Recent advances in neuroimaging of bladder, bowel and sexual function

PURPOSE OF REVIEW: In this review, we summarize recent advances in the understanding of the neural control of the bladder, bowel and sexual function, in both men and women. RECENT FINDINGS: Evidence of supraspinal areas controlling the storage of urine and micturition in animals, such as the pontine micturition centre, emerged in the early 20th century. Neurological stimulation and lesion studies in humans provided additional indirect evidence for additional bladder-related brain areas. Thereafter, functional neuroimaging in humans with PET and fMRI provided more direct evidence of the involvement of these brain areas. The areas involved in the storage and expulsion of urine also seem to be involved in the central control of storage and expulsion of feces. Furthermore, most knowledge on the brain control of sexual function is obtained from dynamic imaging in human volunteers. Relatively little is known about the dysfunctional central circuits in patients with pelvic organ dysfunction. SUMMARY: fMRI has been the most widely used functional neuroimaging technique in the last decade to study the central control of bladder function, anorectal function and sexual function. The studies described in this review show which sensory and motor areas are involved, including cortical and subcortical areas. We propose the existence of a switch-like phenomenon located in the pons controlling micturition, defecation and orgasm

Transcutaneous Electrical Stimulation of the Abdomen, Ear, and Tibial Nerve Modulates Bladder Contraction in a Rat Detrusor Overactivity Model:A Pilot Study

Purpose: The global prevalence of overactive bladder (OAB) is estimated at 11.8%. Despite existing treatment options such as sacral neuromodulation, a substantial number of patients remain untreated. One potential alternative is noninvasive transcutaneous electrical stimulation. This form of stimulation does not necessitate the implantation of an electrode, thereby eliminating the need for highly skilled surgeons, expensive implantable devices, or regular hospital visits. We hypothesized that alternative neural pathways can impact bladder contraction. Methods: In this pilot study, we conducted transcutaneous electrical stimulation of the abdominal wall (T6-L1), the ear (vagus nerve), and the ankle (tibial nerve) of 3 anesthetized female Sprague-Dawley rats. Stimulation was administered within a range of 20 Hz to 20 kHz, and its impact on intravesical pressure was measured. We focused on 3 primary outcomes related to intravesical pressure: (1) the pressure change from the onset of a contraction to its peak, (2) the average duration of contraction, and (3) the number of contractions within a specified timeframe. These measurements were taken while the bladder was filled with either saline or acetic acid (serving as a model for OAB). Results: Transcutaneous stimulation of the abdominal wall, ear, and ankle at a frequency of 20 Hz decreased the number of bladder contractions during infusion with acetic acid. As revealed by a comparison of various stimulation frequencies of the tibial nerve during bladder infusion with acetic acid, the duration of contraction was significantly shorter during stimulation at 1 kHz and 3 kHz relative to stimulation at 20 Hz (P=0.025 and P=0.044, respectively). Conclusions: The application of transcutaneous electrical stimulation to the abdominal wall, ear, and tibial nerve could provide less invasive and more cost-effective treatment options for OAB relative to percutaneous tibial nerve stimulation and sacral neuromodulation. A follow-up study involving a larger sample size is recommended.</p

Two-Staged Sacral Neuromodulation for the Treatment of Nonobstructive Urinary Retention:A Multicenter Study Assessing Predictors of Success

Objectives: The aims of this study were to 1) determine the success rate of the tined lead test phase in patients with nonobstructive urinary retention (NOUR), 2) determine predictive factors of a successful test phase in patients with NOUR, and 3) determine long-term treatment efficacy and satisfaction in patients with NOUR. Materials and Methods: The first part was a multicenter retrospective study at two centers in The Netherlands. Patients with NOUR received a four-week tined lead test phase. Success was defined as a ≥50% reduction of clean intermittent catheterization frequency or postvoid residual. We analyzed possible predictors of success with multivariable logistic regression. Second, all patients received a questionnaire to assess efficacy, perceived health (Patient Global Impression of Improvement), and treatment satisfaction. Results: This study included 215 consecutive patients (82 men and 133 women) who underwent a tined lead test phase for the treatment of NOUR. The success rate in women was significantly higher than in men, respectively 62% (83/133) and 22% (18/82, p &lt; 0.001). In women, age per ten years (odds ratio [OR] 0.74, 95% CI: 0.59–0.93) and a history of psychiatric illness (OR 3.92, 95% CI: 1.51–10.2), including posttraumatic stress disorder (PTSD), significantly predicted first stage sacral neuromodulation (SNM) success. In men, age per ten years (OR 0.43, 95% CI: 0.25–0.72) and previous transurethral resection of the prostate and/or bladder neck incision (OR 7.71, 95% CI: 1.43–41.5) were significant predictors of success. Conversely, inability to void during a urodynamic study (for women, OR 0.79, 95% CI: 0.35–1.78; for men, OR 3.06, 95% CI: 0.83–11.3) was not predictive of success. Of the patients with a successful first stage, 75% (76/101) responded to the questionnaire at a median follow-up of three years. Of these patients, 87% (66/76) continued to use their SNM system, and 92% (70/76) would recommend SNM to other patients. Conclusions: A history of psychiatric illness, including PTSD, in women with NOUR increased the odds of first stage SNM success 3.92 times. A previous transurethral resection of the prostate and/or bladder neck incision in men increased the odds of success 7.71 times. In addition, a ten-year age increase was associated with an OR of 0.43 in men and 0.74 in women, indicating a 2.3- and 1.3-times decreased odds of success, respectively.</p

Bladder irrigation with tap water to reduce antibiotic treatment for catheter-associated urinary tract infections: an evaluation of clinical practice

IntroductionCatheter-associated urinary tract infection (CAUTI) is a common complication among patients with urinary catheters and is often treated with antibiotics. With increasing rates of antibiotic resistance, it is necessary to explore alternative treatment options for CAUTIs. The aims of this study were 1) to assess the efficacy and treatment satisfaction of bladder irrigation (BI) with tap water to prevent and treat CAUTIs, 2) and to evaluate the current use of BI for CAUTIs among Dutch clinicians.MethodsThe first part of this study consisted of a cross-sectional study among patients with intermittent or indwelling catheters who performed BI with tap water between March 2020 and May 2021. Efficacy, treatment satisfaction, and Patient Global Impression of Improvement (PGI-I) were assessed using questionnaires. Outcomes were compared between neurogenic lower urinary tract dysfunction (NLUTD) and non-NLUTD patients. Factors associated with overall treatment satisfaction were determined using logistic regression analysis. Second, a nationwide survey of Dutch clinicians was conducted to evaluate the current use of BI for CAUTIs.ResultsA total of 99 patients who were performing BI for at least three months were included. The median age was 61.9 years, 41.4% had NLUTD, and 72.2% performed BI &gt;1 year. The majority of both NLUTD (65.9%) and non-NLUTD patients (68.4%) were (very) satisfied with BI. Women had higher odds of reporting higher satisfaction and each additional CAUTI decreased the odds. Most NLUTD (85.4%) and non-NLUTD (65.5%) patients reported an improvement on the PGI-I with a difference in favour of NLUTD patients (p=0.002). In addition, 40.4% of the patients had no CAUTI, and 59.6% reported 1.39 (SD 2.06) CAUTIs. Only half of these self-reported CAUTIs were treated with antibiotics. In addition, 33 (58.9%) clinicians used BI for CAUTIs, of which ten used tap water as irrigation agent.DiscussionThis study provides first evidence supporting the efficacy of BI with tap water in the treatment of CAUTIs and reducing the use of antibiotics. Patients are overall satisfied and experience improvement in their condition with BI. In addition, the majority of the surveyed Dutch clinicians use BI for CAUTIs. However, irrigation with tap water is still not widely used

Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder

Studies of the major psychoses, schizophrenia (SZ) and bipolar disorder (BD), have traditionally focused on genetic and environmental risk factors, although more recent work has highlighted an additional role for epigenetic processes in mediating susceptibility. Since monozygotic (MZ) twins share a common DNA sequence, their study represents an ideal design for investigating the contribution of epigenetic factors to disease etiology. We performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from a unique sample of MZ twin pairs discordant for major psychosis. Numerous loci demonstrated disease-associated DNA methylation differences between twins discordant for SZ and BD individually, and together as a combined major psychosis group. Pathway analysis of our top loci highlighted a significant enrichment of epigenetic changes in biological networks and pathways directly relevant to psychiatric disorder and neurodevelopment. The top psychosis-associated, differentially methylated region, significantly hypomethylated in affected twins, was located in the promoter of ST6GALNAC1 overlapping a previously reported rare genomic duplication observed in SZ. The mean DNA methylation difference at this locus was 6%, but there was considerable heterogeneity between families, with some twin pairs showing a 20% difference in methylation. We subsequently assessed this region in an independent sample of postmortem brain tissue from affected individuals and controls, finding marked hypomethylation (>25%) in a subset of psychosis patients. Overall, our data provide further evidence to support a role for DNA methylation differences in mediating phenotypic differences between MZ twins and in the etiology of both SZ and BD

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

Transcutaneous Electrical Nerve Stimulation and Percutaneous Tibial Nerve Stimulation to Treat Idiopathic Nonobstructive Urinary Retention: A Systematic Review

Context: Transcutaneous electrical nerve stimulation (TENS) and percutaneous tibial nerve stimulation (PTNS) provide minimally invasive ways to treat idiopathic nonobstructive urinary retention (NOUR). Objective: To assess the efficacy of TENS and PTNS for treating idiopathic NOUR. Evidence acquisition: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Embase, Medline, Web of Science Core Collection, and the Cochrane CENTRAL register of trials were searched for all relevant publications until April 2020. Evidence synthesis: A total of 3307 records were screened based on the title and abstract. Eight studies met the inclusion criteria and none of the exclusion criteria. Five studies, all from the same group, reported the efficacy of PTNS and two that of TENS in adults with idiopathic NOUR. One study reported the efficacy of TENS in children with idiopathic NOUR. Objective success was defined as a ≥50% decrease in the number of catheterizations per 24 h or in the total catheterized volume in 24 h. The objective success rate of PTNS ranged from 25% to 41%. Subjective success was defined as the patient's request for continued chronic treatment with PTNS, and ranged from 46.7% to 59%. Eighty percent of women who underwent transvaginal stimulation reported an improvement such as a stronger stream when voiding. TENS in children reduced postvoid residual and urinary tract infections. Conclusions: The efficacy of TENS and PTNS in the treatment of idiopathic NOUR is limited and should be verified in larger randomized studies before application in clinical practice. Patient summary: The outcomes of transcutaneous electrical nerve stimulation and percutaneous tibial nerve stimulation for the treatment of urinary retention of unknown origin were reviewed. Whether these treatments are superior to other treatments could not be established

Androgen receptors in the forebrain: A study in adult male cats

Androgens and their receptors are present throughout the body. Various structures such as muscles, genitals, and prostate express androgen receptors. The central nervous system also expresses androgen receptors. Androgens cross the blood–brain barrier to reach these central areas. In the central nervous system, androgens are involved in multiple functions. The current study investigated in which forebrain areas androgens are expressed in the male cat. Androgen receptor immunoreactive (AR-IR) nuclei were plotted and the results were quantified with a Heidelberg Topaz II + scanner and Linocolor 5.0 software. The density and intensity of the labeled cells were the main outcomes of interest. The analysis revealed a dense distribution of AR-IR nuclei in the preoptic area, periventricular complex of the hypothalamus, posterior hypothalamic area, ventromedial hypothalamic, parvocellular hypothalamic, infundibular, and supramammillary nucleus. Numerous AR-IR cells were also observed in the dorsal division of the anterior olfactory nucleus, lateral septal nucleus, medial and lateral divisions of the bed nucleus of the stria terminalis, lateral olfactory tract nucleus, anterior amygdaloid area, and the central and medial amygdaloid nuclei. AR-IR nuclei were predominantly observed in areas involved in autonomic and neuroendocrinergic responses which are important for many physiological processes and behaviors

Variation of diagnosis and treatment of catheter-associated urinary tract infections: an online survey among caretakers involved

Background: The diagnosis of a clinically significant catheter-associated urinary tract infection (CAUTI) in patients performing clean intermittent catheterization (CIC) or with an indwelling catheter (IC) can be challenging. Objective: To get an insight into the variation of the used definition, diagnosis and management of CAUTIs by relevant healthcare workers in the Netherlands. Design: An online clinical scenario-based survey. Methods: The survey was built in Limesurvey and distributed to healthcare workers from randomly selected urology departments, rehabilitation departments/centres and general practice offices between January and May 2022. Questions regarding their field of experience, management strategies, used guidelines and two hypothetical cases with clinical scenarios of a possible CAUTI were included. Results: A total of 172 individuals participated, of which 112 completed the survey. In all, 32 individuals who completed the survey partially were also included. Participants consisted of 68 [44 urologists, 22 rehabilitation doctors (RDs) and 2 general practitioners (GPs)] doctors, 60 nurses (46 from the urology department and 14 from rehabilitation centres/departments) and 16 medical assistants (13 from urology department and 3 from GP offices). The majority consulted patients with an IC or on CIC on a daily/weekly or monthly basis. In all, 35 urologists (79.5%), 9 RDs (40.9%), 21 (45.7%) nurses in the urology department and 6 (42.9%) nurses from a rehabilitation department/centre indicated bladder irrigation as a treatment option for prevention/treatment of CAUTIs, treatment of symptoms or treatment of blockage of the catheter. In the clinical scenarios presented, treatment discrepancies were seen between subspecialties and healthcare workers. Various guidelines were named for the definition of CAUTIs. Conclusion: A considerable variation in diagnoses and management of CAUTIs between the healthcare workers involved was seen. Uniformity in diagnosing and managing CAUTIs, to prevent overtreatment and possible resistance to antibiotics, is advised. Suitable multidisciplinary guidelines are preferred