STOMp: sexual function trial of overactive bladder medication.

Background: Female sexual function has been shown to improve with overactive bladder (OAB) treatment. Aim: The objective of this study was to evaluate the effects of anticholinergics (ACHs) or a beta-agonist (BAG) on female sexual function. Methods: This was a prospective multicenter cohort study. Sexually active women with OAB completed the Overactive Bladder questionnaire (OAB-q) and Female Sexual Function Index (FSFI) prior to and after 12 weeks of therapy. Sample sizes of 63 per group were calculated to detect a clinically relevant difference in the FSFI. Outcomes: The primary outcome was FSFI change from baseline at 12 weeks. Results: A total of 157 patients were recruited, and 91 completed follow-up (58/108, ACH; 31/49, BAG). There were within-group FSFI differences from pre- to posttreatment: a worsening of arousal in the ACH group (P = .046) and an improvement in overall FSFI (P = .04) and pain (P = .04) in the BAG group. After treatment, postmenopausal women in the BAG group had significantly better overall FSFI (P = .01), desire (P = .003), arousal (P = .009), and orgasm (P = .01). Clinical Implications: While further research is necessary, this study provides information about the comparative effects of OAB treatments on female sexual function, which may ultimately lead to better patient selection and outcomes. Strengths and Limitations: While there was no difference between the subjects who completed the study and those who did not, the study remained underpowered after the loss to follow-up. The multicenter cohort design allows for generalizability of results. Conclusion: Although this study was underpowered, an improvement in overall sexual function was seen with BAGs, while ACHs were associated with worsening aspects of sexual function.

Expression of immune response genes in human corneal epithelial cells interacting with Aspergillus flavus conidia.

BACKGROUND: Aspergillus flavus, one of the causative agents of human fungal keratitis, can be phagocytosed by human corneal epithelial (HCE) cells and the conidia containing phagosomes mature into phagolysosomes. But the immunological responses of human corneal epithelial cells interacting with A. flavus are not clear. In this study, we report the expression of immune response related genes of HCE cells exposed to A. flavus spores using targeted transcriptomics. METHODS: Human corneal epithelial cell line and primary cultures were grown in a six-well plate and used for coculture experiments. Internalization of the conidia was confirmed by immunofluorescence microscopy of the colocalized endosomal markers CD71 and LAMP1. Total RNA was isolated, and the quantity and quality of the isolated RNA were assessed using Qubit and Bioanalyzer. NanoString nCounter platform was used for the analysis of mRNA abundance using the Human Immunology panel. R-package and nSolver software were used for data analysis. KEGG and FunRich 3.1.3 tools were used to analyze the differentially expressed genes. RESULTS: Different morphotypes of conidia were observed after 6 h of coculture with human corneal epithelial cells and found to be internalized by epithelial cells. NanoString profiling showed more than 20 differentially expressed genes in immortalized human corneal epithelial cell line and more than ten differentially expressed genes in primary corneal epithelial cells. Distinct set of genes were altered in their expression in cell line and primary corneal epithelial cells. KEGG pathway analysis revealed that genes associated with TNF signaling, NF-KB signaling, and Th17 signaling were up-regulated, and genes associated with chemokine signaling and B cell receptor signaling were down regulated. FunRich pathway analysis showed that pathways such as CDC42 signaling, PI3K signaling, and Arf6 trafficking events were activated by the clinical isolates CI1123 and CI1698 in both type of cells. CONCLUSIONS: Combining the transcript analysis data from cell lines and primary cultures, we showed the up regulation of immune defense genes in A. flavus infected cells. At the same time, chemokine signaling and B cell signaling pathways are downregulated. The variability in the expression levels in the immortalized cell line and the primary cultures is likely due to the variable epigenetic reprogramming in the immortalized cells and primary cultures in the absence of any changes in the genome. It highlights the importance of using both cell types in host-pathogen interaction studies.

Human Corneal Epithelial Cells Internalize Aspergillus flavus Spores by Actin-Mediated Endocytosis.

Human corneal epithelial (HCE) cells play a significant role in the innate immune response by secreting cytokines and antimicrobial peptides when they encounter fungal pathogens. But the detailed mechanism of attachment and engulfment of the fungal conidia by HCE cells is not well understood. Here, we show the phagocytosis of Aspergillus flavus conidia by RCB2280 cells and primary HCE cultures using confocal microscopy and proteomic analysis of conidium-containing phagosomes. Phalloidin staining showed actin polymerization, leading to an actin ring around engulfed conidia. Cytochalasin D inhibited the actin-mediated endocytosis of the conidia. Immunolabeling of the early endosomal markers CD71 and early endosomal antigen (EEA1) and the late endosomal markers lysosome-associated membrane protein 1 (LAMP1), Rab7, and cathepsin G showed that endosomal proteins were recruited to the site of conidia and showed maturation of the conidium-containing phagosomes. Lysotracker red DND 99 labeling showed the acidification of the phagosomes containing conidia. Phagosome-specific proteome analysis confirmed the recruitment of various phagosomal and endosomal proteins to the conidium-containing phagosomes. These results show that the ocular surface epithelium contributes actively to antifungal defense by the phagocytosis of invading fungal conidia.

Impact of postoperative instructions on physical activity following pelvic reconstructive surgery: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: There is little information on the impact that postoperative instructions have on physical activity to help guide physicians in providing these recommendations after surgery. Our study objective was to evaluate the impact of postoperative instructions on physical activity. We hypothesized that there would be no differential effect of instructions on activity. METHODS: In this randomized controlled trial, patients undergoing prolapse repair were randomized to receive either liberal or restricted postoperative activity instructions between February 2017 and February 2019. Physical activity was measured using the Activities Assessment Scale (AAS) and tri-axial accelerometers measured at baseline and 2 and 6 weeks after surgery. A sample size of 146 patients was planned to compare these activity measurements. AAS scores and accelerometer readings of the two groups were compared using separate variance t tests. RESULTS: A total of 157 women were recruited between February 2017 and February 2019, including 146 patients with completed study data (n = 72 liberal, n = 74 restricted). There was no difference in physical activity at 2 weeks between the liberal and the restricted instruction groups, as measured by AAS scores (70.47 ± 12.83, 69.54 ± 12.22, p = 0.66), total steps (4,582.20 ± 2,164.5, 5,014.47 ± 3,025.46, p = 0.32), active minutes (4.22 ± 6.17, 4.96 ± 9.65, p = 0.25), and 10-min intervals (0.76 ± 1.11, 0.77 ± 0.93, p = 0.95) respectively. Similarly, there was no difference in activity at 6 weeks between the liberal and the restricted instruction groups. as measured by AAS scores (81.86 ± 8.25, 81.31 ± 10.31, p = 0.72), total steps (6,316.25 ± 3,173.53, 6,589.94 ± 3,826.43, p = 0.64), active minutes (8.79 ± 10.5,11.36 ± 18.18, p = 0.98), and 10-min intervals (1.37 ± 1.34, 1.34 ± 1.40, p = 0.89) respectively. CONCLUSION: Postoperative instructions do not have an impact on physical activity measures in patients who have undergone pelvic reconstructive surgery.

Low Bladder Compliance in Women: A Clinical Overview.

Bladder compliance refers to the ability of the bladder to accommodate large volumes of urine. Patients with low bladder compliance may present with persistent urinary incontinence and/or evidence of upper tract damage. Clinicians often may not consider low bladder compliance in their differential for patients complaining of bothersome lower urinary tract symptoms. In this article, we aim to provide further guidance in the management of women with low bladder compliance given the lack of information on this topic in the medical literature.

Posterior Compartment Surgery Provides No Differential Benefit for Defecatory Symptoms Before or After Concomitant Mesh-Augmented Apical Suspension.

OBJECTIVES: The aim of this study was to determine the value of posterior compartment surgery during concomitant mesh-augmented apical suspension by comparing obstructed defecatory symptoms after laparoscopic sacrocolpopexy (LSC) with LSC with posterior repair (LSC + PR) and laparoscopic sacrocolpoperineopexy (LSCP) procedures. METHODS: This was a retrospective cohort study of women who underwent LSC, LSC + PR, and LSCP between July 2007 and July 2016 at a tertiary referral center in Indianapolis, Ind. Our primary outcome was differential change in Colorectal-Anal Distress Inventory (CRADI-8) and Colorectal-Anal Impact Questionnaire (CRAIQ-7) scores between the groups including patient-specific symptoms of splinting, straining, incomplete emptying, and pain with defecation. Our secondary outcomes were the rates of postoperative persistent, new, and resolved obstructed defecation symptoms. Anatomic outcomes were also compared between the groups as measured by change in Pelvic Organ Prolapse Quantification System points Ap, GH, and PB. RESULTS: A total of 312 women were included in the study (47 LSC, 133 LSC + PR, and 132 LSCP), with a median follow-up time of 366 days. The majority of patients who underwent surgery had stage III pelvic organ prolapse (61%). Baseline demographics were similar between groups, including preoperative CRADI-8 and CRAIQ-7 scores. All surgical groups demonstrated improvement in CRADI-8 and CRAIQ-7 scores postoperatively (P < 0.001). However, despite differential change in Pelvic Organ Prolapse Quantification System points Ap, GH, and PB, there was no change in CRADI-8 and CRAIQ-7 scores or rates of persistent, new, and resolved symptoms of splinting to defecate, incomplete emptying, and pain with defecation between the groups. The only factor that seemed to be differentially improved by the addition of a posterior compartment repair was postoperative straining. There was a greater rate of de novo straining in the LSC group compared with LSCP (P = 0.01) (LSC + PR v LSCP, P = NS, for both). CONCLUSIONS: We cannot recommend posterior compartment surgery as providing any patient-centered benefit beyond improved cosmesis because the addition of perineal body stabilization either before (LSCP) or posterior repair after (LSC + PR) concomitant mesh-augmented apical suspension did not differentially affect bowel symptoms compared with LSC alone.

Risk factors for vaginal mesh exposure after mesh-augmented anterior repair: a retrospective cohort study.

OBJECTIVES: The aim of this study is to identify risk factors for vaginal mesh exposure after mesh-augmented repair of anterior prolapse. METHODS: We performed a retrospective cohort study of all patients who had mesh-augmented anterior repair by 1 surgeon between January 2007 and February 2012. Data were extracted from medical records. The primary outcome was the rate of anterior or apical vaginal mesh exposure. Both univariate and multivariate analyses were performed. RESULTS: A total of 201 subjects were included. The mean (SD) follow-up was 14.3 (12.4) months. All cases were done using a type 1 macroporous monofilament polypropylene mesh. The overall mesh exposure rate was 8.5% (17/201). Univariate analysis showed a statistically significant positive association between exposure rates and the following risk factors: lower body mass index (BMI) (P = 0.016), menopause in combination with the use of hormone replacement therapy (P = 0.023), midline sagittal vaginal incision (compared with distal transverse incision) (P = 0.026), concurrent total hysterectomy (P < 0.001), surgery time (P = 0.002), and worse apical prolapse at baseline (P = 0.007). After multivariate analysis using logistic regression, only BMI (P < 0.001) and concomitant total hysterectomy (odds ratio, 48; P < 0.001) remained relevant. The exposure rate was 23.5% (16/68) when concomitant hysterectomy was performed compared with 0.8% (1/133) when no hysterectomy was done. Exposure rates stratified by BMI class were 12.9% (8/62) for BMI less than 25 kg/m, 9.5% (8/84) for BMI of 25 to 29.9 kg/m, 3.1% (1/32) for BMI of 30 to 34.9 kg/m, and 0% (0/23) for BMI greater than or equal to 35 kg/m. CONCLUSIONS: Concomitant total hysterectomy is an independent risk factor for mesh exposure after mesh-augmented anterior repair, whereas BMI may negatively correlate with exposure rates.