Female sexual dysfunction and lower urinary tract symptoms associated with vulvovaginal atrophy symptoms: Results of the GENJA study.

OBJECTIVES: To investigate the main symptoms of female sexual dysfunction (FSD) and lower urinary tract symptoms associated with vulvovaginal atrophy (VVA) symptoms as the core symptoms of genitourinary syndrome of menopause. METHODS: We extracted the data of 4134 Japanese women aged 40-79 years who participated in the GENitourinary syndrome of menopause in JApanese women (GENJA) study. All participants responded to web-based questionnaires assessing their health situation, including the Vulvovaginal Symptoms Questionnaire, the Female Sexual Function Index (FSFI), and the Core Lower Urinary Tract Symptom Score. Multivariable regression and multivariable logistic regression analyses were applied to analyze the association between VVA symptoms and FSD, and between VVA symptoms and lower urinary tract symptoms. RESULTS: Multivariable regression analysis revealed that VVA symptoms were associated with lower scores for arousal, lubrication, orgasm, satisfaction, and pain domains in the FSFI in sexually active women (p < 0.01). Regression coefficients were higher for lubrication and pain domains than for the other domains. Multivariable logistic regression analysis revealed that women reporting VVA symptoms were more likely to have increased daytime urinary frequency, nocturia, urgency, slow stream, straining to void, feeling of incomplete emptying, bladder pain, and feeling a bulge/lump from or in the vagina (p < 0.05). Adjusted odds ratios were particularly high for straining to void, feeling of incomplete emptying, and bladder pain. CONCLUSIONS: Vulvovaginal atrophy symptoms were significantly associated with decreased lubrication and dyspareunia in FSD, and urinary symptoms of straining to void, feeling of incomplete emptying, and bladder pain.

Enhanced visualization of female squirting.

INTRODUCTION: Squirting is the involuntary expulsion of fluid from the female urethra following stimulation of the anterior vaginal wall before or during orgasm. The mechanism underlying squirting has not been established. PURPOSE: To elucidate the mechanism of squirting. METHODS: The subjects in the current study were women who were able to squirt. They were not sex workers. A urethral catheter was inserted before sexual stimulation and the bladder was emptied. Then, a mixture of indigo carmine (10 ml) and saline (40 ml) was injected into the bladder. Sexual stimulation was provided to facilitate squirting, which was videotaped and verified. The secretions were collected in sterile cups, and prostate specific antigen (PSA) and glucose levels were measured. RESULTS: Five women (2 in the 30s, 2 in the 40s, and 1 in the 50s) participated in this study. All women were able to squirt; three squirted only with manual sexual stimulation and two with penetrative sexual stimulation. The discharged fluid was blue in all cases, confirming the bladder as the source. The fluid was PSA-positive in four patients. CONCLUSIONS: The main component of squirt fluid is urine, but may also contain fluid from Skene's glands (female prostate). This is the first report in which visualization of squirting was enhanced.

Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study.

OBJECTIVE: To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients. METHODS: Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47). The study drug was intravesically administered every 2 weeks for 12 weeks. RESULTS: For the primary endpoint, the change in the mean O'Leary-Sant Interstitial Cystitis Symptom Index score from baseline to week 12 was -5.2 in the KRP-116D group and -3.4 in the placebo group. The estimated difference between the KRP-116D and placebo groups was -1.8 (95% confidence interval -3.3, -0.3; P = 0.0188). Statistically significant improvements for KRP-116D were also observed in the secondary endpoints including O'Leary-Sant Interstitial Cystitis Problem Index score, micturition episodes/24 h, voided volume/micturition, maximum voided volume/micturition, numerical rating scale score for bladder pain, and global response assessment score. The adverse drug reactions were mild to moderate, and manageable. CONCLUSIONS: This first randomized, double-blind, placebo-controlled trial shows that KRP-116D improves symptoms, voiding parameters, and global response assessment, compared with placebo, and has a well-tolerated safety profile in interstitial cystitis/bladder pain syndrome patients with the bladder-centric phenotype.

OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis).

OBJECTIVE: To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. METHODS: This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or ß3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes. RESULTS: In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P < 0.001), and significantly greater improvement for all secondary end-points (P < 0.05). Urinary tract infection, dysuria, urinary retention and post-void residual urine volume increased represented adverse events occurring at a higher rate in the onabotulinumtoxinA group. The majority of these were mild or moderate in severity. CONCLUSIONS: Statistically significant and clinically relevant improvements in symptoms and patient-reported outcomes, and tolerability were seen in patients with overactive bladder and urinary incontinence who had been inadequately managed with overactive bladder medications after using onabotulinumtoxinA.

Blue light-excited LOV1 and LOV2 domains cooperatively regulate the kinase activity of full-length phototropin2 from Arabidopsis.

Phototropin2 (phot2) is a blue-light (BL) receptor that regulates BL-dependent activities for efficient photosynthesis in plants. phot2 comprises two BL-receiving light-oxygen-voltage-sensing domains (LOV1 and LOV2) and a kinase domain. BL-excited LOV2 is thought to be primarily responsible for the BL-dependent activation of the kinase. However, the molecular mechanisms by which small BL-induced conformational changes in the LOV2 domain are transmitted to the kinase remain unclear. Here, we used full-length wild-type and mutant phot2 proteins from Arabidopsis to study their molecular properties in the dark and under BL irradiation. Phosphorylation assays and absorption measurements indicated that the LOV1 domain assists the thermal relaxation of BL-excited LOV2 and vice versa. Using small-angle X-ray scattering and electron microscopy, we observed that phot2 forms a dimer and has a rod shape with a maximum length of 188 Å and a radius of gyration of 44 Å. Under BL, phot2 displayed large conformational changes that bent the rod shape. By superimposing the crystal structures of the LOV1 dimer, LOV2, and a homology model of the kinase to the observed changes, we inferred that the BL-dependent change consisted of positional shifts of both LOV2 and the kinase relative to LOV1. Furthermore, phot2 mutants lacking the photocycle in LOV1 or LOV2 still exhibited conformational changes under BL, suggesting that LOV1 and LOV2 cooperatively contribute to the conformational changes that activate the kinase. These results suggest that BL-activated LOV1 contributes to the kinase activity of phot2. We discuss the possible intramolecular interactions and signaling mechanisms in phot2.

Classification of ab initio models of proteins restored from small-angle X-ray scattering.

In structure analyses of proteins in solution by using small-angle X-ray scattering (SAXS), the molecular models are restored by using ab initio molecular modeling algorithms. There can be variation among restored models owing to the loss of phase information in the scattering profiles, averaging with regard to the orientation of proteins against the direction of the incident X-ray beam, and also conformational fluctuations. In many cases, a representative molecular model is obtained by averaging models restored in a number of ab initio calculations, which possibly provide nonrealistic models inconsistent with the biological and structural information about the target protein. Here, a protocol for classifying predicted models by multivariate analysis to select probable and realistic models is proposed. In the protocol, each structure model is represented as a point in a hyper-dimensional space describing the shape of the model. Principal component analysis followed by the clustering method is applied to visualize the distribution of the points in the hyper-dimensional space. Then, the classification provides an opportunity to exclude nonrealistic models. The feasibility of the protocol was examined through the application to the SAXS profiles of four proteins.

Diffraction apparatus and procedure in tomography X-ray diffraction imaging for biological cells at cryogenic temperature using synchrotron X-ray radiation.

X-ray diffraction imaging is a technique for visualizing the structure of biological cells. In X-ray diffraction imaging experiments using synchrotron radiation, cryogenic conditions are necessary in order to reduce radiation damage in the biological cells. Frozen-hydrated biological specimens kept at cryogenic temperatures are also free from drying and bubbling, which occurs in wet specimens under vacuum conditions. In a previous study, the diffraction apparatus KOTOBUKI-1 [Nakasako et al. (2013), Rev. Sci. Instrum. 84, 093705] was constructed for X-ray diffraction imaging at cryogenic temperatures by utilizing a cryogenic pot, which is a cooling device developed in low-temperature physics. In this study a new cryogenic pot, suitable for tomography experiments, has been developed. The pot can rotate a biological cell over an angular range of ±170° against the direction of the incident X-ray beam. Herein, the details and the performance of the pot and miscellaneous devices are reported, along with established experimental procedures including specimen preparation. The apparatus has been used in tomography experiments for visualizing the three-dimensional structure of a Cyanidioschyzon merolae cell with an approximate size of 5 µm at a resolution of 136 nm. Based on the experimental results, the necessary improvements for future experiments and the resolution limit achievable under experimental conditions within a maximum tolerable dose are discussed.

A protocol for searching the most probable phase-retrieved maps in coherent X-ray diffraction imaging by exploiting the relationship between convergence of the retrieved phase and success of calculation.

Coherent X-ray diffraction imaging (CXDI) is a technique for visualizing the structures of non-crystalline particles with size in the submicrometer to micrometer range in material sciences and biology. In the structural analysis of CXDI, the electron density map of a specimen particle projected along the direction of the incident X-rays can be reconstructed only from the diffraction pattern by using phase-retrieval (PR) algorithms. However, in practice, the reconstruction, relying entirely on the computational procedure, sometimes fails because diffraction patterns miss the data in small-angle regions owing to the beam stop and saturation of the detector pixels, and are modified by Poisson noise in X-ray detection. To date, X-ray free-electron lasers have allowed us to collect a large number of diffraction patterns within a short period of time. Therefore, the reconstruction of correct electron density maps is the bottleneck for efficiently conducting structure analyses of non-crystalline particles. To automatically address the correctness of retrieved electron density maps, a data analysis protocol to extract the most probable electron density maps from a set of maps retrieved from 1000 different random seeds for a single diffraction pattern is proposed. Through monitoring the variations of the phase values during PR calculations, the tendency for the PR calculations to succeed when the retrieved phase sets converged on a certain value was found. On the other hand, if the phase set was in persistent variation, the PR calculation tended to fail to yield the correct electron density map. To quantify this tendency, here a figure of merit for the variation of the phase values during PR calculation is introduced. In addition, a PR protocol to evaluate the similarity between a map of the highest figure of merit and other independently reconstructed maps is proposed. The protocol is implemented and practically examined in the structure analyses for diffraction patterns from aggregates of gold colloidal particles. Furthermore, the feasibility of the protocol in the structure analysis of organelles from biological cells is examined.

Outpatient mid-urethral tissue fixation system sling for urodynamic stress urinary incontinence: 3-year surgical and quality of life results.

INTRODUCTION: To evaluate the clinical effectiveness and quality of life (QOL) of outpatient mid-urethral tissue fixation system sling (TFS) procedures for urodynamic stress urinary incontinence (SUI) at 3-year follow-up. METHODS: We analyzed 50 mid-urethral TFS sling operations between 2007 and 2012 at Yokohama Motomachi Women's Clinic LUNA. The primary outcome was success defined as a negative 24-h pad test, negative cough and Valsalva stress test, and no re-treatment for SUI. Secondary outcome was improvement in quality of life, which was assessed using the Incontinence Questionnaire-Short Form (ICIQ-SF) and the Incontinence Impact Questionnaire Short Form (IIQ-7). The 3-year postoperative scores were compared with baseline scores using the Wilcoxon signed rank test. A 5% two-sided significance level was used for all statistical testing. RESULTS: All operations were carried out on an outpatient basis with no intraoperative complications. The primary cure rate result at 3-year follow-up was 90%. Median total ICIQ-SF score changed from 12 (6-20) to 0 (0-14) and median total IIQ-7 score changed from 156 (0-300) to 0 (0.00-16.7) at 3-year follow-up. CONCLUSIONS: Results show that the TFS mid-urethral sling operation is a simple, safe, effective procedure that may be done without difficulty at a freestanding clinic on an outpatient basis and favorably improves subjective QOL of the patient.

Retropubic tissue fixation system tensioned mini-sling carried out under local anesthesia cures stress urinary incontinence and intrinsic sphincter deficiency: 1-year data.

OBJECTIVES: To assess the outcomes of the tissue fixation system midurethral sling for the treatment of intrinsic sphincter deficiency. METHODS: We retrospectively studied a total of 96 intrinsic sphincter deficiency patients treated with the tissue fixation system midurethral sling at Yokohama Motomachi Women's Clinic from 2006 to 2015. We evaluated intraoperative and 1-year postoperative results. Regarding the cure rate, we divided patients into three groups: (i) patients with maximum urethral closure pressure <20 and Valsalva leak point pressure <65 combined (n = 17); (ii) patients with maximum urethral closure pressure <20 (n = 55); and (iii) patients with Valsalva leak point pressure <65 (n = 47). RESULTS: The median age was 63 years (range 38-89 years). The median operating time including local anesthesia was 24 min (range 12-55 min) and median blood loss was 5.0 mL (range 3-69 mL). All operations were day surgery under local anesthesia. Postoperative pain was minimal. All patients were discharged the same day. There were no intraoperative complications except one bladder perforation. There were no tape rejections. The 1-year postoperative cure rates were: 88.2% among patients with maximum urethral closure pressure <20 and Valsalva leak point pressure <65, 90.9% for patients with maximum urethral closure pressure <20, and 85.1% among patients with Valsalva leak point pressure <65. CONCLUSIONS: The tissue fixation system midurethral sling operation is a simple, safe and effective operation for older women with intrinsic sphincter deficiency, and it can be carried out under local anesthesia.

Classification and assessment of retrieved electron density maps in coherent X-ray diffraction imaging using multivariate analysis.

Coherent X-ray diffraction imaging (CXDI) is one of the techniques used to visualize structures of non-crystalline particles of micrometer to submicrometer size from materials and biological science. In the structural analysis of CXDI, the electron density map of a sample particle can theoretically be reconstructed from a diffraction pattern by using phase-retrieval (PR) algorithms. However, in practice, the reconstruction is difficult because diffraction patterns are affected by Poisson noise and miss data in small-angle regions due to the beam stop and the saturation of detector pixels. In contrast to X-ray protein crystallography, in which the phases of diffracted waves are experimentally estimated, phase retrieval in CXDI relies entirely on the computational procedure driven by the PR algorithms. Thus, objective criteria and methods to assess the accuracy of retrieved electron density maps are necessary in addition to conventional parameters monitoring the convergence of PR calculations. Here, a data analysis scheme, named ASURA, is proposed which selects the most probable electron density maps from a set of maps retrieved from 1000 different random seeds for a diffraction pattern. Each electron density map composed of J pixels is expressed as a point in a J-dimensional space. Principal component analysis is applied to describe characteristics in the distribution of the maps in the J-dimensional space. When the distribution is characterized by a small number of principal components, the distribution is classified using the k-means clustering method. The classified maps are evaluated by several parameters to assess the quality of the maps. Using the proposed scheme, structure analysis of a diffraction pattern from a non-crystalline particle is conducted in two stages: estimation of the overall shape and determination of the fine structure inside the support shape. In each stage, the most accurate and probable density maps are objectively selected. The validity of the proposed scheme is examined by application to diffraction data that were obtained from an aggregate of metal particles and a biological specimen at the XFEL facility SACLA using custom-made diffraction apparatus.

Specimen preparation for cryogenic coherent X-ray diffraction imaging of biological cells and cellular organelles by using the X-ray free-electron laser at SACLA.

Coherent X-ray diffraction imaging (CXDI) allows internal structures of biological cells and cellular organelles to be analyzed. CXDI experiments have been conducted at 66 K for frozen-hydrated biological specimens at the SPring-8 Angstrom Compact Free-Electron Laser facility (SACLA). In these cryogenic CXDI experiments using X-ray free-electron laser (XFEL) pulses, specimen particles dispersed on thin membranes of specimen disks are transferred into the vacuum chamber of a diffraction apparatus. Because focused single XFEL pulses destroy specimen particles at the atomic level, diffraction patterns are collected through raster scanning the specimen disks to provide fresh specimen particles in the irradiation area. The efficiency of diffraction data collection in cryogenic experiments depends on the quality of the prepared specimens. Here, detailed procedures for preparing frozen-hydrated biological specimens, particularly thin membranes and devices developed in our laboratory, are reported. In addition, the quality of the frozen-hydrated specimens are evaluated by analyzing the characteristics of the collected diffraction patterns. Based on the experimental results, the internal structures of the frozen-hydrated specimens and the future development for efficient diffraction data collection are discussed.

Light-induced conformational changes of LOV1 (light oxygen voltage-sensing domain 1) and LOV2 relative to the kinase domain and regulation of kinase activity in Chlamydomonas phototropin.

Phototropin (phot), a blue light (BL) receptor in plants, has two photoreceptive domains named LOV1 and LOV2 as well as a Ser/Thr kinase domain (KD) and acts as a BL-regulated protein kinase. A LOV domain harbors a flavin mononucleotide that undergoes a cyclic photoreaction upon BL excitation via a signaling state in which the inhibition of the kinase activity by LOV2 is negated. To understand the molecular mechanism underlying the BL-dependent activation of the kinase, the photochemistry, kinase activity, and molecular structure were studied with the phot of Chlamydomonas reinhardtii. Full-length and LOV2-KD samples of C. reinhardtii phot showed cyclic photoreaction characteristics with the activation of LOV- and BL-dependent kinase. Truncation of LOV1 decreased the photosensitivity of the kinase activation, which was well explained by the fact that the signaling state lasted for a shorter period of time compared with that of the phot. Small angle x-ray scattering revealed monomeric forms of the proteins in solution and detected BL-dependent conformational changes, suggesting an extension of the global molecular shapes of both samples. Constructed molecular model of full-length phot based on the small angle x-ray scattering data proved the arrangement of LOV1, LOV2, and KD for the first time that showed a tandem arrangement both in the dark and under BL irradiation. The models suggest that LOV1 alters its position relative to LOV2-KD under BL irradiation. This finding demonstrates that LOV1 may interact with LOV2 and modify the photosensitivity of the kinase activation through alteration of the duration of the signaling state in LOV2.

Coherent X-Ray Diffraction Imaging of Chloroplasts from Cyanidioschyzon merolae by Using X-Ray Free Electron Laser.

Coherent X-ray diffraction imaging (CXDI) is a lens-less technique for visualizing the structures of non-crystalline particles with the dimensions of submicrometer to micrometer at a resolution of several tens of nanometers. We conducted cryogenic CXDI experiments at 66 K to visualize the internal structures of frozen-hydrated chloroplasts of Cyanidioschyzon merolae using X-ray free electron laser (XFEL) as a coherent X-ray source. Chloroplast dispersed specimen disks at a number density of 7/(10×10 µm(2)) were flash-cooled with liquid ethane without staining, sectioning or chemical labeling. Chloroplasts are destroyed at atomic level immediately after the diffraction by XFEL pulses. Thus, diffraction patterns with a good signal-to-noise ratio from single chloroplasts were selected from many diffraction patterns collected through scanning specimen disks to provide fresh specimens into the irradiation area. The electron density maps of single chloroplasts projected along the direction of the incident X-ray beam were reconstructed by using the iterative phase-retrieval method and multivariate analyses. The electron density map at a resolution of 70 nm appeared as a C-shape. In addition, the fluorescence image of proteins stained with Flamingo™ dye also appeared as a C-shape as did the autofluorescence from Chl. The similar images suggest that the thylakoid membranes with an abundance of proteins distribute along the outer membranes of chloroplasts. To confirm the present results statistically, a number of projection structures must be accumulated through high-throughput data collection in the near future. Based on the results, we discuss the feasibility of XFEL-CXDI experiments in the structural analyses of cellular organelles.

Data processing software suite SITENNO for coherent X-ray diffraction imaging using the X-ray free-electron laser SACLA.

Coherent X-ray diffraction imaging is a promising technique for visualizing the structures of non-crystalline particles with dimensions of micrometers to sub-micrometers. Recently, X-ray free-electron laser sources have enabled efficient experiments in the `diffraction before destruction' scheme. Diffraction experiments have been conducted at SPring-8 Angstrom Compact free-electron LAser (SACLA) using the custom-made diffraction apparatus KOTOBUKI-1 and two multiport CCD detectors. In the experiments, ten thousands of single-shot diffraction patterns can be collected within several hours. Then, diffraction patterns with significant levels of intensity suitable for structural analysis must be found, direct-beam positions in diffraction patterns determined, diffraction patterns from the two CCD detectors merged, and phase-retrieval calculations for structural analyses performed. A software suite named SITENNO has been developed to semi-automatically apply the four-step processing to a huge number of diffraction data. Here, details of the algorithm used in the suite are described and the performance for approximately 9000 diffraction patterns collected from cuboid-shaped copper oxide particles reported. Using the SITENNO suite, it is possible to conduct experiments with data processing immediately after the data collection, and to characterize the size distribution and internal structures of the non-crystalline particles.

IDATEN and G-SITENNO: GUI-assisted software for coherent X-ray diffraction imaging experiments and data analyses at SACLA.

Using our custom-made diffraction apparatus KOTOBUKI-1 and two multiport CCD detectors, cryogenic coherent X-ray diffraction imaging experiments have been undertaken at the SPring-8 Angstrom Compact free electron LAser (SACLA) facility. To efficiently perform experiments and data processing, two software suites with user-friendly graphical user interfaces have been developed. The first is a program suite named IDATEN, which was developed to easily conduct four procedures during experiments: aligning KOTOBUKI-1, loading a flash-cooled sample into the cryogenic goniometer stage inside the vacuum chamber of KOTOBUKI-1, adjusting the sample position with respect to the X-ray beam using a pair of telescopes, and collecting diffraction data by raster scanning the sample with X-ray pulses. Named G-SITENNO, the other suite is an automated version of the original SITENNO suite, which was designed for processing diffraction data. These user-friendly software suites are now indispensable for collecting a large number of diffraction patterns and for processing the diffraction patterns immediately after collecting data within a limited beam time.

Dark-field phase retrieval under the constraint of the Friedel symmetry in coherent X-ray diffraction imaging.

Coherent X-ray diffraction imaging (CXDI) is a lensless imaging technique that is suitable for visualizing the structures of non-crystalline particles with micrometer to sub-micrometer dimensions from material science and biology. One of the difficulties inherent to CXDI structural analyses is the reconstruction of electron density maps of specimen particles from diffraction patterns because saturated detector pixels and a beam stopper result in missing data in small-angle regions. To overcome this difficulty, the dark-field phase-retrieval (DFPR) method has been proposed. The DFPR method reconstructs electron density maps from diffraction data, which are modified by multiplying Gaussian masks with an observed diffraction pattern in the high-angle regions. In this paper, we incorporated Friedel centrosymmetry for diffraction patterns into the DFPR method to provide a constraint for the phase-retrieval calculation. A set of model simulations demonstrated that this constraint dramatically improved the probability of reconstructing correct electron density maps from diffraction patterns that were missing data in the small-angle region. In addition, the DFPR method with the constraint was applied successfully to experimentally obtained diffraction patterns with significant quantities of missing data. We also discuss this method's limitations with respect to the level of Poisson noise in X-ray detection.

Reinforcement of suspensory ligaments under local anesthesia cures pelvic organ prolapse: 12-month results.

INTRODUCTION AND HYPOTHESIS: In 2005, a new minimally invasive procedure, the tissue fixation system (TFS) was reported. Like TVT (tension-free vaginal tape), the TFS works by creating a foreign body collagenous tissue reaction that reinforces a weakened pelvic ligament. The objective was to assess the effectiveness and perioperative safety of TFS in a day surgery clinic for the treatment of pelvic organ prolapse (POP). METHODS: The TFS tape was applied in a tunnel adjacent to natural ligaments to repair the anterior cervical ring and cardinal ligament, paravaginal tissues and uterosacral ligaments under local anesthesia/sedation. We prospectively studied 60 patients, mean age 67, between October 2008 and February 2010 at Women's Clinic LUNA. Levels of POP were grade 2 (n = 20; 7 %), grade 3 (n = 30; 55 %), and grade 4 (n = 4; 7 %) according to the ICS POPQ classification. Fifty-four patients (90 %) who underwent a total of 162 POP operations presented for review. Follow-up was performed at 12 months. We defined surgical failure according to the ICS POPQ classification. We used prolapse quality of life (P-QOL) questions for QOL measurement. RESULTS: Ninety-eight percent of patients were discharged on the day of surgery. Of the 162 TFS operations reviewed, 157 were successful and 5 failed. The 5 failed operations comprised 4 cystoceles and 1 rectocele. Two patients developed cervical protrusions at the introitus at 6 months with no prolapse of the uterine body. We found 5 cases of erosion in 162 tape insertions. The total number of patients who had no complications, no surgical failures, no erosions, no sensation of bulging, and no cervical protrusions was 47 (87 %). CONCLUSIONS: The TFS uses the same surgical principle for repair as the TVT; this principle vastly minimizes the volume of mesh used, erosions, and other complications.

Effect of propiverine hydrochloride on stress urinary incontinence.

OBJECTIVES: To investigate whether the anticholinergic agent, propiverine hydrochloride, is clinically effective for stress urinary incontinence. METHODS: The participants were adult female patients with the chief complaint of stress incontinence. Propiverine (20 mg once daily) was given for 8 weeks. If the response was inadequate after 4 weeks of treatment, the dose was increased to 40 mg/day. Before and after 4 and 8 weeks of treatment, lower urinary tract symptoms were assessed. The urethral pressure and blood catecholamine levels were also measured. RESULTS: A total of 37 patients (mean age 69 ± 11 years) were enrolled, including 15 patients with stress incontinence and 22 with mixed incontinence. The number of episodes of stress incontinence decreased significantly from 2.6 ± 2.3 times per day to 1.3 ± 2.2 times per day after 4 weeks, and 0.4 ± 0.6 times per day after 8 weeks. The daytime and night-time frequency of urination, and quality of life score showed significant improvement. The maximum urethral closing pressure and the functional urethral length increased significantly after treatment, but blood catecholamine levels, blood pressure and pulse rate at 8 weeks were not significantly different from those at baseline. CONCLUSIONS: Propiverine could be an effective drug for stress urinary incontinence by increasing urethral closing pressure without increasing blood catecholamine levels.

Coherent diffraction imaging analysis of shape-controlled nanoparticles with focused hard X-ray free-electron laser pulses.

We report the first demonstration of the coherent diffraction imaging analysis of nanoparticles using focused hard X-ray free-electron laser pulses, allowing us to analyze the size distribution of particles as well as the electron density projection of individual particles. We measured 1000 single-shot coherent X-ray diffraction patterns of shape-controlled Ag nanocubes and Au/Ag nanoboxes and estimated the edge length from the speckle size of the coherent diffraction patterns. We then reconstructed the two-dimensional electron density projection with sub-10 nm resolution from selected coherent diffraction patterns. This method enables the simultaneous analysis of the size distribution of synthesized nanoparticles and the structures of particles at nanoscale resolution to address correlations between individual structures of components and the statistical properties in heterogeneous systems such as nanoparticles and cells.