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Objective: This study aimed to examine changes in the demographics and regions of work of Australian doctors over a period of 9 years. Methods: A 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. Results: The 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. Conclusion: The 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. What is known about the topic? Changes in the medical workforce over time are likely to impact health service delivery. What does this paper add? This paper examined changes in the gender, age, origin of qualification, and the region of work of Australia's medical workforce from 2013 to 2022. What are the implications for practitioners? An increase in gender parity and a decrease in the mean hours worked suggests improvements in workforce participation and sustainability, but lack of growth in medical workforce was noted in remote and very remote regions of Australia. [ABSTRACT FROM AUTHOR]

Graduate-entry, following a science degree, is the preferred pathway into many medical schools, however little is known about how the learning approaches of medical students compare to those of science students. This study compared the learning approaches and achievement orientations of science students with those aiming to enter graduate-entry medicine programs. The two factor study process questionnaire and the achievement goal orientation survey were used to compare students in; stage one: third year science students (n = 86) to graduate-entry medicine students (n = 158); stage two: applicants to graduate medicine (n = 84); stage three: first year science students (n = 363) to first year pre-medicine students (n = 68). Medical students and applicants to medicine demonstrated a greater preference for deep learning than third year science students (p < 0.0001). Pre-medicine students were similar to medical students. Medical students, applicants to medicine and pre-medicine students also all had a greater preference for a learning goal orientation. The preference for a deeper approach to learning and stronger learning goal orientation in students enrolled in medicine or aiming to gain entry to graduate medicine indicates a motivation towards the acquisition of knowledge. Medical educators need to ensure that students continue to develop positive and beneficial styles of learning to assist them to develop into life-long learners. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Standard setting of assessment is critical in quality assurance of medical programs. The aims of this study were to identify and compare the impact of methods used to establish the passing standard by the 13 medical schools who participated in the 2014 Australian Medical Schools Assessment Collaboration (AMSAC). Methods: A survey was conducted to identify the standard setting procedures used by participating schools. Schools standard setting data was collated for the 49 multiple choice items used for benchmarking by AMSAC in 2014. Analyses were conducted for nine schools by their method of standard setting and key characteristics of 28 panel members from four schools. Results: Substantial differences were identified between AMSAC schools that participated in the study, in both the standard setting methods and how particular techniques were implemented. The correlation between the item standard settings data by school ranged from − 0.116 to 0.632. A trend was identified for panel members to underestimate the difficulty level of hard items and overestimate the difficulty level of easy items for all methods. The median derived cut-score standard across schools was 55% for the 49 benchmarking questions. Although, no significant differences were found according to panel member standard setting experience or clinicians versus scientists, panel members with a high curriculum engagement generally had significantly lower expectations of borderline candidates (p = 0.044). Conclusion: This study used a robust assessment framework to demonstrate that several standard setting techniques are used by Australian medical schools, which in some cases use different techniques for different stages of their program. The implementation of the most common method, the Modified Angoff standard setting approach was found to vary markedly. The method of standard setting used had an impact on the distribution of expected minimally competent student performance by item and overall, with the passing standard varying by up to 10%. This difference can be attributed to the method of standard setting because the ASMSAC items have been shown over time to have consistent performance levels reflecting similar cohort ability. There is a need for more consistency in the method of standard setting used by medical schools in Australia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: The urinary bladder purinergic system is reported to change with age and with bladder dysfunction. Here, we examined the expression of purinergic P2X1 receptors in detrusor and mucosa (urothelium+lamina propria) from male control bladder and investigated age-related P2X1 receptor mRNA expression in control and obstructed detrusor. Biopsy specimens were obtained at cystoscopy from control patients (n =46, age range 30–86years) and patients diagnosed with outlet obstruction (n =29, 46–88years). Calponin expression (measured by RT-PCR) was similar in control and obstructed detrusor and did not change with age. Quantitative competitive RT-PCR was used to measure P2X1 receptor and GAPDH mRNA in control and obstructed detrusor. P2X1 receptor mRNA expression was 9-fold (p <0.0001) higher in the detrusor than in the mucosa. Expression of mRNA for the internal control GAPDH remained stable with age and across control and obstructed detrusor. No difference in P2X1 receptor expression was observed between control and obstructed detrusor (p =0.35). However, an age-related decrease in P2X1 mRNA expression was observed in control (n =27; p =0.0054; Spearman coefficient r =−0.520) but not obstructed detrusor (n =19; p =0.093; r =−0.396). Downregulation of P2X1 mRNA expression might occur as a result of an increased component of neural ATP release in the aging bladder. [Copyright &y& Elsevier]

The effects of a range of antidepressants were investigated on neuronal voltage-gated Na+ and K+ channels. With the exception of phenelzine, all antidepressants inhibited batrachotoxin-stimulated 22Na+ uptake, most likely via negative allosteric inhibition of batrachotoxin binding to neurotoxin receptor site-2 on the Na+ channel. Imipramine also produced a differential action on macroscopic Na+ and K+ channel currents in acutely dissociated rat dorsal root ganglion neurons. Imipramine produced a use-dependent block of Na+ channels. In addition, there was a hyperpolarizing shift in the voltage-dependence of steady-state Na+ channel inactivation and slowed repriming kinetics consistent with imipramine having a higher affinity for the inactivated state of the Na+ channel. At higher concentrations, imipramine also blocked delayed-rectifier and transient outward K+ currents in the absence of alterations to the voltage-dependence of activation or the kinetics of inactivation. These actions on voltage-gated ion channels may underlie the therapeutic and toxic effects of these drugs. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Background: Sedation at the end of life is used to relieve distressing symptoms including agitation and delirium. Standard care may include infused benzodiazepines or antipsychotics. These agents often result in deep sedation with loss of interaction with loved ones, which may be distressing., Objective: The DREAMS (Dexmedetomidine for the Reduction of End-of-life Agitation and for optiMised Sedation) trial aimed to compare the sedative and antidelirium effects of the alpha-2 agonist dexmedetomidine, a novel palliative care sedative, compared with midazolam, a benzodiazepine when administered by subcutaneous infusion at the end of life, with doses of both agents targeting lighter, or potentially interactive sedation., Methods: Participants were recruited from adult inpatients admitted for end-of-life care under a palliative care team in regional New South Wales, Australia. Inclusion criteria included patients older than 18 years, with a preference for lighter sedation at the end of life. Exclusion criteria included severe cardiac dysfunction (contraindication to dexmedetomidine). Participants consented and were placed on a treatment-pending list. Upon experiencing terminal deterioration, patients were randomized to either arm 1 (dexmedetomidine) or arm 2 (midazolam) as their treatment arm. These treatments were administered by continuous subcutaneous infusion. The level of consciousness and agitation of the patients were measured by the Richmond Agitation-Sedation Scale-Palliative version and the Memorial Delirium Assessment Score. Richmond Agitation-Sedation Scale-Palliative version assessments were performed by both nursing and medical staff, while Memorial Delirium Assessment Score assessments were carried out by medical staff only. Families and patients were asked to complete, as able, a patient comfort assessment form, to gauge perceptions of distress. Data were collected and matched with the breakthrough medication doses administered, along with qualitative comments in the medical record. In addition, the study tracked symptoms and patient functional status that were recorded as part of the Palliative Care Outcomes Collaborative, a national tracking project for monitoring symptom outcomes in palliative care., Results: The DREAMS trial was funded in May 2020, approved by the ethics committee in November 2020, and started recruiting participants in May 2021. Data collection commenced in May 2021 and is anticipated to continue until December 2024. Publication of results is anticipated from 2024 to 2026., Conclusions: The evidence base for sedative dosing in palliative care for distress and agitation is not robust, with standard care based primarily on clinical experience and not robust scientific evidence. This study is important because it will compare a standard and a novel sedative used in end-of-life treatment. By assessing the potential efficacy and benefits of both, it seeks to optimize the quality of dying by providing targeted sedation that can improve the communication between dying patients and their loved ones., Trial Registration: Australia New Zealand Clinical Trials Register ACTRN12621000052831; https://uat.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380889., International Registered Report Identifier (irrid): DERR1-10.2196/55129., (©Benjamin Thomas, Greg Barclay, Wing-Shan Angela Lo, Judy Mullan, Kylie Mansfield. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.09.2024.)

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).)

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.

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.

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.)

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: 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.

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.

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.)

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.)

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.)

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.

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.)

Aim: Dietary modification is integral to the management of end stage kidney disease. However, adherence to the renal diet is poor. Few studies have explored the perspectives of renal dietitians and how they work with patients to facilitate dietary change. The objectives of this study were to explore the experiences of renal dietitians about educating patients with end stage kidney disease; and to describe the strategies perceived to help patients understand the renal diet., Methods: Semi-structured interviews based on Sensemaking theory were conducted with renal dietitians (n = 27) working in Australia and New Zealand from a range of metropolitan, regional and remote areas., Results: Five major themes across two categories were derived from the data. The renal dietitians in this study experienced feelings of frustration, frequently worked in practice environments with limited or inadequate resources and perceived that establishing trust and demonstrating empathy were important to sense making. Renal dietitians helped patients make sense of and understand the diet by clarifying ambiguities and conflicting information; and simplifying complexity by using simple explanations, individualised advice and practical support. These strategies were considered critical to the renal diet sense making process., Conclusions: The experience of providing renal diet advice to adults with end stage kidney disease was emotionally and professionally challenging. Alternative approaches to patient education may help dietitians to empower patients to better understand the renal diet. Further research exploring the experiences of learning about the renal diet from the patient and carer perspective would also help to inform future alternative approaches., (© 2018 Dietitians Association of Australia.)

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.

Objective: Mobile phone applications (apps) are increasingly being used by patients with chronic kidney disease (CKD). We sought to describe the main purpose of commonly available renal diet apps and to quantify the accuracy of information, technical quality, and health literacy demand of renal diet apps., Design: The design was content analysis. All eligible renal diet apps in the Australian Apple App Store, Google Play, Windows Phone, and Blackberry App World were evaluated., Subjects: Eligible apps were in English and were related to kidney disease in humans (of any type or stage). Exclusion criteria included apps which were prohibited because of password protection., Main Outcome Measure: Renal diet information in the apps was compared with evidence-based guidelines for the management of kidney disease to quantify information accuracy. App information was evaluated using the Silberg Scale. Technical quality and health literacy demand were evaluated using the Mobile Application Rating Scale., Results: A total of 21 apps were eligible for evaluation. The main purpose of these apps was to provide food and nutrition information (57.1%) or for educative purposes for CKD patients (38.1%). Only 47.6% (10/21) of apps contained accurate evidence-based information. Overall, app technical quality was considered acceptable (mean Mobile Application Rating Scale score 3.19 ± 0.35 out of 5), with 80.9% of apps scoring acceptable or greater for app technical quality. Scores for health literacy demand also indicated that most apps (15/21, 71.4%) were acceptable., Conclusions: A range of apps currently exist that may provide individuals with CKD with useful food and nutrition information or increase their knowledge of the renal diet. These apps are also mainly of acceptable technical quality and health literacy demand. However, caution is required when using renal diet apps because more than half of the apps evaluated were not accurate and evidence based., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The damaging effects of oxidative stress and transforming growth factor-beta (TGFbeta)-induced transdifferentiation of lens epithelial cells have both been implicated independently in the etiology of cataract. The aim of this study was to investigate whether the presence of antioxidant systems in the lens influences the ability of lens epithelial cells to respond to TGFbeta., Methods: Whole lenses from young rats were cultured with or without TGFbeta in the presence or absence of reduced glutathione (GSH). Lens epithelial explants from weanling rats were used to investigate the effects of GSH and catalase on TGFbeta-induced cataract-related changes. Lenses were monitored for opacification for three to four days, photographed, and then processed for routine histology. Explants were assessed by phase contrast microscopy, enzyme-linked immunosorbent assay (ELISA) of alpha-smooth muscle actin (alphaSMA), and/or immunolocalization of alphaSMA and Pax6, markers for transdifferentiation and normal lens epithelial phenotype, respectively., Results: In cultured lenses, GSH strongly suppressed TGFbeta-induced opacification and subcapsular plaque formation. In explants, both GSH and catalase suppressed changes typically associated with TGFbeta-induced transdifferentiation including wrinkling of the lens capsule, cell-surface blebbing, apoptotic cell loss, induction of alphaSMA, and loss of Pax6 expression., Conclusions: This study suggests that antioxidant systems present in the normal lens, which protect the epithelium against the damaging effects of reactive oxygen species, may also serve to protect it against the potentially cataractogenic effects of TGFbeta. Taken together with other recent studies, it also raises the possibility that TGFbeta may induce cataract-related changes in lens epithelial cells via release of hydrogen peroxide.

Purpose: Many patients whose sight is initially restored by cataract surgery eventually suffer secondary loss of vision because of posterior capsule opacification (PCO; after-cataract), a condition in which lens epithelial cells left behind at surgery become aberrant and migrate into the light path. The aim of this study was to determine whether dexamethasone (DEX), an anti-inflammatory agent widely used before and after cataract surgery, influences the behavior of lens cells under conditions relevant to PCO development., Methods: An established rat PCO model was used in which explanted epithelial cells attached to the lens capsule are exposed sequentially to TGFbeta2 and FGF-2. Cultures with or without DEX (100 nM), and appropriate controls, were maintained for up to 30 days and assessed by light and scanning electron microscopy or immunolocalization of PCO markers (alpha-smooth muscle actin or fibronectin) or a marker for lens epithelial cell phenotype (Pax-6)., Results: In the absence of DEX, explants become multilayered and plaques that express PCO markers form. Cells tend to gather up into the plaques, leaving the surrounding lens capsule denuded. Changes in lens cell behavior with addition of DEX included rapid formation of long, needle-like cells, less extracellular matrix deposited on explant surface, and plaques surrounded by a monolayer of migratory cells. Immunolocalization confirmed that the latter were not normal lens epithelial cells., Conclusions: Lens cell behavior in this PCO model was significantly affected by inclusion of DEX, highlighting the possibility that its use as an anti-inflammatory at the time of cataract surgery may influence PCO development.

Purpose: While cataract surgery initially benefits most patients, many suffer secondary loss of vision because of posterior capsule opacification (PCO). Lens epithelial cells left behind at surgery become aberrant and migrate into the light path. TGF-beta (TGFbeta) appears to play a key role in this process by inducing the cells to undergo an epithelial-mesenchymal transition. Paradoxically, it also typically induces them to undergo apoptotic death. The present study was undertaken to investigate the hypothesis that FGF plays a role in PCO formation by promoting the survival of abnormal cells with PCO-like characteristics., Methods: Rat lens epithelial explants were cultured for one day with TGFbeta2 (25-100 pg/ml) then in control medium with or without FGF-2 (5-100 ng/ml) for up to 31 days, with assessment by light and scanning electron microscopy and immunolocalization., Results: Survival of TGFbeta treated cells was promoted by FGF-2 but not by EGF, PDGF, IGF, or HGF. In the absence of FGF virtually all cells were lost from explants within 5 days. However, when FGF was included cells remained viable throughout culture. These cells, which no longer expressed the lens epithelial marker Pax6, exhibited immunoreactivity for non-lens cell proteins associated with PCO (alpha-smooth muscle actin, type I collagen, and fibronectin) and also beta-crystallin. FGF inclusion also promoted ECM production, multilayering, and plaque formation, features of PCO known to contribute to visual loss., Conclusions: This study points to a key role for FGF in the etiology of PCO and suggests that FGF inhibitors may be useful in preventing PCO.

Purpose: Culturing rat lenses with transforming growth factor-beta (TGFbeta) results in the formation of anterior, opaque subcapsular plaques which exhibit many of the features of human subcapsular cataract. The present study was undertaken to determine whether this process is influenced by the presence of fibroblast growth factor (FGF), a normal component of the lens environment in situ., Methods: Rat lenses were cultured for 4-8 days with TGFbeta-2, alone or in combination with FGF-2, PDGF-AA, or the growth factor inhibitors poly(4-styrenesulfonic acid) (PSS) and suramin. Responses were assessed by monitoring opacification, by routine histology and immunolocalization of markers for fibrotic change (a-smooth muscle actin, fibronectin, and type I collagen), or by measuring DNA accumulation in the epithelial region., Results: Supplementing TGFbeta at a barely cataractogenic dose with 2.5-30 ng/ml FGF-2 resulted in a very strong opacification response. The exceptionally large plaques that formed were similar histologically to those induced by TGFbeta alone at higher concentrations and showed immunoreactivity for all markers. PDGF at a concentration equivalent to FGF in terms of proliferative potential did not demonstrate this effect. Addition of either PSS or suramin reduced the opacification response induced by a cataractogenic dose of TGFbeta alone., Conclusions: FGF has been identified as a factor capable of exacerbating the cataractogenic effects of TGFbeta. Thus FGF inhibitors, as well as TGFbeta inhibitors, have the potential to protect the lens against TGFbeta-induced cataractous changes.