Auto Poisoning of the Respiratory Chain by a Quorum-Sensing-Regulated Molecule Favors Biofilm Formation and Antibiotic Tolerance.

Bacterial programmed cell death and quorum sensing are direct examples of prokaryote group behaviors, wherein cells coordinate their actions to function cooperatively like one organism for the benefit of the whole culture. We demonstrate here that 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), a Pseudomonas aeruginosa quorum-sensing-regulated low-molecular-weight excreted molecule, triggers autolysis by self-perturbing the electron transfer reactions of the cytochrome bc1 complex. HQNO induces specific self-poisoning by disrupting the flow of electrons through the respiratory chain at the cytochrome bc1 complex, causing a leak of reducing equivalents to O2 whereby electrons that would normally be passed to cytochrome c are donated directly to O2. The subsequent mass production of reactive oxygen species (ROS) reduces membrane potential and disrupts membrane integrity, causing bacterial cell autolysis and DNA release. DNA subsequently promotes biofilm formation and increases antibiotic tolerance to beta-lactams, suggesting that HQNO-dependent cell autolysis is advantageous to the bacterial populations. These data identify both a new programmed cell death system and a novel role for HQNO as a critical inducer of biofilm formation and antibiotic tolerance. This newly identified pathway suggests intriguing mechanistic similarities with the initial mitochondrial-mediated steps of eukaryotic apoptosis.

Single-incision mini-slings versus standard midurethral slings in surgical management of female stress urinary incontinence: an updated systematic review and meta-analysis of effectiveness and complications.

CONTEXT: An updated systematic review and meta-analysis of randomised controlled trials (RCTs) comparing single-incision mini-slings (SIMS) versus standard midurethral slings (SMUS) in the surgical management of female stress urinary incontinence (SUI). OBJECTIVE: To evaluate the clinical efficacy, safety, and cost effectiveness of SIMS compared with SMUS in the treatment of female SUI. EVIDENCE ACQUISITION: A literature search was performed for all RCTs and quasi-RCTs comparing SIMS with either transobturator tension-free vaginal tape (TO-TVT) or retropubic tension-free vaginal tape (RP-TVT). The literature search had no language restrictions and was last updated on May 2, 2013. The primary outcomes were patient-reported and objective cure rates at 12 to 36 mo follow-up. Secondary outcomes included operative data; peri- and postoperative complications, and repeat continence surgery. Data were analysed using RevMan software. Meta-analyses of TVT-Secur versus SMUS are presented separately as the former was recently withdrawn from clinical practice. EVIDENCE SYNTHESIS: A total of 26 RCTs (n=3308 women) were included. After excluding RCTs evaluating TVT-Secur, there was no evidence of significant differences between SIMS and SMUS in patient-reported cure rates (risk ratio [RR]: 0.94; 95% confidence interval [CI], 0.88-1.00) and objective cure rates (RR: 0.98; 95% CI, 0.94-1.01) at a mean follow-up of 18.6 mo. These results pertained on comparing SIMS versus TO-TVT and RP-TVT separately. SIMS had significantly lower postoperative pain scores (weighted means difference [WMD]: -2.94; 95% CI, -4.16 to -1.73) and earlier return to normal activities and to work (WMD: -5.08; 95% CI, -9.59 to -0.56 and WMD: -7.20; 95% CI, -12.43 to -1.98, respectively). SIMS had a nonsignificant trend towards higher rates of repeat continence surgery (RR: 2.00; 95% CI, 0.93-4.31). CONCLUSIONS: This meta-analysis shows that, excluding TVT-Secur, there was no evidence of significant differences in patient-reported and objective cure between currently used SIMS and SMUS at midterm follow-up while associated with more favourable recovery time. Results should be interpreted with caution due to the heterogeneity of the trials included.

Evaluation of transobturator tension-free vaginal tapes in the surgical management of mixed urinary incontinence: 3-year outcomes of a randomized controlled trial.

PURPOSE: We evaluate the clinical effectiveness of transobturator tension-free vaginal tape procedures in the surgical management of mixed urinary incontinence in women at 3-year followup. MATERIALS AND METHODS: In this secondary analysis of a prospective, single-blind, randomized controlled trial 83 of 341 women (24%) with mixed urinary incontinence were randomized to undergo an outside-in (Aris® transobturator sling system 42) or inside-out (TVT™-O 41) transobturator tension-free vaginal tape procedure. Patients were contacted by postal questionnaire at a minimum of 3 years postoperatively. The primary outcome was the patient reported success rate, defined as very much improved/much improved on the PGI-I (Patient Global Impression of Improvement). Secondary outcomes included improvement in quality of life, impact on preoperative urgency/urgency incontinence and repeat surgical treatment for stress urinary incontinence. Outcomes at 3 years were compared between groups (outside-in vs inside-out) and to 1-year outcomes. Analysis was performed using SPSS® version 20 with significance levels set at p = 0.05. RESULTS: A total of 66 women with mixed urinary incontinence completed the 3-year followup (outside-in 35 vs inside-out 31). In each group 2 women underwent further continence surgery. The patient reported success rate was 73.8% with no significant differences between the groups (OR 1.035, 95% CI 0.342-3.134, p = 0.951). Overall 34 (50.1%) and 26 women (56.5%) reported cure of preoperative urgency and urgency incontinence, respectively, and 52 women (86.7%) had a clinically significant improvement in quality of life (18 points or more in total KHQ [King's Health Questionnaire] score) compared to baseline. CONCLUSIONS: Transobturator tape procedures are associated with a good (73.8%) patient reported success rate at a minimum of 3 years of followup in the surgical management of mixed urinary incontinence in women with predominant stress urinary incontinence symptoms. Nearly half of the women reported cure of urgency/urgency incontinence.