BACKGROUND: Promoting the health and well-being of couples where one partner has dementia is an overlooked area of care practice. Most postdiagnostic services currently lack a couple-centered approach and have a limited focus on the couple relationship. To help address this situation, we developed a tablet-based self-management guide (DemPower) focused on helping couples enhance their well-being and relationship quality. OBJECTIVE: The aim of this study is to investigate the feasibility and acceptability of the DemPower app. METHODS: A nonrandomized feasibility design was used to evaluate the DemPower intervention over 3 months among couples where a partner had a diagnosis of dementia. The study recruited 25 couples in the United Kingdom and 19 couples in Sweden. Outcome measures were obtained at baseline and postintervention. The study process and interventions were evaluated at various stages. RESULTS: The study was completed by 48% (21/44) of couples where one partner had dementia, of whom 86% (18/21) of couples accessed all parts of the DemPower app. Each couple spent an average of 8 hours (SD 3.35 hours) using the app during the study period. In total, 90% (19/21) of couples reported that all sections of DemPower were useful in addressing various aspects of daily life and helped to focus on how they interacted in their relationship. Of the 4 core subjects on which the DemPower app was structured, home and neighborhood received the highest number of visits. Couples used activity sections more often than the core subject pages. The perception of DemPower's utility varied with each couple's lived experience of dementia, geographic location, relationship dynamics, and opportunities for social interaction. A 5.2-point increase in the dementia quality of life score for people with dementia and a marginal increase in the Mutuality scale (+1.23 points) for caregiver spouses were found. Design and navigational challenges were reported in the DemPower app. CONCLUSIONS: The findings suggest that the DemPower app is a useful resource for couples where one partner has dementia and that the implementation of the app requires the support of memory clinics to reach couples at early diagnosis. TRIAL REGISTRATION: ISRCTN Registry ISRCTN10122979; http://www.isrctn.com/ISRCTN10122979.

Regulation of intestinal immunity and tissue repair by enteric glia.

Tissue maintenance and repair depend on the integrated activity of multiple cell types1. Whereas the contributions of epithelial2,3, immune4,5 and stromal cells6,7 in intestinal tissue integrity are well understood, the role of intrinsic neuroglia networks remains largely unknown. Here we uncover important roles of enteric glial cells (EGCs) in intestinal homeostasis, immunity and tissue repair. We demonstrate that infection of mice with Heligmosomoides polygyrus leads to enteric gliosis and the upregulation of an interferon gamma (IFNγ) gene signature. IFNγ-dependent gene modules were also induced in EGCs from patients with inflammatory bowel disease8. Single-cell transcriptomics analysis of the tunica muscularis showed that glia-specific abrogation of IFNγ signalling leads to tissue-wide activation of pro-inflammatory transcriptional programs. Furthermore, disruption of the IFNγ-EGC signalling axis enhanced the inflammatory and granulomatous response of the tunica muscularis to helminths. Mechanistically, we show that the upregulation of Cxcl10 is an early immediate response of EGCs to IFNγ signalling and provide evidence that this chemokine and the downstream amplification of IFNγ signalling in the tunica muscularis are required for a measured inflammatory response to helminths and resolution of the granulomatous pathology. Our study demonstrates that IFNγ signalling in enteric glia is central to intestinal homeostasis and reveals critical roles of the IFNγ-EGC-CXCL10 axis in immune response and tissue repair after infectious challenge.

Implementation of the StandingTall programme to prevent falls in older people: a process evaluation protocol.

INTRODUCTION: One in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally. METHODS AND ANALYSIS: This project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. TRIAL REGISTRATION NUMBER: ACTRN12619001329156.

Exploring Dementia Care Systems Across the African Caribbean Diaspora: A Scoping Review and Consultation Exercise.

BACKGROUND AND OBJECTIVES: Understanding the influences of marginalized cultural and social identities as experienced by the African Caribbean diaspora within the context of dementia care is essential to minimize the gaps in current practice and policy in the health care setting. This study explores the impact of marginalized identities upon the meaning-making process, access to services and experience of care provisions through a scoping review and consultancy exercises with key stakeholders. RESEARCH DESIGN: Fourteen databases were searched using key terms. Primary studies in English, any year, study design, and country of origin were eligible. Titles, abstracts, and full texts were screened for inclusion and data were extracted in stages. Thematic analysis was performed and the findings were discussed in a series of consultation meetings with people with dementia, carers, and health care professionals in Manchester (United Kingdom) and Jamaica. RESULTS: The scoping review retrieved n = 1,989 research articles. Nineteen were included, most were qualitative (n = 14), 3 quantitative, and 2 mixed-method. The findings revealed limited insight into cultural and multiple individual identities in explaining conceptualization and service access. Consultation meetings confirmed these findings and highlighted differences in health care services and systems in the United Kingdom and Jamaica. DISCUSSION AND IMPLICATIONS: This study suggests there is a complex interaction of sociocultural processes that marginalize African Caribbean persons in and across various national settings within the context of dementia care. The study highlights the importance of acknowledging and addressing how prevalent racialized- and class-based divides and related marginalized social locations are reflected in inequities in access to and use of dementia services.

What is important to people living with dementia?: the 'long-list' of outcome items in the development of a core outcome set for use in the evaluation of non-pharmacological community-based health and social care interventions.

BACKGROUND: Core outcome sets (COS) prioritise outcomes based on their importance to key stakeholders, reduce reporting bias and increase comparability across studies. The first phase of a COS study is to form a 'long-list' of outcomes. Key stakeholders then decide on their importance. COS reporting is described as suboptimal and this first phase is often under-reported. Our objective was to develop a 'long-list' of outcome items for non-pharmacological interventions for people with dementia living at home. METHODS: Three iterative phases were conducted. First, people living with dementia, care partners, health and social care professionals, policymakers and researchers (n = 55) took part in interviews or focus groups and were asked which outcomes were important. Second, existing dementia trials were identified from the ALOIS database. 248 of 1009 pharmacological studies met the inclusion criteria. Primary and secondary outcomes were extracted from a 50% random sample (n = 124) along with eight key reviews/qualitative papers and 38 policy documents. Third, extracted outcome items were translated onto an existing qualitative framework and mapped into domains. The research team removed areas of duplication and refined the 'long-list' in eight workshops. RESULTS: One hundred seventy outcome items were extracted from the qualitative data and literature. The 170 outcome items were consolidated to 54 in four domains (Self-Managing Dementia Symptoms, Quality of Life, Friendly Neighbourhood & Home, Independence). CONCLUSIONS: This paper presents a transparent blueprint for 'long-list' development. Though a useful resource in their own right, the 54 outcome items will be distilled further in a modified Delphi survey and consensus meeting to identify core outcomes.

Designing and Implementing a Home-Based Couple Management Guide for Couples Where One Partner has Dementia (DemPower): Protocol for a Nonrandomized Feasibility Trial.

BACKGROUND: The increasing rate of dementia and high health and social care costs call for effective measures to improve public health and enhance the wellbeing of people living with dementia and their relational networks. Most postdiagnostic services focus on the condition and the person with dementia with limited attention to the caring spouse or partner. The key focus of the study is to develop a guide for couples where one partner has a diagnosis of dementia. This couple management guide is delivered in the form of an app, DemPower. OBJECTIVE: This study aims to investigate the feasibility and acceptability of DemPower and to assess the criteria for a full-integrated clinical and economic randomized control trial. DemPower couple management app will be introduced to couples wherein one partner has dementia. METHODS: The study will recruit 25 couples in the United Kingdom and 25 couples in Sweden. Couples will be given 3 months to engage with the app, and the amount of time taken to complete the guide (can be <3 or >3 months) will be reviewed. A set of outcome measures will be obtained at baseline and postintervention stages. RESULTS: The proposed study is at the recruitment phase. The DemPower app is being introduced to couples from consultation groups at a pretrial phase for identifying any bugs and exploring if any navigation challenges exist. The feasibility testing will begin in April 2018. CONCLUSIONS: The study will determine how much support couples need to engage with DemPower and whether or not they make use of it in their everyday lives. If there is support for app use, a future study will assess whether it is superior to "usual care." TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 10122979; http://www.isrctn.com/ISRCTN10122979 (Archived by WebCite at http://www.webcitation.org/70rB1iWYI). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9087.

Living Life and Doing Things Together: Collaborative Research With Couples Where One Partner Has a Diagnosis of Dementia.

The aim of this study is to identify relevant content for a self-management guide by using the outcomes of previous research in combination with knowledge and experiences from couples where one partner has a diagnosis of dementia. The study was carried out in three phases: (a) literature search of previous research related to well-being and couplehood in dementia; (b) interviews with couples with dementia based on the findings of the literature search; and (c) further authentication of the findings within expert groups of people with dementia and carers. For analysis of data, we used a hybrid approach of thematic analysis with combined deductive and inductive approaches. The findings of this study indicated that the four main themes "Home and Neighborhood," "Meaningful Activities and Relationships," "Approach and Empowerment," and "Couplehood" with related subthemes could be appropriate targets for a self-management guide for couples where one partner has a diagnosis of dementia.

Lineage-dependent spatial and functional organization of the mammalian enteric nervous system.

The enteric nervous system (ENS) is essential for digestive function and gut homeostasis. Here we show that the amorphous neuroglia networks of the mouse ENS are composed of overlapping clonal units founded by postmigratory neural crest-derived progenitors. The spatial configuration of ENS clones depends on proliferation-driven local interactions of ENS progenitors with lineally unrelated neuroectodermal cells, the ordered colonization of the serosa-mucosa axis by clonal descendants, and gut expansion. Single-cell transcriptomics and mutagenesis analysis delineated dynamic molecular states of ENS progenitors and identified RET as a regulator of neurogenic commitment. Clonally related enteric neurons exhibit synchronous activity in response to network stimulation. Thus, lineage relationships underpin the organization of the peripheral nervous system.

The assessment and management of pain in patients with dementia in hospital settings: a multi-case exploratory study from a decision making perspective.

BACKGROUND: Pain is often poorly managed in people who have a dementia. Little is known about how this patient population is managed in hospital, with research to date focused mainly on care homes. This study aimed to investigate how pain is recognised, assessed and managed in patients with dementia in a range of acute hospital wards, to inform the development of a decision support tool to improve pain management for this group. METHODS: A qualitative, multi-site exploratory case study. Data were collected in four hospitals in England and Scotland. Methods included non-participant observations, audits of patient records, semi-structured interviews with staff and carers, and analysis of hospital ward documents. Thematic analysis was performed through the lens of decision making theory. RESULTS: Staff generally relied on patients' self-report of pain. For patients with dementia, however, communication difficulties experienced because of their condition, the organisational context, and time frames of staff interactions, hindered patients' ability to provide staff with information about their pain experience. This potentially undermined the trials of medications used to provide pain relief to each patient and assessments of their responses to these treatments. Furthermore, given the multidisciplinary environment, a patient's communication about their pain involved several members of staff, each having to make sense of the patient's pain as in an 'overall picture'. Information about patients' pain, elicited in different ways, at different times and by different health care staff, was fragmented in paper-based documentation. Re-assembling the pieces to form a 'patient specific picture of the pain' required collective staff memory, 'mental computation' and time. CONCLUSIONS: There is a need for an efficient method of eliciting and centralizing all pain-related information for patients with dementia, which is distributed in time and between personnel. Such a method should give an overall picture of a patient's pain which is rapidly accessible to all involved in their care. This would provide a much-needed basis for making decisions to support the effective management of the pain of older people with dementia in hospital.

Structuring Roles and Gender Identities Within Families Explaining Suicidal Behavior in South India.

BACKGROUND: This paper examines the social structures, culture, gendered roles, and their implications for suicidal behavior in South India. Exploring the cultural process within the structures of family and society to understand suicide and attempted suicide from the perspectives of survivors, mental health professionals, and traditional healers has not been achieved in the existing suicide-related research studies conducted in India to date. AIMS: This study aimed to explore the cultural implications of attempted suicide by examining the survivors' life stories, their perceptions, and service providers' interpretations of problem situation. METHOD: A qualitative design was used drawing on constant comparison method and thematic analysis. The analysis was underpinned by the theoretical concepts of Bourdieu's work. In-depth interviews were conducted with 15 survivors of attempted suicide, eight mental health professionals, and eight traditional healers from Southern India. RESULTS: The study found interactions among visible and invisible fields such as faith, power, control, culture, family, religion, and social systems to have strengthened the disparities in gender and role structures within families and societies and to have impacted survivors' dispositions to situations. CONCLUSION: The role of culture in causing suicide and attempted suicide is explained by unraveling the negative impact of interacting cultural and structural mechanisms.

Using sense-making theory to aid understanding of the recognition, assessment and management of pain in patients with dementia in acute hospital settings.

BACKGROUND: The recognition, assessment and management of pain in hospital settings is suboptimal, and is a particular challenge in patients with dementia. The existing process guiding pain assessment and management in clinical settings is based on the assumption that nurses follow a sequential linear approach to decision making. In this paper we re-evaluate this theoretical assumption drawing on findings from a study of pain recognition, assessment and management in patients with dementia. AIM: To provide a revised conceptual model of pain recognition, assessment and management based on sense-making theories of decision making. METHODS: The research we refer to is an exploratory ethnographic study using nested case sites. Patients with dementia (n=31) were the unit of data collection, nested in 11 wards (vascular, continuing care, stroke rehabilitation, orthopaedic, acute medicine, care of the elderly, elective and emergency surgery), located in four NHS hospital organizations in the UK. Data consisted of observations of patients at bedside (170h in total); observations of the context of care; audits of patient hospital records; documentary analysis of artefacts; semi-structured interviews (n=56) and informal open conversations with staff and carers (family members). FINDINGS: Existing conceptualizations of pain recognition, assessment and management do not fully explain how the decision process occurs in clinical practice. Our research indicates that pain recognition, assessment and management is not an individual cognitive activity; rather it is carried out by groups of individuals over time and within a specific organizational culture or climate, which influences both health care professional and patient behaviour. CONCLUSIONS: We propose a revised theoretical model of decision making related to pain assessment and management for patients with dementia based on theories of sense-making, which is reflective of the reality of clinical decision making in acute hospital wards. The revised model recognizes the salience of individual cognition as well as acknowledging that decisions are constructed through social interaction and organizational context. The model will be used in further research to develop decision support interventions to assist with the assessment and management of patients with dementia in acute hospital settings.

The gut microbiota keeps enteric glial cells on the move; prospective roles of the gut epithelium and immune system.

The enteric nervous system (ENS) coordinates the major functions of the gastrointestinal tract. Its development takes place within a constantly changing environment which, after birth, culminates in the establishment of a complex gut microbiota. How such changes affect ENS development and its subsequent function throughout life is an emerging field of study that holds great interest but which is inadequately explored thus far. In this addendum, we discuss our recent findings showing that a component of the ENS, the enteric glial cell network that resides in the gut lamina propria, develops after birth and parallels the evolution of the gut microbiota. Importantly, this network was found to be malleable throughout life by incorporating new cells that arrive from the area of the gut wall in a process of directional movement which was controlled by the lumen gut microbiota. Finally, we postulate on the roles of the intestinal epithelium and the immune system as potential intermediaries between gut microbiota and ENS responses.

Microbiota controls the homeostasis of glial cells in the gut lamina propria.

The intrinsic neural networks of the gastrointestinal tract are derived from dedicated neural crest progenitors that colonize the gut during embryogenesis and give rise to enteric neurons and glia. Here, we study how an essential subpopulation of enteric glial cells (EGCs) residing within the intestinal mucosa is integrated into the dynamic microenvironment of the alimentary tract. We find that under normal conditions colonization of the lamina propria by glial cells commences during early postnatal stages but reaches steady-state levels after weaning. By employing genetic lineage tracing, we provide evidence that in adult mice the network of mucosal EGCs is continuously renewed by incoming glial cells originating in the plexi of the gut wall. Finally, we demonstrate that both the initial colonization and homeostasis of glial cells in the intestinal mucosa are regulated by the indigenous gut microbiota.