Machine Learning-Based Classification of Transcriptome Signatures of Non-Ulcerative Bladder Pain Syndrome.

Lower urinary tract dysfunction (LUTD) presents a global health challenge with symptoms impacting a substantial percentage of the population. The absence of reliable biomarkers complicates the accurate classification of LUTD subtypes with shared symptoms such as non-ulcerative Bladder Pain Syndrome (BPS) and overactive bladder caused by bladder outlet obstruction with Detrusor Overactivity (DO). This study introduces a machine learning (ML)-based approach for the identification of mRNA signatures specific to non-ulcerative BPS. Using next-generation sequencing (NGS) transcriptome data from bladder biopsies of patients with BPS, benign prostatic obstruction with DO, and controls, our statistical approach successfully identified 13 candidate genes capable of discerning BPS from control and DO patients. This set was validated using Quantitative Polymerase Chain Reaction (QPCR) in a larger patient cohort. To confirm our findings, we applied both supervised and unsupervised ML approaches to the QPCR dataset. A three-mRNA signature TPPP3, FAT1, and NCALD, emerged as a robust classifier for non-ulcerative BPS. The ML-based framework used to define BPS classifiers establishes a solid foundation for comprehending the gene expression changes in the bladder during BPS and serves as a valuable resource and methodology for advancing signature identification in other fields. The proposed ML pipeline demonstrates its efficacy in handling challenges associated with limited sample sizes, offering a promising avenue for applications in similar domains.

Laparoscopic sacrocolpopexy mesh excision step-by-step.

INTRODUCTION AND HYPOTHESIS: The objective was to demonstrate the surgical procedure of laparoscopic mesh removal after sacrocolpopexy to aid clinicians facing mesh complications. METHODS: Video footage shows the laparoscopic management of mesh failure and mesh erosion after sacrocolpopexy with narrated video sequences of two patients. RESULTS: Laparoscopic sacrocolpopexy represents the gold standard in advanced prolapse repair. Mesh complications occur infrequently but infections, failure of prolapse repair and mesh erosions necessitate mesh removal and repeat sacrocolpopexy if applicable. The video deals with two women referred to our tertiary referral urogynecology unit in the University Women's Hospital of Bern, Switzerland, after laparoscopic sacrocolpopexies that were carried out in remote hospitals. Both patients were asymptomatic more than 1 year after surgery. CONCLUSIONS: Complete mesh removal after sacrocolpopexy and repeat prolapse surgery can be challenging but is feasible and is aimed at improving patients' complaints and symptoms.

The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats.

Treatment with the anti-CGRP antibody fremanezumab is successful in the prevention of chronic and frequent episodic migraine. In preclinical rat experiments, fremanezumab has been shown to reduce calcitonin gene-related peptide (CGRP) release from trigeminal tissues and aversive behaviour to noxious facial stimuli, which are characteristic pathophysiological changes accompanying severe primary headaches. To further decipher the effects of fremanezumab that underlie these antinociceptive effects in rats, immunohistochemistry and ELISA techniques were used to analyse the content and concentration of CGRP in the trigeminal ganglion, as well as the ratio of trigeminal ganglion neurons which are immunoreactive to CGRP and CGRP receptor components, 1-10 days after subcutaneous injection of fremanezumab (30 mg/kg) compared to an isotype control antibody. After fremanezumab treatment, the fraction of trigeminal ganglion neurons which were immunoreactive to CGRP and the CGRP receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) was significantly lowered compared to the control. The content and concentration of CGRP in trigeminal ganglia were not significantly changed. A long-lasting reduction in CGRP receptors expressed in trigeminal afferents may contribute to the attenuation of CGRP signalling and antinociceptive effects of monoclonal anti-CGRP antibodies in rats.

Involuntary reflexive pelvic floor muscle training in addition to standard training versus standard training alone for women with stress urinary incontinence: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: Although involuntary reflexive pelvic floor muscle contractions seem crucial during stress urinary incontinence-provoking situations, hitherto existing guidelines feature voluntary pelvic floor muscle training only. Two pelvic floor muscle protocols were compared regarding their effect on stress urinary incontinence in women: one focusing on standard physiotherapy with voluntary pelvic floor muscle training, the other additionally including involuntary reflexive pelvic floor muscle training. METHODS: This study was designed as a triple-blind prospective randomized controlled trial with women suffering from stress urinary incontinence with two physiotherapy intervention groups (control group: standard physiotherapy, n = 48, experimental group: standard physiotherapy plus involuntary reflexive pelvic floor muscle training triggered by whole-body movements such as jumps n = 48). Both interventions lasted 16 weeks (9 personal physiotherapy consultations and 78 home training sessions). Group differences and development over time were analyzed concerning the primary outcome International Consultation on Incontinence Modular Questionnaire Urinary Incontinence short form (ICIQ-UIsf) by mixed effect regression models. RESULTS: The ICIQ-UIsf score decreased significantly over time for both groups by about 3 points from about 10 to about 7 points with no group differences at any point in time. DISCUSSION: This trial did not find any additional benefit for stress urinary incontinence by adding involuntary reflexive pelvic floor muscle training to standard training. Both training protocols showed similar clinically relevant improvements; however, there was still moderate incontinence after interventions. Future studies should test and apply pelvic floor muscle function-oriented training methods for pelvic floor muscle hypertrophy, intramuscular coordination, and power, which are more in line with conventional skeletal muscle training, i.e., performed with higher intensities and workout.

Postpartum urinary retention: what are the sequelae? A long-term study and review of the literature.

INTRODUCTION AND HYPOTHESIS: Postpartum urinary retention (PUR) may cause long-term urogenital tract morbidity. The incidence ranges from 0.18 to 14.6%, but the importance of prompt diagnosis and appropriate management is often underappreciated. The paucity of data on long-term outcome after PUR contributes to these drawbacks. The aim of this study was to assess long-term persistence of elevated PVR (post-void residual urine) volume after PUR. Pathophysiology, risk factors and management of PUR are reviewed. METHODS: In our tertiary referral urogynecology unit in the University Women's Hospital of Bern, Switzerland, all patients who were referred for PUR were asked to participate in this study. PVR was measured sonographically every 2 days until day 15, then after 6, 12, 24 and 36 months and, if increased, the patients were instructed to perform clean intermittent self-catheterization. If retention persisted longer than the lactation period, multichannel urodynamics was performed. RESULTS: Sixty-two patients were included. The median PVR normalized at day 7. Long-term voiding disorders were found in 8.2%, 6.7%, and 4.9% after 1, 2, and 3 years respectively. Multichannel urodynamics confirmed in all patients with persisting retention an acontractile detrusor and de novo stress urinary incontinence in 4 cases. Quantile regression did not reveal any factor contributing to earlier recovery. Eighty-nine percent of the patients with PUR had operative vaginal deliveries, emphasizing the importance of this risk factor for PUR. CONCLUSIONS: In most cases PUR resolves early, but voiding difficulties persist more often than previously thought, and for these patients the consequences are devastating. Obstetric awareness, early active management, and developing management strategies in the postpartum period might preclude lower urinary tract morbidity.

CGRP measurements in human plasma - a methodological study.

BACKGROUND: Calcitonin gene-related peptide plasma levels have frequently been determined as a biomarker for primary headaches. However, published data is often inconsistent resulting from different methods that are not precisely described in most studies. METHODS: We applied a well-proven enzyme-linked immunosorbent assay to measure calcitonin gene-related peptide concentrations in human blood plasma, we modified parameters of plasma preparation and protein purification and used calcitonin gene-related peptide-free plasma for standard solutions, which are described in detail. RESULTS: Calcitonin gene-related peptide levels are stable in plasma with peptidase inhibitors and after deep-freezing. Calcitonin gene-related peptide standard solutions based on synthetic intercellular fluid or pooled plasma with pre-absorbed calcitonin gene-related peptide influenced the measurements but yielded both comprehensible results. In a sample of 56 healthy subjects the calcitonin gene-related peptide plasma levels varied considerably from low (<50 pg/mL) to very high (>500 pg/mL) values. After a 12-hour exposure of these subjects to normobaric hypoxia the individual calcitonin gene-related peptide levels remained stable. CONCLUSION: Buffering with peptidase inhibitors and immediate freezing or processing of plasma samples is essential to achieve reliable measurements. Individuals show considerable differences and partly high calcitonin gene-related peptide plasma levels without detectable pathological reason. Thus plasma measurements are suited particularly to follow calcitonin gene-related peptide levels in longitudinal studies.The use of data for this study was approved by the Ethics Committee of the MedicalUniversity of Innsbruck (https://www.i-med.ac.at/ethikkommission/; EK Nr: 1242/2017).

Seven-year efficacy and safety outcomes of Bulkamid for the treatment of stress urinary incontinence.

AIMS: Bulking agents are a minimally invasive treatment option for women with stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (MUI). The aim of this study was to evaluate long-term efficacy and safety following treatment with Bulkamid as a primary procedure for SUI or stress-predominant MUI. METHODS: This was an Institutional Review Board-approved single-center retrospective study of female patients with SUI or stress-predominant MUI who had undergone injection with Bulkamid since 2005 and had completed 7 years of follow up. The primary endpoint was patient satisfaction measured on a four-point scale as cured, improved, unchanged, or worse. Secondary outcomes included the number of incontinence pads used, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI SF) scores, Visual Analog Scale Quality of Life (VAS QoL), reinjection rates, and perioperative and postoperative complications. RESULTS: A total of 1,200 patients were treated with Bulkamid since 2005 and of these, 388 (32.3%) had completed 7 years of follow-up. A total of 67.1% of the patients reported feeling cured or improved if Bulkamid was a primary procedure, 11.1% reported no change, and 2.3% reported worsening of incontinence. A total of 19.5% of patients received a subsequent other incontinence procedure. The ICIQ-UI SF was reduced by 8.6 points. VAS QoL improved by a mean of 4.3 points. Postoperative complications were transient. Prolonged bladder emptying time was reported in 15.3% of patients and urinary tract infection in 3.5%. CONCLUSIONS: Bulkamid injections are an effective and safe first-line treatment option for women with SUI or stress-predominant MUI providing durable outcomes at 7 years.

Activation patterns of pelvic floor muscles in women with incontinence while running: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: Running is known to cause urinary leakage in women with stress urinary incontinence (SUI). Task-specific fiber-type recruitment while running can be estimated using wavelets. The aim of this study was to compare the effect of a new physiotherapy program including involuntary, reflexive training with a standard physiotherapy program on pelvic floor muscle (PFM) activation patterns and fiber-type recruitment behavior while running. METHODS: In this triple-blinded randomized controlled trial, women with SUI were randomly allocated to the control group (CON), which performed a standard physiotherapy program, or the experimental group (EXP), which received additional involuntary, reflexive training. PFM electromyography (EMG) was recorded during 10 s at three running speeds and analyzed using Morse wavelets. The relative distribution of power (%) over the frequencies from 20 to 200 Hz was extracted and analyzed within six-time intervals of 30 ms. Statistical nonparametric mapping was performed to identify power spectra differences. RESULTS: Thirty-nine (CON) and 38 (EXP) women were included. The power spectra showed no statistically significant group differences. The time intervals from 30 ms before to 30 ms after initial contact showed significantly lower intensities than the intervals from 30 to 150 ms after initial contact in the lowest and higher intensities in the highest frequencies for all running speeds and both groups. CONCLUSIONS: Power spectra shifts toward higher frequency bands in the pre-initial contact phase could indicate a feed-forward anticipation and a muscle tuning for the expected impact of initial contact event in order to maintain continence.

Integrated mRNA-miRNA transcriptome analysis of bladder biopsies from patients with bladder pain syndrome identifies signaling alterations contributing to the disease pathogenesis.

BACKGROUND: Interstitial cystitis, or bladder pain syndrome (IC/BPS), is a chronic bladder disorder characterized by lower abdominal pain associated with the urinary bladder and accompanied by urinary frequency and urgency in the absence of identifiable causes. IC/PBS can be separated into the classic Hunner's ulcerative type and the more prevalent non-ulcerative disease. Our aim was to unravel the biological processes and dysregulated cell signaling pathways leading to the bladder remodeling in non-ulcerative bladder pain syndrome (BPS) by studying the gene expression changes in the patients' biopsies. METHODS: We performed paired microRNA (miRNA) and mRNA expression profiling in the bladder biopsies of BPS patients with non-Hunner interstitial cystitis phenotype, using comprehensive Next-generation sequencing (NGS) and studied the activated pathways and altered biological processes based on the global gene expression changes. Paired mRNA-miRNA transcriptome analysis delineated the regulatory role of the dysregulated miRNAs by identifying their targets in the disease-induced pathways. RESULTS: EIF2 Signaling and Regulation of eIF4 and p70S6K Signaling, activated in response to cellular stress, were among the most significantly regulated processes during BPS. Leukotriene Biosynthesis nociceptive pathway, important in inflammatory diseases and neuropathic pain, was also significantly activated. The biological processes identified using Gene Ontology over-representation analysis were clustered into six main functional groups: cell cycle regulation, chemotaxis of immune cells, muscle development, muscle contraction, remodeling of extracellular matrix and peripheral nervous system organization and development. Compared to the Hunner's ulcerative type IC, activation of the immune pathways was modest in non-ulcerative BPS, limited to neutrophil chemotaxis and IFN-γ-mediated signaling. We identified 62 miRNAs, regulated and abundant in BPS and show that they target the mRNAs implicated in eIF2 signalling pathway. CONCLUSIONS: The bladders of non-ulcerative BPS patients recruited in this study had alterations consistent with a strong cell proliferative response and an up-regulation of smooth muscle contractility, while the contribution of inflammatory processes was modest. Pathway analysis of the integrated mRNA-miRNA NGS dataset pinpointed important regulatory miRNAs whose dysregulation might contribute to the pathogenesis. Observed molecular changes in the peripheral nervous system organization and development indicate the potential role of local bladder innervation in the pain perceived in this type of BPS.

Predictive Factors for Voiding Dysfunction after Surgery for Deep Infiltrating Endometriosis.

STUDY OBJECTIVE: To evaluate the prognostic value of pre- and perioperative factors for voiding dysfunction after surgery for deep infiltrating endometriosis (DIE). DESIGN: Single-center retrospective cohort study. SETTING: University hospital. PATIENTS: A total of 198 women with DIE in the posterior compartment who underwent surgery and a postoperative bladder scan. INTERVENTIONS: Surgical resection of the DIE nodule from the dorsal compartment. MEASUREMENTS AND MAIN RESULTS: After surgery, 41% of the patients initially experienced voiding dysfunction (defined as >100 mL postvoid residual urine volume at second bladder scan). The number decreased to 11% by the time of hospital discharge. Among those with a need for self-catheterization after discharge (n = 17), voiding dysfunction lasted for a median of 41 days before a return to normal bladder function, with a residual urine volume of <100 mL. The preoperative presence of DIE nodules in the ENZIAN compartment B was associated with postoperative voiding dysfunction (p = .001). The hazard ratio for elevated residual urine volume was highest when the disease stage was B3 (hazard ratio 6.43; CI, 2.3-18.2; p <.001), describing a nodule diameter of >3 cm in lateral distension. Receiver operating characteristic curve analyses showed that a first residual urine volume >220 mL has a good predictive value for the risk of intermittent self-catheterization (area under the receiver operating characteristic curve 0.893; p <.001). CONCLUSION: Postoperative voiding dysfunction is frequent; of note, in most cases the problem is temporary. When DIE with an ENZIAN classification B is noted intraoperatively and, most of all, when the diameter of the lesion is >3 cm, a higher risk of postoperative voiding dysfunction is to be expected.

Electromyography of pelvic floor muscles with true differential versus faux differential electrode configuration.

INTRODUCTION AND HYPOTHESIS: In pelvic floor muscle (PFM) electromyography (EMG) two different bipolar configurations are applied: "true differential" configuration (TD) measures neuromuscular activity with two ipsilateral electrodes, whereas "faux differential" configuration (FD) has two electrodes placed on each side of the PFMs. The aim of the study was to determine possible differences and the relationship between both configurations. METHODS: A secondary data analysis of 28 continent (CON) and 22 stress urinary incontinent (SUI) women was performed. Surface EMG was measured using a vaginal probe during maximal voluntary (MVC) and fast voluntary (FVC) contractions. TD and FD were explored with amplitude- and time-related EMG parameters, cross-correlation coefficients (R(0)) and statistical parametric mapping (SPM). RESULTS: Of a total of 62 comparisons of EMG parameters of MVC and FVC, only one comparison showed significant differences between the two configurations (CON group, FVC4peak TD versus FD, p = 0.015). R(0) were high in both groups for all MVC and FVC variables (R(0) ≥ 0.989). SPM detected 3 out of 28 comparisons with short (0.124-0.404 s) significant supra-threshold clusters (p < 0.025). CONCLUSIONS: The findings suggest that TD and FD might measure neuromuscular activity almost the same. Very high cross-correlation coefficients and a very limited number of significant results from EMG parameters, as well as SPM, suggest that in the measured sample the choice of TD or FD might remain practically irrelevant. To gain further insight into the scientific and clinical relevance of choosing either of the electrode configurations, the comparisons should be re-evaluated on a sample with more severe incontinence symptoms.

Pelvic floor muscle activity during fast voluntary contractions in continent and incontinent women.

AIMS: Stress urinary incontinence (SUI) has also been attributed to a lower speed of contraction of the pelvic floor muscles (PFM). Therefore, PFM assessment and training implement fast voluntary contractions (FVC). The purpose of the study was to explore FVC regarding feasibility, on-/offset and rate of activity determination, as well as differences between continent (CON) and stress urinary incontinent (SUI) women. METHODS: Fifty women were included and examined by means of PFM EMG during rest, maximum voluntary contractions (MVC), and five FVC. MVC-peak activity was used to normalize EMG-data. On-/offset of muscle activity was determined as mean of rectified rest activity plus 1 standard deviation. Linear regression was calculated for rate of activity from onset to peak, peak to offset, and within 200 ms after both onset and peak. Peak activity and time variables related to onset, peak, and offset were calculated. RESULTS: On-/offsets were evaluable for 234/222 of 250 FVC by a computer-based algorithm, 16/28 on-/offsets had to be determined manually. There was no significant difference between groups (CON/SUI) regarding FVC peak (92.1/99.3 %MVC), time to peak (514.2/525.6 ms), and increase of activity (182.8/182.1 %MVC/s). The SUI group showed a significantly slower activity decrease (-120.7/-74.4 %MVC/s). CONCLUSIONS: FVC analyses were shown to be feasible. The significant difference observed between the groups did not refer to activity increase but instead to a prolonged relaxation phase in the SUI group. This prompts to reconsider the interpretation of FVC in PFM testing and training.

Pelvic floor muscle displacement during jumps in continent and incontinent women: An exploratory study.

INTRODUCTION: The prevalence of stress urinary incontinence during high-impact activities is high. Enhanced comprehension of pelvic floor muscle (PFM) displacement and activity is clinically relevant for the development of specific approaches in rehabilitation. The aim of the study is to investigate and to compare PFM displacement between the continent and incontinent women during jumps. METHODS: A cross-sectional, exploratory design was applied to investigate PFM displacement during drop jumps (DJ) and countermovement jumps (CMJ). PFM displacement was assessed in craniocaudal translation and forward-backward rotation with an electromagnetic tracking system. RESULTS: Twenty-eight continent and 22 incontinent women were included. During the first landing of DJ, a primary caudal, during the second landing of DJ/CMJ a primary cranial translation and during all jump a primary backward rotation was observed. No significant difference between the groups was found. DISCUSSION: PFM displacement during running demonstrated caudal translation/forward rotation before and cranial translation/backward rotation after heel strike. During the second landing of DJ/CMJ a cranial translation/backward rotation and during the first landing of DJ a caudal translation/backward rotation has been observed after ground contact. This may be due to the longer lasting bodyweight force in the first landing of DJ. No eccentric-concentric stretch-shortening cycle could be seen. CONCLUSION: This study indicates that during jumps two opposite reactions of involuntary PFM displacement happen, but no stretch-shortening cycle with an eccentric-concentric contraction could be found. Jumping stimuli inducing involuntary PFM displacement should be used for future investigations to consider a beneficial effect concerning continence.

[Chronic pelvic pain]. / Chronischer Beckenschmerz.

Chronic pelvic pain Abstract. Chronic pelvic pain syndrome (CPPS) is a condition that may occur in combination with endometriosis and has a prevalence of 1 - 11 %. After persistence of pain of more than three months CPPS is likely. After exclusion of inflammatory, traumatic and other conditions the diagnosis may be considered. Symptoms include painful sensations in the pelvic area, tingling feelings, burning sensations, micturition and voiding disorders, overactive bladder including frequency and urgency, painful micturitions and stool passage as well of just the presence of "something being there" with or without pain. Treatment options depend on the leading symptom. As for the pain, the WHO scheme of pain treatment should be considered including anti-inflammatory pain medication. Additionally, physiotherapy, psychotherapy, anticholinergics, alpha-blockers, phytotherapy and physical therapy, acupuncture and local or systemic hormonal therapies may be indicated.

Evaluation of pelvic floor kinematics in continent and incontinent women during running: An exploratory study.

AIMS: Impact activity like running is associated with an increase in intra-abdominal pressure which needs to be sufficiently countered by pelvic floor muscle (PFM) activity to secure continence. The aim of this study was to investigate and compare PFM kinematics in continent and incontinent women during running. METHOS: Three-dimensional position and orientation was measured with the electromagnetic tracking device trakSTAR™. One sensor was attached to the vaginal probe and a second one was secured to the subjects' skin at the height of the second sacral vertebrae. Cranial-caudal and forward-backward displacement of the vaginal probe was measured during 10 sec running on a treadmill at the speeds 7, 11, and 15 km/h. Displacement data from 100 ms before to 300 ms after heel-strike were analyzed. RESULTS: Nineteen incontinent and twenty-seven continent women were included in this study. Before the foot touched the ground caudal translation and forward rotation of the vaginal probe was detected, whereas after heel-strike a cranial translation and backward rotation was measured. Cranial-caudal translation as well as backward-forward-rotation did not differ significantly between continent and incontinent subjects for the three speeds. Analysis of maximum displacements showed significantly increasing displacement with increasing speeds. CONCLUSIONS: Kinematic measurements during impact activity of running demonstrated caudal translation before and cranial translation after heel-strike. The hypothesis of caudal translation through impact activity was not confirmed. Patterns seem similar between continent and incontinent subjects. Associations between the direction of displacement and muscle action of PFMs remain assumptions.

An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for the assessment of sexual health of women with pelvic floor dysfunction.

AIMS: The terminology in current use for sexual function and dysfunction in women with pelvic floor disorders lacks uniformity, which leads to uncertainty, confusion, and unintended ambiguity. The terminology for the sexual health of women with pelvic floor dysfunction needs to be collated in a clinically-based consensus report. METHODS: This report combines the input of members of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA), and the International Continence Society (ICS), assisted at intervals by many external referees. Internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). Importantly, this report is not meant to replace, but rather complement current terminology used in other fields for female sexual health and to clarify terms specific to women with pelvic floor dysfunction. RESULTS: A clinically based terminology report for sexual health in women with pelvic floor dysfunction encompassing over 100 separate definitions, has been developed. Key aims have been to make the terminology interpretable by practitioners, trainees, and researchers in female pelvic floor dysfunction. Interval review (5-10 years) is anticipated to keep the document updated and as widely acceptable as possible. CONCLUSION: A consensus-based terminology report for female sexual health in women with pelvic floor dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research.

An international Urogynecological association (IUGA)/international continence society (ICS) joint report on the terminology for the assessment of sexual health of women with pelvic floor dysfunction.

INTRODUCTION AND HYPOTHESIS: The terminology in current use for sexual function and dysfunction in women with pelvic floor disorders lacks uniformity, which leads to uncertainty, confusion, and unintended ambiguity. The terminology for the sexual health of women with pelvic floor dysfunction needs to be collated in a clinically-based consensus report. METHODS: This report combines the input of members of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA), and the International Continence Society (ICS), assisted at intervals by many external referees. Internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). Importantly, this report is not meant to replace, but rather complement current terminology used in other fields for female sexual health and to clarify terms specific to women with pelvic floor dysfunction. RESULTS: A clinically based terminology report for sexual health in women with pelvic floor dysfunction encompassing over 100 separate definitions, has been developed. Key aims have been to make the terminology interpretable by practitioners, trainees, and researchers in female pelvic floor dysfunction. Interval review (5-10 years) is anticipated to keep the document updated and as widely acceptable as possible. CONCLUSIONS: A consensus-based terminology report for female sexual health in women with pelvic floor dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research.

Pelvic floor muscle activity during jumps in continent and incontinent women: an exploratory study.

PURPOSE: Stress urinary incontinence (SUI) symptoms can be provoked during impact loads such as vertical jumps. To investigate and compare pelvic floor muscle (PFM) activity in women with SUI and continent women (CON) during drop jumps (DJ) and counter movement jumps (CMJ) could clarify the activity of the PFMs during impact loads. METHODS: A tripolar vaginal probe was used to record surface electromyographic (EMG) activity of the PFMs during DJ and CMJ. Time intervals of 30 ms were used to parameterize data from 30 ms before (pre-activity) to 150 ms after (reflex activity) ground contact on a force plate during the landing and take-off phase. EMG signals were normalized to the mean of the peak values of two maximal voluntary contractions (MVC) and expressed in percentage (% MVC). RESULTS: For all time intervals during the landing and take-off phase, no statistically significant differences could be found between women with SUI and CON. EMG values exceeded 100% MVC for all time intervals during all landing and take-off phases. Maximal PFM activation was measured during the first landing of DJ and was 404.1% MVC for SUI and 370.2% MVC for CON. CONCLUSIONS: Vertical jumps seem to stimulate pre-activity before and reflex activity after ground contact during the landing phase and activate PFMs up to 400% MVC. Jumping stimuli inducing involuntary PFM contraction could show a beneficial factor to be integrated in a PFM rehabilitation program.

A Diverse and Versatile Regiospecific Synthesis of Tetrasubstituted Alkylsulfanylimidazoles as p38α Mitogen-Activated Protein Kinase Inhibitors.

An alternative strategy for the synthesis of 1-aryl- and 1-alkyl-2-methylsulfanyl-4-(4-fluorophenyl)-5-(pyridin-4-yl)imidazoles as potential p38α mitogen-activated protein kinase inhibitors is reported. The regioselective N-substitution of the imidazole ring was achieved by treatment of α-aminoketones with different aryl or alkyl isothiocyanates. In contrast to previously published synthesis routes starting from 2-amino-4-methylpyridine, the presented route is characterized by a higher flexibility and a lower number of steps. This strategy was also applied to access 1-alkyl-2-methylsulfanyl-5-(4-fluorophenyl)-4-(pyridin-4-yl)imidazoles in six steps starting from 2-chloro-4-methylpyridine.