Disruption of circadian rhythm as a potential pathogenesis of nocturia.

Increasing evidence suggested the multifactorial nature of nocturia, but the true pathogenesis of this condition still remains to be elucidated. Contemporary clinical medications are mostly symptom based, aimed at either reducing nocturnal urine volume or targeting autonomic receptors within the bladder to facilitate urine storage. The day-night switch of the micturition pattern is controlled by circadian clocks located both in the central nervous system and in the peripheral organs.

Optimization of activity-driven event detection for long-term ambulatory urodynamics.

Lower urinary tract dysfunction (LUTD) is a debilitating condition that affects millions of individuals worldwide, greatly diminishing their quality of life. The use of wireless, catheter-free implantable devices for long-term ambulatory bladder monitoring, combined with a single-sensor system capable of detecting various bladder events, has the potential to significantly enhance the diagnosis and treatment of LUTD. However, these systems produce large amounts of bladder data that may contain physiological noise in the pressure signals caused by motion artifacts and sudden movements, such as coughing or laughing, potentially leading to false positives during bladder event classification and inaccurate diagnosis/treatment.

Contribution of pudendal nerve injury to stress urinary incontinence in a male rat model.

Urinary incontinence is a common complication following radical prostatectomy, as the surgery disturbs critical anatomical structures. This study explored how pudendal nerve (PN) injury affects urinary continence in male rats. In an acute study, leak point pressure (LPP) and external urethral sphincter electromyography (EMG) were performed on six male rats with an intact urethra, the urethra exposed (UE), the PN exposed (NE), and after PN transection (PNT).

Wireless and Catheter-Free Bladder Pressure and Volume Sensor.

Continuous monitoring of bladder activity during normal daily activities would improve clinical diagnostics and understanding of the mechanisms underlying bladder function, or help validate how differing neuromodulation strategies affect the bladder. This work describes a urological monitor of conscious activity (UroMOCA). The UroMOCA included a pressure sensor, urine impedance-sensing electrodes, and wireless battery recharge and data transmission circuitry.

Is the time right for a new initiative in mathematical modeling of the lower urinary tract? ICI-RS 2023.

Introduction: A session at the 2023 International Consultation on Incontinence - Research Society (ICI-RS) held in Bristol, UK, focused on the question: Is the time right for a new initiative in mathematical modeling of the lower urinary tract (LUT)? The LUT is a complex system, comprising various synergetic components (i.e., bladder, urethra, neural control), each with its own dynamic functioning and high interindividual variability.

Can we improve techniques and patients' selection for nerve stimulation suitable for lower urinary tract dysfunctions? ICI-RS 2023.

Aims: Lower urinary tract dysfunctions (LUTD) are very common and, importantly, affect patients' quality of life (QoL). LUTD can range from urinary retention to urgency incontinence and includes a variety of symptoms. Nerve stimulation (NS) is an accepted widespread treatment with documented success for LUTD and is used widely.

Assessing Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury: Animal Models in Preclinical Neuro-Urology Research.

Neurogenic bladder dysfunction is a condition that affects both bladder storage and voiding function and remains one of the leading causes of morbidity after spinal cord injury (SCI). The vast majority of individuals with severe SCI develop neurogenic lower urinary tract dysfunction (NLUTD), with symptoms ranging from neurogenic detrusor overactivity, detrusor sphincter dyssynergia, or sphincter underactivity depending on the location and extent of the spinal lesion. Animal models are critical to our fundamental understanding of lower urinary tract function and its dysfunction after SCI, in addition to providing a platform for the assessment of potential therapies.

A Flexible Implant for Multi-Day Monitoring of Colon Segment Activity.

Monitoring of colon activity is currently limited to tethered systems like anorectal manometry. These systems have significant drawbacks, but fundamentally limit the observation time of colon activity, reducing the likelihood of detecting specific clinical events. While significant technological advancement has been directed to mobile sensor capsules, this work describes the development and feasibility of a stationary sensor for describing the coordinated activity between neighboring segments of the colon.

First in Human Subjects Testing of the UroMonitor: A Catheter-free Wireless Ambulatory Bladder Pressure Monitor.

Purpose: Urodynamics is the standard method of diagnosing bladder dysfunction, but involves catheters and retrograde bladder filling. With these artificial conditions, urodynamics cannot always reproduce patient complaints. We have developed a wireless, catheter-free intravesical pressure sensor, the UroMonitor, which enables catheter-free telemetric ambulatory bladder monitoring.

Brain-Derived Neurotrophic Factor Is Indispensable to Continence Recovery after a Dual Nerve and Muscle Childbirth Injury Model.

In women, stress urinary incontinence (SUI), leakage of urine from increased abdominal pressure, is correlated with pudendal nerve (PN) injury during childbirth. Expression of brain-derived neurotrophic factor (BDNF) is dysregulated in a dual nerve and muscle injury model of childbirth. We aimed to use tyrosine kinase B (TrkB), the receptor of BDNF, to bind free BDNF and inhibit spontaneous regeneration in a rat model of SUI.

Effects of mesenchymal stem cells and heparan sulfate mimetics on urethral function and vaginal wall biomechanics in a simulated rat childbirth injury model.

Introduction And Hypothesis: New treatments are needed for pelvic floor disorders. ReGeneraTing Agent® (RGTA®) is a promising regenerative therapy. Therefore, the objective of this study was to compare regenerative abilities of mesenchymal stem cells (MSCs) and RGTA® on regeneration after simulated childbirth injury in rats.

The Effect of Dosing of on Anal Sphincter Regeneration.

The aim of this study is to investigate if a high dose of the (SDF-1) plasmid improves outcome in a minipig model of chronic anal sphincter injury. Twenty-two female minipigs underwent excision of the posterior hemicircumference of the anal sphincter complex and were allowed to recover for 6 weeks. They were randomly allocated ( = 6) to receive either 5% dextrose (sham) or 2, 4, or 8 mg of SDF-1 plasmid at the defect site.

Detrusor Pressure Estimation from Single-Channel Urodynamics.

Urodynamics is the current gold-standard for diagnosing lower urinary tract dysfunction, but uses non-physiologically fast, retrograde cystometric filling to obtain a brief snapshot of bladder function. Ambulatory urodynamics allows physicians to evaluate bladder function during natural filling over longer periods of time, but artifacts generated from patient movement necessitate the use of an abdominal pressure sensor, which makes long-term monitoring and feedback for closed-loop treatment impractical. In this paper, we analyze the characteristics of single-channel bladder pressure signals from human and feline datasets, and present an algorithm designed to estimate detrusor pressure, which is useful for diagnosis and treatment.

Brain-Derived Neurotrophic Factor Is an Important Therapeutic Factor in Mesenchymal Stem Cell Secretions for Treatment of Traumatic Peripheral Pelvic Injuries.

Traumatic neuromuscular injury to the pudendal nerve and urethra during childbirth does not regenerate well and contributes to stress urinary incontinence in women. Mesenchymal stem cells (MSCs) can improve neuroregeneration their secretions, or secretome, which includes brain-derived neurotrophic factor (BDNF). In this study, we investigated whether BDNF is a key factor in the secretome of MSCs for the facilitation of functional recovery following a dual simulated childbirth injury.

Stromal cell derived factor 1 plasmid to regenerate the anal sphincters.

Unlabelled: The aim of this study was to evaluate regeneration of a chronic large anal sphincter defect in a pig model after treatment with a plasmid encoding Stromal Cell Derived Factor-1(SDF-1).

Methods: Under ethics approved protocol 19 age/weight matched Sinclair mini-pigs were subjected to excision of the posterior 50% of anal sphincter muscle and left to recover for 6 weeks. They were randomly allocated to receive either saline treatment (Saline 1 ml, n = 5), 1 injection of SDF-1 plasmid 2 mg/ml (1 SDF-1, n = 9) or 2 injections of SDF-1, 2 mg/ml each at 2 weeks intervals (2 SDF-1, n = 5).

Mouse Knockout Models for Pelvic Organ Prolapse: a Systematic Review.

Introduction And Hypothesis: Mouse knockout (KO) models of pelvic organ prolapse (POP) have contributed mechanistic evidence for the role of connective tissue defects, specifically impaired elastic matrix remodeling. Our objective was to summarize what mouse KO models for POP are available and what have we learned from these mouse models about the pathophysiological mechanisms of POP development.

Methods: We conducted a systematic review and reported narrative findings according to PRISMA guidelines.

Time course for urethral neuromuscular reestablishment and its facilitated recovery by transcutaneous neuromodulation after simulated birth trauma in rats.

The aims of the study were to determine the time-course of urinary incontinence recovery after vaginal distension (VD), elucidate the mechanisms of injury from VD leading to external urethral sphincter (EUS) dysfunction, and assess if transcutaneous electrical stimulation (TENS) of the dorsal nerve of the clitoris facilitates recovery of urinary continence after VD. Rats underwent 4-h VD, 4-h sham VD (SH-VD), VD plus 1-h DNC TENS, and VD plus 1-h sham TENS (SH-TENS). TENS or SH-TENS were applied immediately and at days 2 and 4 post-VD.

Transurethral versus suprapubic catheterization to test urethral function in rats.

Transurethral and suprapubic catheterization have both been used to test urethral function in rats; however, it is unknown whether these methods affect urethral function or if the order of catheterization affects the results. The aim of this cross-over designed experiment was to compare the effects of catheterization methods and order on leak point pressure (LPP) testing. LPP and simultaneous external urethral sphincter electromyography (EUS EMG) were recorded in anesthetized female virgin Sprague-Dawley rats in a cross-over design to test the effects of transurethral and suprapubic catheterization.

Brain derived neurotrophic factor mediates accelerated recovery of regenerative electrical stimulation in an animal model of stress urinary incontinence.

Objective: Stress urinary incontinence (SUI) is prevalent among older women and can result from insufficient regeneration of the pudendal nerve (PN). Electrical stimulation (ES) of the PN upregulates brain derived neurotrophic factor (BDNF) and accelerates regeneration. Using tyrosine kinase B (TrkB) to reduce the availability of free BDNF, the aim of this study was to determine if BDNF is necessary for accelerated recovery via ES in a model of SUI.

Quantitative Morphometry of Elastic Fibers in Pelvic Organ Prolapse.

Pelvic organ prolapse (POP) is common among older women who have delivered children vaginally. While the pathophysiology is not fully delineated, POP can occur in part from insufficient repair of disrupted elastic matrix fibers. Quantification of structural changes to elastic fibers has not been described previously for POP.

Characterization of Lower Urinary Tract Dysfunction after Thoracic Spinal Cord Injury in Yucatan Minipigs.

There is an increasing need to develop approaches that will not only improve the clinical management of neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI), but also advance therapeutic interventions aimed at recovering bladder function. Although pre-clinical research frequently employs rodent SCI models, large animals such as the pig may play an important translational role in facilitating the development of devices or treatments. Therefore, the objective of this study was to develop a urodynamics protocol to characterize NLUTD in a porcine model of SCI.