European Urogynaecological Association Position Statement: The role of urodynamics in stress urinary incontinence evaluation and treatment decision.

Stress urinary incontinence (SUI) is defined as a condition characterized by the involuntary leakage of urine during activities that increase intra-abdominal pressure which may decrease quality of life with a significant economic impact on health systems, necessitating the implementation of cost-effective management plans. Urodynamics (UDS) has been considered during the last decades as the gold standard for assessment of lower urinary tract symptoms (LUTS) due to their high reproducibility. At the same time, concerns about the systematic use of UDS before SUI surgery were raised due to a limited evidenced base to recommend their routine use. In uncomplicated female patients with SUI, UDS can offer further insights into LUTS, potentially assisting the physician in determining the appropriate therapeutic approach. However, it has not been shown that preoperative UDS can directly impact the surgical outcome for continence. Indeed, evidence supports the conclusion that pre-operative UDS in women with uncomplicated, clinically demonstrable, SUI does not improve the outcome of surgery for SUI. Nevertheless, asymptomatic detrusor overactivity (DO) identified by urodynamic testing or pre-existing voiding dysfunction are associated with an increased occurrence of postoperative overactive bladder (OAB) and voiding dysfunction, respectively. The EUGA Working Group concluded that the evidence does not support the systematic preoperative use of UDS for uncomplicated cases. However, in cases where mixed symptoms, voiding dysfunction, previous surgery, or concomitant prolapse are present, preoperative UDS are advised as they can be beneficial in anticipating postoperative outcomes. This aids in conducting comprehensive and thorough preoperative counseling. The Group recommend performing preoperative UDS considering the patient's specific clinical situation and the surgeon's judgment, with consideration given to the potential benefits, risks, and impact on treatment decisions and patient outcomes.

Freeze-Driven Synthesis of DNA Hairpin-Conjugated Gold Nanoparticle Biosensors for Dual-Mode Detection.

Freeze-based immobilization of deoxyribonucleic acid (DNA) oligonucleotides on gold nanoparticles (AuNPs) is highly efficient for single-stranded oligonucleotides but typically does not accommodate structures such as snap-cooled DNA hairpins (Sc-HPs) and snap-cooled molecular beacons (Sc-MBs) frequently used for biorecognition applications. Recognizing this limitation, we have developed a modified, freeze-based technique specifically designed to enable the adsorption of such hairpin oligonucleotides onto AuNP surfaces while ensuring that they retain their biosensing capabilities. Successful hairpin oligonucleotide conjugation of varying lengths to a wide range of AuNP diameters was corroborated by dynamic light scattering, ζ-potential, and UV-vis spectrophotometry. Moreover, we conducted a thorough evaluation of this modified method, confirming the retention of the sensing functions of Sc-HPs and Sc-MBs. This advancement not only offers a more efficient route for DNA hairpin conjugation but also elucidates the underlying biorecognition functions, with implications for broader applications in molecular diagnostics.

Thermodynamic Analysis of Silk Fibroin-Graphite Hybrid Materials and Their Morphology.

Silk fibroin (SF) is a ß-sheet-rich protein that is responsible for the remarkable tensile strength of silk. In addition to its mechanical properties, SF is biocompatible and biodegradable, making it an attractive candidate for use in biotic/abiotic hybrid materials. A pairing of particular interest is the use of SF with graphene-based nanomaterials (GBNs). The properties of this interface drive the formation of well-ordered nanostructures and can improve the electronic properties of the resulting hybrid. It was previously demonstrated that SF can form lamellar nanostructures in the presence of graphite; however, the equilibrium morphology and associated driving interactions are not fully understood. In this study, we characterize these interactions between SF and SF lamellar with graphite using molecular dynamics (MD) simulations and umbrella sampling (US). We find that SF lamellar nanostructures have strong orientational and spatial preferences on graphite that are driven by the hydrophobic effect, destabilizing solvent-protein interactions and stabilizing protein-protein and protein-graphite interactions. Finally, we show how careful consideration of these underlying interactions can be applied to rationally modify the nanostructure morphology.

Vaginal erbium laser treatment for stress urinary incontinence: A multicenter randomized sham-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of non-ablative vaginal Er:YAG laser device in stress urinary incontinence (SUI) treatment. METHODS: We conducted a multicenter blinded randomized sham-controlled trial in which women with urodynamic SUI were randomization to active arm using Er:YAG laser therapy, and sham arm using sham handpiece. Patients received two treatments 1 month apart. The primary outcomes measure was 1 h pad weight test measured at 6 months. Secondary outcomes were durability of treatment success at 12 months, and questionnaires for assessment of SUI severity (ICIQ-UI SF), sexual function (PISQ-12) and HRQoL (KHQ), and incidence and severity of device related adverse events and pain (VAS). RESULTS: A total of 110 participants with SUI were recruited; 73 in the active arm and 37 in the sham arm. Two participants were excluded; one was assigned the wrong treatment and one withdrew their consent. Treatment success was observed in 36% of the sham arm and 59% of the active arm; in the latter, odds of achieving treatment success were more than three-fold higher (OR 3.63, 95% CI: 1.3-11.2, P = 0.02). HRQoL by KHQ showed significant improvement in the active versus the sham arm (OR 0.36, 95% CI: 0.15-0.87, P = 0.003). Similarly, subjective patient assessment of general and sexual function improvement with PISQ-12 and PGI-I showed superior effect over sham (OR 2.8, 95% CI: 1.2-7.0, P = 0.02 and OR 0.13, 95% CI: 0.05-0.36, P < 0.001, respectively). CONCLUSION: Non-ablative vaginal Er:YAG laser therapy significantly improves SUI symptoms versus sham treatment. Er:YAG laser therapy should be considered as a non-surgical treatment option for SUI patients.

What women want now!

IMPORTANCE: Stress urinary incontinence and pelvic organ prolapse are common conditions affecting women with many different conservative and surgical treatment options available for women. OBJECTIVES: Our primary aim was to determine patient views and preferences surrounding theoretical potential future treatment options for pelvic floor dysfunction (PFD): pelvic organ prolapse/SUI and determine what level of success patients would find acceptable and see if their choice was dependent on severity of their symptoms. All patients had either just completed or were about to start a course of 3 months physiotherapy. All patients with overactive bladder symptoms were excluded. STUDY DESIGN: We conducted an service evaluation study of 100 consecutive women attending our urogynaecology clinic. Patients attending clinic completed a questionnaire. They were asked to choose a preferred treatment between "Option A": A surgical procedure which had an 80% success rate in curing symptoms but would require 1-2 day hospital stay and carry a small risk of complications. Or "Option B": A hypothetical course of outpatient, non-surgical treatments which would have a variable chance of improving (but not curing) symptoms (ranging from 70%, 50% or 25% chance of improvement) but would require no "down-time" and have no long term safety issues. RESULTS: Our results showed 100% of women with severe PFD would chose a surgical procedure. However those with mild/moderate symptoms would prefer a non-surgical treatment (if one were available) which may only improve their symptoms but had no long-term complications. There was a moderate correlation (r = 0.46) between severity of symptoms and chance of success. CONCLUSIONS: This study is important as it highlights a change in patient demand from one of highest efficacy to possibly one with the greatest safety profile and quickest recovery time. Newer treatment technologies such as energy-based devices (radiofrequency, laser and magnetic therapy) have shown to have lower success rates but may be favourable for some women. This supports the need for further research in these areas.

A national survey of urinary incontinence in professional Team England female athletes.

OBJECTIVES: To investigate the prevalence of urinary incontinence in Team England female athletes participating in the 2018 Commonwealth Games, the self-imposed lifestyle modifications used to manage symptoms in training and competition and the impact on performance. STUDY DESIGN: This was a Cross-Sectional Survey. All Team England female athletes participating in 2018 Commonwealth Games were asked to complete a structured questionnaire regarding symptoms and management of urinary incontinence. Chi-squared statistical analysis was applied to relevant data. RESULTS: 103 athletes were included. 52 % reported experiencing urinary incontinence (38 % in training vs 27 % in competition X2 = 2.68, p0.13). Highest rates of incontinence were seen in cycling and gymnastics, with lowest rates of incontinence in swimming and rugby. In sports requiring form fitting garments, 64 % did not feel they could wear a pad in training, compared with 19 % in sports with less form-fitting clothing. In competition, 75 % of athletes wearing form-fitting clothing did not feel they could wear a pad, compared with 24 % of those with less form-fitting attire (X2 = 16.9, p < 0.001 in training; X2 = 24.04, p = <0.001 in competition). 11 % of athletes reported reducing fluid intake to reduce urinary incontinence in training and 8 % reported doing this in competition. Only 3 % of athletes reported that their performance is affected by urinary incontinence. CONCLUSION: Prevalence of urinary incontinence is higher in athletes than in the general population. Tight-fitting sportswear is a barrier to athletes using pads to manage urinary incontinence. Athletes may reduce fluid intake to reduce urinary leakage in training and competition, which may affect performance. However, few athletes report that urinary incontinence has an impact overall.

Laser treatment for genitourinary syndrome of menopause: Scientific Impact Paper No. 72 (July 2022): Scientific Impact Paper No. 72 (July 2022).

Genitourinary syndrome of menopause (GSM) is the term used to describe the group of symptoms including vaginal pain, vaginal dryness, itching, pain during sexual intercourse and fragile vaginal tissues as well as urinary symptoms including urinary frequency, urgency, incontinence, blood in the urine (haematuria) and recurrent urinary tract infections that occur due to a lack of the hormone estrogen. These symptoms can have a significant negative impact on psychosexual issues, sexual function and quality of life in postmenopausal women. Traditionally women have been treated with vaginal lubricants, vaginal moisturisers or low-dose vaginal estrogens. Lasers have been used in the cosmetic industry for collagen remodelling and repair of the skin. Therefore, it has been suggested that laser therapy may be used on the vagina as an alternative treatment for GSM. A review of all the published studies assessing the safety and efficacy of laser therapy for GSM have shown promising beneficial results. The majority of studies to date have been small, short-term, observational studies. However, there are randomised controlled trials underway. Laser treatment may be beneficial for the symptoms of GSM but until more robust evidence is available it should not be adopted into widespread practice, and should be used as part of a research study only.

Insight Into Seeded Tau Fibril Growth From Molecular Dynamics Simulation of the Alzheimer's Disease Protofibril Core.

Aggregates of the microtubule associated tau protein are a major constituent of neurofibrillary lesions that define Alzheimer's disease (AD) pathology. Increasing experimental evidence suggests that the spread of tau neurofibrillary tangles results from a prion-like seeding mechanism in which small oligomeric tau fibrils template the conversion of native, intrinsically disordered, tau proteins into their pathological form. By using atomistic molecular dynamics (MD) simulations, we investigate the stability and dissociation thermodynamics of high-resolution cryo-electron microscopy (cryo-EM) structures of both the AD paired-helical filament (PHF) and straight filament (SF). Non-equilibrium steered MD (SMD) center-of-mass pulling simulations are used to probe the stability of the protofibril structure and identify intermolecular contacts that must be broken before a single tau peptide can dissociate from the protofibril end. Using a combination of exploratory metadynamics and umbrella sampling, we investigate the complete dissociation pathway and compute a free energy profile for the dissociation of a single tau peptide from the fibril end. Different features of the free energy surface between the PHF and SF protofibril result from a different mechanism of tau unfolding. Comparison of wild-type tau PHF and post-translationally modified pSer356 tau shows that phosphorylation at this site changes the dissociation free energy surface of the terminal peptide. These results demonstrate how different protofibril morphologies template the folding of endogenous tau in distinct ways, and how post-translational modification can perturb the folding mechanism.

The effect of modified Pilates-based positions on pelvic floor electromyographic (EMG) activity; a pilot study.

INTRODUCTION: The evidence regarding the effect of exercise, specifically Modified Pilates (MP), on pelvic floor muscles (PFMs) is limited. We report our pilot study using the MAPLe® device to assess the effect of MP type exercises on PFM electomyographic (EMG) activity and whether PFM contraction could be performed during specific MP exercises. METHODS: The MAPLe® device was used to measure EMG activity of PFMs in healthy volunteers in different MP positions. Positions were divided into 'neutral', 'core' and 'plank' and EMG readings were taken at rest, during Valsalva and during active contraction. RESULTS: Twenty volunteers were recruited. The median age was 35 (IQR 27-39.5) years. Higher EMG readings were seen in 'core' and 'plank' positions at rest. No position inhibited a conscious contraction and positions which engaged core muscles provoked an augmented contraction. CONCLUSION: This is the first study to show that when MP positions are held for short periods of time, in asymptomatic women, the changes in PFM EMG are higher. This suggests that a stronger muscle contraction can be achieved when the core is co-contracted. Higher EMG readings were seen during 'core' and 'plank' positions; despite this, further activation with a conscious PFM contraction was still achievable.

Long-term safety and efficacy of laparoscopically placed mesh for apical prolapse.

INTRODUCTION AND HYPOTHESIS: Concerns regarding the use of vaginal mesh for prolapse have led to questions about the safety and efficacy of abdominally placed mesh. Mesh procedures for treating apical prolapse have become popular, either a laparoscopic hysteropexy (LSH) for uterine prolapse or a sacrocolpopexy (LSC) for vaginal vault prolapse. Robust long-term safety and efficacy data for these procedures are essential. METHODS: All patients who had LSH or LSC since 2010 were invited back for face-to-face review and examination. Case notes were reviewed for surgical morbidities and patients were questioned about short- and long-term complications. The Patient Global Impression of Improvement (PGI-I) scale was used to assess prolapse, bladder and bowel symptoms postoperatively. RESULTS: One hundred twelve patients were included in the review, 93 of whom were examined. The median time since surgery was 6 years (range 1-9 years); 2.7% cases had an intraoperative complication, two conversions to laparotomy and one bladder injury. Overall, 17.3% patients sought medical review postoperatively, with 10.7% having problems with their skin incisions. With regard to mesh safety, there was one case of bowel obstruction requiring resection following LSH and two vaginal mesh exposures following LSC; 97% had stage 1 or less apical prolapse at long-term follow-up and 79.6% reported symptoms of prolapse to be 'much better' or 'very much better' on the PGI-I scale. CONCLUSIONS: This study shows excellent long-term results from LSC and LSH with comprehensive follow-up, demonstrating a very low and acceptable level of intraoperative, short- and long-term complications.

Lasers in gynaecology.

The use of lasers to treat gynaecological and urogynaecological conditions including genitourinary syndrome of the menopause, stress urinary incontinence, vaginal prolapse and other conditions, has become increasingly popular over recent years. Following widespread concerns over the use of mesh for treating stress urinary incontinence and pelvic organ prolapse and potential adverse outcomes from the use of mesh, there has been heightened awareness and debate over the introduction and adoption of new technologies and interventions within the speciality. On July 30th 2018 the United States Food and Drug Administration (FDA) issued a warning against the use of energy based devices (EBDS) including laser to perform "vaginal rejuvenation" or vaginal cosmetic procedures. Numerous review articles and editorials have urged for greater evidence on the efficacy and safety of vaginal lasers This review outlines the evidence to date for the use of lasers in the treatment of gynaecological conditions.

Laparoscopic sacrocolpopexy: A comprehensive literature review on current practice.

Sacrocolpopexy is considered the preferred treatment for vaginal vault. However, numerous technical variants are being practiced. We aimed to summarize the recent literature in relation to technical aspects of laparoscopic sacrocolpopexy (LSC). We focused on surgical technique, mesh type, concomitant surgeries, and training aspects. We performed 2 independent literature searches in Medline, Scopus, the Cochrane library, and Embase electronic databases including the keywords: 'sacrocolpopexy', 'sacral colpopexy' and 'promontofixation'. Full text English-language studies of human patients, who underwent LSC, published from January 1, 2008 to February 26, 2019, were included. Levels of evidence using the modified Oxford grading system were assessed in order to establish a report of the available literature of highest level of evidence. Initially, 953 articles were identified. After excluding duplicates and abstracts screening, 35 articles were included. Vaginal fixation of the mesh can be performed with barbed or non-barbed (level 1), absorbable or non-absorbable sutures (level 2). Fixation of the mesh to the promontory can be performed with non-absorbable sutures or non-absorbable tackers (level 2). The current literature supports using type 1 mesh (level 2). Ventral mesh rectopexy can safely be performed with LSC while concurrent posterior repair has no additional benefit (level 2). There is no consensus regarding the preferred type of hysterectomy or the benefit of an additional anti urinary incontinence procedure. A structured learning program, as well as the number of procedures needed in order to be qualified for performing LSC is yet to be established. There are numerous variants for performing LSC. For many of its technical aspects there is little consensus.

Use of an instrumented dual-task timed up and go test in children with traumatic brain injury.

BACKGROUND: Wearable sensors have allowed researchers to instrument tests of gait-related mobility, including the widely used timed 'up-and-go' test (TUG). Currently, there is a lack of instrumented test data on whether children with moderate to severe traumatic brain injury (TBI) perform differently on the TUG compared to typically developed (TD) controls during a cognitive-motor task. RESEARCH QUESTION: The aim was to explore the effects of a cognitive-motor task on TUG subcomponents among children with TBI compared to TD children. METHODS: This observational cross-sectional study included 12 children with moderate to severe TBI (6 males and 6 females, age 10.5 ±â€¯1.5 years of age) and 10 age and sex-matched TD controls (5 males and 5 females, 10.4 ±â€¯1.3 years of age). Each participant completed 6 trials of the TUG wearing a single inertial measurement unit sensor at a self-selected walking pace while listening to an array of 10 randomly presented single digits during each TUG trial. RESULTS: Total time to complete the TUG was not significantly different between groups. The cognitive-motor task led to significantly lower mean turn and peak turn angular velocity values during the turn-around-the-cone and turn-before-sitting TUG subcomponents in children with TBI compared to the TD controls (p ≤ 0.05). Additionally, the cognitive-motor task led to significantly lower values for maximum torso flexion to extension angle, peak flexion and extension angular velocity and peak vertical acceleration for the sit-to-stand subcomponent (p < 0.05). Peak flexion angular velocity during the stand-to-sit subcomponent was lower for the TBI group compared to the children with TD (p < 0.05). SIGNIFICANCE: The study provides new insights into the performance of complex gait-related mobility tasks in the context of an instrumented TUG among children with moderate to severe TBI. Our results highlight the potential benefits of outfitting pediatric inpatients with an IMU while completing the TUG.

The effect of intravesical instillations with Hyaluronic Acid on sexual dysfunction in women with recurrent urinary tract infections (RUTI).

OBJECTIVE: To determine whether sexual dysfunction in women with recurrent urinary tract infections (RUTI) improved following treatment with intravesical Hyaluronic Acid (HA) instillations. STUDY DESIGN: Ethical approval was obtained for a prospective study to be performed. Patients referred for bladder instillations to treat RUTI, and who were sexually active, were recruited to the study. A selection of validated questionnaires (ICIQ-UI, ICIQ-VS, FSDS-R, ICIQ-FLUTS, O'Leary/Sant and PGI-I) were completed at baseline, three, six and 12 months after initiation of treatment with bladder instillations. Treatment consisted of weekly bladder instillations with a preparation containing HA for four weeks then monthly for two further treatments. Results were populated in SPSS for statistical analysis and statistical significance was powered for 22 patients. RESULTS: Thirty women were included in the study. FSDS-R was used to determine sexual dysfunction and showed that 57% patients with RUTI had significant sexual distress. There was a significant improvement in FSDS-R at three, six and 12 months when compared to baseline (Friedman two-way analysis p < 0.001). ICIQ FLUTS F and I scores, O'Leary/Sant, ICIQ VS and PGI-I also showed a statistically significant improvement throughout the period of follow up. A statistically significant, negative correlation was found between FSDS-R and PGI-I at 12 months (r = -0.468, p = 0.009). CONCLUSION: We have reinforced previous work showing the association between RUTI and sexual dysfunction, and an improvement in bladder symptoms following treatment with HA. To our knowledge, this is the first study to prove an improvement in sexual dysfunction following intravesical treatment with HA which is sustained for up to 12 months.

Recurrent pelvic organ prolapse: International Urogynecological Association Research and Development Committee opinion.

INTRODUCTION AND HYPOTHESIS: This committee opinion paper summarizes available evidence about recurrent pelvic organ prolapse (POP) to provide guidance on management. METHOD: A working subcommittee from the International Urogynecological Association (IUGA) Research and Development Committee was formed. The literature regarding recurrent POP was reviewed and summarized by individual members of the subcommittee. Recommendations were graded according to the 2009 Oxford Levels of Evidence. The summary was reviewed by the Committee. RESULTS: There is no agreed definition for recurrent POP and evidence in relation to its evaluation and management is limited. CONCLUSION: The assessment of recurrent POP should entail looking for possible reason(s) for failure, including persistent and/or new risk factors, detection of all pelvic floor defects and checking for complications of previous surgery. The management requires individual evaluation of the risks and benefits of different options and appropriate patient counseling. There is an urgent need for an agreed definition and further research into all aspects of recurrent POP.

The management of lower urogenital changes in the menopause.

Currently, 25% of women seek the advice of a medical professional for symptoms related to the menopause. However, with an increasingly ageing and medically aware population, it is likely this proportion will grow. The main symptoms related to the menopause are systemic vasomotor and localized urogenital symptoms. Numerous forms of estrogen have been used to alleviate these symptoms. Further problems that increase during the menopause include incontinence, pelvic organ prolapse and recurrent urinary tract infections. This article reviews the process by which estrogen affects the tissues of the urogenital tract, what symptoms occur during this period and what modalities of treatments are available.

miR-200 and miR-96 families repress neural induction from human embryonic stem cells.

The role of miRNAs in neuroectoderm specification is largely unknown. We screened miRNA profiles that are differentially changed when human embryonic stem cells (hESCs) were differentiated to neuroectodermal precursors (NEP), but not to epidermal (EPI) cells and found that two miRNA families, miR-200 and miR-96, were uniquely downregulated in the NEP cells. We confirmed zinc-finger E-box-binding homeobox (ZEB) transcription factors as a target of the miR-200 family members and identified paired box 6 (PAX6) transcription factor as the new target of miR-96 family members via gain- and loss-of-function analyses. Given the essential roles of ZEBs and PAX6 in neural induction, we propose a model by which miR-200 and miR-96 families coordinate to regulate neural induction.

Unplanned return to the operating theatre in gynaecology: five years' experience.

OBJECTIVES: To review our incidence of unplanned return to the operating theatre (OT) and compare our findings with the published literature. STUDY DESIGN: Five year retrospective review of case notes in our gynaecology department between January 2005 and April 2010. Women were eligible for recruitment if they returned to the OT for an unplanned operation during the same admission following a gynaecological operation. RESULTS: Seventeen cases were identified, mean age 40 years (range 27-52 years). The incidence of unplanned return to the OT was 0.03%. Elective and emergency initial operations accounted for 72% and 28% respectively. Over 80% of the cases followed a hysterectomy, giving an overall risk of return to OT after hysterectomy of 2%. Reactionary bleeding was the cause in all cases. A specific bleeding site was identified in 82% of the women. The mean time between primary surgery and return to the OT was 7.9 h. The triggering factors were a combination of a change in observations, postoperative bleeding, a drop in haemoglobin level and uncontrolled abdominal pain despite analgesics. Blood transfusion was required in 53% of cases and one woman was admitted to the intensive care unit for one night. No women required further reoperation, and all were discharged home with no long-term sequelae. CONCLUSION: Unplanned reoperation is a potentially life threatening complication, and therefore early recognition; resuscitation and emergency return to the OT to stop the bleeding are the main principles of management.