Central Control Circuit for Context-Dependent Micturition.

Urine release (micturition) serves an essential physiological function as well as a critical role in social communication in many animals. Here, we show a combined effect of olfaction and social hierarchy on micturition patterns in adult male mice, confirming the existence of a micturition control center that integrates pro- and anti-micturition cues. Furthermore, we demonstrate that a cluster of neurons expressing corticotropin-releasing hormone (Crh) in the pontine micturition center (PMC) is electrophysiologically distinct from their Crh-negative neighbors and sends glutamatergic projections to the spinal cord. The activity of PMC Crh-expressing neurons correlates with and is sufficient to drive bladder contraction, and when silenced impairs micturition behavior. These neurons receive convergent input from widespread higher brain areas that are capable of carrying diverse pro- and anti-micturition signals, and whose activity modulates hierarchy-dependent micturition. Taken together, our results indicate that PMC Crh-expressing neurons are likely the integration center for context-dependent micturition behavior.

PIEZO2 in sensory neurons and urothelial cells coordinates urination.

Henry Miller stated that "to relieve a full bladder is one of the great human joys". Urination is critically important in health and ailments of the lower urinary tract cause high pathological burden. Although there have been advances in understanding the central circuitry in the brain that facilitates urination1-3, there is a lack of in-depth mechanistic insight into the process. In addition to central control, micturition reflexes that govern urination are all initiated by peripheral mechanical stimuli such as bladder stretch and urethral flow4. The mechanotransduction molecules and cell types that function as the primary stretch and pressure detectors in the urinary tract mostly remain unknown. Here we identify expression of the mechanosensitive ion channel PIEZO2 in lower urinary tract tissues, where it is required for low-threshold bladder-stretch sensing and urethral micturition reflexes. We show that PIEZO2 acts as a sensor in both the bladder urothelium and innervating sensory neurons. Humans and mice lacking functional PIEZO2 have impaired bladder control, and humans lacking functional PIEZO2 report deficient bladder-filling sensation. This study identifies PIEZO2 as a key mechanosensor in urinary function. These findings set the foundation for future work to identify the interactions between urothelial cells and sensory neurons that control urination.

Creation of bladder assembloids mimicking tissue regeneration and cancer.

Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments1,2. Here we create multilayer bladder 'assembloids' by reconstituting tissue stem cells with stromal components to represent an organized architecture with an epithelium surrounding stroma and an outer muscle layer. These assembloids exhibit characteristics of mature adult bladders in cell composition and gene expression at the single-cell transcriptome level, and recapitulate in vivo tissue dynamics of regenerative responses to injury. We also develop malignant counterpart tumour assembloids to recapitulate the in vivo pathophysiological features of urothelial carcinoma. Using the genetically manipulated tumour-assembloid platform, we identify tumoural FOXA1, induced by stromal bone morphogenetic protein (BMP), as a master pioneer factor that drives enhancer reprogramming for the determination of tumour phenotype, suggesting the importance of the FOXA1-BMP-hedgehog signalling feedback axis between tumour and stroma in the control of tumour plasticity.

A wireless closed-loop system for optogenetic peripheral neuromodulation.

The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system1-5. This type of technology relies largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis (also known as bladder pain syndrome)4,6,7. Conventional, continuous stimulation protocols, however, can cause discomfort and pain, particularly when treating symptoms that can be intermittent (for example, sudden urinary urgency)8. Direct physical coupling of electrodes to the nerve can lead to injury and inflammation9-11. Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. Here we introduce a miniaturized bio-optoelectronic implant that avoids these limitations by using (1) an optical stimulation interface that exploits microscale inorganic light-emitting diodes to activate opsins; (2) a soft, high-precision biophysical sensor system that allows continuous measurements of organ function; and (3) a control module and data analytics approach that enables coordinated, closed-loop operation of the system to eliminate pathological behaviours as they occur in real-time. In the example reported here, a soft strain gauge yields real-time information on bladder function in a rat model. Data algorithms identify pathological behaviour, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalizes bladder function. This all-optical scheme for neuromodulation offers chronic stability and the potential to stimulate specific cell types.

PTHrP attenuates spontaneous contractions in detrusor smooth muscle of the rat bladder by activating spontaneous transient outward potassium currents.

Parathyroid hormone-related protein (PTHrP) released from detrusor smooth muscle (DSM) cells upon bladder distension attenuates spontaneous phasic contractions (SPCs) in DSM and associated afferent firing to facilitate urine storage. Here, we investigate the mechanisms underlying PTHrP-induced inhibition of SPCs, focusing on large-conductance Ca2+-activated K+ channels (BK channels) that play a central role in stabilizing DSM excitability. Perforated patch-clamp techniques were applied to DSM cells of the rat bladder dispersed using collagenase. Isometric tension changes were recorded from DSM strips, while intracellular Ca2+ dynamics were visualized using Cal520 AM -loaded DSM bundles. DSM cells developed spontaneous transient outward potassium currents (STOCs) arising from the opening of BK channels. PTHrP (10 nM) increased the frequency of STOCs without affecting their amplitude at a holding potential of - 30 mV but not - 40 mV. PTHrP enlarged depolarization-induced, BK-mediated outward currents at membrane potentials positive to + 20 mV in a manner sensitive to iberiotoxin (100 nM), the BK channel blocker. The PTHrP-induced increases in BK currents were also prevented by inhibitors of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) (CPA 10 µM), L-type voltage-dependent Ca2+ channel (LVDCC) (nifedipine 3 µM) or adenylyl cyclase (SQ22536 100 µM). PTHrP had no effect on depolarization-induced LVDCC currents. PTHrP suppressed and slowed SPCs in an iberiotoxin (100 nM)-sensitive manner. PTHrP also reduced the number of Ca2+ spikes during each burst of spontaneous Ca2+ transients. In conclusion, PTHrP accelerates STOCs discharge presumably by facilitating SR Ca2+ release which prematurely terminates Ca2+ transient bursts resulting in the attenuation of SPCs.

Urothelium-derived prostanoids enhance contractility of urinary bladder smooth muscle and stimulate bladder afferent nerve activity in the mouse.

The transitional epithelial cells (urothelium) that line the lumen of the urinary bladder form a barrier between potentially harmful pathogens, toxins, and other bladder contents and the inner layers of the bladder wall. The urothelium, however, is not simply a passive barrier, as it can produce signaling factors, such as ATP, nitric oxide, prostaglandins, and other prostanoids, that can modulate bladder function. We investigated whether substances produced by the urothelium could directly modulate the contractility of the underlying urinary bladder smooth muscle. Force was measured in isolated strips of mouse urinary bladder with the urothelium intact or denuded. Bladder strips developed spontaneous tone and phasic contractions. In urothelium-intact strips, basal tone, as well as the frequency and amplitude of phasic contractions, were 25%, 32%, and 338% higher than in urothelium-denuded strips, respectively. Basal tone and phasic contractility in urothelium-intact bladder strips were abolished by the cyclooxygenase (COX) inhibitor indomethacin (10 µM) or the voltage-dependent Ca2+ channel blocker diltiazem (50 µM), whereas blocking neuronal sodium channels with tetrodotoxin (1 µM) had no effect. These results suggest that prostanoids produced in the urothelium enhance smooth muscle tone and phasic contractions by activating voltage-dependent Ca2+ channels in the underlying bladder smooth muscle. We went on to demonstrate that blocking COX inhibits the generation of transient pressure events in isolated pressurized bladders and greatly attenuates the afferent nerve activity during bladder filling, suggesting that urothelial prostanoids may also play a role in sensory nerve signaling.NEW & NOTEWORTHY This paper provides evidence for the role of urothelial-derived prostanoids in maintaining tone in the urinary bladder during bladder filling, not only underscoring the role of the urothelium as more than a barrier but also contributing to active regulation of the urinary bladder. Furthermore, cyclooxygenase products greatly augment sensory nerve activity generated by bladder afferents during bladder filling and thus may play a role in perception of bladder fullness.

Conception and implementation of an MRI-compatible device to elicit the bulbocavernosus reflex for an open spinal cord study.

OBJECTIVE: Functional MRI (fMRI) can be employed to assess neuronal activity in the central nervous system. However, investigating the spinal cord using fMRI poses several technical difficulties. Enhancing the fMRI signal intensity in the spinal cord can improve the visualization and analysis of different neural pathways, particularly those involved in bladder function. The bulbocavernosus reflex (BCR) is an excellent method for evaluating the integrity of the sacral spinal cord. Instead of stimulating the glans penis or clitoris, the BCR can be simulated comfortably by tapping the suprapubic region. In this study, we explain the necessity and development of a device to elicit the simulated BCR (sBCR) via suprapubic tapping while conducting an fMRI scan. METHODS: The device was successfully tested on a group of 20 healthy individuals. Two stimulation task block protocols were administered (empty vs. full bladder). Each block consisted of 40 s of suprapubic tapping followed by 40 s of rest, and the entire sequence was repeated four times. RESULTS: Our device can reliably and consistently elicit sBCR noninvasively as demonstrated by electromyographic recording of pelvic muscles and anal winking. Participants did note mild to moderate discomfort and urge to void during the full bladder task. CONCLUSION: Our device demonstrates an efficacious approach to elicit sBCR within an MRI bore to assess sacral spinal cord functional activity without generating any significant motion artifacts. SIGNIFICANCE: This device can explore the mechanisms and processes controlling urinary, digestive, or sexual function within this region in humans.

Surgeon Upper Extremity Kinematics During Error and Error-Free Retropubic Trocar Passage.

INTRODUCTION AND HYPOTHESIS: Surgeon kinematics play a significant role in the prevention of patient injury. We hypothesized that elbow extension and ulnar wrist deviation are associated with bladder injury during simulated midurethral sling (MUS) procedures. METHODS: We used motion capture technology to measure surgeons' flexion/extension, abduction/adduction, and internal/external rotation angular time series for shoulder, elbow, and wrist joints. Starting and ending angles, minimum and maximum angles, and range of motion (ROM) were extracted from each time series. We created anatomical multibody models and applied linear mixed modeling to compare kinematics between trials with versus without bladder penetration and attending versus resident surgeons. A total of 32 trials would provide 90% power to detect a difference. RESULTS: Out of 85 passes, 62 were posterior to the suprapubic bone and 20 penetrated the bladder. Trials with versus without bladder penetration were associated with more initial wrist dorsiflexion (-27.32 vs -9.03°, p = 0.01), less final elbow flexion (39.49 vs 60.81, p = 0.03), and greater ROM in both the wrist (27.48 vs 14.01, p = 0.02), and elbow (20.45 vs 12.87, p = 0.04). Wrist deviation and arm pronation were not associated with bladder penetration. Compared with attendings, residents had more ROM in elbow flexion (14.61 vs 8.35°, p < 0.01), but less ROM in wrist dorsiflexion (13.31 vs 20.33, p = 0.02) and arm pronation (4.75 vs 38.46, p < 0.01). CONCLUSIONS: Bladder penetration during MUS is associated with wrist dorsiflexion and elbow flexion but not internal wrist deviation and arm supination. Attending surgeons exerted control with the wrist and forearm, surgical trainees with the elbow. Our findings have direct implications for MUS teaching.

Social isolation uncovers a circuit underlying context-dependent territory-covering micturition.

The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploited a behavioral paradigm in which mice, depending on strain, social experience, and sensory context, either vigorously cover an arena with small urine spots or deposit urine in a few isolated large spots. We refer to these micturition modes as, respectively, high and low territory-covering micturition (TCM) and find that the presence of a urine stimulus robustly induces high TCM in socially isolated mice. Comparison of the brain networks activated by social isolation and by urine stimuli to those upstream of the PMC identified the lateral hypothalamic area as a potential modulator of micturition modes. Indeed, chemogenetic manipulations of the lateral hypothalamus can switch micturition behavior between high and low TCM, overriding the influence of social experience and sensory context. Our results suggest that both inhibitory and excitatory signals arising from a network upstream of the PMC are integrated to determine context- and social-experience-dependent micturition patterns.

Preliminary Experience with Three Alternative Motion Sensors for 0.55 Tesla MR Imaging.

Due to limitations in current motion tracking technologies and increasing interest in alternative sensors for motion tracking both inside and outside the MRI system, in this study we share our preliminary experience with three alternative sensors utilizing diverse technologies and interactions with tissue to monitor motion of the body surface, respiratory-related motion of major organs, and non-respiratory motion of deep-seated organs. These consist of (1) a Pilot-Tone RF transmitter combined with deep learning algorithms for tracking liver motion, (2) a single-channel ultrasound transducer with deep learning for monitoring bladder motion, and (3) a 3D Time-of-Flight camera for observing the motion of the anterior torso surface. Additionally, we demonstrate the capability of these sensors to simultaneously capture motion data outside the MRI environment, which is particularly relevant for procedures like radiation therapy, where motion status could be related to previously characterized cyclical anatomical data. Our findings indicate that the ultrasound sensor can track motion in deep-seated organs (bladder) as well as respiratory-related motion. The Time-of-Flight camera offers ease of interpretation and performs well in detecting surface motion (respiration). The Pilot-Tone demonstrates efficacy in tracking bulk respiratory motion and motion of major organs (liver). Simultaneous use of all three sensors could provide complementary motion information outside the MRI bore, providing potential value for motion tracking during position-sensitive treatments such as radiation therapy.

Effect of Prewarming on Skin Temperature Changes After Spinal Anesthesia in Transurethral Resection of the Bladder.

PURPOSE: Monitoring of peripheral skin temperature changes is an objective and rapid method to evaluate the success of neuraxial block after spinal anesthesia. The aim of this study is to investigate the effect of prewarming on peripheral temperature changes after the administration of spinal anesthesia. DESIGN: Randomized, prospective, single-blind study. METHODS: In this study, patients scheduled for transurethral resection of the bladder surgery under spinal anesthesia were divided into two groups: those with active prewarming and those without active prewarming. The groups were compared in core and skin temperature changes after administration of spinal anesthesia, length of stay in the postanesthesia care unit, shivering score, and the thermal comfort scale. FINDINGS: A statistically significant difference was found between the groups on time for a 1 °C increase in ankle and toe skin temperatures (P < .001). There was a statistically significant difference between the groups in core temperature measurements (P < .001). When thermal comfort was compared between the groups, a statistically significant difference was found (P < .001). Patients' shivering score (P = .704), and length of stay in the postanesthesia care unit (P = .059) between the groups were similar. CONCLUSIONS: Skin temperature changes in the prewarming group were lower, and this group had a lower rate of increase than the nonprewarming group. Therefore, skin temperature changes in the lower extremity can be used to determine the success of spinal anesthesia in patients who are prewarmed, with the awareness of these differences.

[Biological function of bladder smooth muscle cells regulated by multi-modal biomimetic stress].

Previous studies have shown that growth arrest, dedifferentiation, and loss of original function occur in cells after multiple generations of culture, which are attributed to the lack of stress stimulation. To investigate the effects of multi-modal biomimetic stress (MMBS) on the biological function of human bladder smooth muscle cells (HBSMCs), a MMBS culture system was established to simulate the stress environment suffered by the bladder, and HBSMCs were loaded with different biomimetic stress for 24 h. Then, cell growth, proliferation and functional differentiation were detected. The results showed that MMBS promoted the growth and proliferation of HBSMCs, and 80 cm H 2O pressure with 4% stretch stress were the most effective in promoting the growth and proliferation of HBSMCs and the expression level of α-smooth muscle actin and smooth muscle protein 22-α. These results suggest that the MMBS culture system will be beneficial in regulating the growth and functional differentiation of HBSMCs in the construction of tissue engineered bladder.

Pharmacological Studies on the Ca2+ Influx Pathways in Platelet-Activating Factor (PAF)-Induced Mouse Urinary Bladder Smooth Muscle Contraction.

Platelet-activating factor (PAF) not only acts as a mediator of platelet aggregation, inflammation, and allergy responses but also as a constrictor of various smooth muscle (SM) tissues, including gastrointestinal, tracheal/bronchial, and pregnancy uterine SMs. Previously, we reported that PAF induces basal tension increase (BTI) and oscillatory contraction (OC) in mouse urinary bladder SM (UBSM). In this study, we examined the Ca2+ influx pathways involved in PAF-induced BTI and OC in the mouse UBSM. PAF (10-6 M) induced BTI and OC in mouse UBSM. However, the PAF-induced BTI and OC were completely suppressed by extracellular Ca2+ removal. PAF-induced BTI and OC frequencies were markedly suppressed by voltage-dependent Ca2+ channel (VDCC) inhibitors (verapamil (10-5 M), diltiazem (10-5 M), and nifedipine (10-7 M)). However, these VDCC inhibitors had a minor effect on the PAF-induced OC amplitude. The PAF-induced OC amplitude in the presence of verapamil (10-5 M) was strongly suppressed by SKF-96365 (3 × 10-5 M), an inhibitor of receptor-operated Ca2+ channel (ROCC) and store-operated Ca2+ channel (SOCC), but not by LOE-908 (3 × 10-5 M) (an inhibitor of ROCC). Overall, PAF-induced BTI and OC in mouse UBSM depend on Ca2+ influx and the main Ca2+ influx pathways in PAF-induced BTI and OC may be VDCC and SOCC. Of note, VDCC may be involved in PAF-induced BTI and OC frequency, and SOCC might be involved in PAF-induced OC amplitude.

Simulation of the female pelvic mobility and vesical pressure changes employing fluid-structure interaction method.

INTRODUCTION AND HYPOTHESIS: This study aims to develop a fluid-structural interaction (FSI) method to pinpoint the effects of pressure changes inside the bladder and their impact on the supporting structure and the urethra mobility. METHODS: A physiological model of the nulliparous female pelvis, including the organs, supportive structures, and urine, was developed based on magnetic resonance images. Soft tissues with nonlinear hyperelastic material characteristics were modeled. The Navier-Stokes equations governing the fluid flow within the computational domain (urine) were solved. The urine and soft tissue interactions were simulated by the FSI method. The vesical pressure and its impact on the urethral mobility and supportive structures were investigated during the Valsalva maneuver. Moreover, the simulation results were validated by comparing with a urodynamic test and other research. RESULTS: The results demonstrated that the vesical pressure simulated by the FSI method could predict the nonlinear behavior of the urodynamic test pressure. The urethra retropubic bladder neck and the bladder neck-pubic bone angle changed 58.92% and -55.76%, respectively. The retropubic urethral length distance changed by -48.74%. The error compared to the statistical results of other research is < 5%. CONCLUSIONS: The total deformation and mobility of the urethra predicted by the FSI model were consistent with clinical observations in a subject. The urethra supports dependence on the tissues' mechanical properties, interaction between the tissues, and effect of urine fluid inside the bladder. This simulation effectively depicts the patterns of urethra mobility, which provides a better understanding of the behavior of the pelvic floor.

Application of Machine Learning Algorithms to the Discretization Problem in Wearable Electrical Tomography Imaging for Bladder Tracking.

The article presents the implementation of artificial intelligence algorithms for the problem of discretization in Electrical Impedance Tomography (EIT) adapted for urinary tract monitoring. The primary objective of discretization is to create a finite element mesh (FEM) classifier that will separate the inclusion elements from the background. In general, the classifier is designed to detect the area of elements belonging to an inclusion revealing the shape of that object. We show the adaptation of supervised learning methods such as logistic regression, decision trees, linear and quadratic discriminant analysis to the problem of tracking the urinary bladder using EIT. Our study focuses on developing and comparing various algorithms for discretization, which perfectly supplement methods for an inverse problem. The innovation of the presented solutions lies in the originally adapted algorithms for EIT allowing for the tracking of the bladder. We claim that a robust measurement solution with sensors and statistical methods can track the placement and shape change of the bladder, leading to effective information about the studied object. This article also shows the developed device, its functions and working principle. The development of such a device and accompanying information technology came about in response to particularly strong market demand for modern technical solutions for urinary tract rehabilitation.

Molecular Mechanisms of Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury.

This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder-urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.

[Analysis of surgical complications of reconstructive plastic surgery according to the ClavienDindo classification].

INTRODUCTION: The systematization of surgical complications has long been a serious problem since different types of surgical procedures have specific complications, in addition to general consequences. Created in 1992 and improved in 2004, the Clavien-Dindo classification was successfully validated in surgical centers in different countries and recognized as an important tool for the qualitative assessment of surgical complications. AIM: To improve reconstructive procedures by systematizing complications based on the ClavienDindo classification. MATERIALS AND METHODS: The results of substitution ileocystoplasty in 95 patients with contracted bladder due to tuberculosis and other diseases are presented. In 50 (52.6%) cases, the length of the bowel segment was 30-35 cm (group 1, main), while in 45 patients (47.4%) a segment of 45-60 cm was chosen (group 2, control). RESULTS: Early complications of grade II developed in 11 (22.0%) patients in the group 1 and in 13 (28.9%) in group 2, while grade III in 5 (10.0%) and 6 (13.3%) cases, respectively. Complications of IIIb grade were seen among patients of the main group in 9 (18.0%) cases compared to 12 (26.7%) in the control group. Severe complications of IVa and IVb grades were documented with the same frequency in both groups, in one case each. Complications of V grade (death) were recorded only in the group 2. Late complications were registered in 63 out of 94 patients. In group 1, there were 26 complications (16 somatic and 10 surgical), while in group 2, a total of 37 complications (24 somatic and 13 surgical) were seen, which indicates a significant higher rate in the control group (p<0.05). In group 1, transurethral resection of urethral-enteric anastomosis and ureteral reimplantation were performed less frequently than in group 2, while transurethral resection of the prostate was done with the same frequency. At the same time, percutaneous nephrostomy was required more often in the group 1 (6% vs. 4.5% in the group 2). After intestinal cystoplasty with a shortened fragment of the ileum, the voiding volume was significantly lower but corresponded to the physiological value (more than 150 ml). In this group, there was sufficient capacity of neobladder with a minimum amount of residual urine, effective emptying, satisfactory urinary continence, and low intraluminal pressure, which contributes to the protection of kidneys from reservoir-ureteral-pelvic reflux. The serum chloride level after surgery was 106.2+/-0.4 in the group 1 compared to 109.7+/-0.3 in the group 2, while base excess was -0.93+/-0.3 and -3.4+/-0.65, respectively (p<0.05). CONCLUSION: Early serious postoperative complications according to Clavien-Dindo were registered with approximately the same frequency in both groups, while late complications developed significantly more often in the group 2. The urodynamic parameters of a neobladder formed from ileum segment of 30-35 cm are satisfactory. In addition, a decrease in the length of the intestinal segment prevents the development of hyperchloremic metabolic acidosis.

Spatiotemporal mapping of sensory and motor innervation of the embryonic and postnatal mouse urinary bladder.

The primary function of the urinary bladder is to store urine (continence) until a suitable time for voiding (micturition). These distinct processes are determined by the coordinated activation of sensory and motor components of the nervous system, which matures to enable voluntary control at the time of weaning. Our aim was to define the development and maturation of the nerve-organ interface of the mouse urinary bladder by mapping the organ and tissue distribution of major classes of autonomic (motor) and sensory axons. Innervation of the bladder was evident from E13 and progressed dorsoventrally. Increasing defasciculation of axon bundles to single axons within the muscle occurred through the prenatal period, and in several classes of axons underwent further maturation until P7. Urothelial innervation occurred more slowly than muscle innervation and showed a clear regional difference, from E18 the bladder neck having the highest density of urothelial nerves. These features of innervation were similar in males and females but varied in timing and tissue density between different axon classes. We also analysed the pelvic ganglion, the major source of motor axons that innervate the lower urinary tract and other pelvic organs. Cholinergic, nitrergic (subset of cholinergic) and noradrenergic neuronal cell bodies were present prior to visualization of these axon classes within the bladder. Examination of cholinergic structures within the pelvic ganglion indicated that connections from spinal preganglionic neurons to pelvic ganglion neurons were already present by E12, a time at which these autonomic ganglion neurons had not yet innervated the bladder. These putative preganglionic inputs increased in density prior to birth as axon terminal fields continued to expand within the bladder tissues. Our studies also revealed in numerous pelvic ganglion neurons an unexpected transient expression of calcitonin gene-related peptide, a peptide commonly used to visualise the peptidergic class of visceral sensory axons. Together, our outcomes enhance our understanding of neural regulatory elements in the lower urinary tract during development and provide a foundation for studies of plasticity and regenerative capacity in the adult system.

SKA-31-induced activation of small-conductance calcium-activated potassium channels decreased modulation of detrusor smooth muscle function in a rat model of obesity.

Increased excitability and contractility of detrusor smooth muscle (DSM) cells are associated with overactive bladder (OAB), which is often induced by obesity. Small-conductance Ca2+-activated K+ (SK) channels regulate the excitability and contractility of DSM cells. Selective pharmacological activation of SK channels attenuates hyperpolarization and the decreased relaxation effect in DSM cells in obesity-induced OAB. However, additional data are needed to confirm the regulatory effect of SK channels on the function of DSM cells in obesity-related OAB. The tested hypothesis was that activation of SK channels decreases modulation of DSM function in a rat model of obesity-related OAB. Female Sprague Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD), weighed after 12 weeks, and subjected to urodynamic study, patch-clamp electrophysiology, and isometric tension recording. The average body weight and incidence of OAB were increased in the HFD group. Patch-clamp studies revealed that pharmacological activation of SK channels with SKA-31 had attenuated hyperpolarization of DSM cells. In addition, isometric tension recordings indicated that SKA-31 decreased relaxation of spontaneous phasic contractions of DSM strips in the HFD group. Attenuated function of SK channels increased the excitability and contractility of DSM cells, which contributed to the occurrence of OAB, suggesting that SK channels are potential therapeutic targets for control of OAB.

Lower urinary tract electrical sensory assessment: a systematic review and meta-analysis.

OBJECTIVES: To summarize the current literature on lower urinary tract electrical sensory assessment (LUTESA), with regard to current perception thresholds (CPTs) and sensory evoked potentials (SEPs), and to discuss the applied methods in terms of technical aspects, confounding factors, and potential for lower urinary tract (LUT) diagnostics. METHODS: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline (PubMed), Embase and Scopus were searched on 13 October 2020. Meta-analyses were performed and methodological qualities of the included studies were defined by assessing risk of bias (RoB) as well as confounding. RESULTS: After screening 9925 articles, 80 studies (five randomized controlled trials [RCTs] and 75 non-RCTs) were included, comprising a total of 3732 patients and 692 healthy subjects (HS). Of these studies, 61 investigated CPTs exclusively and 19 reported on SEPs, with or without corresponding CPTs. The recording of LUTCPTs and SEPs was shown to represent a safe and reliable assessment of LUT afferent nerve function in HS and patients. LUTESA demonstrated significant differences in LUT sensitivity between HS and neurological patients, as well as after interventions such as pelvic surgery or drug treatments. Pooled analyses showed that several stimulation variables (e.g. stimulation frequency, location) as well as patient characteristics might affect the main outcome measures of LUTESA (CPTs, SEP latencies, peak-to-peak amplitudes, responder rate). RoB and confounding was high in most studies. CONCLUSIONS: Preliminary data show that CPT and SEP recordings are valuable tools to more objectively assess LUT afferent nerve function. LUTESA complements already established diagnostics such as urodynamics, allowing a more comprehensive patient evaluation. The high RoB and confounding rate was related to inconsistency and inaccuracy in reporting rather than the technique itself. LUTESA standardization and well-designed RCTs are crucial to implement LUTESA as a clinical assessment tool.