Efficient Voiding Research Articles

Recent Developments in On-Demand Voiding Therapies.

One cannot survive without regularly urinating and defecating. People with neurologic injury (spinal cord injury, traumatic brain injury, stroke) or disease (multiple sclerosis, Parkinson's disease, spina bifida) and many elderly are unable to voluntarily initiate voiding. The great majority of them require bladder catheters to void urine and "manual bowel programs" with digital rectal stimulation and manual extraction to void stool. Catheter-associated urinary tract infections frequently require hospitalization, whereas manual bowel programs are time consuming (1 to 2 hours) and stigmatizing and cause rectal pain and discomfort. Laxatives and enemas produce defecation, but onset and duration are unpredictable, prolonged, and difficult to control, which can produce involuntary defecation and fecal incontinence. Patients with spinal cord injury (SCI) consider recovery of bladder and bowel function a higher priority than recovery of walking. Bladder and bowel dysfunction are a top reason for institutionalization of elderly. Surveys indicate that convenience, rapid onset and short duration, reliability and predictability, and efficient voiding are priorities of SCI individuals. Despite the severe, unmet medical need, there is no literature regarding on-demand, rapid-onset, short-duration, drug-induced voiding therapies. This article provides in-depth discussion of recent discovery and development of two candidates for on-demand voiding therapies. The first, [Lys3,Gly8,-R-γ-lactam-Leu9]-NKA(3-10) (DTI-117), a neurokinin2 receptor agonist, induces both urination and defecation after systemic administration. The second, capsaicin (DTI-301), is a transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor agonist that induces defecation after intrarectal administration. The review also presents clinical studies of a combination drug therapy administered via iontophoresis and preclinical studies of neuromodulation devices that induce urination and defecation. SIGNIFICANCE STATEMENT: A safe and effective, on-demand, rapid-onset, short-duration, drug-induced, voiding therapy could eliminate or reduce need for bladder catheters, manual bowel programs, and colostomies in patient populations that are unable to voluntarily initiate voiding. People with spinal injury place more importance on restoring bladder and bowel control than restoring their ability to walk. This paradigm-changing therapy would reduce stigmatism and healthcare costs while increasing convenience and quality of life.

Real-time monitoring of self-sensing cementitious composite incorporating hybrid silicon carbide and graphite for enhanced structural health monitoring

This manuscript presents a comprehensive exploration of Silicon Carbide-Graphite Cement Composites (SCGCCs) by investigating their mechanical, electrical, and self-sensing properties. The study systematically varies SiC and graphite content, leading to remarkable insights. In terms of mechanical strength, specimens S50G1 and S50 stand out, exhibiting impressive enhancements of 15.6 % and 9.8 % in compressive strength, respectively, showcasing the pivotal role of particle content in bolstering structural integrity. Electrical resistivity analysis uncovers a percolation threshold at 25 % SiC and 2 % graphite, resulting in a substantial 97 % reduction in resistivity. This critical finding underscores the delicate balance required for optimal conductive networks within the composite material. The self-sensing capabilities of SCGCCs under flexural stress reveal a synergistic effect between SiC and graphite, with specimen S25G2 displaying the lowest voltage drop. The compressive stress analysis unveils a distinctive conductive path reconstruction behavior, offering valuable insights into the material's response to varying stress levels. Advanced CT scan porosity analysis further refines our understanding, indicating a significant reduction in porosity from 4.2 % to 3.1 % in specimen S25. Furthermore, specimens with lower graphite and SiC proportions exhibit efficient void compaction, resulting in a well-integrated microstructure with porosity as low as 2.5 %. These findings not only contribute to the fundamental understanding of SCGCCs but also offer practical applications in smart materials and structural health monitoring. Moreover, the inherent advantage of real-time monitoring within the context of smart mortar extends to the prognostication of an advanced warning signal for impeding the complete failure of the smart concrete matrix.

Treating Neurogenic Lower Urinary Tract Dysfunction in Chronic Spinal Cord Injury Patients-When Intravesical Botox Injection or Urethral Botox Injection Are Indicated.

Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further deteriorate the patient's QoL. Botulinum toxin A (BoNT-A) injection within the detrusor muscle or urethral sphincter yields satisfactory therapeutic effects for treating urinary incontinence or facilitating efficient voiding; however, adverse effects inevitably follow its therapeutic efficacy. It is important to weigh the merits and demerits of BoNT-A injection for LUTS and provide an optimal management strategy for SCI patients. This paper summarizes different aspects of the application of BoNT-A injection for lower urinary tract dysfunctions in SCI patients and provides an overview of the benefits and drawbacks of this treatment.

MP60-08 COMPARISON OF LOWER URINARY TRACT DYSFUNCTION AFTER SPINAL CORD INJURY (SCI) BETWEEN FEMALE AND MALE MICE

You have accessJournal of UrologyCME1 Apr 2023MP60-08 COMPARISON OF LOWER URINARY TRACT DYSFUNCTION AFTER SPINAL CORD INJURY (SCI) BETWEEN FEMALE AND MALE MICE Mamoru Hashimoto, Kang Jun Cho, Stephanie L Daugherty, PA Pittsburgh, Nobutaka Shimizu, Pradeep Tyagi, Akihide Hirayama, Hirotsugu Uemura, Jonathan M Beckel, Sergei Karnup, and Naoki Yoshimura Mamoru HashimotoMamoru Hashimoto More articles by this author , Kang Jun ChoKang Jun Cho More articles by this author , Stephanie L DaughertyStephanie L Daugherty More articles by this author , PA PittsburghPA Pittsburgh More articles by this author , Nobutaka ShimizuNobutaka Shimizu More articles by this author , Pradeep TyagiPradeep Tyagi More articles by this author , Akihide HirayamaAkihide Hirayama More articles by this author , Hirotsugu UemuraHirotsugu Uemura More articles by this author , Jonathan M BeckelJonathan M Beckel More articles by this author , Sergei KarnupSergei Karnup More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003318.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In humans, voiding occurs during synergic relaxation of the external urethral sphincter (EUS), and SCI induces detrusor-sphincter dyssynergia (DSD) shown by tonic EUS contraction during voiding. However, EUS bursting activity is known to be an important mechanism for efficient voiding in spinal intact (SI) and SCI rats while such data are less available in mice. Thus, we evaluated gender-specific EUS function during voiding in male and female mice with or without SCI. METHODS: C57BL/6N mice at 9-10-weeks old were used. SCI mice underwent complete transection of the Th8-9 spinal cord. Six weeks after SCI, cystometrograms (CMGs) and EUS- electromyography (EMG) were performed under an awake condition. Thereafter, L6-S1 dorsal root ganglia (DRG) were harvested to evaluate the transcripts of TRPV1 and Piezo2 using qPCR. RESULTS: In female SI mice, voiding occurred during an EUS relaxation period. Female SCI mice voided urine during notch like reductions in bladder pressure, which corresponded to EMG signal reduction periods during tonic EMG activity (DSD). On the other hand, male SI and SCI mice voided during EUS bursting activity characterized by alternating active and silent phases of EMG activity, with the longer active phase and low voiding efficiency in SCI vs. SI mice (Table and Figure). The mRNA levels of TRPV1 and Piezo2 in L6-S1 DRG were significantly higher in SCI male mice (n=4) and female mice (n=4) vs. SI mice (n=4). CONCLUSIONS: Lower urinary tract function during the voiding phase was different between male and female mice. Female SI mice, in which voiding occurs during EUS relaxation, and female SCI mice, which exhibit DSD with periodic EUS relaxations, seem to be more suitable for the study of SCI-induced EUS dysfunction in humans, compared to SI and SCI male mice that exhibit EUS bursting activity during voiding. Source of Funding: NIH R01DK129194 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e846 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mamoru Hashimoto More articles by this author Kang Jun Cho More articles by this author Stephanie L Daugherty More articles by this author PA Pittsburgh More articles by this author Nobutaka Shimizu More articles by this author Pradeep Tyagi More articles by this author Akihide Hirayama More articles by this author Hirotsugu Uemura More articles by this author Jonathan M Beckel More articles by this author Sergei Karnup More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF downloadLoading ...

Initiating daily acute intermittent hypoxia (dAIH) therapy at 1-week after contusion spinal cord injury (SCI) improves lower urinary tract function in rat

Spinal cord injury (SCI) above the level of the lumbosacral spinal cord produces lower urinary tract (LUT) dysfunction, resulting in impairment of urine storage and elimination (voiding). While spontaneous functional recovery occurs due to remodeling of spinal reflex micturition pathways, it is incomplete, indicating that additional strategies to further augment neural plasticity following SCI are essential. To this end, acute intermittent hypoxia (AIH) exposure has been proposed as a therapeutic strategy for improving recovery of respiratory and other somatic motor function following SCI; however, the impact of AIH as a therapeutic intervention to improve LUT dysfunction remains to be determined. Therefore, we examined the effects of daily AIH (dAIH) on both spontaneous micturition patterns and reflex micturition event (rME) behaviors in adult female Sprague-Dawley rats with mid-thoracic moderate contusion SCI. For these experiments, dAIH gas exposures (five alternating 3 min 12% O2 and 21% O2 episodes) were delivered for 7 consecutive days beginning at 1-week after SCI, with awake micturition patterns being evaluated weekly for 2–3 sessions before and for 4 weeks after SCI and rME behaviors elicited by continuous infusion of saline into the bladder being evaluated under urethane anesthesia at 4-weeks after SCI; daily normoxia (dNx; 21% O2 episodes) served as a control. At 1-week post-SCI, both an areflexic phenotype (i.e., no effective voiding events) and a functional voiding phenotype (i.e., infrequent voiding events with large volumes) were observed in spontaneous micturition patterns (as expected), and subsequent dAIH, but not dNx, treatment led to recovery of spontaneous void frequency pattern to pre-SCI levels; both dAIH- and dNx-treated rats exhibited slightly increased void volumes. At 4-weeks post-SCI, rME behaviors showed increased effectiveness in voiding in dAIH-treated (compared to dNx-treated) rats that included an increase in both bladder contraction pressure (delta BP; P = 0.014) and dynamic voiding efficiency (P = 0.018). Based on the voiding and non-voiding bladder contraction behaviors (VC and NVC, respectively) observed in the BP records, bladder dysfunction severity was classified into mild, moderate, and severe phenotypes, and while rats in both treatment groups included each severity phenotype, the primary phenotype observed in dAIH-treated rats was mild and that in dNx-treated rats was moderate (P = 0.044). Taken together, these findings suggest that 7-day dAIH treatment produces beneficial improvements in LUT function that include recovery of micturition pattern, more efficient voiding, and decreased NVCs, and extend support to the use of dAIH therapy to treat SCI-induced LUT dysfunction.

Weekly Acute Intermittent Hypoxia as a Strategy to Restore Spontaneous Micturition Patterns in Awake Rats with Moderate Contusion SCI: Therapeutic Efficacy and Time Course

Both daily and weekly exposures to neuroplasticity‐inducing acute intermittent hypoxia (AIH) have been proposed as non‐invasive therapeutic paradigms to improve respiratory and motor function following spinal cord injury (SCI). SCI can also lead to bladder dysfunction that results in inefficient voiding and urine retention that are associated with a high degree of morbidity and a poor quality of life. Our ongoing preclinical studies have been investigating the therapeutic potential of AIH as a strategy to promote restoration of lower urinary tract (LUT; bladder) function in SCI. We have found that in rats with moderate contusion SCI, exposure to a single episode of AIH results in an immediate short‐term reduction in non‐voiding bladder contractions and induction of more efficient voiding while exposure to daily AIH for 7 consecutive days leads to sustained beneficial improvements in both spontaneous voiding pattern and reflex bladder function that persist for at least 2 weeks following completion of therapy. Here, we investigated the impact of weekly AIH (wAIH) exposures composed of five alternating 3‐min episodes of 12% O2 and 21% O2 on micturition patterns in adult female SD rats with mid‐thoracic moderate contusion SCI; weekly normoxia (wNx; 21% O2) exposures in a separate group of SCI rats served as a control. Overnight (awake) micturition chamber (MC) measurements were used to evaluate voiding patterns weekly before and for 10 weeks after SCI, with wAIH and wNx exposures being administered 3x per week for 4 weeks beginning at 4 weeks after SCI. Data acquired between 9:00 PM and 6:00 AM were used to quantify voiding pattern features (i.e., number of voids (#); inter‐void interval (IVI)) and voiding volumes (total volume; volume per void), with weekly pre‐SCI MC measurements averaged and set to 100% for each rat. To evaluate the magnitudes of the deficits and progression of recovery of micturition pattern behaviors, weekly post‐SCI MC measurements were compared to their pre‐SCI level. For both groups of rats, the voiding pattern at 1‐week post‐SCI was characterized by infrequent voiding events with large volumes (~50% decrease in number of voids; ~100% increase in IVI; ~4 fold increase in volume per void), and by 4‐weeks post‐SCI, similar limited partial spontaneous recovery of voiding pattern was noted in both groups, albeit deficits were still present. Subsequent wAIH treatment led to further improvements in voiding pattern, such that following 2‐weeks of wAIH treatment, the number of voids and IVI were restored to pre‐SCI levels, but with a sustained elevation in volume per void. The restoration of voiding pattern and elevated volume per void persisted for the remaining MC measurements, including those obtained at 2‐weeks following completion of wAIH treatment. In contrast, no further recovery of any voiding pattern features was observed in wNx‐treated rats. These observations suggest that wAIH therapy improves SCI‐induced bladder dysfunction, leading to restoration of spontaneous micturition patterns in awake rats with SCI.

Weekly Acute Intermittent Hypoxia Elicits Sustained Beneficial Improvements in Reflex Bladder Function in Rats with Moderate Contusion SCI

Acute intermittent hypoxia (AIH) administered either as daily or weekly therapy has been shown to improve both respiratory and motor function in preclinical and clinical studies in spinal cord injury (SCI). SCI can also severely impact bladder function, leading to problems with urine storage and emptying of the bladder that include detrusor overactivity, decreased voiding efficiency, and increased residual volume. Ongoing work in our laboratory has been evaluating the impact of AIH treatments delivered as either a single episode or daily episodes for 7 consecutive days as a strategy to promote improvements in bladder function in rats with moderate contusion SCI. In our studies, a single AIH treatment results in immediate short‐term reductions in bladder overactivity (i.e., non‐voiding bladder contractions, NVCs) and induction of more efficient voiding, while daily (7‐d) AIH treatments result in sustained similar improvements and restoration of urination pattern. In the current study, we investigated the effects of weekly AIH (wAIH) treatment administered 3x per week for 4 weeks on SCI‐induced bladder dysfunction in adult female SD rats with mid‐thoracic moderate contusion SCI. wAIH treatment consisted of five alternating 3‐min episodes of 12% O2 and 21% O2 and was initiated 4 weeks after SCI; weekly normoxia (wNx; 21% O2 episodes using the same timing) served as a gas delivery control. Prior to initiating weekly gas treatments, the magnitude of SCI‐induced deficits and progression of spontaneous recovery of both hindlimb motor function (BBB scores) and lower urinary tract (LUT) function (manual expression of urine volumes during post‐operative care) were assessed. These measurements revealed that the deficits and initial stages of recovery were similar in rats assigned to both treatment groups. 2 weeks after completion of the weekly gas treatments (which corresponds to 10 weeks after SCI), reflex bladder function was assessed during bladder filling and voiding in urethane‐anesthetized rats. For these experiments, reflex micturition events (rMEs) were elicited by continuous infusion of saline (0.04‐0.09 ml/min) into the bladder while intravesical bladder pressure (BP) was continuously measured. We found that in nearly all of the wAIH‐treated rats (~86%), the BP record during filling was characterized by an almost complete absence of NVCs per voiding contraction (VC), while in nearly all of the wNx‐treated rats (~80%), the BP record during filling was characterized by a severe degree of LUT dysfunction that included 3‐10 NVCs preceding each VC. Comparisons of VC features between these groups of rats revealed that wNx‐treated rats exhibited long inter‐contraction intervals (ICI; despite higher infusion rates; P=0.0326) and correspondingly larger fill (P=0.0187) and void (P=0.0029) volumes while wAIH‐treated rats exhibited shorter contraction duration (P=0.0381) and contraction area (P=0.0110). These findings suggest that wAIH treatment elicits sustained beneficial improvements in rME behaviors, resulting in a mild degree of LUT dysfunction in rats with chronic SCI.

Fast and efficient void detection in carbonates by combined ERT and borehole data: A case study from Chania Airport in Greece

A typical approach for karstic carbonate risk assessment is to utilize integrated geophysical research and calibrate the data with either pre- or postmeasurement acquisition borehole information. Here, we present a case study of a time-demanding investigation on the detection of subsurface areas prone to new building foundation stability at a site rich in karstic structures belonging to the Trypali Unit (Triassic-Jurassic). During excavation and construction to expand the airport in Chania, Crete, Greece, a large karstic void was revealed, which triggered an alert that led to an immediate work stoppage and the demand for an investigation of the subsurface of the whole area. The scope was to detect weak zones or voids larger than 0.5 m with a fast and timely approach because the costs of a long project stop are high. To meet the time demands with an efficient approach, we utilized the electrical resistivity tomography method, which guided a fast postacquisition borehole program and was supplemented by in-borehole video recordings, aiding in the direct detection of karstic structures. The 3D inversion of the electrical data provided electrical resistivity tomography images of the subsurface, which characterized the area as highly karstified and fractured and detected voids with sizes ranging from 0.5 to 6 m.

Load Transfer Efficiency Analysis and Void Evaluation of Composite Pavement Cement Concrete Slab

The void at the bottom of a cement concrete slab is a common problem of composite pavements. It is of great significance to evaluate the spring stiffness, void size, and soil base elastic modulus at the bottom of cement concrete slab timely and accurately for the maintenance and guarantee of the pavement performance. In this paper, the composite pavement at a joint is modeled and the load transfer mechanism is realized by using spring groups for simulating the dowels that connect the two slabs of the joint. A database is established based on a large number of simulation results of joint load transfer efficiency and voids and the changing law of load transfer efficiency of cement concrete slab reveals their relationship. Taking into consideration the spring stiffness, void size, and soil base elastic modulus, the void evalua\tion method of composite pavement cement concrete slab is established by using back propagation neural network algorithm. The results show that the void evaluation method can provide the void determination map with two parameters. The values of the two parameters can be determined by the deflection basin. After querying the Atlas, the void determination can be more accurate. The research results provide scientific guidance for the void identification of the composite pavement and can effectively extend the service life of the pavement.

An Efficient Void Aware Framework for Enabling Internet of Underwater Things

The Internet of Underwater Things (IoUT) is an emerging area in marine science and engineering. It has witnessed significant research and development attention from both academia and industries due to its growing underwater use cases in oceanographic data collection, pollution monitoring, seismic monitoring, tactical surveillance, and assisted navigation for waterway transport. Information dissemination in the underwater network environment is very critical considering network dynamism, unattainable nodes, and limited resources of the tiny IoUT devices. Existing techniques are majorly based on location-centric beacon messages, which results in higher energy consumption, and wastage of computing resources in tiny IoUT devices. Towards this end, this paper presents an efficient void aware (EVA) framework for information dissemination in IoUT environment. Network architecture is modeled considering potential void region identification in the underwater network environment. An efficient void aware (EVA) information dissemination framework is proposed focusing on detecting void network region, and intelligent void aware data forwarding. The comparative performance evaluation attests to the benefits of the proposed framework in terms of energy consumption, network lifetime, packet delivery ratio, and end-to-end delay for information dissemination in IoUT.

Age is associated with reduced urethral pressure and afferent activity in rat.

Age‐related changes in the lower urinary tract (LUT) can affect the coordination of reflexes and increase the incidence of bladder disorders in elderly. This study examines the age‐related loss of urethral signaling capability by measuring the afferent activity directly. We find that less urethral pressure develops in response to fluid flow in old rats compared to young rats and that pressure and flow evoke less urethral afferent activation. These findings are consistent with our previous study demonstrating that the urethra‐to‐bladder reflex, which is required for efficient voiding, becomes weaker with age. We measured the pudendal afferent response in young (4–7 months) and old (18–24 months) rats to fluid flow in the urethra across a range of flow rates. We used paraffin embedding and hematoxylin and eosin staining to quantify age‐related changes in the sensory branch of the pudendal nerve. Urethral afferent signaling in response to the same urethral flow rates was weaker in older animals. That is, the sensitivity of urethra afferents to flow decreased with age, and higher flow rates were required in older animals to recruit urethra afferents. There was also a reduction in the myelin thickness of pudendal afferents in old rats, which is a possible contributing factor to the sensory activity. Furthermore, the same flow rates evoked less pressure in the urethras of old animals, indicating there is an age‐related change of the urethral tissue that reduces the pressure stimulus to which these afferents respond. These results help characterize the underlying changes in LUT system with age.

Building Efficient Ion Pathway in Highly Densified Thick Electrodes with High Gravimetric and Volumetric Energy Densities

A common practice in thick electrode design is to increase porosity to boost charge transport kinetics. However, a high porosity offsets the advantages of thick electrodes in both gravimetric and volumetric energy densities. Here we design a freestanding thick electrode composed of highly densified active material regions connected by continuous electrolyte-buffering voids. By wet calendering of the phase-inversion electrode, the continuous compact active material region and continuous ion transport network are controllably formed. Rate capabilities and cycling stability at high LiFePO4 loading of 126 mg cm-2 were achieved for the densified cathode with porosity as low as 38%. The decreased porosity and efficient void utilization enable high gravimetric/volumetric energy densities of 330 Wh kg-1 and 614 Wh L-1, as well as improved power densities. The versatility of this method and the industrial compatible "roll-to-roll" fabrication demonstrate an important step toward the practical application of thick electrodes.

Daily acute intermittent hypoxia therapy 1‐week after moderate contusion spinal cord injury improves lower urinary tract function in rats

There is an increasing interest in the use of non-invasive acute intermittent hypoxia (AIH) as a therapeutic intervention to improve respiratory and locomotor function in spinal cord injury (SCI). SCI, however, also significantly disrupts normal bladder function, leading to detrusor overactivity, decreased voiding efficiency, and increased residual volume. Ongoing studies in our laboratory investigating the effects of AIH exposure in rats as a strategy for improving lower urinary tract (LUT) function following mid-thoracic SCI indicate that a single bout of AIH decreases the incidence of non-voiding bladder contractions (NVCs) and increases voiding efficiency. In the current study, we begin to evaluate the potential for AIH to be used as a therapy for inducing long-lasting improvements in SCI-induced LUT dysfunction. To accomplish this, we examined the effects of daily AIH (dAIH) administered for 7 consecutive days on both spontaneous awake micturition patterns and reflex micturition event (rME) behaviors in adult female Sprague-Dawley rats with mid-thoracic moderate contusion (200 kdyn) SCI. For these experiments, dAIH composed of five alternating 3-min exposures of hypoxia (12% O2) and normoxia (21% O2) was initiated 1-week after SCI, with awake micturition patterns being evaluated by overnight metabolic chamber measurements weekly for 2-3-weeks before and 4 weeks after SCI and rME behaviors elicited by continuous infusion of saline (0.04-0.09 ml/min) into the bladder being evaluated by cystometry at 4-weeks after SCI; daily normoxia (dNx; 21% O2 episodes) served as a control. The impact of SCI on hindlimb motor and LUT function prior to initiating dAIH or dNx treatment was evaluated using BBB scores and manually expressed urine volumes during post-operative care, and these measurements revealed that deficits and initial stages of recovery were similar (as expected) in both treatment groups. Serial metabolic chamber measurements in both dAIH- and dNx-treated rats that exhibited functional voids at 1-week post-SCI demonstrated that most rats exhibited some degree of functional recovery of micturition pattern behaviors. Only dAIH-treated rats, however, exhibited a recovery of void frequency pattern (i.e., number of voids and inter-void interval)to pre-SCI levels albeit with slightly increased void volumes; dNx-treated rats also had increased void volumes. Intravesical bladder pressure (BP) measurements during terminal cystometry experiments in urethane-anesthetized (1.4 g/kg) rats revealed that dAIH-treated rats exhibited a decreased incidence of NVCs and that voiding contractions had increased delta BP (peak BP-minimum BP) and dynamic voiding efficiency (void volume/fill volume) compared to dNx-treated rats. Taken together, these findings suggest that dAIH treatment produces beneficial improvements in LUT function lasting at least two weeks that include more efficient voiding and decreased NVCs, and further support the use of dAIH therapy to treat SCI-induced LUT dysfunction.

Restoring both continence and micturition after chronic spinal cord injury by pudendal neuromodulation

Neurogenic bladder management after spinal cord injury (SCI) is very challenging. Daily urethral catheterization is most commonly used to empty the bladder, which causes frequent infections of the lower urinary tract. This study reports a novel idea to restore both continence and micturition after SCI by an implantable pudendal nerve stimulator (PNS). The PNS was surgically implanted in four cats with complete SCI at T9-T10 spinal level and tested weekly for 13–14 weeks under awake conditions. These chronic SCI cats consistently exhibited large residual bladder volumes (average 40–50 ml) due to their inability to void efficiently, while urine leakage also occurred frequently. The PNS which consisted of stimulating the pudendal nerve at 20–30 Hz to trigger a spinal reflex bladder contraction and at the same time blocking the pudendal nerves bilaterally with 10 kHz stimulation to relax the external urethral sphincter and reduce the urethral outlet resistance successfully induced highly efficient (average 80–100%), low pressure (<50 cmH2O) voiding. The PNS at 5 Hz also promoted urine storage by inhibiting reflex bladder activity and increasing bladder capacity. At the end of 14-week chronic testing, low pressure efficient voiding induced by PNS was further confirmed under anesthesia by directly measuring voiding pressure using a bladder catheter inserted through the bladder dome. This study demonstrated the efficacy and safety of the PNS in awake chronic SCI cats, suggesting that a novel neuroprosthesis can be developed for humans to restore bladder function after SCI by stimulating and/or blocking the pudendal nerves.

A general framework for automatic closed-loop control of bladder voiding induced by intraspinal microstimulation in rats

Individuals with spinal cord injury or neurological disorders have problems in voiding function due to the dyssynergic contraction of the urethral sphincter. Here, we introduce a closed-loop control of intraspinal microstimulation (ISMS) for efficient bladder voiding. The strategy is based on asynchronous two-electrode ISMS with combined pulse-amplitude and pulse-frequency modulation without requiring rhizotomy, neurotomy, or high-frequency blocking. Intermittent stimulation is alternately applied to the two electrodes that are implanted in the S2 lateral ventral horn and S1 dorsal gray commissure, to excite the bladder motoneurons and to inhibit the urethral sphincter motoneurons. Asynchronous stimulation would lead to reduce the net electric field and to maximize the selective stimulation. The proposed closed-loop system attains a highly voiding efficiency of 77.2–100%, with an average of 91.28 ± 8.4%. This work represents a promising approach to the development of a natural and robust motor neuroprosthesis device for restoring bladder functions.

Frontiers in the Clinical Applications of Botulinum Toxin A as Treatment for Neurogenic Lower Urinary Tract Dysfunction.

Patients with neurogenic lower urinary tract dysfunction (NLUTD) experience urinary incontinence with or without difficult urination, which might promote recurrent urinary tract infection (UTI) and exacerbate upper urinary tract function. Nonetheless, appropriate bladder management has been shown to reduce urological complications and improve quality of life. In addition to pharmacological therapy and surgical intervention, botulinum toxin A (BoNT-A) has been widely utilized in NLUTD. The therapeutic efficacy of detrusor BoNT-A injections for neurogenic detrusor overactivity due to spinal cord injury (SCI), multiple sclerosis, or other central nervous system lesions, such as cerebrovascular accident, Parkinson disease, early dementia, and pediatric NLUTD due to myelomeningocele, has been well established, with repeated BoNT-A injections every 6 to 9 months being necessary to maintain its therapeutic effects. Urethral BoNT-A injection can decrease urethral sphincter resistance and facilitate efficient voiding in patients with NLUTD who wish to preserve self-voiding. Detrusor BoNT-A injection can also decrease the occurrence of autonomic dysreflexia in patients with SCI, even after failed augmentation enterocystoplasty, with additional benefits including reduced UTI episodes and preserved renal function with repeated injections. However, this treatment does have some side effects. Complete informed consent for BoNT-A injection therapy with full disclosure of its potential complications should therefore be obtained before this procedure is undertaken.

Application of plasma cleaning process in MEMS filter micro-assembly

To solve the problems of low efficiency and high void rate in the process of the MEMS filter (die) attach and increase the strength of wire bonding between the die and microwave circuit board, plasma cleaning process was introduced in the micro-assembly process of the MEMS filter switch module. The spreading area of the solder melted on the copper was analyzed before and after the plasma cleaning process. Process parameters including plasma flow, radio frequency time and radio frequency power were optimized by the orthogonal test. It is demonstrated that the plasma cleaning process is effective to decrease the void rates in die attach and enhance the wire bonding strength, thus improve the reliability of the MEMS filter module micro-assembly.

Voiding Behavior and Efferent Bladder Function Altered in Mice Following Social Defeat but Not Witness Trauma.

Psychological stress is associated with bladder dysfunction, however, the local bladder mechanisms affected are not well understood. This study aimed to determine how psychological stress, caused by social defeat or witness trauma, affects voiding behavior and bladder function. Pairs of male C57Bl/6J mice were placed in a custom-made plexiglass chamber with an aggressor ARC(S) mouse for 1 h/day for 10 days. The social defeat mouse was in physical contact with the aggressor, while the witness was physically separated but could observe interactions between its cage-mate and the aggressor. Age matched control pairs were used for comparison. Voiding analysis was conducted periodically over the 10 days. An ex vivo whole bladder preparation was used to assess functional changes after the period of stress. Plasma corticosterone levels were significantly increased by both social defeat and witness trauma stress when compared to unstressed controls. Voiding analysis revealed a significant decrease in voiding frequency in the social defeat group compared to control animals, indicating an altered voiding phenotype. Witness trauma did not alter voiding behavior. Bladder contractile responses to cholinergic stimulation were not significantly altered in either stress group, nor was relaxation to the beta-adrenoceptor agonist isoprenaline. However, nerve evoked contractile responses were significantly increased at all frequencies in bladders from social defeat but not witness trauma mice. Purinergic contractile responses were also significantly enhanced in this group. Social defeat also resulted in increased urothelial acetylcholine release during bladder distension, with no change in ATP release. In conclusion, functional bladder changes are dependent upon stressor type. Enhanced urothelial acetylcholine may desensitize bladder sensory nerves, which, coupled with more efficient voiding contractions due to enhanced nerve-mediated and purinergic detrusor responses, may account for the altered voiding phenotype observed. This study reports a male model of social defeat stress with reduced urinary frequency, with no voiding changes observed in the witness.

Propriospinal Neurons of L3-L4 Segments Involved in Control of the Rat External Urethral Sphincter

Coordination of activity of external urethral sphincter (EUS) striated muscle and bladder (BL) smooth muscle is essential for efficient voiding. In this study we examined the morphological and electrophysiological properties of neurons in the L3/L4 spinal cord (SC) that are likely to have an important role in EUS-BL coordination in rats. EUS-related SC neurons were identified by retrograde transsynaptic tracing following injection of pseudorabies virus (PRV) co-expressing fluorescent markers into the EUS of P18-P20 male rats. Tracing revealed not only EUS motoneurons in L6/S1 but also interneurons in lamina X of the L6/S1 and L3/L4 SC. Physiological properties of fluorescently labeled neurons were assessed during whole-cell recordings in SC slices followed by reconstruction of biocytin-filled neurons. Reconstructions of neuronal processes from transverse or longitudinal slices showed that some L3/L4 neurons have axons projecting toward and into the ventro-medial funiculus (VMf) where axons extended caudally. Other neurons had axons projecting within laminae X and VII. Dendrites of L3/L4 neurons were distributed within laminae X and VII. The majority of L3/L4 neurons exhibited tonic firing in response to depolarizing currents. In transverse slices focal electrical stimulation (FES) in the VMf or in laminae X and VII elicited antidromic axonal spikes and/or excitatory synaptic responses in L3/L4 neurons; while in longitudinal slices FES elicited excitatory synaptic inputs from sites up to 400 μm along the central canal. Inhibitory inputs were rarely observed. These data suggest that L3/L4 EUS-related circuitry consists of at least two neuronal populations: segmental interneurons and propriospinal neurons projecting to L6/S1.

Low pressure voiding induced by a novel implantable pudendal nerve stimulator.

To validate the functionality of an implantable pudendal nerve stimulator under development for Food and Drug Administration approval to restore bladder function after spinal cord injury. In nine cats under anesthesia, two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves and one bipolar cuff electrode was implanted on the right pudendal nerve central to the tripolar cuff electrode. The pudendal nerve stimulator was implanted subcutaneously on the left lower back along the lumbosacral spine and connected to the cuff electrodes. In five cats, a double lumen catheter was inserted into the bladder through the urethra to infuse saline and measure bladder pressure and another catheter was inserted into the distal urethra to perfuse and measure the back pressure caused by urethral contraction. In four cats, a bladder catheter was inserted into the bladder dome and the urethra was left open so that voiding could occur without urethral outlet obstruction. The implantable pudendal nerve stimulator was controlled wirelessly and successfully provided the required stimulation waveforms to different cuff electrodes. Pudendal nerve stimulation (PNS) at 5 Hz increased bladder capacity to about 200% of control capacity. PNS at 20 to 30 Hz induced large (80-100 cmH2 O) bladder contractions under isovolumetric conditions. When combined with ipsilateral or bilateral pudendal nerve block induced by 6 to 10 kHz stimulation, PNS at 20 to 30 Hz elicited low pressure (<40 cmH 2 O) efficient (70%) voiding. The implantable stimulator generated the required stimulation waveforms and successfully induced low pressure efficient voiding in anesthetized cats.