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Background: The global discourse on future health care emphasises that learning to collaborate across professions is crucial to assure patient safety and meet the changing demands of health care. The research on interprofessional education (IPE) is diverse but with gaps in curricula design and how IPE is enacted in practice., Purpose and Aims: This research project will identify. 1) how IPE in clinical placements emerges, evolves, and is enacted by students when embedded in local health care practices, 2) factors critical for the design of IPE for students at clinical placements across the four countries., Methods: A study involving four countries (Sweden, Norway, Australia and New Zealand) using the theory of practice architectures will be undertaken between 2023 and 2027. The project is designed as an international, collaborative multiple-case ethnographic study, using the theoretical framework of practice architectures (TPA). It will include four ethnographic case studies of IPE, one in each country. Data will be collected in the following sequence: (1) participant observation of students during interprofessional placements, (2) interviews with students at clinical placement and stakeholders/professionals, (3) Non-clinical documents may be used to support the analysis, and collection of photos may be use as memory aids for documenting context. An analysis of "sayings, doings and relatings" will address features of the cultural- discursive, material-economic, social-political elements making up the three key dimensions of TPA. Each of the four international cases will be analysed separately. A cross case analysis will be undertaken to establish common learning and critical IPE design elements across the four collaborating universities., Discussion: The use of TPA framework and methodology in the analysis of data will make it possible to identify comparable dimensions across the four research sites, enabling core questions to be addressed critical for the design of IPE. The ethnographic field studies will generate detailed descriptions that take account of country-specific cultural and practice contexts. The study will also generate new knowledge as to how IPE can be collaboratively researched., (© 2024. The Author(s).)

ObjectiveThis study aimed to examine changes in the demographics and regions of work of Australian doctors over a period of 9years.MethodsA retrospective study of Australian Health Practitioner Regulation Agency (AHPRA) registration data was performed. Data were sourced from the Health Workforce Dataset Online Data Tool which was derived from annual registration data from AHPRA for 2013-2022. The demographic factors analysed were gender, age, and origin of qualification. Regions of work were defined using the Modified Monash (MM) model.ResultsThe number of registered doctors increased from 82,408 in 2013 to 111,908 in 2022 but mean hours worked per week decreased from 41 to 39 leading up to 2020. Trends in age and origin of qualification remained stable, but the proportion of female workers increased from 38.5% in 2013 to 44.5% in 2022. While female hours per week (~37) were consistent from 2013 to 2020, male hours per week decreased from 43 to 41. The number of registrations and total full-time equivalent (FTE) outcomes increased consistently in metropolitan (MM1) and rural (MM2-5) regions but did not increase for remote and very remote (MM6-7) regions.ConclusionThe Australian medical workforce both grew and changed between 2013 and 2022. An overall decrease in mean hours worked appears to be driven by a decline in hours worked by male workers and the increased proportion of female workers. While increased gender parity and a decrease in hours worked per week were positive outcomes, a lack of growth in the medical workforce was noted in remote and very remote regions of Australia.

Doctors who work in areas of workforce shortage, such as regional, rural and remote areas or areas of low socioeconomic means need to be more self-motivated, adaptable and self-directed than their metropolitan counterparts. This study aimed to examine the goal orientation and learning characteristics of students recruited into two medical programmes, one from the Northern hemisphere and one from the Southern hemisphere; both with a commitment to producing doctors to practice medicine in rural locations. Three survey tools were administered to 263 medical students: 1. achievement goal orientation survey; 2. learning characteristics survey and 3. the study process questionnaire. Medical students from both cohorts showed a learning goal orientation, which significantly increased with age (P0.007). In terms of learning characteristics, the students from the south had significantly higher scores for curiosity (P0.003), while the northern students had significantly higher scores for methodical ( p  < 0.001). Both cohorts were similar for adaptability and consciousness. Across the entire student cohort, three of the four learning disposition characteristics were also seen to correlate with learning goal orientation. In both cohorts of medical students deep learning scores exceeded surface learning scores. Selection of students with a learning goal orientation and learning characteristics of curiosity, adaptability and conscientiousness could potentially help students to flourish in rural placement environments.

Introduction: The distribution of health care workers differs greatly across Australia, which is likely to impact health delivery., Objective: To examine demographic and workplace setting factors of doctors, nurses and midwives, and allied health professionals across Modified Monash Model (MMM) regions and identify factors associated with shortfalls in the health care workforce., Design: Descriptive cross-sectional analysis. The study included all health professionals who were registered with the Australian Health Practitioner Regulation Agency in 2021, and who were working in Australia in their registered profession. The study examined number of registrations and full-timed equivalent (FTE) registrations per MMM region classification, adjusted for population. Associated variables included age, gender, origin of qualification, Indigenous status and participation in the private or public (including government, non-government organisation and not-for-profit organisations) sectors., Findings: Data were available for 31 221 general practitioners, 77 277 other doctors, 366 696 nurses and midwives, and 195 218 allied health professionals. The lowest FTE per 1000 people was seen in MM5 regions for general practitioners, other doctors, nurses and midwives, and allied health professionals. Demographic factors were mostly consistent across MM regions, although MM5 regions had a higher percentage of nurses and midwives and allied health professionals aged 55 and over. In the private sector, FTE per 1000 people was lowest in MM5-7 regions. In the public sector, FTE per 1000 people was lowest in MM5 regions., Discussion: A disproportionate shortfall of health workers was seen in MM5 regions. This shortfall appears to be primarily due to low FTE per capita of private sector workers compared with MM1-4 regions and a low FTE per capita of public sector workers compared with MM6-7 regions., Conclusion: In Australia, small rural towns have the lowest number of health care workers per capita which is likely to lead to poor health outcomes for those regions., (© 2024 The Authors. Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)

Background: Many women are embarrassed to discuss pelvic floor exercises with health professionals during pregnancy; instead they search the internet for information on pelvic floor exercises., Aims: This project investigated the quality and health literacy demand in terms of readability, understandability and actionability of information available on the internet relating to pelvic floor exercises., Materials and Methods: An analysis was conducted on 150 websites and 43 videos obtained from three consecutive Google searches relating to pelvic floor exercises. Websites were assessed for Health on the Net certification. Readability was assessed using a readability calculator, and understandability/actionability of website and video information was assessed using the Patient Education Materials Assessment Tool (PEMAT) for Print or Audiovisual Materials., Results: Less than one-third (24%) of the websites were certified for quality. The median readability score for the websites was grade 9 and the websites and videos both rated highly for understandability and actionability. The median understandability score for the website information was 87%, and the median actionability score was 71%. The median understandability score of the video information was 95.5% and the median actionability score was 100%. The understandability and actionability of video information was also significantly greater than that for website information (P < 0.01)., Conclusion: Clinicians could consider directing patients to video-based resources when advising online pelvic floor exercise resources for women during pregnancy, especially those with lower health literacy., (© 2024 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background and Objectives: Doctors are well placed to facilitate nutrition care to support dietary improvements due, in part, to their regular contact with their patients. Limited literature exists which explores the perspective of patients regarding the nutrition care provided by medical professionals across the continuum of care. This article explores the perspective of patients regarding perceptions of nutrition advice and care received from doctors and expectations of this care, including key skills and attributes the patients perceive as important., Method: Six online focus groups were conducted with Australian service users (n=32)., Results: Framework analysis identified four key themes: perceptions of doctors' role in nutrition care, expectations and experiences; the importance of individualised care; barriers and enablers to nutrition care; and topics, skills and attributes perceived as important in nutrition care., Discussion: Patients have a desire for individualised and collaborative nutrition care but experienced systemic barriers in practice.

Objectives: To describe cancer survivors' and care partners' perceived stress and social support during the COVID-19 pandemic and assess the feasibility of audio diaries for assessing role-related needs and resources., Methods: Participants (N = 51; n = 28 survivors, n = 23 care partners) recorded three monthly audio diaries reporting stress and support experiences. Diaries were transcribed and content-analyzed using a hybrid approach. Stress-related content was inductively coded, and social support content was deductively coded by type (instrumental, information, emotional, companionship, appraisal; κ = 0.75) then inductively coded. Descriptive statistics summarized sociodemographic data and compared coding frequencies by role. We developed narrative summaries of stress and support categories and selected quotes for contextual detail., Results: Cancer-related stressors were most prevalent (28.8%), followed by work (26.8%), family (23.1%), social isolation (13.4%), and finances (8.0%). While no significant difference in reporting frequency was observed between roles, cancer-related stress was more prevalent for survivors while work-related stress was mentioned more by care partners. Emotional support was the most prevalent support type (32.1%), followed by companionship (25.3%), appraisal (17.9%), instrumental (16.67%), and informational support (8%). Survivors reported more appraisal support than care partners (χ 2  = 6.48, df = 1, P = .011) and more support for self-care, while care partners expressed more other-oriented concerns and focused more on managing responsibilities and interactions outside the household., Conclusions: The pandemic complicated and intensified role-based stressors already present in the survivorship context. Our findings highlight the importance of informal social support networks, particularly when access to formal services is limited, and suggest that audio diaries can be an effective tool for assessing support needs and resources., Implications for Nursing Practice: Nurses and healthcare providers should tailor social support assessments to address the distinct support needs and individual resources of cancer survivors and their care partners. This is especially critical in contexts that limit access to care and formal services., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sarah Wawrzynski reports financial support was provided by National Institute of Nursing Research. Jacqueline Kent-Marvick reports financial support was provided by National Institute of Nursing Research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), have an unclear impact on bladder mucosal physiology. This study investigates UPEC's effects on the urothelium and lamina propria using an ex vivo porcine bladder model. Bladder mucosal strips were analysed for contractile responses to acetylcholine, serotonin, and neurokinin A. Given rising antibiotic resistance, non-antibiotic agents such as cranberry and d-mannose were also evaluated for their potential to prevent UPEC-induced damage. The findings of the current study revealed that UPEC significantly compromised urothelial integrity, barrier function, and permeability, with loss of urothelial cells, uroplakins, and tight junction protein ZO-1 expression. Additionally, infected bladders exhibited a markedly enhanced contractile response to serotonin compared to uninfected controls. Notably, neither cranberry nor d-mannose offered protection against UPEC-mediated damage or mitigated the heightened serotonin-induced contractility. This study provides novel insights into how UPEC disrupts bladder cell biology and highlights the possible involvement of serotonin in the pathophysiology of UTIs., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Background: Significant research, regulatory bodies and even governmental resolutions have identified meaningful nutrition education for medical and other healthcare professionals as a priority. Doctors are well placed to provide nutrition care, yet nutrition education in medicine remains inadequate regardless of country, setting, or year of training. There remains a need to establish an accepted benchmark on nutrition competencies for medicine, as without consensus standards there is little likelihood of uniform adoption., Objective: This study aimed to establish consensus on nutrition competencies using a Delphi process to inform a framework for nutrition education in medicine., Methods: A three-round modified online Delphi survey of experts in healthcare practice, education and training, and experts by experience (service users) was conducted to provide a comprehensive consensus on nutrition competencies for medical practice., Results: Fifty-two experts (15.1% response rate) participated in Round 1, 42 completed Round 2 and 47 completed Round 3. Participants included medical professionals, dietitians, academics working in health professions education and policymakers from Australia, New Zealand, the UK and Northern Ireland. Twenty-seven service users (57.5% response rate) completed the Round 1 questionnaire, 19 completed Round 2 and 16 completed Round 3. By consensus, 25 nutrition competencies for medicine were defined. The service user panel identified an additional seven skills and attributes considered important in the receipt of nutrition care. Competencies that achieved consensus broadly fell into themes of team-based care, communication, professionalism (eg, attributes) and health promotion and disease prevention. This informs broad skills that may be taught in a nutrition context but could be included in other domains., Conclusions: The findings suggest doctors need the knowledge and skills to consider the findings from nutrition screening and assessment, coordinate nutrition care when an individual may benefit from further assessment or intervention and provide support for advice delivered by other experts as part of a multidisciplinary approach., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: The shortfall in medical workers in rural and remote Australia has led to health discrepancies in these regions. The University of Wollongong's medical program was designed to encourage graduates to work in these regions to address this shortfall., Objective: To compare rural and regional locations of work and choices of speciality between University of Wollongong's graduates and graduates from all Australian universities., Design: We conducted a longitudinal analysis on data available from the Medical Schools Outcome database, with graduate exit surveys linked to registrations of location and speciality. Rural and remote locations were identified as MM2-7 regions using the Modified Monash Model. In total, 716 graduates from the University of Wollongong and 26 915 graduates from all Australian medical schools completed the MSOD exit survey in 2010-2021 and registered with the Australian Health Practitioner Regulation Agency in 2022. The main outcome was the relative likelihood (relative risk) of cohorts working in rural and regional areas and of cohorts choosing general practice as their speciality., Findings: University of Wollongong's medical graduates were 1.51 times or 51% more likely to work in regional or rural areas (RR 1.51, 95% CI 1.34 to 1.71, p < 0.0001). Respondents who were 10 or more years post graduation were 1.57 times or 57% more likely to specialise in general practice than all other Australian medical graduates (RR 1.57 95% CI: 1.40 to 1.79, p < 0.0001)., Discussion: The University of Wollongong's medical school is producing graduates to meet Australia's rural health workforce needs. This may be due to a higher intake of rural students, and a higher percentage of students taking rural placements., Conclusions: Rural health workforce needs can be addressed through rural-focussed education strategies., (© 2023 The Authors. Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)

Ulcerative Colitis (UC), a type of Inflammatory Bowel Disease (IBD), is a chronic, relapsing gastrointestinal condition with increasing global prevalence. The gut microbiome profile of people living with UC differs from healthy controls and this may play a role in the pathogenesis and clinical management of UC. Probiotics have been shown to induce remission in UC; however, their impact on the gut microbiome and inflammation is less clear. Anthocyanins, a flavonoid subclass, have shown anti-inflammatory and microbiota-modulating properties; however, this evidence is largely preclinical. To explore the combined effect and clinical significance of anthocyanins and a multi-strain probiotic, a 3-month randomised controlled trial will be conducted in 100 adults with UC. Participants will be randomly assigned to one of four groups: anthocyanins (blackcurrant powder) + placebo probiotic, probiotic + placebo fruit powder, anthocyanin + probiotic, or double placebo. The primary outcome is a clinically significant change in the health-related quality-of-life measured with the Inflammatory Bowel Disease Questionnaire-32. Secondary outcomes include shotgun metagenomic sequencing of the faecal microbiota, faecal calprotectin, symptom severity, and mood and cognitive tests. This research will identify the role of adjuvant anti-inflammatory dietary treatments in adults with UC and elucidate the relationship between the gut microbiome and inflammatory biomarkers in this disease, to help identify targeted individualised microbial therapies. ANZCTR registration ACTRN12623000630617., (© The Author(s) 2024.)

Introduction: Addressing the imbalance of the health workforce between metropolitan and rural areas requires a clear understanding of trends in choices of work location of health care staff., Objective: Here, we provide an automated and highly reproducible protocol to examine the location of health care workers over multiple years using medical graduates as a case study., Design: Data linkage cohort study. The study cohort examined was University of Wollongong Medical graduates from 2010 to 2021 who were registered to practice in Australia. The main outcome measure was graduate location of practice in Modified Monash regsions MM1 or MM2-7 across multiple postgraduate years. This protocol used R Markdown., Findings: An automated and reproducible protocol was used to analyse choices of work location for the University of Wollongong's medical graduates. Over 90% of graduates were registered with AHPRA. Around 25%-30% of graduates were found to work in MM2-7 regions across their careers, exceeding the national average., Discussion: The protocol presented allows for a fast and reproducible analysis of work location by region for health care workers. This will allow comparisons of outcomes between universities or health professions., (© 2023 The Authors. Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)

Introduction: The main function of the urinary tract is to form an impermeable barrier against urinary solutes and bacteria. However, this barrier can be compromised by urinary tract infections, most commonly caused by uropathogenic Escherichia coli (UPEC). This can result in damage to the epithelial barrier, leading to decreased epithelial thickness, loss of tight junctions, loss of epithelial integrity, and apoptosis. Due to the rise in antimicrobial resistance, there is worldwide interest in exploring non-antibiotic agents as alternative therapy., Methods: Using the Madin-Darby canine kidney (MDCK) cell line, a widely accepted epithelial cell model for the urinary tract, and the UPEC strain UTI89, this paper aimed to investigate the impact of UPEC on cell integrity, permeability, and barrier functions, and determine whether cranberry, D-mannose and ibuprofen could counteract the effects induced by UPEC. Furthermore, the study examined the protective potential of these agents against UPEC-induced increase in reactive oxygen species (ROS) production and programmed death-ligand 1 (PD-L1) expression., Results: The results demonstrated that UTI89 caused a marked reduction in cell viability and monolayer integrity. Cranberry (3 mg/mL) was protective against these changes. In addition, cranberry exhibited protective effects against UPEC-induced damage to cell barrier integrity, escalation of oxidative stress, and UPEC/TNFα-triggered PD-L1 expression. However, no effect was observed for D-mannose and ibuprofen in alleviating UPEC-induced cell damage and changes in ROS and PD-L1 levels., Conclusion: Overall, cranberry, but not D-mannose or ibuprofen, has a protective influence against UPEC associated damage in urinary epithelial cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Konesan, Wang, Moore, Mansfield and Liu.)

Background: Poor diet is implicated in multiple chronic diseases. Although doctors may be well placed to facilitate nutrition care, nutrition remains a low priority in medical education internationally. Consensus is required on nutrition competencies as a benchmark for education with a regulatory framework to ensure implementation. The aim of this qualitative study was to explore work roles, attitudes, barriers and enablers in the delivery of nutrition care among a cohort of Australian and UK doctors., Method: Semi-structured interviews were conducted with primary care doctors/general practitioners (n = 14) and medical specialists (n = 8) based in Australia and the United Kingdom to explore work roles, attitudes, barriers and enablers in the delivery of nutrition care., Results: Framework analysis identified five key themes: (1) knowledge and skills in nutrition to support medical nutrition care, (2) the delivery of nutrition education, (3) multidisciplinary and interdisciplinary care, (4) systemic barriers and facilitators to care and (5) the need for a paradigm shift. Participants acknowledged nutrition as an important component of medical care but recognised they are currently ill-equipped to support such care, identifying limitations to the systems supporting integrated care. Participants identified that nutrition sits within both a health promotion and medical/treatment model, but they currently work only within the latter., Conclusion: Participants highlighted a lack of knowledge and training regarding nutrition, without which change is not possible. Efforts to improve the nutrition capacity of the medical workforce must be matched by increased investments in primary prevention, including nutrition - a paradigm shift from the medical model., (© 2022 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is a cause for concern. Optimal treatment of UTI relies upon the selection of an agent which displays appropriate pharmacokinetic-pharmacodynamic (PK-PD) properties that will deliver appropriately high concentrations in the urinary tract after oral administration. Alternatively, high local concentrations of antibiotic at the urothelial surface can be achieved by direct instillation into the urinary tract. For antibiotics with the appropriate physicochemical properties, this can be of critical importance in cases for which an intracellular urothelial bacterial reservoir is suspected. In this review, we summarise the underpinning biopharmaceutical barriers to effective treatment of UTI and provide an overview of the evidence for the deployment of the intravesical administration route for antibiotics.

The use of antibiotics in the treatment of UTIs is contributing to resistance. Hence, the outcome of human clinical trials of nonantibiotic remedies for preventing or treating UTI is of significant interest. This systematic review aimed to identify, summarise and evaluate the evidence for the outcomes of different nonantibiotic options including cranberry, D-mannose and non-steroidal anti-inflammatory drugs (NSAIDs). PubMed, Embase and Scopus were searched for manuscripts relating to nonantibiotic treatment of UTI including cranberry, mannose and NSAIDs. After title and abstract screening, data were extracted from 21 papers that were published in English and related to the treatment or prevention of uncomplicated UTI in adult women. We identified twelve papers examining the effects of cranberry, two papers examining D-mannose, two papers examining combination treatments (cranberry and D-mannose) and five manuscripts investigating the effects of NSAIDs. There is low-level evidence, from a small number of studies, supporting the use of D-mannose or combination treatments for potentially preventing UTIs in adult women without producing burdening side effects. However, larger and more randomised double-blinded trials are needed to confirm this. In comparison, the multiple studies of cranberry and NSAIDs produced conflicting evidence regarding their effectiveness.

Purpose: This qualitative secondary analysis describes the perceived importance of familial, peer, and health system social support for an understudied group of cancer survivors: young adults (YAs), including those who are lesbian, gay, bisexual, transgender, and/or queer (LGBTQ). Methods: Semistructured interviews were conducted with YA cancer survivors as part of a study of social support networks and interactions. Team members conducted content analysis of interview transcripts; coding decisions were reviewed and discussed among the research team. Descriptions of social support were ultimately organized around family, peer, and health care system support. Results: Twelve YA survivors recruited using two National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and social media participated between August 2019 and May 2020. Survivors averaged 28.2 years old. Half of survivors self-identified as female; four survivors were LGBTQ. Participants described both the positives of social support, as well as barriers to meeting support needs, within the following three levels: familial, peer, and health care providers or system. Conclusion: YA survivors have needs that are often addressed by their families, peers, and the health care system. However, barriers such as complex relationship history and lack of targeted/tailored support programs can prevent survivors from receiving adequate support. The growing diversity and intersectionality represented in the YA population call for targeted support and training by the health care system to sufficiently support this population.

A recurrent urinary tract infection (UTI) is a common debilitating condition whereby uropathogens are able to survive within the urinary tract. In this study, we aimed to determine if the common uropathogens Escherichia coli , Enterococcus faecalis , and Group B Streptococcus possessed virulence mechanisms that enable the invasion of urothelial cells. Urothelial cells were isolated from women with detrusor overactivity and recurrent UTIs; the intracellular localisation of the uropathogens was determined by confocal microscopy. Uropathogens were also isolated from women with acute UTIs and their intracellular localisation and virulence mechanisms were examined (yeast agglutination, biofilm formation, and haemolysis). Fluorescent staining and imaging of urothelial cells isolated from women with refractory detrusor overactivity and recurrent UTIs demonstrated that all three uropathogens were capable of intracellular colonisation. Similarly, the bacterial isolates from women with acute UTIs were also seen to intracellularly localise using an in vitro model. All Enterococcus and Streptococcus isolates possessed a haemolytic capacity and displayed a strong biofilm formation whilst yeast cell agglutination was unique to Escherichia coli . The expression of virulence mechanisms by these uropathogenic species was observed to correlate with successful urothelial cell invasion. Invasion into the bladder urothelium was seen to be a common characteristic of uropathogens, suggesting that bacterial reservoirs within the bladder contribute to the incidence of recurrent UTIs.

Purpose: The purpose of this study was to test the feasibility, usability, and acceptability of implementing a web-based method for collecting social network and longitudinal daily interaction data from cancer survivors and their caregivers., Methods: Young adult and sexual/gender minority cancer survivors and their informal caregivers were recruited as dyads. Feasibility data, including enrollment and retention, were captured. Individual social network data were collected at baseline and used to individualize daily electronically delivered surveys assessing characteristics of daily social support-related interactions with identified network members for 14 days. Follow-up questionnaires assessing usability and exit interviews assessing acceptability were completed at the end of the 2-week study period., Results: Fourteen survivor-caregiver dyads (28 individual participants) were enrolled and completed all baseline and final measures. Participants completed 85.2% of daily diary reports and reported excellent usability ratings. Acceptability was also high. In qualitative interviews, participants reported enjoying the daily reflection on social support facilitated by our methods., Conclusions: Our method has been shown to be highly feasible, usable, and acceptable., Implications for Cancer Survivors: Developing better data collection tools can lead to better understanding of the social support cancer survivors and their caregivers receive, and how the social network structure facilitates or creates barriers to accessing this support., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The purpose of the study was to understand care partner (CP) perceptions of an interdisciplinary diabetes self-management education and support (DSMES) intervention and explore how the interdisciplinary DSMES intervention influences diabetes-specific day-to-day interactions from the CP's perspective., Methods: A multiple-methods research design comprised of an online survey including demographics and supportive behaviors and a semistructured interview was conducted. The survey was completed by 16 CPs. Of the 16 CPs, 11 participated in semistructured interviews. Survey data were analyzed using descriptive statistics. Thematic analysis of semistructured interviews was conducted., Results: CPs provided support in 3 primary areas: (1) meal planning and preparation (87.5%), (2) participating in physical activity (56.3%), and (3) assisting with technology (43.8%). The main themes described by CPs include (1) the importance of diabetes education for caregivers, including the information they retained from the program, the acquisition of tools to support the person with diabetes, and the desire for more and ongoing education; (2) diabetes education enhances the CP's ability to provide social support and the challenges associated with support; and (3) partners described collaborative diabetes management such as finding middle ground and making changes together., Conclusion: CPs play a significant role in patient diabetes self-management by providing social support and partnership. DSMES programs should seek to include CPs to enhance patient support.

Overactive bladder (OAB) is a clinical syndrome defined by urinary urgency, increased daytime urinary frequency and/or nocturia, with or without urinary incontinence, that affects approximately 11% of the western population. OAB is accepted as an idiopathic disorder, and is charactersied clinically in the absence of other organic diseases, including urinary tract infection. Despite this, a growing body of research provides evidence that a significant proportion of OAB patients have active bladder infection. This review discusses the key findings of recent laboratory and clinical studies, providing insight into the relationship between urinary tract infection, bladder inflammation, and the pathophysiology of OAB. We summarise an array of clinical studies that find OAB patients are significantly more likely than control patients to have pathogenic bacteria in their urine and increased bladder inflammation. This review reveals the complex nature of OAB, and highlights key laboratory studies that have begun to unravel how urinary tract infection and bladder inflammation can induce urinary urgency and urinary frequency. The evidence presented in this review supports the concept that urinary tract infection may be an underappreciated contributor to the pathophysiology of some OAB patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mansfield, Chen, Moore and Grundy.)

Background: Pediatric palliative care (PPC) consultation is infrequent among children on extracorporeal membrane oxygenation (ECMO). Objective: Investigate intensive care unit (ICU) team members' perceptions of automatic PPC consultation for children on ECMO in an ICU in the United States. Methods: Cross-sectional survey assessing benefits, barriers to PPC, and consultation processes. Results: Of 291 eligible respondents, 48% ( n  = 140) completed the survey and 16% ( n  = 47) answered an open-ended question. Benefits included support in decision-making ( n  = 98; 70%) and identification of goals of care ( n  = 89; 64%). Barriers included perception of giving up on families ( n  = 59; 42%) and poor acceptability by other team members ( n  = 58; 41%). Respondents endorsed communication with the primary ICU team before ( n  = 122; 87%) and after ( n  = 129; 92%) consultation. Open-ended responses showed more positive (79% vs. 13%) than negative statements. Positive statements reflected on expanding PPC to other critically-ill children where negative statements revealed unrecognized value in PPC. Conclusions: Results demonstrate opportunities for education about the scope of PPC and improvements in PPC delivery.

Patients undergoing chemotherapy with cyclophosphamide experience cystitis due to excretion of a toxic metabolite, acrolein. Cystitis, an inflammation of the bladder, is associated with damage to the integrity of the urothelial barrier. The purinergic P2X7 receptor (P2X7R) is increasingly recognized for its role in inflammation and cell death. P2X7R is expressed abundantly on the bladder urothelium. The aim of this study was to investigate the role of P2X7R in acrolein-induced inflammatory damage in primary cultured porcine bladder urothelial cells. Confluent urothelial cells in culture were treated with acrolein to induce damage; also, with the P2X7R selective antagonist, A804598. Cell viability assay, immunocytochemistry, and trans-epithelial electrical resistance (TEER) studies were carried out to investigate the effect of treatments on urothelial cell function. Acrolein induced a significant reduction in urothelial cell viability, which was protected by the presence of A804598 (10 µM). The urothelial barrier function, indicated by TEER values, was also significantly reduced by acrolein, whereas pre-incubation with P2X7R antagonist significantly protected the urothelial cell barrier from acrolein-induced TEER reduction. The structure of urothelial cell tight junctions was similarly impacted by acrolein treatment, showing the fragmentation of zona occludens-1 (ZO-1) immunoreactivity. Pre-treatment of cells with A804598 countered against the actions of acrolein and maintained ZO-1 expression level and cell structure. The damaging effect of acrolein on urothelial cells integrity could be impaired by inhibition of P2X7R, therefore P2X7R blockade may be a possible therapy in patients with bladder cystitis caused by cyclophosphamide treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Taidi, Mansfield, Sana-Ur-Rehman, Moore and Liu.)

Purpose: The purpose of this study was to describe the social support networks and daily support interactions of cancer-affected individuals, including young adult (YA) and LGBTQIA+ survivors and care partners., Methods: Participants were recruited at two United States cancer centers and via social media for a pilot study testing a novel online method for collecting prospective, daily social support interaction data (N=28). All participants were aged 18+; survivors had a current or recent cancer diagnosis and were engaged in treatment and/or services; care partners were identified by the survivors. Enrollment also purposefully targeted YA and LGBTQIA+ survivors. Social network data (up to 10 members) were assessed at baseline. Daily online surveys assessed support interactions between participants and specific network members over 14 days. Descriptive statistics summarized data and explored between-group (YA/non-YA, LGBTQIA+/non-LGBTQIA+) differences in social network characteristics (size, heterogeneity, density, centralization, cohesion) and support interactions (support source and type)., Results: There were no significant differences between YA and non-YA participants on any measures. LGBTQIA+ participants' support networks were less dense (Mdn=0.69 vs. 0.82, p=.02), less cohesive (Mdn=0.85 vs. 0.91,.02), more centered on the participant (Mdn=0.40 vs. 0.24, p=.047), and included more LGBTQIA+ members (Mdn=0.35 vs. 0.00, p<.001). LGBTQIA+ participants reported having more interactions with LGBTQIA+ network members (Mdn=14.0 vs. Mdn=0.00, p<.001) and received significantly more of all types of support from LGBTQIA+ vs. non-LGBTQIA+ members. LGBTQIA+ participants also reported receiving more appraisal support than non-LGBTQIA+ (Mdn 21.64 vs. 9.12, p=.008) including more appraisal support from relatives (Mdn=11.73 vs 6.0, p+.037)., Conclusions: Important information related to support access, engagement, and needs is embedded within the everyday contexts of the social networks of cancer-affected people. Individualized, accessible, and prospective assessment could help illuminate how their "real world" support systems are working and identify specific strengths and unmet needs. These insights would inform the development of more culturally competent and tailored interventions to help people understand and leverage their unique support systems. This is particularly critical for groups like YA and LGBTQIA+ survivors and care partners that are underserved by formal support services and underrepresented in cancer, caregiving, and social support research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cloyes, Guo, Tennant, McCormick, Mansfield, Wawrzynski, Classen, Jones and Reblin.)

Aims: Application of exogenous nucleotides can modulate wound healing via the activation of purinergic receptors. However, evidence for the release of endogenous nucleotides and the subsequent activation of purinergic receptors in this process has not been well defined. Therefore, the current study aimed to investigate wound-mediated nucleotide release and autocrine purinergic signalling during HaCaT keratinocyte wound closure following scratch injury., Main Methods: An in vitro scratch wound apparatus was employed to study wound healing over 24-h in the presence of modulators of ATP release, P2 receptors and pathways downstream of P2 receptor activation., Key Findings: Adenosine 5'-triphosphate (ATP) was released from scratched cells. The ectonucleotidase apyrase and pharmacological inhibition of the nucleotide release hemichannel, pannexin-1, decreased wound closure over time. The non-selective P2Y receptor antagonist suramin and the selective P2Y 2 receptor antagonist AR-C118925XX, but not other P2 antagonists, decreased wound closure. AR-C118925XX decreased wound closure in a concentration-dependent fashion. However, exogenous P2Y 2 receptor agonists, ATP or uridine 5'-triphosphate, did not enhance wound closure. PCR and immunoblotting confirmed P2Y 2 receptor expression in HaCaT cells. U73122, a phospholipase C antagonist, and 2-aminoethoxydiphenylborate, an inositol 1,4,5-trisphosphate receptor-sensitive Ca 2+ -release channel antagonist, decreased wound closure consistent with P2Y 2 receptor activation. Absence of extracellular or intracellular Ca 2+ or inhibition of intracellular Ca 2+ -release also impaired wound closure., Significance: These data describe a novel autocrine signalling mechanism in which wound-mediated release of endogenous ATP in response to mechanical scratching of HaCaT cells activates P2Y 2 receptors to facilitate wound closure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Transitioning from education to practice is stressful for new nurses and those entering new roles and can lead to workforce attrition and burnout. This dynamic is likely complicated when graduates are transitioning to practice during a pandemic., Purpose: The purpose of this study was to describe recent nurse graduates' perceptions of the impact of the COVID-19 pandemic on their transition from education to practice., Methods: We conducted an online survey of BSN, RN-BSN, and DNP students who graduated between December 2019 and April 2020 (n = 82), including demographics, employment information, and free-response questions about the impact of the pandemic on their transition experiences, post-graduation plans, and perceptions of nursing. We used a qualitative descriptive approach to content analysis to synthesize and summarize the data., Results: Participants expressed three overarching concerns: 1) altered plans such as difficulty finding employment; 2) logistical, system-related stressors including licensing delays and chaotic onboarding; and 3) feeling pride in profession despite perceiving ambivalence in public discourse., Conclusion: COVID-19 exacerbated challenges often experienced by new graduates. Common stressors, intensified during the pandemic, could exert long-term effects on the workforce. Educators and healthcare organizations must work to ensure nursing graduates receive the necessary support for a successful transition., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Inflammatory conditions of the urinary bladder have been shown to be associated with urothelial damage and loss of function. The purinergic P2X7 receptor has been implicated in several inflammatory conditions. The aim of this study was to investigate the role of the P2X7 receptor in acrolein-induced inflammatory damage using the porcine urinary bladder. For this purpose, an ex-vivo model of porcine urothelial damage induced by direct instillation of acrolein into the whole bladder lumen was used. To determine the role of the P2X7 receptor, the bladders were pre-incubated with a selective P2X7 receptor antagonist, A804598 (10 μM), for 1 h. The effects of the acrolein-induced urothelial damage on the bladder's function were assessed by examining the bladder wall contractile response, structure changes, apoptosis, and oxidative stress in the bladder tissues. The acrolein treatment led to significant damage to the urothelium histology, tight junction expression, and contractile responses. Acrolein also induced apoptosis in the mucosa layer. All these acrolein-induced responses were attenuated by pre-treatment with the P2X7 receptor antagonist A804598. Acrolein also significantly induced DNA oxidation in the submucosal layer; however, the P2X7 receptor antagonism did not show any protective effect towards the acrolein-induced oxidative stress. These findings suggested that the P2X7 receptor is involved in the acrolein-induced damage to the urothelium; therefore, the P2X7 receptor antagonists may be a new therapeutic option for the treatment of bladder inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Taidi, Zhou, Moore, Mansfield and Liu.)

Bacterial infection may have a pathophysiological role in refractory Detrusor Overactivity (DO). The aim of this study was to observe any impact of antibiotic therapy upon bacterial colonization of urothelial cells, and to determine whether a relationship existed between colonization and symptom severity. Mid-stream urine samples were collected as part of a clinical trial of antibiotics in women with refractory DO. Wright stained urothelial cells were categorized according to the degree of bacterial colonization as; 'clear' (free of bacteria), or as associated with bacteria that were 'adjacent' to the cell or 'intracellular' at low or high density. The average percentages were compared with routine microbiology cultures, over the 26 week trial, and with patient clinical outcome measures of DO severity. In patients receiving placebo, 'high-density intracellular bacteria' significantly increased during urinary tract infection (P = 0.0008). In antibiotic patients, 'clear' cells were more prevalent. Amoxicillin & Clavulanic Acid significantly decreased bacterial colonization within urothelial cells, suggesting that these antibiotics possess the greatest intracellular efficacy. 'High-density intracellular bacteria' positively correlated with symptom severity, measured by leakage on pad test (P = 0.014), leaks per day (P = 0.004), and voids per day (P = 0.005). Thus, by decreasing high density intracellular bacteria, antibiotic treatment may improve the refractory DO condition., (© The Author(s) 2021. Published by Oxford University Press on behalf of FEMS. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

For men with newly diagnosed prostate cancer the decisions about treatment options are complex and difficult. The aim of this study was to investigate any association between the extent to which men wanted to be involved in the decision making process, their satisfaction with that process, and their levels of decision regret after treatment. The study population consisted of men diagnosed with prostate cancer at a regional center in Australia. Men ( n = 324) were invited to complete a mail out survey which included demographic questions, the treatment chosen, and three validated tools: The Control Preference Scale to measure the degree of control assumed when making decisions about medical interventions; the Treatment Decision-Making Satisfaction Scale (TDM- SAT) to assess satisfaction with the treatment decision making process; and the Decision Regret Scale to assess the level of regret after treatment. The majority of the 151 respondents (47% response rate) expressed an active decision control preference. There was no correlation between age and the treatment chosen or the degree of control men exerted over the decision-making process. Men who preferred a passive role were less satisfied with the decision-making process than were those who took an active or collaborative approach. A strong inverse correlation was demonstrated between regret experienced and satisfaction with the decision-making process. In conclusion, for men newly diagnosed with prostate cancer, taking an active role in the treatment decision making process led to greater satisfaction with that process, which in turn reduced their chances of experiencing regret following treatment.

Pediatric palliative care (PPC) provides an extra layer of support for families caring for a child with complex heart disease as these patients often experience lifelong morbidities with frequent hospitalizations and risk of early mortality. PPC referral at the time of heart disease diagnosis provides early involvement in the disease trajectory, allowing PPC teams to longitudinally support patients and families with symptom management, complex medical decision-making, and advanced care planning. We analyzed 113 hospitalized pediatric patients with a primary diagnosis of heart disease and a PPC consult to identify timing of first PPC consultation in relation to diagnosis, complex chronic conditions (CCC), and death. The median age of heart disease diagnosis was 0 days with a median of two CCCs while PPC consultation did not occur until a median age of 77 days with a median of four CCCs. Median time between PPC consult and death was 33 days (interquartile range: 7-128). Death often occurred in the intensive care unit ( n  = 36, 67%), and the most common mode was withdrawal of life-sustaining therapies ( n  = 31, 57%). PPC referral often occurred in the context of medical complexity and prolonged hospitalization. Referral close to the time of heart disease diagnosis would allow patients and families to fully utilize PPC benefits that exist outside of end-of-life care and may influence the mode and location of death. PPC consultation should be considered at the time of heart disease diagnosis, especially in neonates and infants with CCCs., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Objective: Globally, 11 million deaths are attributable to suboptimal diet annually, and nutrition care has been shown to improve health outcomes. While medically trained clinicians are well-placed to provide nutrition care, medical education remains insufficient to support clinicians to deliver nutrition advice as part of routine clinical practice. Competency standards provide a framework for workforce development and a vehicle for aligning health priorities with the values of a profession. Although, there remains an urgent need to establish consensus on nutrition competencies for medicine. The aim of this review is to provide a critical synthesis of published nutrition competencies for medicine internationally., Design: Integrative review., Data Sources: CINAHL, Medline, Embase, Scopus, Web of Science and Global Health were searched through April 2020., Eligibility Criteria: We included published Nutrition Competency Frameworks. This search was complemented by handsearching reference lists of literature deemed relevant., Data Extraction and Synthesis: Data were extracted into summary tables and this matrix was then used to identify common themes and to compare and analyse the literature. Miller's pyramid, the Knowledge to Action Cycle and the Dreyfus model of skill acquisition were also used to consider the results of this review., Results: Using a predetermined search strategy, 11 articles were identified. Five common themes were identified and include (1) clinical practice, (2) health promotion and disease prevention, (3) communication, (4) working as a team and (5) professional practice. This review also identified 25 nutrition competencies for medicine, the majority of which were knowledge-based., Conclusions: This review recommends vertical integration of nutrition competencies into existing medical education based on key, cross-cutting themes and increased opportunities to engage in relevant, skill-based nutrition training., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Poor diet is a leading cause of death worldwide. Doctors are well placed to provide dietary advice, yet nutrition remains insufficiently integrated into medical education. Enforcement of curriculum or accreditation requirements such as nutrition requires relevant regulatory frameworks. The aim of this review was to identify nutrition content or requirements for nutrition education in accreditation standards or formal curriculum guidance for medical education internationally., Design: Non-systematic comparative analysis., Data Sources: An internet search using the Google Search engine, the WHO Directory of Medical Schools and Foundation for Advancement of International Medical Education and Research Directory of Organizations that Recognise/Accredit Medical Schools was conducted through September 2020 to identify government and organisational reports as well as publications from regulatory and professional bodies relevant to medical education., Eligibility Criteria: Eligible publications included (A) accreditation standards, (B) competency standards or a framework, (C) curricula, and (D) assessment content., Data Extraction and Synthesis: We stratified findings by country or region and both preregistration and postregistration education. Findings were synthesised based on the existence of nutrition content or requirements for nutrition education within systems used to guide medical education internationally., Results: This review found that despite an emphasis on meeting the needs of the community and the demands of the labour market, only 44% of accreditation and curriculum guidance included nutrition. Nutrition remains inadequately represented in accreditation and curriculum guidance for medical education at all levels internationally. Accreditation standards provide a mandated framework for curricula and inclusion of nutrition in accreditation frameworks provides an incentive for the integration of nutrition into medical education., Conclusions: This review is a call to action for the medical profession including government, health agencies and educational and accreditation entities. The inclusion of nutrition in medical education has appeared throughout medical education literature for more than five decades, yet without consensus standards there is little likelihood of uniform adoption., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Over 50% of women with detrusor overactivity (DO), who do not respond to therapy have been shown to have bacteriuria, which may stimulate the release of inflammatory cytokines than can enhance nerve signalling, leading to symptoms of urgency. This study made use of a consecutive series of urine samples collected from women with refractory DO, who participated in a clinical trial of rotating antibiotic therapy. The aim was to determine the effect of bacteriuria and antibiotic treatment on the levels of urinary cytokines, and to correlate the cytokine concentration with patient outcome measures relating to urgency or urge incontinence. The urinary cytokines chosen were IL-1α, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, CXCL10 (IP-10), MCP-1 and TNF-α. The presence of bacteriuria stimulated a significant increase in the concentrations of IL-1α (P 0.0216), IL-1 receptor antagonist (P 0.0264), IL-6 (P 0.0003), IL-8 (P 0.0043) and CXCL-10 (P 0.009). Antibiotic treatment significantly attenuated the release of IL-1α (P 0.005), IL-6 (P 0.0027), IL-8 (P 0.0001), IL-10 (P 0.049), and CXCL-10 (P 0.042), i.e. the response to the presence of bacteria was less in the antibiotic treated patients. Across the 26 weeks of the trial, antibiotic treatment reduced the concentration of five of the nine cytokines measured (IL-1α, IL-6, IL-8, IL-10 and CXCL-10); this did not reach significance at every time point. In antibiotic treated patients, the urinary concentration of CXCL-10 correlated positively with four of the six measures of urgency. This study has shown that cytokines associated with activation of the innate immune system (e.g. cytokines chemotactic for or activators of macrophages and neutrophils) are reduced by antibiotic therapy in women with refractory DO. Antibiotic therapy is also associated with symptom improvement in these women, therefore the inflammatory response may have a role in the aetiology of refractory DO., Competing Interests: The authors have declared that no competing interests exist.

Aim: Because bacterial cystitis is common in women with refractory detrusor overactivity, the aim was to compare the efficacy of 6 weeks of rotating antibiotics versus placebo, in conjunction with an anticholinergic, in controlling the symptoms of urge incontinence., Methods: In a multicenter phase IIb double-blinded randomized placebo-controlled trial, women with urodynamically proven refractory detrusor overactivity were randomized in a 2:1 ratio of antibiotics versus placebo for 6 weeks, in addition to darifenacin for 6 months. Any woman with disabling cystitis symptoms was given appropriate antibiotics ("clinical override"). The primary outcome was the degree of urge incontinence change at 6 weeks and 6 months on 24-h pad test. Secondary outcomes were changes in leaks and voids per day measured on 3-day bladder diary and quality of life measures. Microbiological data were collected at all visits., Results: Although 278 women were screened, only 36 were randomized and 33 (91.7%) completed the trial. Leakage on 24-h pad test decreased at 6 months by 75 g in patients receiving antibiotics versus 35 g in placebo. Cure of urge incontinence occurred at 6 months in 10/21 (48%) of antibiotics versus 2/12 (17%) of placebo. Clinical override, necessitating treatment of cystitis, occurred in 41.6% of placebo versus 16.7% of the antibiotic group by 6 months., Conclusion: Despite the small sample size, the study showed a significant reduction in pad leakage and leaks per day over 24 h in the active treatment group over a 6-month period. Nearly half of patients on placebo had disabling urinary tract infection symptoms that required clinical override treatment., (© 2020 Wiley Periodicals LLC.)

The prevalence of lifestyle-related chronic disease is increasing. Doctors in primary care are ideally placed to support patient nutrition care, but recent reviews show education is still lacking. This study aimed to identify medical students' attitudes towards the role of nutrition in health, nutrition knowledge, and perceptions of nutrition education, in postgraduate (Australia) and undergraduate (New Zealand) programs in order to identify gaps in nutrition knowledge and skills to better inform future education. Second-year graduate and third-year undergraduate students participated in semi-structured focus groups and interviews. A general inductive approach was used to investigate students' 1) attitudes toward the role of nutrition in health, 2) nutrition knowledge based on nutrition-specific competencies and 3) perceived adequacy of nutrition education received. Interviews (nine) and focus groups (seven) identified four common themes: 1) role of medical practitioners in nutrition care, 2) barriers to nutrition education, 3) nutrition knowledge, and 4) nutrition-related skills. Students perceive that doctors are well-placed to provide some level of nutrition care, but poor translation of nutrition knowledge to clinical contexts is a key limitation in nutrition education. In summary, nutrition education may be insufficient to support the nutrition-related competency development of the undergraduate and postgraduate student participants in this study. Focusing on the integration of these skills into the curriculum may be a priority., Competing Interests: The authors declare no conflict of interest.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic lower urinary tract condition. Patients with IC/BPS suffer from debilitating pain and urinary urgency. The underlying etiology of IC/BPS is unknown and as such current treatments are mostly symptomatic with no real cure. Many theories have been proposed to describe the etiology of IC/BPS, but this review focuses on the role of inflammation. In IC/BPS patients, the permeability of the urothelium barrier is compromised and inflammatory cells infiltrate the bladder wall. There are increased levels of many inflammatory mediators in patients with IC/BPS and symptoms such as pain and urgency that have been associated with the degree of inflammation. Recent evidence has highlighted the role of purinergic receptors, specifically the P2X7 receptor, in the process of inflammation. The results from studies in animals including cyclophosphamide-induced hemorrhagic cystitis strongly support the role of P2X7 receptors in inflammation. Furthermore, the deletion of the P2X7 receptor or antagonism of this receptor significantly reduces inflammatory mediator release from the bladder and improves symptoms. Research results from IC/BPS patients and animal models of IC/BPS strongly support the crucial role of inflammation in the pathophysiology of this painful disease. Purinergic signaling and purinergic receptors, especially the P2X7 receptor, play an undisputed role in inflammation. Purinergic receptor antagonists show positive results in treating different symptoms of IC/BPS., Competing Interests: Competing interests: The authors have declared that no competing interests exist., (© 2013-2019, Bladder, All rights reserved.)

Psoriasis is a chronic inflammatory skin disorder, characterised by epidermal hyperplasia (acanthosis) and leukocyte infiltration of the skin. Current therapies are inadequate, highlighting the need for new therapeutic targets. The P2X7 receptor is implicated in the pathogenesis of psoriasis. This study investigated the role of P2X7 in imiquimod (IMQ)-induced psoriasis-like inflammation. Topically applied IMQ caused twofold greater ear swelling in BALB/c mice compared to C57BL/6 mice, which encode a partial loss-of-function missense mutation in the P2RX7 gene. However, there was no difference in histological skin pathology (acanthosis and leukocyte infiltration) between the two strains. IMQ treatment up-regulated P2X7 expression in skin from both mouse strains. Additionally, IMQ induced ATP release from cultured human keratinocytes, a process independent of cell death. Injection of the P2X7 antagonist Brilliant Blue G (BBG) but not A-804598 partly reduced ear swelling compared to vehicle-injected control mice. Neither antagonist altered skin pathology. Moreover, no difference in ear swelling or skin pathology was observed between C57BL/6 and P2X7 knock-out (KO) mice. Flow cytometric analysis of IMQ-treated skin from C57BL/6 and P2X7 KO mice demonstrated similar leukocyte infiltration, including neutrophils, macrophages and T cells. In conclusion, this study demonstrates that P2X7 is not essential for development of IMQ-induced psoriasis-like inflammation but does not exclude a role for this receptor in psoriasis development in humans or other mouse models of this disease.

ATP release from urinary bladder is vital for afferent signaling. The aims of this study were to localize calcium homeostasis modulator 1 (CALHM1) and pannexin-1 expression and to determine their involvement in mediating ATP release in the bladder. To determine gene expression and cellular distribution, PCR and immunohistochemistry were performed, respectively, in the porcine bladder. CALHM1 and pannexin-1-mediated ATP release in response to hypotonic solution (0.45% NaCl)-induced stretch, and extracellular Ca 2+ depletion ([Ca 2+ ] 0 ) was measured in isolated urothelial, suburothelial, and detrusor muscle cells. CALHM1 and pannexin-1 mRNA and immunoreactivity were detected in urothelial, suburothelial, and detrusor muscle layers, with the highest expression on urothelium. Hypotonic stretch caused a 2.7-fold rise in ATP release from all three cell populations ( P < 0.01), which was significantly attenuated by the pannexin-1 inhibitor, 10 Panx1, and by the CALHM1 antibody. Brefeldin A, a vesicular transport inhibitor, and ruthenium red, a nonselective CALHM1 channel blocker, also significantly inhibited stretch-mediated ATP release from urothelial cells. [Ca 2+ ] 0 caused a marked, but transient, elevation of extracellular ATP level in all three cell populations. CALHM1 antibody and ruthenium red inhibited [Ca 2+ ] 0 -induced ATP release from urothelial cells, but their effects on suburothelial and detrusor cells were insignificant. 10 Panx1 showed no significant inhibition of [Ca 2+ ] 0 -induced ATP release in any types of cells. The results presented here provide compelling evidence that pannexin-1 and CALHM1, which are densely expressed in the porcine bladder, function as ATP release channels in response to bladder distension. Modulation of extracellular Ca 2+ may also regulate ATP release in the porcine bladder through voltage-gated CALHM1 ion channels., (Copyright © 2017 the American Physiological Society.)

Evidence-based medical practice is best achieved by developing research understanding in medical practitioners. To this end, medical councils worldwide increasingly recognise the importance of medical schools graduating students with well-developed research skills and research capacity. To meet this need, the principles of programmatic assessment were implemented in designing a research and critical analysis curriculum and assessment program that aimed to enhance the research and critical analysis skills of medical students. The program was developed by mapping assessment tasks to a research capabilities framework that was in turn scaffolded to different levels of Miler's pyramid. The curriculum and assessments were integrated with the science, clinical, and professional aspects of the medical course. The progressive longitudinal development of research skills, with feedback and academic mentoring, culminated in the students' capacity to undertake an independent research project. Designing an assessment program for learning encouraged students to develop their research capacity by involving them in their learning., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The role of subclinical infection in patients with urge incontinence has been largely ignored. The aim of this study was to test for the presence of intracellular bacteria in exfoliated urothelial cells obtained from the urine of patients with detrusor overactivity or mixed incontinence +/- a history of UTI, and compare this to a control group of patients with stress incontinence and no history of infection. Bacterial cystitis was assessed by routine microbiology and compared to microscopic analysis of urine by Wright staining. Subsequent analysis of urothelial cells by confocal microscopy was performed to determine the existence of intracellular bacteria. Bacterial cystitis was seen in 13% of patients based on routine microbiology. Wright staining of concentrated urothelial cells demonstrated the presence of bacteria in 72% of samples. Filamentous bacterial cells were observed in 51% of patients and were significantly more common in patients with detrusor overactivity. Intracellular Escherichia coli were observed by confocal microscopy. This study supports the possibility that a subset of patients with urge incontinence may have unrecognised chronic bacterial colonisation, maintained via an intracellular reservoir. In patients with negative routine microbiology, application of the techniques used in this study revealed evidence of infection, providing further insights into the aetiology of urge incontinence., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc/μl) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/μl). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ∼80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients., (Copyright © 2016 the American Physiological Society.)

Atlanto-occipital dislocation (AOD) is being increasingly recognized as a potentially survivable injury as a result of improved prehospital management of polytrauma patients and increased awareness of this entity, leading to earlier diagnosis and more aggressive treatment. However, despite overall improved outcomes, AOD is still associated with significant morbidity and mortality. The purpose of this paper is to review the biomechanical aspects, clinical features, radiologic criteria, and treatment strategies of AOD. Given that the diagnosis of AOD can be very challenging, a high degree of clinical suspicion is essential to ensure timely recognition and treatment, thus preventing neurological decline or death.

Inflammation is an important contributor to the aetiology of a number of bladder dysfunctions including interstitial cystitis, painful bladder syndrome, and overactive bladder. The aim of this study was to examine the effects of inflammatory mediators on urothelial ATP release. Human urothelial RT4 cells were exposed to normal buffer or varying concentrations of inflammatory mediators (bradykinin, histamine, and serotonin) in the presence or absence of hypotonic stretch stimuli (1 : 2 dilution of Krebs-Henseleit buffer). Others have demonstrated that bradykinin increased stretch-induced ATP release; however, we observed no change in control or stretch-induced ATP release with bradykinin. Pretreatment of RT4 cells with histamine or serotonin decreased stretch-induced ATP release (P = 0.037, P = 0.040, resp.). Previous studies have demonstrated increased ATP release in response to inflammation utilising whole bladder preparations in contrast to our simple model of cultured urothelial cells. The current study suggests that it is unlikely that there is a direct interaction between the release of inflammatory mediators and increased ATP release, but rather more complex interactions occurring in response to inflammation that lead to increased bladder sensation.