Why are pediatric urologists unable to predict renal deterioration using urodynamics? A focused narrative review of the shortcomings of the literature.

In this focused narrative review we set out to review the current literature addressing the utilization of UDS in patients with spina bifida (SB). We specifically analyzed 6 urodynamic parameters and their roles as predictors of upper tract deterioration in pediatric SB patients. The material available did not allow a systematic analysis or the usage of metanalysis methodology, due to the predominance of small retrospective cohorts, and high heterogeneity. We identified 10 retrospective chart reviews that met our study criteria. The results of each of these papers, as well as other studies deemed relevant to the discussion, are included in our narrative review of the literature. We summarize the current literature, offer explanations for divergences in opinion, and identify future research directions and emerging solutions with a focus on machine learning.

Accelerated resolution therapy and a thematic approach to military experiences in US Special Operations Veterans.

Accelerated Resolution Therapy (ART) is an emerging therapeutic intervention that has demonstrated effectiveness in treating post-traumatic stress, anxiety and depression. The ART protocol aligns with first-line trauma-focused psychotherapies and clinical guides in the USA and UK. This review addresses previous ART research that includes members of US Special Operations Forces. Observations from that research has led to a thematic conceptualisation of trauma through ART interventions. These include three clusters of traumatic memories and several themes relevant to individual distress but not necessarily symptoms that meet diagnostic criteria for PTSD. ART represents a movement in treatment away from the symptoms, to the individuals' story. Not only the story of an event, but how that experience becomes incorporated into one's sense of identity. The themes identified (and treated with ART) appear to have broader application to the entirety of one's military experience, not just PTSD. These themes may be helpful in directing treatment and may help to focus on significant aspects of service not traditionally associated with PTSD. Theoretically, some of these areas may have protective implications in suicide.

Local negative permittivity and topological phase transition in polar skyrmions.

Topological solitons such as magnetic skyrmions have drawn attention as stable quasi-particle-like objects. The recent discovery of polar vortices and skyrmions in ferroelectric oxide superlattices has opened up new vistas to explore topology, emergent phenomena and approaches for manipulating such features with electric fields. Using macroscopic dielectric measurements, coupled with direct scanning convergent beam electron diffraction imaging on the atomic scale, theoretical phase-field simulations and second-principles calculations, we demonstrate that polar skyrmions in (PbTiO3)n/(SrTiO3)n superlattices are distinguished by a sheath of negative permittivity at the periphery of each skyrmion. This enhances the effective dielectric permittivity compared with the individual SrTiO3 and PbTiO3 layers. Moreover, the response of these topologically protected structures to electric field and temperature shows a reversible phase transition from the skyrmion state to a trivial uniform ferroelectric state, accompanied by large tunability of the dielectric permittivity. Pulsed switching measurements show a time-dependent evolution and recovery of the skyrmion state (and macroscopic dielectric response). The interrelationship between topological and dielectric properties presents an opportunity to simultaneously manipulate both by a single, and easily controlled, stimulus, the applied electric field.

Optimizing the linearity in high-speed photodiodes.

Analog photonic links require high-fidelity, high-speed optical-to-electrical conversion for applications such as radio-over-fiber, synchronization at kilometer-scale facilities, and low-noise electronic signal generation. Photodetector nonlinearity is a particularly vexing problem, causing signal distortion and excess noise, especially in systems utilizing ultrashort optical pulses. Here we show that photodetectors designed for high power handling and high linearity can perform optical-to-electrical conversion of ultrashort optical pulses with unprecedented linearity over a large photocurrent range. We also corroborate and expand upon the physical understanding of how the broadband, complex impedance of the circuit following the photodiode modifies the linearity - in some cases quite significantly. By externally manipulating the circuit impedance, we extend the detector's linear range to higher photocurrents, with over 50 dB rejection of amplitude-to-phase conversion for photocurrents up to 40 mA. This represents a 1000-fold improvement over state-of-the-art photodiodes and significantly extends the attainable microwave power by a factor of four. As such, we eliminate the long-standing requirement in ultrashort pulse detection of precise tuning of the photodiode's operating parameters to coincide with a nonlinearity minimum. These results should also apply more generally to reduce nonlinear distortion in a range of other microwave photonics applications.

Back to the future: The Cecil-Culp technique for salvage penile reconstructive procedures.

INTRODUCTION: Re-operative penile reconstruction is challenging and requires tension-free skin closure. The repair popularized by Cecil and Culp in the 1940s, using the scrotum to provide a temporary vascularized bed for complex hypospadias repairs, fell out of favor due to temporal trends towards single-stage repairs and concern for utilizing hair-bearing skin on the penile shaft. OBJECTIVE: It was hypothesized that a modified Cecil-Culp (CC) concept of penile scrotalization, leaving the penis attached to the scrotum for 1 year rather than 6 weeks as originally described, improves outcomes with this reconstruction for ventral skin deficiency or poor vascular support. METHODS: Institutional Review Board-approved registries were reviewed to identify patients who underwent a CC repair during 1987-2016 at two institutions. Cecil-Culp technique was utilized in multi-stage hypospadias complication repairs or for insufficient ventral penile shaft skin coverage. Anatomic abnormality, number and type of prior surgeries, and complications before and after CC were recorded. RESULTS: Thirty-nine patients underwent CC: 23 failed hypospadias repairs, three hypospadias after bladder exstrophy, 10 penile curvature following circumcision, and three with skin loss from trauma. Mean age at CC was 61.8 months (hypospadias), and 59.8 months (non-hypospadias). Hypospadias patients underwent a mean of 3.6 surgeries (range 1-9) prior to CC. Four of the 39 patients (10.3%) had perioperative complications after CC, including scrotal abscess, skin infections, and difficulty removing the urethral stent. Eight of 37 (21.6%) patients had longer-term complications related to their hypospadias repair, including fistulae, diverticula, dehiscence, and stricture. Mean time from CC placement to release was 345 and 473 days for hypospadias and non-hypospadias cases, respectively. There was no apparent scrotal skin transferred to the penile shaft at the final take-down. Mean follow-up was 22.3 months. DISCUSSION: Embedding the penis into the scrotum for added vascularity and ventral skin coverage has been used effectively in cases of the most tenacious fistulas and for significant skin loss and trauma. Limitations of this study were its retrospective approach at two institutions over an extended period of time by multiple surgeons, so patient selection and procedure may have varied. CONCLUSIONS: Modification of CC repair by delaying 9-12 months before CC take-down enhanced the benefits of a robust vascular bed for wound healing, and helped to avoid transfer of hair-bearing scrotal skin to the penile shaft. The CC technique is an important tool for penile reconstructive surgery of complex hypospadias repairs with inadequate skin, and for traumatic injuries.

Outcomes of externalized pyeloureteral versus internal ureteral stent in pediatric robotic-assisted laparoscopic pyeloplasty.

INTRODUCTION: After pyeloplasty, urinary drainage options include internal double-J (DJ) ureteral stents or externalized pyeloureteral (EPU) stents, which can avoid bladder symptoms and additional anesthetic exposure from stent removal. Comparative outcome studies, however, are lacking following primary pediatric robotic-assisted laparoscopic pyeloplasty (RALP). OBJECTIVE: To compare operative success, operative time, hospitalization, and postoperative complications of EPU versus DJ stents following RALP. STUDY DESIGN: Consecutive children undergoing primary RALP from 10/2013 to 9/2015 were retrospectively identified. Data collected included patient demographics, stent type and duration, postoperative complications, and operative success. To control for confounding by indication for EPU stent, propensity score weighting was used to balance baseline covariates. Weighted regression analyses compared between-group differences in study outcomes. RESULTS: At median follow-up of 12.3 months, 44 and 17 patients underwent DJ and EPU stenting, respectively. At baseline, DJ stent patients were older than EPU stent patients (median 7.7 vs 1.2 years, P = 0.01) and were less likely to be on postoperative antibiotic prophylaxis (25 vs 76%, P < 0.001). After weighting, these differences disappeared. All EPU stents were removed in the outpatient clinic; all DJ stents were removed under anesthesia. On weighted regression analyses (Summary Fig.), EPU stents had no different associations than DJ stents with operative success (95 vs 94%, between-group difference 1%, 95% CI -11, 13; P = 0.86), complications, or operative time, but did have 0.6 of a day more hospitalization (95% CI 0.04, 1.2; P = 0.04). DISCUSSION: Patients receiving EPU stents were different at baseline from those receiving DJ stents. After propensity score weighting balanced these covariates, EPU stents were associated with similar operative success, complications, and operative time to DJ stents. Further study is warranted in larger prospective cohorts. CONCLUSION: Use of EPU stents provided a viable alternative, particularly in younger patients, to DJ stenting with comparable success and complications, while avoiding the need for an additional anesthetic.

Genitourinary involvement and management in children with Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are devastating hypersensitivity disorders that cause epidermal cell death and can affect all epidermal surfaces, including the urethra, vagina, labial and scrotal skin. Despite the well-described ocular and orofacial manifestations of SJS/TEN, there is a paucity of reports on the genitourinary (GU) symptoms and their management. Specifically, consulting services often ask the pediatric urology team if it is safe to place a urethral catheter, but there is no data in the literature to help guide management. The present study sought to review all pediatric cases of SJS/TEN in a tertiary care hospital to determine the incidence and optimal management of GU manifestations, including the use of urethral catheters. METHODS: With IRB approval, cases of SJS and TEN that were managed as an inpatient between January 2008 and June 2015 were retrospectively reviewed in order to identify the extent of GU involvement/manifestations, the treatment provided, use of urethral catheterization and long-term follow-up or complications. RESULTS: Thirty-one patients (15 female, 16 male; age range 2-18 years) presented with SJS or TEN over the study period. Etiologies for SJS/TEN included mycoplasma infection (48%) and medications (45%). Incidences of GU manifestations at presentation and their management are shown in Summary Table. Overall, 74% of patients had genital involvement of skin lesions. In 12 cases (39%), urology consultation was obtained. Twenty patients (61%) complained of dysuria and one child had gross hematuria in the setting of meatal lesion. Petroleum jelly was used in the majority of patients. A urethral catheter was placed in eight patients (25.8%, four female, four male) with a range of duration of 7-23 days. No patient developed hematuria or any other complications (i.e. strictures or urinary symptoms) after catheter removal. One boy required lysis of penile adhesions in the short-term. One of each gender developed penile and labial adhesions on long-term follow-up that self-resolved. CONCLUSIONS: GU involvement in SJS/TEN occurred in almost three-quarters of patients and was managed conservatively like other skin/mucosal manifestations. Long-term sequelae were rare and urethral catheterization appeared to be safe, without any short-term or long-term complications.

Effects of exogenous phytase supplementation on phosphorus metabolism and digestibility of beef cattle.

Objectives were to determine interactions between phytase inclusion and dietary P concentration on P utilization by beef cattle fed a starch-based diet. Six ruminally-fistulated steers (BW = 750 ± 61 kg) were allotted to a 6 × 6 Latin square design with a 3 × 2 factorial arrangement of treatments. Factors included phytase inclusion, at 0, 500, or 2,000 phytase units (FTU)/kg of diet DM, and dietary P concentrations, at 0.10% and 0.30% of total diet DM. Feed ingredients, fecal samples, and orts were composited within period, lyophilized and ground. Samples were analyzed for NDF, ADF, CP, fat, ash, total P, and other minerals. Data were analyzed using the MIXED procedure of SAS with animal as the experimental unit. The CORR procedure was used to compare blood and urinary P concentrations. There were no treatment interactions (P ≥ 0.30) for any parameter measured. There were no main effects (P ≥ 0.45) of phytase inclusion on DMI, total fecal output, apparent DM digestibility, water intake, or urinary output. Steers fed 0.10% P had decreased (P < 0.01) DMI and total fecal output, but increased (P < 0.01) apparent DM digestibility compared with steers fed 0.30% P. Although N intake and retention were not affected by treatment, steers fed the 0.10% P diet tended (P = 0.10) to absorb more N compared with steers fed 0.30% P; and, steers fed the 0.10% P diets excreted more N in the urine (P = 0.02) and less N in the feces (P < 0.01) compared with steers fed the 0.30% P diets. Steers fed the 0.10% P diets also consumed 70.1% less (P < 0.01) total P each day, and excreted 51.9% less (P < 0.01) P in feces and 94.6% less P in the urine (P < 0.01) compared with steers fed 0.30% P. Excretion of water-soluble P in the feces was greater (P < 0.01) on a g/d basis for steers fed 0.30% P when compared with steers fed 0.10% P. However, the proportion of total fecal P excreted as water-soluble P increased (P < 0.05) by 23.0% in steers fed 0.10% P compared with steers fed 0.30% P, regardless of phytase inclusion level. There was no effect of dietary phytase concentration on blood or urinary (P ≥ 0.27) P concentrations. Blood P concentration was positively correlated (r = 0.60; P < 0.01) to urinary P concentration when steers were fed 0.10% P; however, when steers were fed 0.30% P, there was no correlation (r = 0.36; P = 0.16) between blood and urine P. Regardless of dietary P concentration, phytase supplementation did not increase calculated P absorption or retention.

Hypospadias: Are we as good as we think when we correct proximal hypospadias?

OBJECTIVE: Hypospadias surgery is a humbling art form. Although outcomes with distal hypospadias are favorable, recent publications have suggested that the complication rates are much higher than previously anticipated for proximal hypospadias. The present review examined the literature concerning proximal hypospadias, to explore some of the inadequacies and identify some of the reasons behind these shortfalls in the reported data. METHODS: A systematic review of the published literature was conducted using keywords relevant to proximal hypospadias and long-term outcomes. RESULTS: The literature for hypospadias was reviewed, and outcomes for distal vs proximal variants were compared. The quality of the literature for proximal hypospadias was examined, and the shortcomings that led to underreporting of the surgical outcomes were identified. Special focus was on the lack of standardized documentation, the subsequent inability to objectify the severity of the phenotype, and the underestimation of complications due to lack of long-term follow-up. There was also a great deal of variability in the utilized techniques, and the literature was filled with small case series from single institutions. To enable scientific assessment of outcomes, it is proposed that the following be implemented: acceptance and incorporation of standardized phenotype assessment scores in the pre-operative period, objective intraoperative hypospadias characterization, and postoperative score assessment. CONCLUSIONS: Treatment of proximal hypospadias is much less successful than the distal variant. A specialty wide commitment to standardize the hypospadias language is required to make advancement in surgical outcomes. Boys need to be followed through puberty into adulthood, and honest reporting of outcomes must be discussed so that surgical techniques for this complicated disease process can be advanced.

Pediatric calyceal diverticulum treatment: An experience with endoscopic and laparoscopic approaches.

INTRODUCTION: The symptomatic calyceal diverticulum is a rare event in the pediatric population. In adults, surgical options include ureteroscopy, percutaneous ablation, and laparoscopic decortication but there is a lack of experience in the literature with these techniques. OBJECTIVE: We present our experience with both the ureteroscopic and laparoscopic approach to treating the pediatric calyceal diverticulum. STUDY DESIGN: We performed a retrospective case series looking at patients who underwent treatment for calyceal diverticulum at our institution from January 2009 to May 2014. We reviewed patient demographics, indications for intervention, radiographic appearance, type of intervention, and perioperative outcomes. Ureteroscopic approach included dilation of infundibulum and ablation of diverticular cavity. Laparoscopic approach included ablation of the diverticulum with argon diathermy with or without surgical closure of the ostium. RESULTS: There were 13 patients who underwent 15 procedures for symptomatic calyceal diverticulum (Table). Median age was 11 years. Indications for intervention were: pain and increasing size of diverticulum (8/15, 55%), hematuria (3/15, 20%), UTI (3/15, 20%), and calculi (1/15, 5%). 11/15 (73%) procedures were managed endoscopically and 4/15 (27%) were managed with laparoscopic decortication. Ureteral stent was left in all patients for a mean duration of 51 days (15-120 days). Follow up imaging at median of 2.1 years (0.5-4 years) revealed an initial success rate of 85% (11/13 patients). Two patients failed initial intervention (persistent pain/increasing size) necessitating successful secondary minimally invasive procedures. There were 2 (13%) complications: a perinephric hematoma post endoscopic ablation which resolved spontaneously and a deep venous thrombosis in a patient with a coagulation disorder in the laparoscopic group. DISCUSSION: Limitations of our study include its retrospective design, lack of standardization of the treatment approach amongst the four treating surgeons, and the small number of patients requiring intervention for this relatively rare diagnosis. Our study is the largest to date in the pediatric population and is the first to report outcomes with ureteroscopic management of the calyceal diverticulum. CONCLUSIONS: We found that the pediatric calyceal diverticulum can be successfully treated in a minimally invasive manner. The endoscopic approach should be the first line option for patients with small, endophytic diverticula, particularly those located in the upper and mid pole. The laparoscopic approach is more invasive but should be considered for large diverticula that are exophytic with thin overlying parenchyma.

Mechanistic investigation of adult myotube response to exercise and drug treatment in vitro using a multiplexed functional assay system.

The ability to accurately measure skeletal muscle functional performance at the single-cell level would be advantageous for exercise physiology studies and disease modeling applications. To that end, this study characterizes the functional response of individual skeletal muscle myotubes derived from adult rodent tissue to creatine treatment and chronic exercise. The observed improvements to functional performance in response to these treatments appear to correlate with alterations in hypertrophic and mitochondrial biogenesis pathways, supporting previously published in vivo and in vitro data, which highlights the role of these pathways in augmenting skeletal muscle output. The developed system represents a multiplexed functional in vitro assay capable of long-term assessment of contractile cellular outputs in real-time that is compatible with concomitant molecular biology analysis. Adoption of this system in drug toxicity and efficacy studies would improve understanding of compound activity on physical cellular outputs and provide more streamlined and predictive data for future preclinical analyses.

Genetic or pharmacologic disruption of the calcineurin-nuclear factor of activated T-cells axis prevents social stress-induced voiding dysfunction in a murine model.

OBJECTIVE: Social stress can suppress the voiding reflex, with resultant diminished voiding frequency and increased volumes. The calcineurin-NFAT (nuclear factor of activated T cells) pathway is important in memory development. It was hypothesized that interruption of the calcineurin-NFAT pathway might prevent social stress-induced voiding dysfunction. METHODS: Mice were subjected to social stress in an established resident-intruder model for 1 h, followed by 23 h of barrier separation. NFATc3, NFATc4 knockout (KO) and wild-type (WT) mice were studied. At two weeks, voiding patterns were collected; this was followed by sacrifice. Corticotropin-releasing factor (CRF) mRNA expression in Barrington's nucleus (BN) was determined by in-situ hybridization. RESULTS: Social stress decreased voiding frequency and increased voided volumes in WT strains. At baseline, NFATc3 KO mice showed decreased voids and increased volumes, while the NFATc4 KO mice resisted social stress. However, CRF mRNA increased in WT mice following social stress and was increased at baseline in NFATc3 KO mice. It was found that CRF mRNA did not increase following social stress in NFATc4 KO mice. The administration of CsA to WT mice normalized voiding patterns following social stress, albeit with no effect on CRF mRNA in BN. CONCLUSION: Disrupting the calcineurin-NFAT axis by either genetic or pharmacologic approaches confers resistance to the development of social stress-induced voiding and dysfunction.

A multiplexed chip-based assay system for investigating the functional development of human skeletal myotubes in vitro.

This report details the development of a non-invasive in vitro assay system for investigating the functional maturation and performance of human skeletal myotubes. Data is presented demonstrating the survival and differentiation of human myotubes on microscale silicon cantilevers in a defined, serum-free system. These cultures can be stimulated electrically and the resulting contraction quantified using modified atomic force microscopy technology. This system provides a higher degree of sensitivity for investigating contractile waveforms than video-based analysis, and represents the first system capable of measuring the contractile activity of individual human muscle myotubes in a reliable, high-throughput and non-invasive manner. The development of such a technique is critical for the advancement of body-on-a-chip platforms toward application in pre-clinical drug development screens.

Adaptation to various sources of dietary sulfur by ruminants.

The objective of these experiments was to determine adaptation by ruminants to dietary sulfur. In Exp. 1, lambs (n = 54; BW = 33.6 ± 0.4 kg) were allotted to 3 treatments: 1) 0% added dietary S (0%S), 2) 0.2% added dietary S (0.2%S), or 3) 0.4% added dietary S (0.4%S). Sulfur was added to the diet as Na(2)SO(4). Lambs fed the 0.2%S and 0.4%S diets had greater (P < 0.01) ADG and G:F compared to those fed the 0%S diet. There was time × diet interaction (P < 0.01) on ruminal hydrogen sulfide gas (H(2)S) concentrations. Ruminal H(2)S was not detected in lambs fed 0%S at any time. Ruminal H2S were not affected (P > 0.19) by diet on d 1 or 8; however, H(2)S were greater (P < 0.01) for lambs fed 0.2%S and 0.4%S than for lambs fed 0%S on d 15, 22, and 29 (0.2% was 931, 846, and 1,131 mg/L and 0.4% was 975, 737, and 1,495 mg/L on d 15, 22, and 29, respectively). These data suggest it takes at least 29 d for peak ruminal H(2)S to occur after exposure to Na(2)SO(4). In Exp. 2, lambs (n = 66; BW = 51.1 ± 0.4 kg) were allotted to 3 treatments: 1) 60% dried distillers grains with solubles (DDGS), 2) corn-based diet with Na(2)SO(4), or 3) corn-based diet with H(2)SO(4). All diets were formulated to contain 0.4%S. Lambs fed Na(2)SO(4) had greater (P < 0.05) ADG, DMI, and G:F than those fed H(2)SO(4) or 60% DDGS. A time × diet interaction occurred (P < 0.01) for ruminal H(2)S. There was no difference (P = 0.82) in H(2)S of lambs on d 1. However, at d 14 and 27 lambs fed supplemental Na(2)SO(4) had the lowest H(2)S concentrations while lambs fed 60% DDGS had the greatest (P < 0.01 on both d); lambs fed H(2)SO(4) were intermediate and different than both. These data suggest that at the same dietary S concentration, acidic S sources increased H(2)S and decreased DMI and ADG. In Exp. 3, Angus cross calves (n = 72; average initial BW = 324 ± 3 kg) were allotted to 3 treatments: 1) corn-based control d 0 through 85 (0%DDGS), 2) gradual step up to 60% DDGS diet (20% DDGS d 0 to 6, 40% DDGS d 7 to 13, 50% DDGS d 14 to 20, and 60% DDGS d 21 to 85; Step-up), or 3) 60% DDGS d 0 to 85 (60%DDGS). Overall, cattle fed 0%DDGS had increased (P < 0.05) DMI and ADG compared with those fed 60%DDGS or Step-up, and G:F was not affected (P = 0.42) by dietary treatment. On d 14, ruminal H(2)S concentrations were greater (P < 0.01) for cattle fed 60%DDGS and Step-up than for those fed 0%DDGS, and they did not differ (P ≥ 0.22) between DDGS-containing diets. These data illustrate that source of S impacts ruminal S metabolism and that S from DDGS is more readily reduced than S from Na(2)SO(4) or H(2)SO(4).

Correlation of embryonic skeletal muscle myotube physical characteristics with contractile force generation on an atomic force microscope-based bio-microelectromechanical systems device.

Rigorous analysis of muscle function in in vitro systems is needed for both acute and chronic biomedical applications. Forces generated by skeletal myotubes on bio-microelectromechanical cantilevers were calculated using a modified version of Stoney's thin-film equation and finite element analysis (FEA), then analyzed for regression to physical parameters. The Stoney's equation results closely matched the more intensive FEA and the force correlated to cross-sectional area (CSA). Normalizing force to measured CSA significantly improved the statistical sensitivity and now allows for close comparison of in vitro data to in vivo measurements for applications in exercise physiology, robotics, and modeling neuromuscular diseases.

A functional system for high-content screening of neuromuscular junctions in vitro.

High-content phenotypic screening systems are the logical extension of the current efficient, yet low information content, pre-clinical screens for drug discovery. A physiologically accurate in vitro neuromuscular junction (NMJ) screening system would therefore be of tremendous benefit to the study of peripheral neuropathies as well as for basic and applied neuromuscular research. To date, no fully-defined, selective assay system has been developed which would allow investigators to determine the functional output of cultured muscle fibers (myotubes) when stimulated via the NMJ in real time for both acute and chronic applications. Here we present the development of such a phenotypic screening model, along with evidence of NMJ formation and motoneuron initiated neuromuscular transmission in an automated system. Myotubes assembled on silicon cantilevers allowed for measurement of substrate deflection in response to contraction and provided the basis for monitoring the effect of controlled motoneuron stimulation on the contractile behavior. The effect was blocked by treatment with D-tubocurarine, confirming NMJ functionality in this highly multiplexed assay system.