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The identification of the host defence peptides as target effectors in the innate defence of the uro-genital tract creates new translational possibilities for immunomodulatory therapies, specifically vaginal therapies to treat women suffering from rUTI, particularly those carrying the TLR5_C1174T SNP. Urinary tract infections (UTIs) are a microbial disease reported worldwide. Women are particularly susceptible with many suffering debilitating recurrent (r) infections. Treatment is by antibiotics, but such therapy is linked to antibiotic resistance and re-infection. This study explored the innate protective mechanisms of the urogenital tract with the aim of boosting such defences therapeutically. Modelling UTIs in vitro, human vaginal and bladder epithelial cells were challenged with uropathogenic Escherichia coli (CFT073) and microbial PAMPs including flagellin, LPS and peptidoglycan. Flagellin functioning via the TLR5/NFκB pathway was identified as the key UPEC virulence factor causing a significant increase (P < 0.05) in the production of the host-defence peptide (HDP), BD2. BD2-depleted urine samples from bladder infected mice supported increased UPEC growth, strengthening the significance of the HDPs in protecting the urogenital tissues from infection. Clinically, vaginal-douche BD2 concentrations were reduced (p < 0.05) in women suffering rUTIs, compared to age-matched healthy controls with concentrations further decreased (p < 0.05) in a TLR5392Stop SNP rUTI subgroup. Topical vaginal estrogen treatment increased (p < 0.001) BD2 concentrations in all women, including those carrying the SNP. These data identify therapeutic and antibiotic sparing roles for vaginal immunomodulatory agents that specifically target HDP induction, facilitate bacterial killing and disrupt the UPEC infection cycle.

Objectives: To identify patterns of exercise behaviour, attitudes towards exercise, barriers and enablers of exercise for people living with Pulmonary Hypertension (PH). Accessibility of rehabilitation services from a patient perspective was also explored. Methods: a voluntary, international survey of people living with PH was conducted, with mixed quantitative and qualitative data collection, in an online and paper format. Results: Data from 187 participants in 19 countries were included in the analyses. 52% (95/183) of people with PH reported that they attempted to engage in regular physical activity. This was less than the proportion who did so prior to diagnosis (61%, 112/184, p=0.006), and was accompanied by uncertainty and anxiety about exercise. 63% (113/180) of the cohort reported experiencing previous adverse events whilst exercising, which was associated with a greater likelihood of ongoing exercise concerns and anxiety. Fear, frustration and uncertainty about exercise were noted as common barriers to engaging in exercise with PH. Other barriers to exercise included intrinsic factors such as debilitating breathlessness and fatigue, and external factors such as cost and access to appropriate services. Most respondents (76%, 128/169) did not have access to a multi-disciplinary rehabilitation service, although an overwhelming majority (92%, 159/172) reported this would be helpful. Respondents rated education; a supervised, structured exercise program; and psychology input as the most important components of a multi-disciplinary rehabilitation service for PH. Conclusion: Health professionals must work together with consumers to co-design rehabilitation services that will facilitate exercise and increased activity for people living with PH.

The use of intermittent catheterization following urogynaecological surgery is associated with a more rapid return to normal micturition and a shorter hospital stay, although the clinical significance of the difference is perhaps limited.

Our results suggest that in patients who respond to onabotulinumA treatment, the duration of response declines after the fifth treatment, suggesting a possible tolerance effect and a subsequent decline in efficacy.

Dual non-parenteral therapy appears safe and effective and should be considered for PAH patients who are deteriorating on monotherapy to improve long-term outcomes.

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