Colonic Motility Is Improved by the Activation of 5-HT2B Receptors on Interstitial Cells of Cajal in Diabetic Mice.

BACKGROUND & AIMS: Constipation is commonly associated with diabetes. Serotonin (5-HT), produced predominantly by enterochromaffin (EC) cells via tryptophan hydroxylase 1 (TPH1), is a key modulator of gastrointestinal (GI) motility. However, the role of serotonergic signaling in constipation associated with diabetes is unknown. METHODS: We generated EC cell reporter Tph1-tdTom, EC cell-depleted Tph1-DTA, combined Tph1-tdTom-DTA, and interstitial cell of Cajal (ICC)-specific Kit-GCaMP6 mice. Male mice and surgically ovariectomized female mice were fed a high-fat high-sucrose diet to induce diabetes. The effect of serotonergic signaling on GI motility was studied by examining 5-HT receptor expression in the colon and in vivo GI transit, colonic migrating motor complexes (CMMCs), and calcium imaging in mice treated with either a 5-HT2B receptor (HTR2B) antagonist or agonist. RESULTS: Colonic transit was delayed in males with diabetes, although colonic Tph1+ cell density and 5-HT levels were increased. Colonic transit was not further reduced in diabetic mice by EC cell depletion. The HTR2B protein, predominantly expressed by colonic ICCs, was markedly decreased in the colonic muscles of males and ovariectomized females with diabetes. Ca2+ activity in colonic ICCs was decreased in diabetic males. Treatment with an HTR2B antagonist impaired CMMCs and colonic motility in healthy males, whereas treatment with an HTR2B agonist improved CMMCs and colonic motility in males with diabetes. Colonic transit in ovariectomized females with diabetes was also improved significantly by the HTR2B agonist treatment. CONCLUSIONS: Impaired colonic motility in mice with diabetes was improved by enhancing HTR2B signaling. The HTR2B agonist may provide therapeutic benefits for constipation associated with diabetes.

Detecting Illegal Intercountry Trade of Mercury Using Discrepancies in Mirrored Trade Data.

The ongoing international movement to phase out mercury, mainly led by the Minamata Convention on Mercury, raises concerns about illegal intercountry trade, including smuggling. This study aims to detect the existence of illegal intercountry mercury trade under the social mercury phase-out movement, focusing on discrepancies in each country's trade statistics. To analyze the trends by year and country for discrepancies in intercountry mercury trade, an intraclass correlation coefficient (ICC) was applied to the mirrored exports and imports from trade statistics of each country provided by the UN Comtrade. The year-based ICC analysis identified a tendency to reduce the detection of discrepancies in the reported mirrored exports and imports for mercury at the intercountry level under the recent mercury phase-out movement. Through an ICC analysis focusing on exporting and importing countries, the validity of the ICC analysis was verified as a way to detect illegal intercountry trade of mercury. Our analyses detecting the illegal trade of related countries contribute to the effectiveness evaluation and custom capacity building required in the Minamata Convention by offering a data-driven method to enable the effective detection of illegal mercury trade.

METTL3 contributes to slow transit constipation by regulating miR-30b-5p/PIK3R2/Akt/mTOR signaling cascade through DGCR8.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic RNA, and methyltransferase-like 3 (METTL3) plays a vital role in multiple cell functions. This study aimed to investigate the role of m6A methylase METTL3 in slow transit constipation (STC). MATERIAL AND METHOD: The expression of METTL3 and DGCR8 was measured in STC tissues and glutamic acid-induced interstitial cells of Cajal (ICCs). The effects of METTL3, miR-30b-5p, and DGCR8 on the biological characteristics of ICCs were investigated on the basis of loss-of-function analyses. Luciferase reporter assay was used to identify the direct binding sites of miR-30b-5p with PIK3R2. RESULTS: The results showed that the METTL3, DGCR8, miR-30b-5p, and the methylation level of m6A were significantly increased in STC tissues and glutamic acid-induced ICCs. Silencing of METTL3 and miR-30b-5p inhibited apoptosis, autophagy, and pyroptosis of glutamic acid-induced ICCs. Moreover, overexpression of miR-30b-5p reversed the cytoprotection of METTL3 knockdown in glutamic acid-induced ICCs. Besides, DGCR8 knockdown could facilitate cell growth and decrease apoptotic glutamic acid-induced ICCs. Mechanically, we illustrated that METTL3 in glutamic acid-induced ICCs significantly accelerated the maturation of pri-miR-30b-5p by m6A methylation modification, resulting in the reduction of PIK3R2, which results in the inhibition of PI3K/Akt/mTOR pathway and ultimately leads to the cell death of STC. CONCLUSIONS: Collectively, these data demonstrated that METTL3 promoted the apoptosis, autophagy, and pyroptosis of glutamic acid-induced ICCs by interacting with the DGCR8 and successively modulating the miR-30b-5p/PIK3R2 axis in an m6A-dependent manner, and METTL3 may be a potential therapeutic target for STC.

A 15-year retrospective review of urodynamic studies in children at Red Cross War Memorial Children's Hospital, Cape town, South Africa.

BACKGROUND: Despite the undeniable diagnostic benefits of urodynamic studies (UDS), their adoption into clinical practice in Africa has been slow. This study aimed to review the use of invasive UDS in children at a tertiary paediatric hospital in South Africa. METHODS: A retrospective analysis of 1108 UDS was conducted. Patient demographic characteristics, primary diagnosis, indication and urodynamic outcomes were reviewed. Presence of urodynamic high-risk features were documented, and a comparison was made between the first study and follow-up study. RESULTS: This study revealed increasing trends in the use of UDS from 2015. Referrals were from Urology (37.7%), Spinal defects clinic (34.4%), Nephrology (20.8%) and other departments (7.0%). The most common reason for referral was review of medical treatment (36.5%). Spinal dysraphism (58.3%) accounted for the majority of conditions seen. Majority (59.1%) of the patients were receiving more than one type of bladder treatment at the time of their first study, with clean intermittent catheterisation (46.5%) being the most common form of bladder management. 97.5% of studies were performed using transurethral bladder catheterization. Urodynamic diagnosis was neurogenic in 74.0%, anatomical (12.2%), functional (8.8%) and normal (5.0%). There was statistically significant improvement in bladder compliance, detrusor leak point pressure and detrusor sphincter dyssynergia between the first study and a subsequent study following therapeutic intervention. CONCLUSIONS: The unique ability of UDS to demonstrate changes in detrusor pressures, which is a common reason for therapy failure, makes UDS an invaluable tool in the diagnosis and management of children with lower urinary tract dysfunction.

Adolescents' Political Socialization at School, Citizenship Self-efficacy, and Expected Electoral Participation.

Adolescents' political socialization is crucial for their future political participation. Little research has examined this relationship and the importance of citizenship self-efficacy in an Asian context. This study focused on the effectiveness of Korean adolescents' political socialization and self-efficacy on their expected electoral participation. Data from Korean 8th graders participating in the 2016 International Civic and Citizenship Education Study were examined (N = 2601; Mage = 14.02; 46% female). Political socialization included open classroom discussion, active learning strategies, and formal citizenship education. The result showed that citizenship self-efficacy is the most important predictor for Korean adolescents' future engagement, but open classroom discussion is not significant. It indicates that citizenship education needs to consider countries' social and cultural contexts.

Measuring Nanoscale Distances by Structured Illumination Microscopy and Image Cross-Correlation Spectroscopy (SIM-ICCS).

Since the introduction of super-resolution microscopy, there has been growing interest in quantifying the nanoscale spatial distributions of fluorescent probes to better understand cellular processes and their interactions. One way to check if distributions are correlated or not is to perform colocalization analysis of multi-color acquisitions. Among all the possible methods available to study and quantify the colocalization between multicolor images, there is image cross-correlation spectroscopy (ICCS). The main advantage of ICCS, in comparison with other co-localization techniques, is that it does not require pre-segmentation of the sample into single objects. Here we show that the combination of structured illumination microscopy (SIM) with ICCS (SIM-ICCS) is a simple approach to quantify colocalization and measure nanoscale distances from multi-color SIM images. We validate the SIM-ICCS analysis on SIM images of optical nanorulers, DNA-origami-based model samples containing fluorophores of different colors at a distance of 80 nm. The SIM-ICCS analysis is compared with an object-based analysis performed on the same samples. Finally, we show that SIM-ICCS can be used to quantify the nanoscale spatial distribution of functional nuclear sites in fixed cells.

Examining measurement equivalency within the Latin American module of the International Civic Competence Study 2009.

The International Civic and Citizenship Education Study (ICCS) studies are intercontinental studies on the civic education of youth from Asia, Europe, and Latin America. Before we engage in comparative studies on youth from different world regions, we must first establish the equivalency of the scales and items within the databases. The purpose of this study was to examine the level of differential functioning on the Attitudes Towards Neighborhood Diversity 10-item scale in the Latin American module within the ICCS 2009 database for youth from Colombia, Guatemala, and Chile. We first examined the unidimensionality of the scale within each country by assessing configural invariance. Of countries that demonstrated at least adequate fit for configural invariance, we proceeded to examine differential functioning at the item and scale levels. Findings demonstrated that configural invariance held for Chile and Guatemala only. While differential functioning was present on nine of the 10 items between Chile and Guatemala, in all cases the amounts were negligible. There was no differential functioning on the overall scale. Whilst equivalency holds for certain countries on certain scales, in other cases it did not. Thus scholars may consider scale refinement methods before making comparative analyses.

[Elimination disorders - ICD-11 classification and definitions]. / Ausscheidungsstörungen ­ Klassifikation und Definition nach ICD-11.

Elimination disorders - ICD-11 classification and definitions Abstract. Elimination disorders are common in children and are can be divided into three main groups: nocturnal enuresis, daytime urinary incontinence, and encopresis or fecal incontinence. There are also many subgroups that can be diagnosed exactly. This review critically presents the definitions and the classification suggestions of the ICD-11. It compares the definitions of enuresis according to ICD-11 with those of nocturnal enuresis and daytime urinary incontinence of the ICCS. It also contrasts encopresis according to ICD-11 with functional constipation and nonretentive fecal incontinence by the Rome-IV criteria. It becomes apparent that the ICD-11 does not reflect current research findings; that it does not render specific diagnoses, which are prerequisites for effective treatment; and that it is not exact enough for research. In conclusion, the ICCS and Rome-IV definitions are the preferred classification systems in clinical practice and research.

Development and Validation of a Magnetic Resonance Index for Assessing Fistulas in Patients With Crohn's Disease.

BACKGROUND & AIMS: There is no validated magnetic resonance imaging (MRI) index for assessment of perianal fistulas in patients with Crohn's disease (CD). We developed and internally validated a new instrument. METHODS: We used paired baseline and week-24 MRI scans from 160 participants in a randomized placebo-controlled trial of stem cell therapy for patients with perianal fistulizing CD. Four radiologists scored disease activity using index items identified during previous studies and exploratory items. Reliability was assessed using intraclass correlation coefficients. We developed an index using backward elimination linear regression analysis, in which potential independent variables were items having intraclass correlation coefficients of at least 0.4 and the dependent variable was perianal fistulizing disease activity, measured on a 100-mm visual analogue scale. The final model was internally validated using the .632 bootstrap method to correct model optimism and quantify calibration accuracy. We evaluated responsiveness of the index by assessing longitudinal validity and estimating standardized effect sizes. RESULTS: We developed the magnetic resonance novel index for fistula imaging in CD (MAGNIFI-CD) using 6 items. The optimism-corrected R2 of the model was 0.71, which was comparable to R2 for the original sample (0.74). The calibration slope for the model was 0.98. Compared with the original and modified versions of the Van Assche Index, the MAGNIFI-CD had improved operating characteristics. Estimates of intraclass correlation coefficients for MAGNIFI-CD, the modified Van Assche Index, and Van Assche Index were 0.85 (95% confidence interval [CI], 0.77-0.90), 0.81 (95% CI, 0.74-0.86), and 0.81 (95% CI, 0.71-0.86) for intra-rater reliability, and 0.74 (95% CI, 0.63-0.80), 0.67 (95% CI, 0.55-0.75) and 0.68 (95% CI, 0.56-0.77) for inter-rater reliability. Corresponding standardized effect size estimates were 1.02 (95% CI, 0.65-1.39), 0.84 (95% CI, 0.48-1.21), and 0.68 (95% CI, 0.33-1.03). CONCLUSIONS: We developed an index called the MAGNIFI-CD, which is based on 6 items. It assesses MRI data and determines perianal fistulizing CD activity with improved operating characteristics compared to previous indices. This index may be used as an outcome measure in clinical trials comparing treatment effects in patients with perianal fistulizing CD. Although the performance of the MAGNIFI-CD indicates its stability and reasonable external validity, external validation is needed.

Metastasis-associated protein 1 (MTA1) regulates the catecholamine production homeostasis via transcriptional repression of aromatic l-amino acid decarboxylase (Aadc) in the interstitial cells of Cajal of mouse prostate.

Based on the lately identified role for the interstitial cells of Cajal (ICCs) of mouse prostate in catecholamine production, as well as the well-established role for the master coregulator metastasis-associated protein 1 (MTA1) in inflammation, we probed into the functional link between aberrant MTA1 expression and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using both a MTA1-/- mouse model of experimental autoimmune prostatitis (EAP) and an in vitro chronic prostatitis model in cultured murine ICCs. EAP-induced MTA1 expression was enriched in ICCs of mouse prostate. EAP resulted in a higher increase in the pelvic pain response in MTA1-/- mice compared to WT mice. Consistently, the ICCs from MTA1-/- mice produced higher levels of catecholamines upon induction of in vitro chronic prostatitis. Mechanistically, MTA1 could directly suppress the transcription of Aadc, a rate-limiting enzyme during catecholamine synthesis, in a HDAC2-depdendent manner. Importantly, treatment with AADC inhibitor NSD-1015 significantly ameliorated EAP-elicited pain response and catecholamine overactivity in MTA1-/- mice. Taken together, our findings reveal an inherent regulatory role of the MTA1/AADC pathway in the maintenance of catecholamine production homeostasis in prostate ICCs, and also point to a potential use of HDAC inhibitors and/or AADC inhibitors to treat CP/CPPS.

Involvement of prostatic interstitial cells of Cajal in inflammatory cytokines-elicited catecholamines production: Implications for the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

In a previous work using guinea pig prostate, we have identified a novel interstitial cells of Cajal (ICCs) which possess close contacts between sympathetic nerve bundles and smooth muscle cells. The ability of prostatic ICCs in mediating excitatory neural inputs was therefore studied using isolated murine prostate ICCs by collagenase digestion combined with FACS method. RT-PCR and Western blotting analyses revealed that prostatic ICCs under a quiescent state expressed abundantly the rate-limiting enzymes essential for catecholamine synthesis. Moreover, distinct proinflammatory cytokines (e.g. IL-1ß, IL-8, ICAM-1 and TNF-α) could significantly stimulate the expression levels of the rate-limiting enzymes of catecholamine production in prostate ICCs. Mechanistically, the above-mentioned stimulatory effects of proinflammatory cytokines appeared to be mediated via activation of NF-κB, HIF-1α and HDACs signaling pathways. Considering that prostatic catecholamine overactivity serves as an essential etiology of pelvic pain by indirectly stimulating the smooth muscle cell proliferation, or by directly causing muscular spasm, our results collectively suggest that targeting the NF-κB, HIF-1α and HDACs pathways in prostate ICCs be considered as a new strategy for treatment of chronic pelvic pain syndrome (CPPS) induced by chronic prostatitis (CP). Overall, the current study should shed novel light on the biology of this unique prostate ICCs.

EP3 activation facilitates bladder excitability via HCN channels on ICCs.

EP3 is a receptor for prostaglandin E2 (PGE2), and although its effect on bladder excitability has attracted considerable attention, the underlying mechanism remains unclear. To investigate whether the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the interstitial cells of Cajal (ICCs) of the bladder are involved in the effect of EP3 activation on bladder excitability, wild-type mice, HCN1 knockout (HCN1-/-) mice and rats were used in our study. Double immunofluorescence staining and immunoprecipitation assays demonstrated the interaction between EP3 and the HCN channels. Sulprostone is a selective agonist of EP3. The current density of HCN channels was enhanced by sulprostone or PGE2 using whole-cell patch clamping. Western blot analyses showed that the expression levels of HCN1 and HCN4 were higher in bladders that had undergone intravesical instillation with sulprostone than in bladders treated with normal saline (NS). Both PGE2 and sulprostone increased the calcium concentration of the ICCs, and their effects were inhibited by ZD7288 (antagonist of HCN channels) treatment. In bladder detrusor strip testing, both PGE2 and sulprostone enhanced the amplitude of the bladder detrusor in HCN1-/- mice; however, these effects were less than those in the wild-type mice. Furthermore, the effects of PGE2 and sulprostone were inhibited by ZD7288. Taken together, our results indicate that EP3 is expressed in bladder ICCs and facilitates bladder excitability via HCN channels. This study provides more comprehensive insights into the mechanism between inflammation and bladder excitability and highlights methods that can resolve bladder hyperactivity.

Reference values for frequency volume chart and uroflowmetry parameters in adolescent and adult enuresis patients.

AIMS: Reference values of Frequency Volume Chart (FVC) and uroflowmetry parameters for adolescent and adult enuresis patients are lacking. In this study, we aim to describe those parameters, in order to interpret findings from FVCs and uroflowmetries in those patients. METHODS: Retrospective, descriptive cohort study, concerning 907 patients aged 11 years and older, suffering from enuresis of at least one wet night per fortnight, treated in a secondary/tertiary centre, between 2003 and 2013. The main FVC parameters of interest were: maximum voided volume (MVV), 24 hr urine production and nocturnal urine volume (NUV) including first morning void (FMV). Nocturnal polyuria (NP) was defined based on both International Children's Continence Society (ICCS, 2014) and International Continence Society (ICS, 2002) definitions. Data of all patients were collected from the medical files. RESULTS: Age had an impact on diurnal and nocturnal FVC parameters. Median MVV excluding FMV was 250 ml in the youngest, 11-year-old males and 363 ml in the eldest, ≥18-yr-old males. For females, these values were 230 ml and 310 ml. Median 24 hr urine production increased from 1,025 ml to 1,502 ml (males) and from 1,007 ml to 1,557 ml (females). Median NUV showed an increase from 387 ml to 519 ml (males) and from 393 ml to 525 (females). Forty-two percent of men and 30% of women had a small MVV (for age). Prevalence of NP differed when assessed by the ICS or the ICCS definition: following ICS guidelines, NP was present in 96% of our male and 93% of our female population, compared to 27% and 41%, respectively, following ICCS guidelines. CONCLUSIONS: Both small MVV and NP were found frequently in our adolescent and adult enuresis patients, which is in line with the current thoughts on causal factors. NP prevalence is quite different when using ICS or ICCS definitions, respectively. We would like to encourage the development of an unambiguous definition of NP to use both in pediatric and adult urology. Neurourol. Urodynam. 36:463-468, 2017. © 2016 Wiley Periodicals, Inc.

Stem Cell Factor/Kit Signal Insufficiency Contributes to Hypoxia-Induced Intestinal Motility Dysfunctions in Neonatal Mice.

BACKGROUND: Gastrointestinal (GI) motility disorders represent a group of problems that more constantly encountered in preterm infants. However, whether hypoxia exposure contributes to the GI dysfunctions is still unclear. METHODS: Newborn mice were exposed to hypoxia (10%) from P1 to P7. Intestinal motilities were examined by a strain gauge transducer. The proliferation of ICCs was detected by using immunostaining for BrdU, Ki67, Kit, Ano1, and insulin-like growth factor 1 receptor (IGF-1R+). Smooth muscle cells and enteric neurons were revealed by immunostaining for α-SMA and NF200, respectively. Apoptosis was assessed by TUNEL assay. Kit signal pathway was examined by western blot and qPCR. RESULTS: Intestinal motilities were found weakened significantly in the hypoxic small intestines as compared to controls on P8. Kit+ or Ano1+ interstitial cells of Cajal (ICCs) were found obviously decreased in the myenteric ICCs (ICC-MY) of neonatal mice after exposed to hypoxia. A large number of ICC progenitors (IGF-1R+) were found highly mitotic (BrdU+ Ki67+) to populate ICC during early postnatal development in the normoxic mice. We found the ICC proliferation was significantly inhibited upon hypoxia exposure, without increasing apoptosis (TUNEL+). We next identified that Kit phosphorylation was inhibited 3 days after hypoxia exposure. The inhibition of Kit signaling was largely due to decreased the expression of the ligand of Kit receptor, stem cell factor (SCF), in the intestinal walls. Exposure to imatinib, a Kit receptor inhibitor, for 3 days from P4 phenocopied the effect of hypoxia on the neonatal pups that resulted in inhibited intestinal motilities and decreased Kit+ ICC numbers. CONCLUSION: All together, our findings indicate the SCF/Kit signaling insufficiency may contribute to the underdevelopment of ICCs and intestinal motility dysfunction upon hypoxia exposure. The decease in ICC density is likely due to the cell cycle arrest of ICC progenitor cells.

Adolescents' expected civic participation: the role of civic knowledge and efficacy beliefs.

In the present study we examined the role of civic knowledge and efficacy beliefs as factors that can promote adolescents' expectations to participate in civic activities, while also taking into consideration the influences of socio-economic background and gender differences. Structural equation modelling techniques were used to examine data from the International Civic and Citizenship Study, collected from 3352 eighth grade Italian students. Gender was found to significantly moderate some relationships between the variables, while efficacy beliefs, rather than civic knowledge, positively influenced expected civic participation. Socio-economic background influenced all the variables included in the study, but it had a very small direct influence on adolescents' expected civic participation. It therefore appears that adolescents' expected civic participation can be encouraged by making them more confident about their civic and political abilities. These results extend our understanding of civic engagement in adolescents, and can inform policies aiming to promote it.

[Classification of enuresis/encopresis according to DSM-5]. / Klassifikation der Enuresis/ Enkopresis im DSM-5.

Elimination disorders are common in childhood and adolescence. Enuresis is traditionally defined as wetting from the age of 5 years and encopresis as soiling from 4 years onwards - after all organic causes have been excluded. In the past decades, many subtypes of elimination disorders have been identified with different symptoms, etiologies, and specific treatment options. Unfortunately, the DSM-5 criteria did not integrate these new approaches. In contrast, classification systems of the International Children's Incontinence Society (ICCS) for enuresis and urinary incontinence as well as the ROME-III criteria for fecal incontinence offer new and relevant suggestions for both clinical and research purposes.

Total Flavonoids of Aurantii Fructus Immaturus Regulate miR-5100 to Improve Constipation by Targeting Fzd2 to Alleviate Calcium Balance and Autophagy in Interstitial Cells of Cajal.

Aurantii Fructus Immaturus total flavonoids (AFIF) is the main effective fraction extracted from AFI, which has a good effect on promoting gastrointestinal motility. This study aimed to investigate AFIF which regulates miR-5100 to improve constipation symptoms in mice by targeting Frizzled-2 (Fzd2) to alleviate interstitial cells of Cajal (ICCs) calcium ion balance and autophagy apoptosis. The constipated mouse model was induced by an antibiotic suspension, and then treated with AFIF. RNA-seq sequencing, luciferase assay, immunofluorescence staining, transmission electron microscopy, ELISA, flow cytometry, quantitative polymerase chain reaction (PCR), and Western blot were applied in this study. The results showed that AFIF improved constipation symptoms in antibiotic-induced constipated mice, and decreased the autophagy-related protein Beclin1 levels and the LC3-II/I ratio in ICCs. miR-5100 and its target gene Fzd2 were screened as key miRNAs and regulator associated with autophagy. Downregulation of miR-5100 caused increased expression of Fzd2, decreased proliferation activity of ICCs, increased apoptotic cells, and enhanced calcium ion release and autophagy signals. After AFIF treatment, miR-5100 expression was upregulated and Fzd2 was downregulated, while autophagy-related protein levels and calcium ion concentration decreased. Furthermore, AFIF increased the levels of SP, 5-HT, and VIP, and increased the expression of PGP9.5, Sy, and Cx43, which alleviated constipation by improving the integrity of the enteric nervous system network. In conclusion, AFIF could attenuate constipation symptoms by upregulating the expression of miR-5100 and targeting inhibition of Fzd2, alleviating calcium overload and autophagic death of ICCs, regulating the content of neurotransmitters, and enhancing the integrity of the enteric nervous system network.

Transcutaneous parasacral electrical neural stimulation in children with primary monosymptomatic enuresis: a prospective randomized clinical trial.

PURPOSE: Parasacral transcutaneous electrical neural stimulation is widely used to treat hyperactive bladder in children and adults. Its use in nonmonosymptomatic enuresis has demonstrated improvement in number of dry nights. We assessed the effectiveness of parasacral transcutaneous electrical neural stimulation in the treatment of monosymptomatic primary enuresis. MATERIALS AND METHODS: This prospective randomized clinical trial included 29 girls and 16 boys older than 6 years with primary monosymptomatic enuresis. Children were randomly divided into 2 groups consisting of controls, who were treated with behavioral therapy, and an experimental group, who were treated with behavioral therapy plus 10 sessions of parasacral transcutaneous electrical neural stimulation. Neural stimulation was performed with the electrodes placed in the sacral region (S2/S3). Sessions always followed the same pattern, with duration of 20 minutes, frequency of 10 Hz, a generated pulse of 700 µs and intensity determined by the sensitivity threshold of the child. Sessions were done 3 times weekly on alternate days. Patients in both groups were followed at 2-week intervals for the first month and then monthly for 6 consecutive months. RESULTS: Rate of wet nights was 77% in controls and 78.3% in the experimental group at onset of treatment (p = 0.82), and 49.5% and 31.2%, respectively, at the end of treatment (p = 0.02). Analyzing the average rate of improvement, there was a significantly greater increase in dry nights in the group undergoing neural stimulation (61.8%) compared to controls (37.3%, p = 0.0038). At the end of treatment percent improvement in children undergoing electrical stimulation had no relation to gender (p = 0.391) or age (p = 0.911). CONCLUSIONS: Treatment of primary monosymptomatic enuresis with 10 sessions of parasacral transcutaneous electrical neural stimulation plus behavioral therapy proved to be effective. However, no patient had complete resolution of symptoms.

Outcomes of targeted treatment for vesicoureteral reflux in children with nonneurogenic lower urinary tract dysfunction.

PURPOSE: There is a known association between nonneurogenic lower urinary tract conditions and vesicoureteral reflux. Whether reflux is secondary to the lower urinary tract condition or coincidental is controversial. We determined the rate of reflux resolution in patients with lower urinary tract dysfunction using targeted treatment for the underlying condition. MATERIALS AND METHODS: Patients diagnosed and treated for a lower urinary tract condition who had concomitant vesicoureteral reflux at or near the time of diagnosis were included. Patients underwent targeted treatment and antibiotic prophylaxis, and reflux was monitored with voiding cystourethrography or videourodynamics. RESULTS: Vesicoureteral reflux was identified in 58 ureters in 36 females and 5 males with a mean age of 6.2 years. After a mean of 3.1 years of treatment reflux resolved with targeted treatment in 26 of 58 ureters (45%). All of these patients had a history of urinary tract infections before starting targeted treatment. Resolution rates of vesicoureteral reflux were similar for all reflux grades. Resolution or significant improvement of reflux was greater in the ureters of patients with dysfunctional voiding (70%) compared to those with idiopathic detrusor overactivity disorder (38%) or detrusor underutilization (40%). CONCLUSIONS: Vesicoureteral reflux associated with lower urinary tract conditions resolved with targeted treatment and antibiotic prophylaxis in 45% of ureters. Unlike the resolution rates reported in patients with reflux without a coexisting lower urinary tract condition, we found that there were no differences in resolution rates among grades I to V reflux in patients with lower urinary tract conditions. Patients with dysfunctional voiding had the most improvement and greatest resolution of reflux. Additionally grade V reflux resolved in some patients.