Practicalities of promoting practice-based learning in end of life care for care home staff: Lessons from "online" supportive conversations and reflection sessions.

INTRODUCTION: Deaths in care homes and "at home" are anticipated to account for a third of UK deaths by 2040. Currently, palliative and end of life care are not part of statutory training in care homes. Reflective practice is a tool that can facilitate practice-based learning and support. Following a feasibly study to test "online" supportive conversations and reflection sessions (OSCaRS) to support care home staff in relation to death/dying during the first months of the COVID pandemic, a one-year practice development follow-up project was undertaken with the aim to create a team of NHS/specialist palliative care (SPC)-based facilitators to lead and support OSCaRS provision in up to 50 care homes in one region in Scotland-the focus of this paper. METHODS: Forty care home managers attended an on-line session explaining the project, with a similar session held for 19 NHS/SPC-based nurses external to care homes. Those interested in facilitating OSCaRS then attended three education sessions. DATA COLLECTED: records of all activities; reflective notes on OSCaRS organised/delivered; a summary of each OSCaRS reflection/learning points; final interviews with NHS/SPC trainee facilitators. RESULTS: A total of 19 NHS/SPC facilitators delivered one or more OSCaRS in 22 participating care homes. However, as of January 2022 only six trained facilitators remained active. Out of the 158 OSCaRS arranged, 96 took place with a total of 262 staff attending. There were three important aspects that emerged: the role, remit, and resources of NHS/SPC supporting OSCaRS; requirements within care homes for establishing OSCaRS; and, the practice-based learning topics discussed at each OSCaRS. CONCLUSION: Attempts to establish a team of NHS/SPC facilitators to lead OSCaRS highlights that end of life care education in care homes does not clearly fall within the contractual remit of either group or risks being missed due to more pressing priorities.

Risk factors for diarrheagenic Escherichia coli infection in children aged 6-24 months in peri-urban community, Nairobi, Kenya.

Escherichia coli commonly inhabits the gut of humans and animals as part of their microbiota. Though mostly innocuous, some strains have virulence markers that make them pathogenic. This paper presents results of a cross-sectional epidemiological study examining prevalence of diarrheagenic E. coli (DEC) pathotypes in stool samples of asymptomatic healthy children (n = 540) in Dagoretti South subcounty, Nairobi, Kenya. E. coli was cultured and pathotyped using PCR to target specific virulence markers associated with Shiga-toxin, enteropathogenic, enterotoxigenic, enteroaggregative, entero-invasive and diffusely adherent E. coli. Overall prevalence of DEC pathotypes was 20.9% (113/540) with enteropathogenic E. coli being the most prevalent (34.1%), followed by enteroaggregative E. coli (23.5%) and Shiga-toxin producing E. coli (22.0%) among positive samples. We found evidence of co-infection with multiple pathotypes in 15% of the positive samples. Our models indicated that at the household level, carriage of DEC pathotypes in children was associated with age group [12-18 months] (OR 1.78; 95%CI 1.03-3.07; p = 0.04), eating matoke (mashed bananas) (OR 2.32; 95%CI 1.44-3.73; p = 0.001) and pulses/legumes (OR 1.74; 95%CI 1.01-2.99; p = 0.046) while livestock ownership or contact showed no significant association with DEC carriage (p>0.05). Our findings revealed significant prevalence of pathogenic DEC circulating among presumptive healthy children in the community. Since there has been no previous evidence of an association between any food type and DEC carriage, unhygienic handling, and preparation of matoke and pulses/legumes could be the reason for significant association with DEC carriage. Children 12-18 months old are more prone to DEC infections due to exploration and hand-to-mouth behavior. A detailed understanding is required on what proportion of positive cases developed severe symptomatology as well as fatal outcomes. The co-infection of pathotypes in the rapidly urbanizing environment needs to be investigated for hybrid or hetero-pathotype circulation that have been implicated in previous infection outbreaks.

Prevalence and risk factors associated with the occurrence of Campylobacter sp. in children aged 6-24 months in peri-urban Nairobi, Kenya.

Introduction: Campylobacter bacteria is a major cause of foodborne-related bacterial gastroenteritis in humans worldwide. It is known to cause diarrhea in young children which has been shown to directly affect their weight and height as a result of malnutrition. Severe cases of diarrhea can also lead to death. Most of the burden is experienced in resource-limited countries in Africa and Southeast Asia where the disease is linked to poor hygiene and sanitation. The objective of this study was to determine the prevalence of Campylobacter in children aged between 6 and 24 months in Nairobi, Kenya and identify potential risk factors associated with their occurrence. Methods: A cross-sectional study was carried out between May to December 2021. A total of 585 randomly selected households were visited in two wards (Uthiru/Ruthimitu and Riruta) in Dagoretti South sub-county, Nairobi. A questionnaire regarding how children's food is handled, the major foods consumed, sanitation and hygiene, and animal ownership was conducted among caregivers to identify associated risk factors. Stool samples were collected from 540/585 children and screened for the presence of Campylobacter using culture-based methods and confirmed through PCR. Results: Of the 540 children's stool samples processed, Campylobacter isolates were detected in 4.8% (26/540). Campylobacter jejuni (C. jejuni) was the most common species in 80.8% of positive samples compared to Campylobacter coli (C. coli) in 26.9% of samples. In six samples, both C. jejuni and C. coli were isolated, while in four samples, it was not possible to speciate the Campylobacter. Drinking cow's milk (OR 4.2, 95% CI 1.4 - 12.6) and the presence of animal feces in the compound (OR 3.4, 95% CI 1.1 - 10.3) were found to be statistically associated with Campylobacter carriage in children. Discussion: The carriage of Campylobacter in children in this community indicates a need for further investigation on source attribution to understand transmission dynamics and inform where to target interventions. Awareness creation among caregivers on good personal and food hygiene is needed, including boiling milk before consumption. Implementation of biosecurity measures at the household level is highly recommended to reduce contact between animals and humans.

A cluster-randomised controlled equivalence trial of the Surprise Soap handwashing intervention among older children living in a refugee settlement in Sudan.

INTRODUCTION: Increasing handwashing with soap (HWWS) among older children in emergency settings can have a large public health impact, however, evidence on what works is limited. One promising approach is the 'Surprise Soap' intervention in which a novel soap with an embedded toy is delivered to children in a short, participatory household session that includes a glitter game and HWWS practice. Here, we evaluate this intervention against a standard intervention in a complex emergency setting. METHODS: A cluster-randomised controlled equivalence trial was conducted in Naivasha refugee settlement, Sudan. Blinding was not possible. 203 randomly selected households, with at least one child aged 5-12, were randomised to receive the Surprise Soap intervention (n=101) or a standard intervention comprising a short household session with health messaging and plain soap distribution (n=102). The primary outcome was the proportion of prespecified potential HWWS events observed for children aged 5-12, accompanied by HWWS, at baseline, 4, 12 and 16 weeks post intervention delivery. RESULTS: 200 households were included in the analyses: 101 intervention and 99 control. No difference in intervention effectiveness was observed at any follow-up (4 weeks: adjusted rate ratio (RR) 1.2, 95% CI 0.8 to 1.7; 12 weeks: RR 0.8, 95% CI 0.5 to 1.1; 16 weeks: RR 1.1, 95% CI 0.8 to 1.5). However, we observed increased HWWS in both arms at 4 weeks (27 and 23 percentage point increase in the intervention and control arm, respectively) that was sustained at 16 weeks. CONCLUSIONS: We find that the Surprise Soap intervention is no more effective at increasing older children's HWWS than a standard, household-level, health-based intervention in this complex humanitarian emergency. There appears to be no marginal benefit in terms of HWWS that would justify the additional cost of implementing the Surprise Soap intervention. Further trials that include a passive control arm are needed to determine the independent effects of each intervention and guide future intervention design.

'I feel more part of the world': Participatory action research to develop post-diagnostic dementia support.

Many people living with dementia are 'on the margins', not accessing services and support, despite policy and care advancements. The COVID-19 pandemic exacerbated this, with the closure of face-to-face support during lockdowns in the UK and globally. The aim of the 'Beyond the Margins' project was to develop, implement, and evaluate a face-face programme of support with, by and for people with direct experience of dementia who are on the margins of existing services and support. In March 2020 the project was interrupted by the outbreak of the COVID-19 pandemic and it changed to an online format. The three-phase participatory action research project included 40 people living with dementia, 26 care partners and 31 health and social care practitioners. A seven-week online personal development programme called Getting On with Life (GO) was developed, delivered, and evaluated. This paper focuses on the participatory approaches used to develop and implement the GO programme, and the resulting aspects of its approach to facilitation and content. Key features include the GO Programme's principles of providing a safe and a respectful space, and the programme's values of: Everyone who comes already knows things, can learn things and can teach things; Doing things 'with' each other, rather than 'for' or 'to' each other; Personalised goals-led by the needs of participants rather than an imposed agenda. A key finding was the importance of developing post-diagnostic programmes as a 'sandwich', providing a safe space for learning that is preceded by understanding pathways to access the programme and followed by explicit consideration of the next steps in increasing social engagement.

Effect of a novel hygiene intervention on older children's handwashing in a humanitarian setting in Kahda district, Somalia: A cluster-randomised controlled equivalence trial.

INTRODUCTION: Improving handwashing with soap (HWWS) among children in humanitarian emergencies has the potential to reduce the transmission of several important infectious diseases. However, there is limited evidence on which approaches are effective in increasing HWWS among children in humanitarian settings. One recent innovation - the "Surprise Soap" intervention - was shown to be successful in a small-scale efficacy trial in a humanitarian setting in Iraq. This intervention includes soap with embedded toys delivered through a short household session comprising a glitter game, instruction of how and when to wash hands, and HWWS practice. Whilst promising, this approach has not been evaluated at programmatic scale in a complex humanitarian setting. METHODS: We conducted a cluster-randomised controlled equivalence trial of the Surprise Soap intervention in IDP camps in Kahda district, Somalia. Proportionate stratified random sampling was employed to recruit 200 households, with at least one child aged 5-12, across the camps. Eligible households were randomly allocated to receive the Surprise Soap intervention (n = 100) or an active comparator handwashing intervention in which plain soap was delivered in a short household session comprising standard health-based messaging and instruction of how and when to wash hands (n = 100). The primary outcome was the proportion of pre-specified occasions when HWWS was practiced by children aged 5-12 years, measured at baseline, 4-weeks, 12 weeks, and 16 weeks post invention delivery. RESULTS: HWWS increased in both groups (by 48 percentage points in the intervention group and 51 percentage points in the control group, at the 4-week follow up), however, there was no evidence of a difference in HWWS between the groups at the 4-week (adjusted RR (aRR) = 1.0, 95% CI 0.9-1.1), 12-week (aRR = 1.1, 95% CI 0.9-1.3), or 16-week (aRR = 1.0, 95% CI 0.9-1.2) follow-up. CONCLUSIONS: In this complex humanitarian setting, where soap availability and past exposure to handwashing promotion was low, it appears that well-designed, household-level targeted handwashing interventions that include soap provision can increase child HWWS and potentially reduce disease risk, but the Surprise Soap intervention offers no marginal benefit over a standard intervention that would justify the additional costs.

Nongovernmental Organization Practitioners' Perspectives on the Challenges and Solutions to Changing Handwashing Behavior in Older Children: A Qualitative Study.

BACKGROUND: Increasing handwashing with soap (HWWS) among older children (aged 5-14 years) can achieve a substantial public health impact. However, HWWS interventions targeting older children have had mixed success. Recent research has attempted to quantitatively identify effective intervention techniques; however, success is likely also influenced by the wider context of implementation. We explore nongovernmental organization (NGO) practitioners' perspectives on the challenges and solutions to HWWS interventions targeting older children to enhance understanding of what is required, beyond intervention content, for them to be effective. METHODS: We conducted in-depth, semistructured interviews in April-November 2020 with 25 practitioners employed across 11 NGOs and involved in HWWS interventions targeting older children in development and humanitarian settings. We used purposive and snowball sampling to recruit participants in roles at the global, national/regional, and local levels. Interviews were audio-recorded, transcribed, and thematically analyzed to identify challenges and solutions to HWWS interventions targeting older children. Results were organized according to program development cycle stages. RESULTS: Twelve themes relating to perceived challenges emerged: (1) lack of prioritization, (2) funding inconsistency, (3) insufficient formative research, (4) demand on resources, (5) unengaging intervention content, (6) non-enabling physical environments, (7) availability of skilled implementers, (8) reaching out-of-school children, (9) community mistrust, (10) lack of coordination, (11) lack of evaluation rigor, and (12) failure to assign older children's HWWS as a primary outcome in evaluations of hygiene interventions. Recommended solutions were at the intervention, organization, and sector levels. CONCLUSION: Intervention design and delivery are important for the success of HWWS interventions for older children, but contextual factors, such as the availability of human and material resources and the level of coordination within and beyond the NGO sector, should also be considered. NGOs need to prioritize HWWS promotion among older children and support programs accordingly.

Improving domestic violence screening practices in the emergency department: an Australian perspective.

INTRODUCTION: Domestic violence (DV) is a major cause of morbidity worldwide. The ED is a location recommended for opportunistic screening. However, screening within EDs remains irregular. OBJECTIVE: To examine intrinsic and extrinsic barriers to routine screening in Australian EDs, while describing actions taken after identification of DV. METHODS: Emergency clinicians at nine public hospitals participated in an anonymous online survey. Factor analysis was performed to identify principal components around attitudes and beliefs towards screening. RESULTS: In total, 496 emergency clinicians participated. Universal screening was uncommon; less than 2% of respondents reported screening all adults or all women. Although willing, nearly half (45%) reported not knowing how to screen. High patient load and no single rooms were 'very or severely limiting' for 88% of respondents, respectively, while 24/7 social work and interpreter services, and online/written DV protocols were top enablers. Factor analysis identified four distinct intrinsic belief components: (1) screening is not futile and could be done in ED, (2) screening will not cause harm, (3) there is a duty to screen and (4) I am willing to screen. CONCLUSION: This study describes a culture of Queensland ED clinicians that believe DV screening in ED is important and interventions are effective. Most ED clinicians are willing to screen. In this setting, availability of social work and interpreter services are important mitigating resources. Clinician education focusing on duty to screen, coupled with a built-in screening tool, and e-links to a local management protocol may improve the uptake of screening and subsequently increase detection.

The effectiveness of hand hygiene interventions for preventing community transmission or acquisition of novel coronavirus or influenza infections: a systematic review.

BACKGROUND: Novel coronaviruses and influenza can cause infection, epidemics, and pandemics. Improving hand hygiene (HH) of the general public is recommended for preventing these infections. This systematic review examined the effectiveness of HH interventions for preventing transmission or acquisition of such infections in the community. METHODS: PubMed, MEDLINE, CINAHL and Web of Science databases were searched (January 2002-February 2022) for empirical studies related to HH in the general public and to the acquisition or transmission of novel coronavirus infections or influenza. Studies on healthcare staff, and with outcomes of compliance or absenteeism were excluded. Study selection, data extraction and quality assessment, using the Cochrane Effective Practice and Organization of Care risk of bias criteria or Joanna Briggs Institute Critical Appraisal checklists, were conducted by one reviewer, and double-checked by another. For intervention studies, effect estimates were calculated while the remaining studies were synthesised narratively. The protocol was pre-registered (PROSPERO 2020: CRD42020196525). RESULTS: Twenty-two studies were included. Six were intervention studies evaluating the effectiveness of HH education and provision of products, or hand washing against influenza. Only two school-based interventions showed a significant protective effect (OR: 0.64; 95% CI 0.51, 0.80 and OR: 0.40; 95% CI 0.22, 0.71), with risk of bias being high (n = 1) and unclear (n = 1). Of the 16 non-intervention studies, 13 reported the protective effect of HH against influenza, SARS or COVID-19 (P < 0.05), but risk of bias was high (n = 7), unclear (n = 5) or low (n = 1). However, evidence in relation to when, and how frequently HH should be performed was inconsistent. CONCLUSIONS: To our knowledge, this is the first systematic review of effectiveness of HH for prevention of community transmission or acquisition of respiratory viruses that have caused epidemics or pandemics, including SARS-CoV-1, SARS-CoV-2 and influenza viruses. The evidence supporting the protective effect of HH was heterogeneous and limited by methodological quality; thus, insufficient to recommend changes to current HH guidelines. Future work is required to identify in what circumstances, how frequently and what product should be used when performing HH in the community and to develop effective interventions for promoting these specific behaviours in communities during epidemics.

Using conjoint analysis to measure the importance of psychosocial traits in the choices of bladder management after spinal cord injury.

OBJECTIVE: To conduct a conjoint analysis experiment to better understand the psychosocial priorities related to bladder management in individuals after spinal cord injury (SCI). METHODS: We developed a conjoint analysis survey that included 11 psychosocial attributes phrased in the context of bladder management (including attributes for urinary infections, and incontinence). We then performed a multi-center prospective cross-sectional study of adults with existing SCI which consisted of a baseline interview, followed by the online conjoint analysis survey (delivered through Sawtooth software). Hierarchical Bayes random effects regression analysis was used to determine the relative importance of the attributes. RESULTS: A total of 345 people complete the study. There was good representation of both men and women, and individuals with cervical and thoracic or lower lesions. The most important attribute was the frequency of urinary infections. Age, sex, and level of SCI were generally not related to the attributes measured in the study. In the subgroup of 256 patients who used a catheter for bladder management, significantly more importance was placed on urinary tract infections, time, fluid intake, and social life among indwelling catheter users compared to intermittent catheter users. CONCLUSIONS: Most bladder-related psychosocial priorities are not impacted by a patient's age, sex or level of SCI. Differences in psychosocial priorities between indwelling and intermittent catheter users may represent factors that should be focused on to optimize bladder management after SCI.

Effectiveness of behaviour change techniques used in hand hygiene interventions targeting older children - A systematic review.

BACKGROUND: Promoting good hand hygiene in older children is an important measure to reduce the burden of common diseases such as diarrhoea and acute respiratory infections. The evidence around what works to change this behaviour, however, is unclear. OBJECTIVES: To aid future intervention design and effective use of resources, this review aims to identify the individual components used in hand hygiene interventions and assesses their contribution to intended behavioural change. METHODS: We systematically searched seven databases for experimental studies evaluating hand hygiene interventions targeting children (age 5-12) and quantitively reporting hand hygiene behaviour. Interventions in each study were categorised as 'promising', or 'non-promising' according to whether they led to a positive change in the targeted behaviour. Behaviour change techniques (BCTs) were identified across interventions using a standard taxonomy and a novel promise ratio calculated for each (the ratio of promising to non-promising interventions featuring the BCT). 'Promising' BCTs were those with a promise ratio of ≥2. BCTs were ranked from most to least promising. RESULTS: Our final analysis included 19 studies reporting 22 interventions across which 32 unique BCTs were identified. The most frequently used were 'demonstration of the behaviour', 'instruction on how to perform the behaviour' and 'adding objects to the environment'. Eight BCTs had a promise ratio of ≥2 and the five most promising were 'demonstration of the behaviour', 'information about social and environmental consequences', 'salience of consequences', 'adding objects to the environment', and 'instruction on how to perform the behaviour'. CONCLUSIONS: Our findings suggest that hand hygiene interventions targeting older children should employ a combination of promising BCTs that ensure children understand the behaviour and the consequences of their hand hygiene habits, appropriate hardware is available, and social support is provided. Researchers are encouraged to consistently and transparently describe evaluated interventions to allow promising components to be identified and replicated.

Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo.

Regulated cell proliferation is an effector mechanism of regeneration, whilst dysregulated cell proliferation is a feature of cancer. We have previously identified microRNA (miRNA) that regulate successful and failed human liver regeneration. We hypothesized that these regulators may directly modify tumor behavior. Here we show that inhibition of miRNAs -503 and -23a, alone or in combination, enhances tumor proliferation in hepatocyte and non-hepatocyte derived cancers in vitro, driving more aggressive tumor behavior in vivo. Inhibition of miRNA-152 caused induction of DNMT1, site-specific methylation with associated changes in gene expression and in vitro and in vivo growth inhibition. Enforced changes in expression of two miRNA recapitulating changes observed in failed regeneration led to complete growth inhibition of multi-lineage cancers in vivo. Our results indicate that regulation of regeneration and tumor aggressiveness are concordant and that miRNA-based inhibitors of regeneration may constitute a novel treatment strategy for human cancers.

Midwives' views on alcohol guidelines: A qualitative study of barriers and facilitators to implementation in UK antenatal care.

OBJECTIVE: Midwives play an important role in health promotion and prevention of alcohol-related harm, but previous research has suggested that although most midwives report advising on abstinence, evidence exist that women are informed that "some" alcohol is not harmful. The aim of this qualitative study was to explore midwives' views on implementation of the 2016 Chief Medical Officers' alcohol guidelines in antenatal care in the UK. METHODS: Focus groups and individual interviews with 22 midwives working in maternity and educational settings in the UK were conducted either in person or over telephone. Data were subjected to thematic analysis. RESULTS: Conflict between guidelines from different sources and lack of knowledge of the abstinence advice issued in the Guidelines were barriers to discussing abstinence. Communication with women and building relationships were key facilitators supporting alcohol discussions. How alcohol was addressed appeared to vary across the UK with no uniform approach. Building a trusted relationship was believed to be the way in which women can disclose alcohol use, though the first antenatal contact was not always viewed as the best time to discuss what was considered a personal matter. CONCLUSION: Despite the release of new guidance in 2016, there was little recognition and awareness of these among midwives. Midwives were by default guided by other national clinical sources or guidelines. Future research should explore how practice-based interventions can address systemic and interpersonal factors to support health professionals to implement the Guidelines, and ensure that women are provided support to change unhealthy behaviours.

Barriers and enablers of implementation of alcohol guidelines with pregnant women: a cross-sectional survey among UK midwives.

BACKGROUND: In 2016, the UK Chief Medical Officers revised their guidance on alcohol and advised women to abstain from alcohol if pregnant or planning pregnancy. Midwives have a key role in advising women about alcohol during pregnancy. The aim of this study was to investigate UK midwives' practices regarding the 2016 Chief Medical Officers Alcohol Guidelines for pregnancy, and factors influencing their implementation during antenatal appointments. METHODS: Online cross-sectional survey of a convenience sample of UK midwives recruited through professional networks and social media. Data were gathered using an anonymous online questionnaire addressing knowledge of the 2016 Alcohol Guidelines for pregnancy; practice behaviours regarding alcohol assessment and advice; and questions based on the Theoretical Domains Framework (TDF) to evaluate implementation of advising abstinence at antenatal booking and subsequent antenatal appointments. RESULTS: Of 842 questionnaire respondents, 58% were aware of the 2016 Alcohol Guidelines of whom 91% (438) cited abstinence was recommended, although 19% (93) cited recommendations from previous guidelines. Nonetheless, 97% of 842 midwives always or usually advised women to abstain from alcohol at the booking appointment, and 38% at subsequent antenatal appointments. Mean TDF domain scores (range 1-7) for advising abstinence at subsequent appointments were highest (indicative of barriers) for social influences (3.65 sd 0.84), beliefs about consequences (3.16 sd 1.13) and beliefs about capabilities (3.03 sd 073); and lowest (indicative of facilitators) for knowledge (1.35 sd 0.73) and professional role and identity (1.46 sd 0.77). Logistic regression analysis indicated that the TDF domains: beliefs about capabilities (OR = 0.71, 95% CI: 0.57, 0.88), emotion (OR = 0.78; 95%CI: 0.67, 0.90), and professional role and identity (OR = 0.69, 95%CI 0.51, 0.95) were strong predictors of midwives advising all women to abstain from alcohol at appointments other than at booking. CONCLUSIONS: Our results suggest that skill development and reinforcement of support from colleagues and the wider maternity system could support midwives' implementation of alcohol advice at each antenatal appointment, not just at booking could lead to improved outcomes for women and infants. Implementation of alcohol care pathways in maternity settings are beneficial from a lifecourse perspective for women, children, families, and the wider community.

A qualitative assessment of psychosocial aspects that play a role in bladder management after spinal cord injury.

STUDY DESIGN: Prospective qualitative study using semi-structured, open-ended interviews. OBJECTIVES: To better understand psychosocial aspects of bladder management after spinal cord injury (SCI). SETTING: People with SCI, recruited through three tertiary care centres in North America. METHODS: Thirty-four community-dwelling individuals with SCI were selected using purposive sampling to ensure men and women with both tetraplegia and paraplegia were represented. The interviews were audio recorded and transcribed. NVivo software was used to code psychosocial domains, medical complications, and methods of bladder management. A qualitative interpretive approach was used, and four participants participated in a debrief session to review the study findings. RESULTS: The median age was 49 (IQR 40-62) years and 61% (21/34) were male. Most had complete injuries (AIS A, 47%, 16/34), and most had a cervical lesion (56%, 19/34). There was a large range of time living with a SCI (median 20 years, IQR 9-31), and most participants managed their bladder with intermittent catheterisation (67% 23/34). The five most common psychosocial domains were anxiety (often in the context of urinary infections, incontinence, or not being able to catheterise), loss of control (due to irregular bladder behaviour), and embarrassment (from incontinence occurring in public); the domains of confidence and independence/planning included both positive and negative examples of bladder management experiences. CONCLUSIONS: This study demonstrated consistent psychosocial topics related to bladder management in people living with SCI. This information will help counsel people regarding bladder management and identify areas for education and optimisation of bladder function from a psychosocial perspective.

Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium.

BACKGROUND: Asthma is a chronic airway disease driven by complex genetic-environmental interactions. The role of epigenetic modifications in bronchial epithelial cells (BECs) in asthma is poorly understood. METHODS: We piloted genome-wide profiling of the enhancer-associated histone modification H3K27ac in BECs from people with asthma (n = 4) and healthy controls (n = 3). RESULTS: We identified n = 4,321 (FDR < 0.05) regions exhibiting differential H3K27ac enrichment between asthma and health, clustering at genes associated predominately with epithelial processes (EMT). We identified initial evidence of asthma-associated Super-Enhancers encompassing genes encoding transcription factors (TP63) and enzymes regulating lipid metabolism (PTGS1). We integrated published datasets to identify epithelium-specific transcription factors associated with H3K27ac in asthma (TP73) and identify initial relationships between asthma-associated changes in H3K27ac and transcriptional profiles. Finally, we investigated the potential of CRISPR-based approaches to functionally evaluate H3K27ac-asthma landscape in vitro by identifying guide-RNAs capable of targeting acetylation to asthma DERs and inducing gene expression (TLR3). CONCLUSION: Our small pilot study validates genome-wide approaches for deciphering epigenetic mechanisms underlying asthma pathogenesis in the airways.

Two Secreted Proteoglycans, Activators of Urothelial Cell-Cell Adhesion, Negatively Contribute to Bladder Cancer Initiation and Progression.

Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-ß and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer.

Distal lung epithelial progenitor cell function declines with age.

Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile. Bronchioles became smaller in their cross-sectional area and diameter. Using long-term EdU incorporation analysis and immunohistochemistry, we found that bronchiolar cell density remained stable with aging, but inferred rates of bronchiolar club progenitor cell self-renewal and differentiation were reduced, indicative of an overall slowdown in cellular turnover. Alveolar Type II progenitor cell density and self-renewal were maintained per unit tissue area with aging, but rates of inferred differentiation into Type I cells, and indeed overall density of Type I cells was reduced. Microarray analysis revealed age-related changes in multiple genes, including some with roles in proliferation and differentiation, and in IGF and TGFß signalling pathways. By characterising how lung stem cell dynamics change with aging, this study will elucidate how they contribute to age-related loss of pulmonary function, and pathogenesis of common age-related pulmonary diseases.

Child handwashing in an internally displaced persons camp in Northern Iraq: A qualitative multi-method exploration of motivational drivers and other handwashing determinants.

BACKGROUND: Children in humanitarian situations are particularly vulnerable to diseases such as diarrhoea. Handwashing with soap can greatly reduce transmission but handwashing rates are often low and traditional interventions ineffective. To aid future intervention design, this study aims to understand the determinants of child handwashing and the key motivational drivers of children's behaviour within a specific humanitarian setting. METHODS: In an internally displaced persons camp in Northern Iraq we conducted a series of 36 friendship-paired interviews with children aged 7-12 years, six semi-structured caregiver interviews, and three semi-structured hygiene promoter interviews. Perceived determinants of child handwashing were explored qualitatively, and motivational drivers were explored quantitatively with children in a rating exercise. Qualitative data were analysed thematically, using an inductive approach, and logistic regression analyses of motive rating data were performed to determine the predicted probabilities of motives being rated as important. RESULTS: Access to soap and water was perceived to be high across all participant groups. Children, caregivers and hygiene promoters all perceive the determinants of child handwashing to be associated with familial role, environmental factors pertaining to location and quality of handwashing materials and facilities, and level of exposure to hygiene promotion, and children also attribute their handwashing to social norms. We find that children in this context are motived most by play and nurture. CONCLUSIONS: Provision of soap and water alone is not sufficient to encourage children to practice handwashing with soap in a humanitarian context. Our findings suggest that equal consideration should be given to the quality and location of handwashing materials and facilities and social norms could be leveraged to promote and enhance child handwashing. Motive-based interventions targeting play or nurture may be a promising approach and are likely most effective when used in conjunction, along with other motivational drivers such as affiliation and love.