Sex differences in lower urinary tract biology and physiology

Abstract Females and males differ significantly in gross anatomy and physiology of the lower urinary tract, and these differences are commonly discussed in the medical and scientific literature. However, less attention is dedicated to investigating the varied development, function, and biology between females and males on a cellular level. Recognizing that cell biology is not uniform, especially in the lower urinary tract of females and males, is crucial for providing context and relevance for diverse fields of biomedical investigation. This review serves to characterize the current understanding of biological sex differences between female and male lower urinary tracts, while identifying areas for future research. First, the differences in overall cell populations are discussed in the detrusor smooth muscle, urothelium, and trigone. Second, the urethra is discussed, including anatomic discussions of the female and male urethra followed by discussions of cellular differences in the urothelial and muscular layers. The pelvic floor is then reviewed, followed by an examination of the sex differences in hormonal regulation, the urinary tract microbiome, and the reticuloendothelial system. Understanding the complex and dynamic development, anatomy, and physiology of the lower urinary tract should be contextualized by the sex differences described in this review

Identification of a novel site of interaction between ataxin-3 and the amyloid aggregation inhibitor polyglutamine binding peptide 1

Amyloid diseases represent a growing social and economic burden in the developed world. Understanding the assembly pathway and the inhibition of amyloid formation is key to developing therapies to treat these diseases. The neurodegenerative condition Machado–Joseph disease is characterised by the self-aggregation of the protein ataxin-3. Ataxin-3 consists of a globular N-terminal Josephin domain, which can aggregate into curvilinear protofibrils, and an unstructured, dynamically disordered C-terminal domain containing three ubiquitin interacting motifs separated by a polyglutamine stretch. Upon expansion of the polyglutamine region above 50 residues, ataxin-3 undergoes a second stage of aggregation in which long, straight amyloid fibrils form. A peptide inhibitor of polyglutamine aggregation, known as polyQ binding peptide 1, has been shown previously to prevent the maturation of ataxin-3 fibrils. However, the mechanism of this inhibition remains unclear. Using nanoelectrospray ionisation-mass spectrometry, we demonstrate that polyQ binding peptide 1 binds to monomeric ataxin-3. By investigating the ability of polyQ binding peptide 1 to bind to truncated ataxin-3 constructs lacking one or more domains, we localise the site of this interaction to a 39-residue sequence immediately C-terminal to the Josephin domain. The results suggest a new mechanism for the inhibition of polyglutamine aggregation by polyQ binding peptide 1 in which binding to a region outside of the polyglutamine tract can prevent fibril formation, highlighting the importance of polyglutamine flanking regions in controlling aggregation and disease

Voided Volume for Assessment of Bladder Emptying After Female Pelvic Floor Surgery: A Randomized Controlled Trial

IMPORTANCE: To study alternative voiding trial (VT) methods after urogynecologic surgery that may potentially decrease catheterization. OBJECTIVE: The aim of the study is to compare voiding assessment based on a minimum spontaneous voided volume of 150 mL with the standard retrograde fill (RF) approach in women after urogynecologic procedures. STUDY DESIGN: Women undergoing urogynecologic surgery were randomized to RF or spontaneous void (SV) groups. Women in the RF group had their bladders backfilled with 300 mL of saline before catheter removal, those in the SV group did not. To pass the VT, patients in the RF group were required to void 150 mL at one time within 60 minutes, and patients in the SV group had to do the same within 6 hours. The primary outcome was the VT failure rate. We also compared the false pass rate, urinary tract infections, satisfaction, and preference of VT method. RESULTS: One hundred nine women were enrolled in the study, 54 had SV and 55 underwent RF. Baseline characteristics were not significantly different other than history of prior hysterectomy. There was no significant difference in procedures between the groups. There was no difference in VT failure rate between the groups-SV (7.4%) and RF (12.7%, P = 0.39). The false pass rate was 0 in each group. Urinary tract infection rates were similar between SV (14.8%) and RF (14.5%) groups ( P = 0.34). Patient satisfaction for VT method was not significantly different. CONCLUSIONS: Spontaneous VT was not superior to retrograde void trial. Therefore, we cannot recommend one method of VT after urogynecologic surgery.CondensationVoiding assessment based on minimum SV of 150 mL is comparable with VT with RF after surgeries for prolapse and urinary incontinence

Assessment of Patient Satisfaction With Home vs Office Indwelling Catheter Removal Placed for Urinary Retention After Female Pelvic Floor Surgery: A Randomized Controlled Trial

BACKGROUND: Postoperative urinary retention is burdensome for patients. We seek to improve patient satisfaction with the voiding trial process. OBJECTIVE: This study aimed to assess patient satisfaction with location of indwelling catheter removal placed for urinary retention after urogynecologic surgery. STUDY DESIGN: All adult women who were diagnosed with urinary retention requiring postoperative indwelling catheter insertion after undergoing surgery for urinary incontinence and/or pelvic organ prolapse were eligible for this randomized controlled study. They were randomly assigned to catheter removal at home or in the office. Those who were randomized to home removal were taught how to remove the catheter before discharge, and were discharged home with written instructions, a voiding hat, and 10-mL syringe. All patients had their catheter removed 2 to 4 days after discharge. Those patients who were allocated to home removal were contacted in the afternoon by the office nurse. Subjects who graded their force of urine stream 5, on a scale of 0 to 10, were considered to have safely passed their voiding trial. For patients randomized to the office removal group, the voiding trial consisted of retrograde filling the bladder to maximum they could tolerate up to 300 mL. Urinating \u3e50% of instilled volume was considered successful. Those who were unsuccessful in either group had catheter reinsertion or self-catheterization training in the office. The primary study outcome was patient satisfaction, measured based on patients\u27 response to a question, How satisfied were you with the overall removal process of the catheter? A visual analogue scale was created to assess patient satisfaction and 4 secondary outcomes. A sample size of 40 participants per group were needed to detect a 10 mm difference in satisfaction between groups on the visual analogue scale. This calculation provided 80% power and an alpha of 0.05. The final number accounted for 10% loss to follow up. We compared the baseline characteristics, including urodynamic parameters, relevant perioperative indices, and patient satisfaction between the groups. RESULTS: Of the 78 women enrolled in the study, 38 (48.7%) removed their catheter at home and 40 (51.3%) had an office visit for catheter removal. Median and interquartile range for age, vaginal parity, and body mass index were 60 (49-72) years, 2 (2-3), and 28 (24-32) kg/m, respectively, in the overall sample. Groups did not differ significantly in age, vaginal parity, body mass index, previous surgical history, or type of concomitant procedures. Patient satisfaction was comparable between the groups, with a median score (interquartile range) of 95 (87-100) in the home catheter removal group and 95 (80-98) in the office catheter removal group (P=.52). Voiding trial pass rate was similar between women who underwent home (83.8%) vs office (72.5%) catheter removal (P=.23). No participants in either group had to emergently come into the office or hospital due to inadequate voiding afterwards. Within 30 days post operatively, a lower proportion of women in the home catheter removal group (8.3%) had urinary tract infection, compared to patients in the office catheter removal group (26.3%) (P=.04). CONCLUSION: In women with urinary retention after urogynecologic surgery, there is no difference in satisfaction concerning the location of indwelling catheter removal when comparing home and office

Efficacy of two formulations of afoxolaner (NexGard® and NexGard Spectra®) for the treatment of generalised demodicosis in dogs, in veterinary dermatology referral centers in Europe

Abstract Background A multi-centre field trial was conducted to evaluate the efficacy of afoxolaner based chewables (NexGard® or NexGard Spectra®) for the treatment of generalised demodicosis caused by Demodex canis in dogs under field conditions in France, Italy and Poland. Methods Client-owned dogs, diagnosed positive for Demodex mites by pre-treatment skin scrapings and presenting clinical signs of generalised demodicosis were included. Dogs were orally treated with afoxolaner three times at monthly intervals. Of the 50 dogs enrolled, 48 completed the whole study. Efficacy of the treatments was assessed monthly by Demodex mite counts and physical examination with special regard to the severity and extension of skin lesions. Results Treatments were well tolerated in all dogs and resulted in a rapid reduction of mites, with all post-treatment mite counts significantly lower than baseline. The number of mites was reduced by 87.6%, 96.5% and 98.1% on Days 28, 56 and 84, respectively. In addition, the skin lesion severity and extent scores as well as the pruritus were all significantly lower at all post-treatment visits compared to the pre-treatment assessment. Conclusions This clinical field study demonstrated that monthly administrations of afoxolaner in NexGard® or NexGard Spectra®, offered a convenient and reliable solution for the treatment of canine generalised demodicosis

Permanent Compared With Absorbable Suture in Apical Prolapse Surgery: A Systematic Review and Meta-Analysis

OBJECTIVE: To explore how permanent compared with absorbable suture affects anatomic success in native tissue vaginal suspension (uterosacral ligament suspension and sacrospinous ligament suspension) and sacrocolpopexy with mesh. DATA SOURCES: MEDLINE, EMBASE, and ClinicalTrials.gov were searched through March 29, 2022. METHODS OF STUDY SELECTION: Our population included women undergoing apical prolapse surgery (uterosacral ligament suspension and sacrospinous ligament suspension and abdominal sacrocolpopexy). Our intervention was permanent suture for apical prolapse surgery, and our comparator was absorbable suture. We determined a single anatomic success proportion per study. Adverse events collected included suture and mesh exposure, surgery for suture and mesh complication, dyspareunia, and granulation tissue. Abstracts were doubly screened, full-text articles were doubly screened, and accepted articles were doubly extracted. Quality of studies was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. In single-arm studies using either permanent or absorbable suture, random effects meta-analyses of pooled proportions were used to assess anatomic success. In comparative studies investigating both suture types, random effects meta-analyses of pooled risk ratios were used. TABULATION, INTEGRATION, AND RESULTS: Of 4,658 abstracts screened, 398 full-text articles were assessed and 63 studies were included (24 vaginal suspension [13 uterosacral ligament suspension and 11 sacrospinous ligament suspension] and 39 sacrocolpopexy). At 2-year follow-up, there was no difference in permanent compared with absorbable suture in uterosacral ligament suspension and sacrospinous ligament suspension (proportional anatomic success rate 88% [95% CI 0.81-0.93] vs 88% [95% CI 0.82-0.92]). Similarly, at 18-month follow-up, there was no difference in permanent compared with absorbable suture in sacrocolpopexy (proportional anatomic success rate 92% [95% CI 0.88-0.95] vs 96% [95% CI 0.92-0.99]). On meta-analysis, there was no difference in relative risk (RR) of success for permanent compared with absorbable suture for uterosacral ligament suspension and sacrospinous ligament suspension (RR 1.11, 95% CI 0.93-1.33) or sacrocolpopexy (RR 1.00, 95% CI0.98-1.03). CONCLUSION: Success rates were similarly high for absorbable and permanent suture after uterosacral ligament suspension, sacrospinous ligament suspension, and sacrocolpopexy, with medium-term follow-up. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021265848

Sex differences in lower urinary tract biology and physiology

Abstract Females and males differ significantly in gross anatomy and physiology of the lower urinary tract, and these differences are commonly discussed in the medical and scientific literature. However, less attention is dedicated to investigating the varied development, function, and biology between females and males on a cellular level. Recognizing that cell biology is not uniform, especially in the lower urinary tract of females and males, is crucial for providing context and relevance for diverse fields of biomedical investigation. This review serves to characterize the current understanding of biological sex differences between female and male lower urinary tracts, while identifying areas for future research. First, the differences in overall cell populations are discussed in the detrusor smooth muscle, urothelium, and trigone. Second, the urethra is discussed, including anatomic discussions of the female and male urethra followed by discussions of cellular differences in the urothelial and muscular layers. The pelvic floor is then reviewed, followed by an examination of the sex differences in hormonal regulation, the urinary tract microbiome, and the reticuloendothelial system. Understanding the complex and dynamic development, anatomy, and physiology of the lower urinary tract should be contextualized by the sex differences described in this review