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Myofibrillar myopathies (MFM) are caused by mutations in at least 6 Z-disc associated proteins, including ZASP, myotilin, desmin, BAG3, αβ-crystallin, and filamin C. MFM are characterized by early and prominent disruption of the Z-disc with focal dissolution of myofibrils and ectopic accumulation of myofibrillar proteins. Similar morphological changes in skeletal muscle in MFM suggest a shared cellular and molecular disease mechanism. ZASP interacts with myotilin, and knock down of ZASP in mice results in alterations in the amounts of other MFM gene products. We hypothesize that ZASP associations with other MFM gene products play a role in the disease mechanism in zaspopathy. To examine the effects of ZASP mutations on the other MFM gene products in skeletal muscle, WT and mutant (A147T and A165V) ZASP-GFP proteins were expressed by electroporation in the tibialis anterior muscles of opposite limbs in wild type mice (n =18). Muscle tissues were harvested at 1, 2, and 4weeks after the electroporation. The amount and distribution of MFM gene products, F-actin, and α-actinin-2 were examined in the electroporated mouse muscle fibers and in skeletal muscle fibers of patients with zaspopathy. Wild type and mutant ZASP interactions with other MFM gene products were examined by co-IP and pulldown assays. Preliminary data suggests that wild type and mutant ZASP associate with myotilin, desmin, and BAG3. The effects of ZASP mutations on the other MFM gene products and the effects of the other MFM gene defects on ZASP will provide insight into shared disease mechanisms in this group of degenerative myopathies. [Copyright &y& Elsevier]

OBJECTIVE: We sought to determine if phenazopyridine improves pain in catheterized patients recovering from gynecologic surgery. STUDY DESIGN: This trial randomized 240 adult women, who were undergoing gynecologic surgery and requiring an indwelling Foley catheter, to placebo or phenazopyridine hydrocholoride. Group assignment was masked by instillation of orange dye in the Foley bag of both groups. The primary outcome was the mean postoperative visual analog score (VAS). Secondary outcomes were pain medicine utilization and blinding efficacy. RESULTS: In all, 219 patients received study medications (112 phenazopyridine and 107 placebo). There was no significant difference in demographics, procedure type, bladder VAS, overall VAS, and pain medication use. Only 25 of the 45 participants who responded guessed their group assignment correctly, suggesting adequate blinding. CONCLUSION: Postoperative VAS scores and pain medicine usage did not change with using routine phenazopyridine following gynecology surgery. Colored dye adequately masks visual side effects of phenazopyridine. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of the study was to determine the effect of initial urogynecologic consultation on the number and type of patient goals. STUDY DESIGN: Charts of women who underwent initial urogynecology consultation were reviewed. Patient goals were collected before and after their consultation. Investigators categorized goals into 6 categories. Category and number of goals were compared before and after their first visit. Predictors of change and clinical associations were assessed. RESULTS: Sixty-three women with a mean age of 53 (range, 18-83) years reported a total number of 313 goals. The number of patients' postconsultation goals was higher than the number of preconsultation goals, (median of 3 +/- 1.2 vs 2 +/- 1.2, respectively; P < .003). Women were less likely to report' symptom' and 'information-seeking' goals (P < .002 and P < .03, respectively) but more likely to report treatment goals after consultation (P < .001). CONCLUSION: Urogynecologic consultation affects patients' goals. It is important to reassess goals following initial consultation. [ABSTRACT FROM AUTHOR]

The article presents a study on urinary incontinence in women. Urinary incontinence is involuntary leakage of urine which is common in older women. There are two types of urinary incontinence, urge incontinence is sudden, urgent urine leakage and stress incontinence is urine leakage with coughing, sneezing or physical activity.

Introduction and hypothesis: The objective was to determine whether standardized, intraoperative urethral measurement improves retropubic mid-urethral sling (RPMUS) positioning and if the intraoperative position remains stable at 2 weeks postoperatively. Methods: Participants undergoing a RPMUS were randomized to mid-urethral placement as per usual surgical care (no Foley catheter measurement, no-FCM) vs urethral mid-point Foley catheter measurement (FCM). The primary outcomes were RPMUS location as determined by 2D and 3D ultrasound 2 weeks postoperatively (as percentage from urethral meatus − relative to the urethral length) and intraoperatively following the RPMUS placement. Results: Forty-four women enrolled, underwent RPMUS, and provided baseline data and intraoperative ultrasound measurements; of these, 36 (82%) had interpretable intraoperative and postoperative ultrasound measurements. Demographic data were similar in the two groups. The mean RPMUS mid-point was 57 % and 55 % in measured and controls (p = 0.685); this same measurement was relatively unchanged at 2 weeks postoperatively at 57% and 54% respectively (p = 0.538). Very much and much improvement was reported on the PGI-I by 84% and 85% of participants in the FCM and no-FCM groups respectively. Conclusions: Intraoperative RPMUS position at 2 weeks after surgery is similar to the intraoperative position. Compared with usual surgical care, intraoperative measurement of urethral mid-point with a Foley catheter did not affect RPMUS sling position. [ABSTRACT FROM AUTHOR]

Background: Many surgical procedures are available for women with urinary stress incontinence, yet few randomized clinical trials have been conducted to provide a basis for treatment recommendations.Methods: We performed a multicenter, randomized clinical trial comparing two procedures--the pubovaginal sling, using autologous rectus fascia, and the Burch colposuspension--among women with stress incontinence. Women were eligible for the study if they had predominant symptoms associated with the condition, a positive stress test, and urethral hypermobility. The primary outcomes were success in terms of overall urinary-incontinence measures, which required a negative pad test, no urinary incontinence (as recorded in a 3-day diary), a negative cough and Valsalva stress test, no self-reported symptoms, and no retreatment for the condition, and success in terms of measures of stress incontinence specifically, which required only the latter three criteria. We also assessed postoperative urge incontinence, voiding dysfunction, and adverse events.Results: A total of 655 women were randomly assigned to study groups: 326 to undergo the sling procedure and 329 to undergo the Burch procedure; 520 women (79%) completed the outcome assessment. At 24 months, success rates were higher for women who underwent the sling procedure than for those who underwent the Burch procedure, for both the overall category of success (47% vs. 38%, P=0.01) and the category specific to stress incontinence (66% vs. 49%, P<0.001). However, more women who underwent the sling procedure had urinary tract infections, difficulty voiding, and postoperative urge incontinence.Conclusions: The autologous fascial sling results in a higher rate of successful treatment of stress incontinence but also greater morbidity than the Burch colposuspension. (ClinicalTrials.gov number, NCT00064662 [ClinicalTrials.gov] .). [ABSTRACT FROM AUTHOR]

Objective To explore the in vivo characteristics of donor fascia used in urogynaecological procedures, in a canine model. Materials and methods Two experiments were conducted. In the first, donor fascia grafts were obtained from 12 dogs, the grafts freeze-dried and half were irradiated. The grafts were used for sacrocolpopexy and suburethral slings in each of five dogs. The dogs were killed at 2, 6 and 12 weeks after graft implantation, the grafts retrieved and assessed using tensilometry. In the second experiment, unirradiated sacrocolpopexy grafts were implanted in eight dogs; four grafts were placed under no tension and four under moderate tension. At 8 weeks, the grafts were retrieved and assessed by tensilometry. Measures of strength in both experiments included the ultimate tensile strength, ultimate strain and stiffness. All measures were compared using Kruskal–Wallis nonparametric tests in both studies. Results In the first experiment, a significant minority (23%) of grafts had complete loss of strength. Measures of graft strength did not vary when analysed according to donor dog, host dog, history of graft irradiation, duration of implantation or location of graft. In the second experiment, grafts placed under no tension tended to have lower tensile strength (χ2(1)= 3.125, P = 0.077), lower stiffness (χ2(1)= 3.125, P = 0.077) and lower ultimate strain (χ 2(1)= 3.182, P = 0.074). Conclusion Graft irradiation as an isolated variable did not predispose grafts to failure in vivo. Biomechanical factors at the implantation site are likely to play a critical role in determining ultimate graft strength. [ABSTRACT FROM AUTHOR]

AbstractThe objective biomization method developed by Prentice et al. (1996) for Europe was extended using modern pollen samples from Beringia and then applied to fossil pollen data to reconstruct palaeovegetation patterns at 6000 and 18,000 14C yr bp. The predicted modern distribution of tundra, taiga and cool conifer forests in Alaska and north-western Canada generally corresponds well to actual vegetation patterns, although sites in regions characterized today by a mosaic of forest and tundra vegetation tend to be preferentially assigned to tundra. Siberian larch forests are delimited less well, probably due to the extreme under-representation of Larix in pollen spectra. The biome distribution across Beringia at 6000 14C yr bp was broadly similar to today, with little change in the northern forest limit, except for a possible northward advance in the Mackenzie delta region. The western forest limit in Alaska was probably east of its modern position. At 18,000 14C yr bp the whole of Beringia was covered by tundra. However, the importance of the various plant functional types varied from site to site, supporting the idea that the vegetation cover was a mosaic of different tundra types. [ABSTRACT FROM AUTHOR]

Objective: To characterise the bladder microbiota of continent adult women.Design: Cross-sectional study of adult women who contributed catheterised urine samples, completed validated symptom questionnaires, and provided demographic data.Setting: US academic medical centre.Population: Well-characterised continent adult women.Methods: Participants contributed symptoms questionnaires, demographic data, and catheterised urine samples that were analysed by enhanced urine culture methodology and 16S rRNA gene sequencing.Main Outcome Measures: Associations between demographics and microbial community state structures (urotypes, defined by the dominant taxon of each specimen).Results: The bladder microbiota (urobiome) of a control group of 224 continent women were characterised, demonstrating variability in terms of urotype. The most common urotype was Lactobacillus (19%), which did not differ with any demographic. In contrast, the Gardnerella (P < 0.001) and Escherichia (P = 0.005) urotypes were more common in younger and older women, respectively.Conclusions: For urobiome research, enhanced culture methods and/or DNA sequencing are the preferred techniques for bacterial detection. The interpretation of clinical tests, such as the standard urine culture, should incorporate the knowledge that some women have Gardnerella or Escherichia urotypes without evidence of any clinical disorder. Clinical care strategies should preserve or restore the beneficial effects of the native urobiome, as disruption of that microbial community could result in unintended vulnerability to uropathogen invasion or opportunistic pathogen overgrowth. Longitudinal studies of urobiome responses to therapies should be encouraged.Tweetable Abstract: In continent adult women bladder microbiome composition differs by age, with relevance for clinical practice. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Most urethral neuromuscular function data focus on efferent rather than afferent innervation. We aimed to determine if changes exist in urethral afferent nerve function before and after reconstructive pelvic surgery (RPS). Secondarily, we compared afferent urethral innervation in women with and without stress urinary incontinence undergoing RPS. Methods: Participants underwent current perception threshold (CPT) and urethral anal reflex (UAR) testing prior to surgery and again post-operatively. Wilcoxon signed ranked test and Spearman's correlations were used and all tests were two-sided. p = 0.05 was considered to indicate statistical significance. Results: Urethral CPT thresholds increased significantly after RPS, consistent with decreased urethral afferent function. Pre-operative urethral CPT thresholds at 5 and 250 Hz were lower in SUI women (10 [IQR 5-29], 40 [32-750]) compared with continent women (63 [14-99], 73 [51-109]; p = 0.45, p = 0.020), signifying increased urethral sensation or easier activation of urethral afferents in SUI women. Conclusions: Reconstructive pelvic surgery is associated with a short-term deleterious impact on urethral afferent function, as demonstrated by the higher levels of stimuli required to activate urethral afferent nerves (decreased urethral sensation) immediately after RPS. Women with SUI required lower levels of stimuli to activate urethral afferent nerves prior to RPS, although UAR latencies were similar regardless of concomitant SUI. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Robotic assistance during laparoscopic surgery for pelvic organ prolapse rapidly disseminated across the United States without level I data to support its benefit over traditional open and laparoscopic approaches [1]. This manuscript describes design and methodology of the Abdominal Colpopexy: Comparison of Endoscopic Surgical Strategies (ACCESS) Trial. Methods: ACCESS is a randomized comparative effectiveness trial enrolling patients at two academic teaching facilities, UCLA (Los Angeles, CA) and Loyola University (Chicago, IL). The primary aim is to compare costs of robotic assisted versus pure laparoscopic abdominal sacrocolpopexy (RASC vs LASC). Following a clinical decision for minimally-invasive abdominal sacrocolpopexy (ASC) and research consent, participants with symptomatic stage≥II pelvic organ prolapse are randomized to LASC or RASC on the day of surgery. Costs of care are based on each patient''s billing record and equipment costs at each hospital. All costs associated with surgical procedure including costs for robot and initial hospitalization and any re-hospitalization in the first 6weeks are compared between groups. Secondary outcomes include post-operative pain, anatomic outcomes, symptom severity and quality of life, and adverse events. Power calculation determined that 32 women in each arm would provide 95% power to detect a $2500 difference in total charges, using a two-sided two sample t-test with a significance level of 0.05. Results: Enrollment was completed in May 2011. The 12-month follow-up was completed in May 2012. Conclusions: This is a multi-center study to assess cost as a primary outcome in a comparative effectiveness trial of LASC versus RASC. [Copyright &y& Elsevier]

Abstract: The modern pollen network in North America and Greenland is presented as a database for use in quantitative calibration studies and paleoenvironmental reconstructions. The georeferenced database includes 4634 samples from all regions of the continent and 134 pollen taxa that range from ubiquitous to regionally diagnostic taxa. Climate data and vegetation characteristics were assigned to every site. Automated and manual procedures were used to verify the accuracy of geographic coordinates and identify duplicate records among datasets, incomplete pollen sums, and other potential errors. Data are currently available for almost all of North America, with variable density. Pollen taxonomic diversity, as measured by the Shannon–Weiner coefficient, varies as a function of location, as some vegetation regions are dominated by one or two major pollen producers, while other regions have a more even composition of pollen taxa. Squared-chord distances computed between samples show that most modern pollen samples find analogues within their own vegetation zone. Both temperature and precipitation inferred from best analogues are highly correlated with observed values but temperature exhibits the strongest relation. Maps of the contemporary distribution of several pollen types in relation to the range of the plant taxon illustrate the correspondence between plant and pollen ranges. [Copyright &y& Elsevier]

Importance: Feasibility of home urogenital microbiome specimen collection is unknown., Objectives: This study aimed to evaluate successful sample collection rates from home and clinical research centers., Study Design: Adult women participants enrolled in a multicentered cohort study were recruited to an in-person research center evaluation, including self-collected urogenital samples. A nested feasibility substudy evaluated home biospecimen collection prior to the scheduled in-person evaluation using a home collection kit with written instructions, sample collection supplies, and a Peezy™ urine collection device. Participants self-collected samples at home and shipped them to a central laboratory 1 day prior to and the day of the in-person evaluation. We defined successful collection as receipt of at least one urine specimen that was visibly viable for sequencing., Results: Of 156 participants invited to the feasibility substudy, 134 were enrolled and sent collection kits with 89% (119/134) returning at least 1 home urine specimen; the laboratory determined that 79% (106/134) of these urine samples were visually viable for analysis. The laboratory received self-collected urine from the research center visit in 97% (115/119); 76% (91/119) were visually viable for sequencing. Among 401 women who did not participate in the feasibility home collection substudy, 98% (394/401) self-collected urine at the research center with 80% (321/401) returned and visibly viable for sequencing., Conclusions: Home collection of urogenital microbiome samples for research is feasible, with comparable success to clinical research center collection. Sample size adjustment should plan for technical and logistical difficulties, regardless of specimen collection site., Competing Interests: Emily S. Lukacz is a scientific advisory board member and consultant for Pathnostics (2021 to present), receives royalties from UpToDate (2015 to present), is an advisory board member for Emmi Solutions (patient education material, 2023 to present), and works for Tegus.com (2023 to present). Furthermore, she is a consultant (study section) for NIDDK and received research funding from NIDDK, NICHD, and PCORI. Cynthia S. Fok received author royalty from UptoDate and is a consultant for UroCure and Medtronic. Melanie R. Meister is an advisory board member for AbbVie Inc. Margaret G. Mueller provides expert testimony for Butler Snow and received educational honoraria from Axonics and NIH funding (NIDDK and NICHD). Ariana L. Smith received research funding from Convatec and PA Department of State, is an associate editor for NAU, and is on the board of directors and a treasurer for SUFU. Ann Stapleton is a consultant for GSK. Daniel McDonald is a consultant for, and has equity in, BiomeSense, Inc. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. Rob Knight is a scientific advisory board member and consultant for BiomeSense, Inc., has equity, and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant and scientific advisory board member for DayTwo and receives income. He has equity in and acts as a consultant for Cybele. He is a cofounder of Biota, Inc. and has equity. He is a cofounder of Micronoma, has equity, and is a scientific advisory board member. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. Linda Brubaker received editorial stipends from JAMA and UptoDate. The rest of the authors reported no disclosures., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

Authorship and dissemination policies vary across NIH research consortia. We aimed to describe elements of real-life policies in use by eligible U01 clinical research consortia. Principal investigators of eligible, active U01 clinical research projects identified in the NIH Research Portfolio Online Reporting Tools database shared relevant policies. The characteristics of key policy elements, determined a priori, were reviewed and quantified, when appropriate. Twenty one of 81 research projects met search criteria and provided policies. K elements (e.g., in quotations): "manuscript proposals reviewed and approved by committee" (90%); "guidelines for acknowledgements" (86%); "writing team formation" (71%); "process for final manuscript review and approval" (71%), "responsibilities for lead author" (67%), "guidelines for other types of publications" (67%); "draft manuscript review and approval" (62%); "recommendation for number of members per consortium site" (57%); and "requirement to identify individual contributions in the manuscript" (19%). Authorship/dissemination policies for large team science research projects are highly variable. Creation of an NIH policies repository and accompanying toolkit with model language and recommended key elements could improve comprehensiveness, ethical integrity, and efficiency in team science work while reducing burden and cost on newly funded consortia and directing time and resources to scientific endeavors.

Objective: Financial strain and unmet social needs are associated with greater risk for lower urinary tract symptoms. Little research has examined financial strain and unmet social needs in relation to the more holistic concept of bladder health. This study utilizes baseline data from RISE FOR HEALTH: A U.S. Study of Bladder Health to examine whether financial strain, unmet social needs, and meeting specific federal poverty level threshold levels are associated with lower urinary tract symptoms and poorer perceived bladder health, well-being, and function., Study Design: Participants were 18 years or older, born female or currently identified as a woman, and from the civilian, noninstitutionalized population residing in 50 counties in the United States that included or surrounded 9 recruitment centers. Data were collected through mailed or internet-based surveys. To address research questions, the 10-item Lower Urinary Tract Dysfunction Research Network - Symptom Index and selected Prevention of Lower Urinary Tract Symptoms Research Consortium bladder health scores were separately regressed on each financial strain, unmet social need, and federal poverty level variable, using linear regression adjusting for covariates (age, race/ethnicity, education, and vaginal parity) and robust variance estimation for confidence intervals (CI). Participants with no missing data for a given analysis were included (range of n=2564-3170). In separate sensitivity analyses, body mass index, hypertension, and diabetes were added as covariates and missing data were imputed., Results: The mean age of participants was 51.5 years (standard deviation=18.4). Not having enough money to make ends meet, housing insecurity, food insecurity, unreliable transportation, and percent federal poverty levels of 300% or less were consistently associated with more reported lower urinary tract symptoms and poorer perceived bladder health. For example, compared to food secure participants, women who worried that their food would run out at the end of the month had a Lower Urinary Tract Dysfunction Research Network - Symptom Index score that was 3.4 points higher (95% CI: 2.5, 4.3), on average. They also had lower mean scores across different bladder health measures, each assessed using a 100-point scale: global bladder health (-8.2, 95% CI: -10.8, -5.7), frequency (-10.2, 95% CI: -13.8, -6.7), sensation (-11.6, 95% CI: -15.1, -8.2), continence (-13.3, 95% CI: -16.7, -9.9), and emotional impact of bladder health status (-13.2, 95% CI: -16.5, -9.9). Across analyses, associations largely remained significant after additional adjustment for body mass index, hypertension, and diabetes. The pattern of results when imputing missing data was similar to that observed with complete case analysis; all significant associations remained significant with imputation., Conclusion: Financial strain and unmet social needs are associated with worse LUTS and poorer bladder health. Longitudinal research is needed to examine whether financial strain and unmet social needs influence the development, maintenance, and worsening of lower urinary tract symptoms; different mechanisms by which financial strain and unmet social needs may impact symptoms; and the degree to which symptoms contribute to financial strain. If supported by etiologic research, prevention research can be implemented to determine whether the amelioration of financial strain and social needs, including enhanced access to preventative care, may promote bladder health across the life course., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this second episode of the Microbiologist in the Clinic series, clinicians and laboratory scientists share their perspectives about a 75-year-old woman who was diagnosed with asymptomatic bacteriuria based on positive urine cultures. The patient and her GP are concerned about this laboratory finding as the patient will become immunosuppressed with planned chemotherapy. The patient has had an overactive bladder (OAB) for approximately 20 years, with good control of her urinary urgency and frequency (no incontinence) with a stable dose of OAB medication. The challenges of this clinical presentation are discussed, with evidence for evaluation and treatment., (© 2024. The International Urogynecological Association.)

This article discusses the urinary microbiome in relation to urinary tract infection (UTI) in women. It makes biologic sense that the microbiota of different niches (bladder, vagina, and gut) interact with each other in health, as well as during a UTI event; however, these relationships remain poorly understood. Future research should close knowledge gaps regarding the interactions between the urinary microbiota and the host, amongst the microbiota of adjacent niches, and between the microbes within the same microbiota. The new knowledge should result in improved UTI treatment in the age of antibiotic stewardship., Competing Interests: Disclosure L. Brubaker discloses editorial stipends from JAMA and UpToDate. T.C. Chai discloses his role as a consultant for Glaxo Smith Kline involved in the commercialization of their new antibiotic, gepotidacin, for uncomplicated UTI. A.J. Wolfe discloses advisory board membership for Pathnostics and Urobiome Therapeutics, funding from Pathnostics, the Craig Neilsen Foundation, National Institutes of Health, United States, and an anonymous donor., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains relatively limited despite substantial disease burden. In light of this, we present a selected review of clinical trials and preclinical studies targeting both the vaginal and gut microbiomes for the prevention or treatment of various gynecologic conditions. Specifically, we explore studies that leverage microbiota transplants, probiotics, prebiotics, diet modifications, and engineered microbial strains. A healthy vaginal microbiome for females of reproductive age consists of lactic acid-producing bacteria predominantly of the Lactobacillus genus, which serves as a protective barrier against pathogens and maintains a balanced ecosystem. The gut microbiota's production of short-chain fatty acids, metabolism of primary bile acids, and modulation of sex steroid levels have significant implications for the interplay between host and microbes throughout the body, ultimately impacting reproductive health. By harnessing interventions that modulate both the vaginal and gut microbiomes, it becomes possible to not only maintain homeostasis but also mitigate pathological conditions. While the field is still working toward making broad clinical recommendations, the current studies demonstrate that manipulating the microbiome holds great potential for addressing diverse gynecologic conditions., Lay Summary: Manipulating the microbiome has recently entered popular culture, with various diets thought to aid the microbes that live within us. These microbes live in different locations of our body and accordingly help us digest food, modulate our immune system, and influence reproductive health. The role of the microbes living in and influencing the female reproductive tract remains understudied despite known roles in common conditions such as vulvovaginal candidiasis (affecting 75% of females in their lifetime), bacterial vaginosis (25% of females in their lifetime), cervical HPV infection (80% of females in their lifetime), endometriosis (6-10% of females of reproductive age), and polycystic ovary syndrome (10-12% of females of reproductive age). Here, we review four different approaches used to manipulate the female reproductive tract and gastrointestinal system microbiomes: microbiota transplants, probiotics, prebiotics, and dietary interventions, and the use of engineered microbial strains. In doing so, we aim to stimulate discussion on new ways to understand and treat female reproductive health conditions.

Background: Urinary microbiome (urobiome) studies have previously reported on specific taxa and community differences in women with mixed urinary incontinence compared with controls. Therefore, a hypothesis was made that higher urinary and vaginal microbiome diversity would be associated with increased urinary incontinence severity., Objective: This study aimed to test whether specific urinary or vaginal microbiome community types are associated with urinary incontinence severity in a population of women with mixed urinary incontinence., Study Design: This planned secondary, cross-sectional analysis evaluated associations between the urinary and vaginal microbiomes and urinary incontinence severity in a subset of Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial participants with urinary incontinence. Incontinence severity was measured using bladder diaries and Urinary Distress Inventory questionnaires collected at baseline. Catheterized urine samples and vaginal swabs were concurrently collected before treatment at baseline to assess the urinary and vaginal microbiomes. Of note, 16S rRNA V4 to V6 variable regions were sequenced, characterizing bacterial taxa to the genus level using the DADA2 pipeline and SILVA database. Using Dirichlet multinomial mixtures methods, samples were clustered into community types based on core taxa. Associations between community types and severity measures (Urinary Distress Inventory total scores, Urinary Distress Inventory subscale scores, and the number of urinary incontinence episodes [total, urgency, and stress] from the bladder diary) were evaluated using linear regression models adjusted for age and body mass index. In addition, alpha diversity measures for richness (total taxa numbers) and evenness (proportional distribution of taxa abundance) were analyzed for associations with urinary incontinence episodes and community type., Results: Overall, 6 urinary microbiome community types were identified, characterized by varying levels of common genera (Lactobacillus, Gardnerella, Prevotella, Tepidimonas, Acidovorax, Escherichia, and others). The analysis of urinary incontinence severity in 126 participants with mixed urinary incontinence identified a Lactobacillus-dominated reference group with the highest abundance of Lactobacillus (mean relative abundance of 76%). A community characterized by fewer Lactobacilli (mean relative abundance of 19%) and greater alpha diversity was associated with higher total urinary incontinence episodes (2.67 daily leaks; 95% confidence interval, 0.76-4.59; P=.007) and urgency urinary incontinence episodes (1.75 daily leaks; 95% confidence interval, 0.24-3.27; P=.02) than the reference group. No significant association was observed between community type and stress urinary incontinence episodes or Urogenital Distress Inventory total or subscores. The composition of vaginal community types and urinary community types were similar but composed of slightly different bacterial taxa. Vaginal community types were not associated with urinary incontinence severity, as measured by bladder diary or Urogenital Distress Inventory total and subscale scores. Alpha diversity indicated that greater sample richness was associated with more incontinence episodes (observed genera P=.01) in urine. Measures of evenness (Shannon and Pielou) were not associated with incontinence severity in the urinary or vaginal microbiomes., Conclusion: In the urobiome of women with mixed urinary incontinence, a community type with fewer Lactobacilli and more diverse bacteria was associated with more severe urinary incontinence episodes (total and urgency) compared with a community type with high predominance of a single genus, Lactobacillus. Whether mixed urinary incontinence severity is due to lesser predominance of Lactobacillus, greater presence of other non-Lactobacillus genera, or the complement of bacteria consisting of urobiome community types remains to be determined., (Copyright © 2023. Published by Elsevier Inc.)

Objective: A small, but growing literature links stressors and mental health disorders (MHDs) across the life course to overactive bladder (OAB) and urinary incontinence symptoms. Mechanisms by which stressors and MHDs may impact bladder health are not fully understood, limiting novel prevention and treatment efforts. Moreover, potential biopsychosocial mechanisms involving the brain and gut have not been considered in an integrated, comprehensive fashion., Methods: Members of the prevention of lower urinary tract symptoms Research Consortium developed conceptual models to inform research on biopsychosocial mechanisms through which stress and MDHs may impact bladder health among girls and women, focusing on brain and gut physiology., Results: Two conceptual models were developed-one to explain central (brain-based) and peripheral (gut-based) mechanisms linking stressors and MHDs to OAB and bladder health, and one to highlight bidirectional communication between the brain, gut, and bladder. Traumatic events, chronic stressors, and MHDs may lead to a maladaptive stress response, including dysregulated communication and signaling between the brain, gut, and bladder. Gut bacteria produce molecules and metabolites that alter production of neurotransmitters, amino acids, short-chain fatty acids, and inflammatory immune response molecules that mediate communication between the gut and brain. Microbiota signal neurogenesis, microglia maturation, and synaptic pruning; they also calibrate brain-gut-bladder axis communication through neurotransmission and synaptogenesis, potentially influencing bladder symptom development. Life course trajectories of risk may be prevented or interrupted by central and peripheral resources for neuropsychological resilience., Conclusions: Depicted pathways, including brain-gut-bladder communication, have implications for research and development of novel prevention and treatment approaches., (© 2023 Wiley Periodicals LLC.)

Importance: The composition of the human vaginal microbiome has been linked to a variety of medical conditions including yeast infection, bacterial vaginosis, and sexually transmitted infection. The vaginal microbiome is becoming increasingly acknowledged as a key factor in personal health, and it is essential to establish methods to collect and process accurate samples with self-collection techniques to allow large, population-based studies. In this study, we investigate if using AssayAssure Genelock, a nucleic acid preservative, introduces microbial biases in self-collected vaginal samples. To our knowledge, we also contribute some of the first evidence regarding the impacts of multiple swabs taken at one time point. Vaginal samples have relatively low biomass, so the ability to collect multiple swabs from a unique participant at a single time would greatly improve the replicability and data available for future studies. This will hopefully lay the groundwork to gain a more complete and accurate understanding of the vaginal microbiome., Competing Interests: E.S.L. is a consultant and advisory board member for Pathnostics. L.B. receives editorial stipends from JAMA, Urogynecology, and Up to Date. R.K. owns stock in and is a scientific advisory board (SAB) member for Gencirq, is a consultant and SAB member for DayTwo, owns stock in and is a consultant for Cybele, owns stock in and is a consultant and SAB member for Biomesense, owns stock in and is an SAB member and co-founder of Micronoma, and owns stock in and is co-founder of Biota. D.M. owns stock in and is a consultant for Biomesense. All other authors declare no conflict of interest.

Purpose: Although maternal depression is associated with adverse outcomes in women and children, its relationship with lower urinary tract symptoms (LUTS) in offspring is less well-characterized. We examined the association between prenatal and postpartum maternal depression and LUTS in primary school-age daughters., Design: Observational cohort study., Subjects and Setting: The sample comprised 7148 mother-daughter dyads from the Avon Longitudinal Study of Parents and Children., Method: Mothers completed questionnaires about depressive symptoms at 18 and 32 weeks' gestation and 21 months postpartum and their children's LUTS (urinary urgency, nocturia, and daytime and nighttime wetting) at 6, 7, and 9 years of age. Multivariable logistic regression models were used to estimate the association between maternal depression and LUTS in daughters., Results: Compared to daughters of mothers without depression, those born to mothers with prenatal and postpartum depression had higher odds of LUTS, including urinary urgency (adjusted odds ratio [aOR] range = 1.99-2.50) and nocturia (aOR range = 1.67-1.97) at 6, 7, and 9 years of age. Additionally, daughters born to mothers with prenatal and postpartum depression had higher odds of daytime wetting (aOR range = 1.81-1.99) and nighttime wetting (aOR range = 1.63-1.95) at 6 and 7 years of age. Less consistent associations were observed for depression limited to the prenatal or postpartum periods only., Conclusions: Exposure to maternal depression in the prenatal and postpartum periods was associated with an increased likelihood of LUTS in daughters. This association may be an important opportunity for childhood LUTS prevention. Prevention strategies should reflect an understanding of potential biological and environmental mechanisms through which maternal depression may influence childhood LUTS., Competing Interests: Conflicts of Interest: Dr Epperson consults to Asarina Pharma, Sweden, and Sage Therapeutics, Cambridge, Massachusetts. Dr Epperson is also a site investigator for a randomized controlled trial sponsored by Sage Therapeutics. The other authors declare that they have no conflict of interest., (Copyright © 2024 by the Wound, Ostomy and Continence Nurses Society.)

Competing Interests: The author has declared that there are no conflicts of interest.

In this first episode of the Microbiologist in the Clinic series, clinicians and laboratory scientists share their perspectives about a 30 y/o woman, who is seeking specialty consultation for frequent episodes of urinary urgency, frequency, and dysuria, which respond to short courses of antibiotics. Although her home dipsticks suggest that she has a UTI, and her urinalysis typically has a moderate number of white blood cells, her urine cultures are always negative. The challenges of this clinical presentation are discussed with evidence for evaluation and treatment., (© 2023. The International Urogynecological Association.)

Problem: Structural racism is embedded within the structure and function of academic medical institutions. Although many institutions have begun to incorporate racial justice within academic medicine, it needs to be integral to every discipline and all aspects of medical education, research, and health system practice. Guidance is lacking, however, on how to create and sustain department-level action to shift culture and encourage antiracist work., Approach: To address the culture, uphold racial justice, and address the challenges of racism in medicine with dynamic and innovative solutions, the Department of Obstetrics, Gynecology and Reproductive Sciences at University of California, San Diego, formed a Culture and Justice Quorum (the Quorum) in September 2020. All department faculty, residents, fellows, and staff were invited to participate in the Quorum as ambassadors who commit to meet and facilitate Quorum work or as supporters who pledge Quorum support without regular meeting participation., Outcomes: In all, 153 of 155 invited individuals (98.7%) responded, with 36 (23.2%) requesting to participate as ambassadors and 117 (75.5%) as supporters. Quorum ambassadors have worked together to assess the climate of the department, university, and health system, including incorporating input and amplifying efforts of the department's resident leadership council. The Quorum has implemented initiatives to promote health equity and developed a report card to demonstrate activities, monitor progress, and ensure accountability., Next Steps: Through the innovative Culture and Justice Quorum, the department aims to address structural racism, foster justice, and dismantle the foundational injustices embedded within departmental clinical, educational, and research work and within the wider culture. The Quorum offers a model for creating and sustaining department-level action to shift culture and encourage antiracist work. Since established, it has received institutional recognition, including receiving the 2022 Inclusive Excellent Award for Department-Organizational Unit, which recognizes outstanding institutional contributions for inclusion and diversity efforts., (Copyright © 2023 by the Association of American Medical Colleges.)

Introduction and Hypothesis: The relationship between external lumbar, hip, and/or pelvic girdle pain and internal vaginal pelvic floor myofascial pain is not well described. We assessed this relationship in a cohort of adult women., Methods: The cohort included women ≥ 18 years old who received care for external lumbar, hip, and/or pelvic girdle pain (reported or elicited on physical examination) who then underwent internal vaginal myofascial levator ani pain assessments, in a tertiary care Female Pelvic Medicine and Reconstructive Surgery pelvic pain clinic over a 2-year period (2013 and 2014)., Results: The cohort of 177 women had an average age of 44.9±16.0 years, an average body mass index of 27.2±7.0 kg/m 2 , and the majority (79.2%) were white. Most patients presented with a chief complaint of pelvic (51.4%), vulvovaginal (18.6%), and/or lumbar (15.3%) pain. Women who reported symptoms of lumbar, hip, or pelvic girdle pain were more likely to have pain on vaginal pelvic floor muscle examination than women without this history (OR, 7.24; 95% CI, 1.95-26.93, p=0.003). The majority (85.9%) of women had bilateral internal vaginal pelvic floor myofascial pain on examination., Conclusions: Although participants did not describe "vaginal pelvic floor myofascial pain," the high detection rate for internal vaginal pelvic floor myofascial pain on clinical examination highlights an opportunity to improve treatment planning. These findings suggest that the vaginal pelvic floor muscle examination should be part of the assessment of all women with lumbar, hip, and/or pelvic girdle pain. The relationship between this finding and clinical outcomes following directed treatment warrants additional study., (© 2022. The International Urogynecological Association.)

Introduction: The spectrum of bladder health and the factors that promote bladder health and prevent lower urinary tract symptoms (LUTS) among women are not well understood. This manuscript describes the rationale, aims, study design, sampling strategy, and data collection for the RISE FOR HEALTH (RISE) study, a novel study of bladder health in women conducted by the Prevention of Lower Urinary Tract Symptom (PLUS) Research Consortium., Methods and Results: RISE is a population-based, multicenter, prospective longitudinal cohort study of community-dwelling, English- and Spanish-speaking adult women based in the United States. Its goal is to inform the distribution of bladder health and the individual factors (biologic, behavioral, and psychosocial) and multilevel factors (interpersonal, institutional, community, and societal) that promote bladder health and/or prevent LUTS in women across the life course. Key study development activities included the: (1) development of a conceptual framework and philosophy to guide subsequent activities, (2) creation of a study design and sampling strategy, prioritizing diversity, equity, and inclusion, and (3) selection and development of data collection components. Community members and cross-cultural experts shaped and ensured the appropriateness of all study procedures and materials. RISE participants will be selected by simple random sampling of individuals identified by a marketing database who reside in the 50 counties surrounding nine PLUS clinical research centers. Participants will complete self-administered surveys at baseline (mailed paper or electronic) to capture bladder health and LUTS, knowledge about bladder health, and factors hypothesized to promote bladder health and prevent LUTS. A subset of participants will complete an in-person assessment to augment data with objective measures including urogenital microbiome specimens. Initial longitudinal follow-up is planned at 1 year., Discussion: Findings from RISE will begin to build the necessary evidence base to support much-needed, new bladder health promotion and LUTS prevention interventions in women., (© 2022 Wiley Periodicals LLC.)

Introduction and Hypothesis: Representatives of two classes of oral medication are often used to treat urgency urinary incontinence (UUI): solifenacin, an M3-receptor-selective antimuscarinic, and mirabegron, a beta-3 agonist. Two previous asynchronous drug-specific studies suggested different interactions between these medications and the urobiome despite identical methodologies, including recruitment, sample procurement, medication dose escalation strategy, determination of 12-week responders versus nonresponders, and data collection. This analysis compares data from these two studies using a uniform analytic approach., Methods: Urine was collected aseptically via transurethral catheter from consenting participants for subsequent processing by the Expanded Quantitative Urine Culture (EQUC) protocol in two cohorts (n=50 and n=47) that were demographically similar. Species accumulation curves were generated to compare the total number of unique species detected. Indices that measure richness, evenness, and/or abundance were used to compare alpha (within sample) diversity. The Bray-Curtis Dissimilarity Index was used to determine between sample (beta) diversity., Results: The majority of the 40 species detected in the pre-treatment urobiomes were detected in both cohorts. Both pre-treatment urobiomes were substantially similar in species richness, evenness, and diversity. Differences in pre-treatment urobiomes were associated with treatment response for solifenacin-treated participants only. In contrast, the pre-treatment urobiomes of mirabegron-treated participants were not associated with treatment response. Changes in the post-treatment urobiomes were detected in both cohorts with an increase in richness for both solifenacin (5-mg dose only) and mirabegron., Conclusions: Pre-treatment urobiome characteristics were associated with treatment response in participants treated with solifenacin, but not mirabegron. Differences exist in urobiome response after treatment with two medications that have known differences in mechanism of action., (© 2022. The International Urogynecological Association.)