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Mycobacterial ESX systems are often related to pathogenesis during infection. However, little is known about the function of ESX systems of Mycobacterium abscessus (Mab). This study focuses on the Mab ESX-3 cluster, which contains major genes such as esxH (Rv0288, low molecular weight protein antigen 7; CFP-7) and esxG (Rv0287, ESAT-6 like protein). An esx-3 (MAB 2224c-2234c)-deletional mutant of Mab (Δesx) was constructed and used to infect murine and human macrophages. We then investigated whether Mab Δesx modulated innate host immune responses in macrophages. Mab Δesx infection resulted in less pathological and inflammatory responses. Additionally, Δesx resulted in significantly decreased activation of inflammatory signaling and cytokine production in macrophages compared to WT. Moreover, recombinant EsxG·EsxH (rEsxGH) proteins encoded by the ESX-3 region showed synergistic enhancement of inflammatory cytokine generation in macrophages infected with Δesx. Taken together, our data suggest that Mab ESX-3 plays an important role in inflammatory and pathological responses during Mab infection.

Objective To evaluate the effect of microsurgical varicocelectomy on sperm morphology in subfertile men with isolated teratozoospermia and a clinically palpable varicocele. Materials and Methods A retrospective review was performed of men with isolated teratozoospermia who had undergone microsurgical varicocelectomy. Semen analyses following varicocelectomy were performed at 2- to 3-month intervals. Responders to the varicocelectomy were defined as those who fulfilled the following criteria in semen analysis: (1) an improvement in percentage of normal forms to ≥4% and (2) normal results for all other semen parameters. Results A total of 80 patients underwent unilateral varicocelectomy (n = 49) or bilateral varicocelectomy (n = 31) (mean age of 36 ± 0.4 years, range 24-44). After a mean postoperative follow-up period of 6.8 months, the mean percentage of normal sperm forms increased from 0.9% to 3.5% ( P P = .004). The number of responders to the surgery was 16 (20%), and their mean percentage of normal forms increased from 1.3% to 9.1%. The mean preoperative and postoperative semen volume and sperm concentration were not different ( P > .05). No differences were observed in age, current smoking status, body mass index, or grade of varicocele between responders and nonresponders. Conclusion Varicocelectomy might be an option for treating subfertile patients with isolated teratozoospermia and a clinically apparent varicocele. However, patients should be advised that the surgery helps in limited patients only because more patients did not benefit from the surgery.

Mycobacterium abscessus is a highly pathogenic drug-resistant rapidly growing mycobacterium. In this study, we evaluated the in vitro , intracellular, and in vivo activities of LCB01-0371, a novel and safe oxazolidinone derivative, for the treatment of M. abscessus infection and compared its resistance to that of other oxazolidinone drugs. LCB01-0371 was effective against several M. abscessus strains in vitro and in a macrophage model of infection. In the murine model, a similar efficacy to linezolid was achieved, especially in the lungs. We induced laboratory-generated resistance to LCB01-0371; sequencing analysis revealed mutations in rplC of T424C and G419A and a nucleotide insertion at the 503 position. Furthermore, LCB01-0371 inhibited the growth of amikacin-, cefoxitin-, and clarithromycin-resistant strains. Collectively, our data indicate that LCB01-0371 might represent a promising new class of oxazolidinones with improved safety, which may replace linezolid for the treatment of M. abscessus .

The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs. Using a Drosophila melanogaster–Mycobacterium marinum infection model, we showed that OMS-A-induced autophagy contributed to the increased survival of infected flies and the limitation of bacterial load. We further showed that OMS triggered AMP-activated protein kinase (AMPK) activation, which was required for OMS-mediated phagosome maturation and antimicrobial responses against Mtb. Moreover, treating BMDMs with OMS led to dose-dependent inhibition of macrophage inflammatory responses, which was also dependent on AMPK activation. Collectively, these data show that OMS is a promising candidate for new anti-mycobacterial therapeutics by activating antibacterial autophagy via AMPK-dependent signaling and suppressing excessive inflammation during Mtb infections.

We assessed the impact of the tension-free vaginal tape procedure on overactive bladder in women with stress urinary incontinence to determine the change in preoperative overactive bladder symptoms and the significance of detrusor overactivity in postoperative outcomes.From January 2003 to December 2004 a total of 549 consecutive women with stress urinary incontinence underwent the tension-free vaginal tape procedure. Of these patients 180 (32.8%) had overactive bladder syndrome. Finally 132 women (mean age 53.2 years) with followup of at least 3 months were included in analysis. Patients with the overactive bladder syndrome with or without detrusor overactivity based on urodynamic study were subdivided into 94 (71.2%) patients with the overactive bladder syndrome without detrusor overactivity and 38 (28.8%) with the overactive bladder syndrome with detrusor overactivity.The complete resolution of all overactive bladder symptoms based on 3-day frequency volume chart and a validated questionnaire was demonstrated in 23.5% (31 of 132 patients). The detrusor overactivity present group showed significantly greater urinary leakage per 1-hour pad test, maximal detrusor pressure and detrusor pressure at maximal flow rate than the detrusor overactivity absent group. There was no significant difference in the 2 groups in terms of cure rate for stress urinary incontinence. The detrusor overactivity present group had a significantly higher resolution rate than the detrusor overactivity absent group for overactive bladder (36.8 vs 18.1 %, p = 0.021).The tension-free vaginal tape procedure can be performed in women with stress urinary incontinence and overactive bladder including urge incontinence even if the patient has detrusor overactivity on urodynamic study. However, patients should be fully advised of the possibility of persistent overactive bladder symptoms and treatment for those symptoms after tension-free vaginal tape should be considered.

Aim: To evaluate the occurrence of classical azoospermia factor (AZF) deletions of the Y chromosome as a routine examination in azoospermic subjects with Klinefelter syndrome (KS). Methods: Blood samples were collected from 95 azoospermic subjects with KS (91 subjects had a 47,XXY karyotype and four subjects had a mosaic 47,XXY/46, XY karyotype) and a control group of 93 fertile men. The values of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. To determine the presence of Y chromosome microdeletions, polymerase chain reaction (PCR) of five sequence-tagged site primers (sY84, sY129, sY134, sY254, sY255) spanning the AZF region, was performed on isolated genomic DNA. Results: Y chromosome microdeletions were not found in any of the 95 azoospermic subjects with KS. In addition, using similar conditions of PCR, no microdeletions were observed in the 93 fertile men evaluated. The level of FSH in KS subjects was higher than that in fertile men (38.2 ± 10.3 mIU/mL vs. 5.4 ± 2.9 mIU/mL, P < 0.001) and the testosterone level was lower than that in the control group (1.7 ± 0.3 ng/mL vs. 4.3 ± 1.3 ng/mL, P < 0.001). Conclusion: Our data and review of the published literature suggest that classical AZF deletions might not play a role in predisposing genetic background for the phenotype of azoospermic KS subjects with a 47,XXY karyotype. In addition, routine screening for the classical AZF deletions might not be required for these subjects. Further studies including partial AZFc deletions (e.g. gr/gr or b2/b3) are necessary to establish other mechanism underlying severe spermatogenesis impairment in KS. (Asian J Androl 2007 Nov; 9: 815–820)

Aim A prospective study was performed to determine the incidence of significant bacteriuria and to identify the risk factors for bacteriuria after urodynamic studies (UDSs) in women with urodynamic stress urinary incontinence (SUI). Methods A total of 225 women with urodynamic SUI were evaluated. All women were negative on double-screened urine cultures, in clean-catch midstream urine (MSU) specimens, before UDS. Another urine specimen was obtained for urinalysis and culture at 3–7 days after UDS. Urinary culture with 105 CFU/ml or more was regarded as significant bacteriuria. To identify the risk factors for significant bacteriuria, the clinical characteristics of all patients including age, BMI, parity, medical and operation history, degree of pelvic organ prolapse, results of urinalysis, and UDS were evaluated. Results The prevalence of significant bacteriuria was 6.2%. The most common identified microorganism was Escherichia coli (57.1%). Univariate analysis demonstrated that a history of recurrent urinary tract infection (UTI; P = 0.002) and urological surgery or procedure (P = 0.02) were significant predictors of significant bacteriuria. On multiple logistic regression analysis the past history of recurrent UTI was the only significant independent risk factor (OR = 28.5, 95% CI = 4.309–188.488, P = 0.009). Conclusions This study suggests that for most women with SUI it may be unnecessary to use preventive prophylactic antibiotics in UDS. However, our results suggest that in patients with a previous history of recurrent UTI or urologic surgery the risk for significant bacteriuria is increased and use of prophylactic antibiotics should be considered. Neurourol. Urodynam. 26:847–851, 2007. © 2007 Wiley-Liss, Inc.

The purpose of this study was to prospectively evaluate symptom change after discontinuation of extracorporeal magnetic stimulation (EMS) in women with overactive bladder (OAB). A total of 48 women with OAB were included. We applied 10 Hz of repetitive magnetic stimulation with a "magnetic chair" for 20 min, twice weekly for 8 weeks. Changes in OAB symptoms at 2, 12, and 24 weeks after discontinuing the EMS were evaluated. Twenty-seven (56.3%) patients were cured compared with the baseline at 2 weeks: the cure rate was determined as 68.8% (33/48 patients), 56.3% (27/48), and 50% (8/16) for urgency, frequency, and urge incontinence, respectively. The mean number of voids per 24 h was decreased by 42.8% (from 14.5 +/- 4.3, to 8.3 +/- 1.5, P < 0.001) at 2 weeks after treatment. Maximum voided volume did not change significantly, but the mean voided volume increased significantly after stimulation. Twenty-six (96.3%) patients among the 27 patients who achieved a cure at 2 weeks, maintained improvement at 24 weeks; the therapeutic effect on urgency, frequency, and urge incontinence persisted in 26 (78.8%) of 33 patients, 26 (96.3%) of 27 patients, and six (75%) of eight patients, respectively. There were no significant changes in urodynamic parameters. Of the 14 patients with detrusor overactivity, the condition was no longer observed in four (28.6%) patients. EMS has a beneficial effect on women with OAB. Our data suggest EMS may have a significant carry-over effect in well-selected OAB patients.

Objectives To report 12 cases of vaginismus that were successfully treated with functional electrical stimulation (FES)-biofeedback with sexual cognitive-behavioral therapy (SCBT) to determine the efficacy of FES-biofeedback with SCBT as a standard therapy for vaginismus. Vaginismus is an involuntary spasm of the musculature of the outer third of the vagina that leads to impossible vaginal penetration, causing personal distress. Various therapeutic approaches, both physiologic and psychological, have been considered. Methods Twelve women with vaginismus referred from a checkup outpatient clinic participated in this study. The patients enrolled in this study had vaginismus according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders. The patients were assessed before and after treatment with gynecologic examinations and structured interviews pertaining to sexual function and psychological adjustment. After the diagnosis of vaginismus, we conducted weekly pelvic floor muscle relaxation using FES-biofeedback. Once the patients became tolerable to vaginal manipulation, the eight-stage SCBT (eight-stage gradual desensitization described by Kaplan using vaginal self-dilation with fingers and vaginal probe insertion) was added for 8 weeks. Results After 8 weeks of treatment, all 12 couples had completed the program, had become tolerable to vaginal insertion of larger size probes, and could achieve satisfactory vaginal intercourse. Conclusions FES-biofeedback with SCBT is an effective aid for patients with vaginismus to learn muscle control. Therefore, it may increase the success rate of treatment of vaginismus.

Objective To assess the relationship between mycoplasma infection and human infertility, we determined the concordance of Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) detection in infertile and fertile couples, and assessed semen parameters in both groups. Methods Fifty infertile couples without a female factor attending a fertility clinic and 48 fertile couples were randomly screened for UU and MH. The concordance between partners was compared between the fertile and infertile groups. Semen and endocervical specimens were evaluated using the commercially available Mycofast Evolution2 test. Results UU was detected in 24 semen specimens (48%) from the infertile men, in 12 specimens from fertile men (25%), in 20 endocervical specimens from infertile women (40%), and 11 from fertile women (22.9%). UU was detected higher in infertile men than in fertile men ( P = .022). The concordance of UU was higher in infertile couples (32%) than in fertile couples (12.5%, P = .022). The concordance of MH between male and female partners in the 2 groups did not differ significantly. The mean values of total motility, progressive motility, normal morphology, vitality, and total motile sperm count were significantly lower in sperm from infertile men than from fertile men. Progressive motility and vitality were significantly lower in UU-positive men than in men without UU, and low total motility and total motile sperm count were significantly related to the presence of MH. Conclusion Clinicians should consider the roles of UU and MH in infertility and routinely screen infertile couples for the presence of these mycoplasma species.

Objectives To determine the efficacy and feasibility of urethral lidocaine spray for rigid cystoscopy in female outpatients, compared with lidocaine gel for patient tolerance of pain. Methods A total of 144 consecutive women scheduled to undergo rigid cystoscopy were randomized to receive either 10 mL of lidocaine gel (group 1, n = 48), five metered doses of 10% lidocaine spray (group 2, n = 48), or 10 mL of plain lubricating gel (group 3, n = 48). Patients recorded their level of pain perception during gel instillation or spray and immediately after the procedure using the visual analogue scale (VAS) and a 5-point verbal descriptor scale. Results The perception of pain was significantly decreased when lidocaine spray was used (mean VAS scores 1.9 ± 1.3 for group 2 versus 3.9 ± 2.2 for group 3; P

The objective of the study was to determine the relative accuracy of a new portable ultrasound unit, BME-150A™, and the BladderScan™ BVI 3000, as assessed in comparison with the catheterized residual urine volume. We used both of these machines to prospectively measure the residual urine volumes of 89 patients (40 men and 49 women) who were undergoing urodynamic studies. The ultrasound measurements were compared with the post-scan bladder volumes obtained by catheterization in the same patients. The ultrasounds were followed immediately (within 5 min) by in-and-out catheterizations while the patients were in a supine position. There were a total of 116 paired measurements made. The BME-150A and the BVI 3000 demonstrated a correlation with the residual volume of 0.92 and 0.94, and a mean difference from the true residual volume of 7.8 and 3.6 ml, respectively. Intraclass correlation coefficients for the accuracy of the two bladder scans were 0.90 for BME-150A and 0.95 for BVI 3000. The difference of accuracy between the two models was not significant (p = 0.2421). There were six cases in which a follow-up evaluation of falsely elevated post-void residual urine volume measurements on the ultrasound studies resulted in comparatively low catheterized volumes, with a range of differences from 66 to 275.5 ml. These cases were diagnosed with an ovarian cyst, uterine myoma, or uterine adenomyosis on pelvic ultrasonography. The accuracy of the BME-150A is comparable to that of the BVI 3000 in estimating the true residual urine volumes and is sufficient enough for us to recommend its use as an alternative to catheterization.

Objectives: Subureteral injection of bulking agents to a refluxing ureteral orifice is an attractive alternative to open repair. We record our experience of the endoscopic subureteral injection of polydimethylsiloxane in women for vesicoureteral reflux (VUR). Methods: From January 1997 to December 2001, 30 women (mean age 34.9 years) with 43 refluxing ureters underwent endoscopic treatment. The grade of VUR was I, II, III, and IV in 10, 16, 13, and 4 ureters, respectively. The indication for the procedure was VUR with a history of pyelonephritis in women of childbearing age or in whom antibiotic prophylaxis had been unsuccessful. All women underwent voiding cystourethrogram at 3 months and then yearly after the procedures. Follow-up ranged from 12 to 60 months (mean 26.5 months). Results: Reflux was corrected in 34 ureters after a single injection; only 3 ureters needed a 2nd injection. The overall success rate was 86.0%: for grades I, II, III, and IV was 90.0%, 87.5%, 76.9%, and 100% respectively. The mean hospital stay was 1.31 days (range 1–8 days), and no remarkable surgical complications occurred. Most of the patients in whom VUR was cured or improved showed a reduction in laboratory-proven urinary infection rates. Conclusions: The endoscopic subureteral injection of polydimethylsiloxane in women with vesicoureteral reflux is an effective therapy with no associated morbidity.