Urinary Dysfunction Research Articles

Impact of subthalamic nucleus stimulation on urinary dysfunction and constipation in Parkinson's disease.

The effect of subthalamic nucleus (STN) deep brain stimulation (DBS) on urinary dysfunction and constipation in Parkinson's disease (PD) is variable. This study aimed to identify potential surgical and nonsurgical variables predictive of these outcomes. The authors used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I to assess urinary dysfunction (item 10) and constipation (item 11) preoperatively and at 6-12 months postoperatively. A multiple linear regression model was used to investigate the impact of global cerebral atrophy (GCA) and active electrode contact location on the urinary dysfunction and constipation follow-up scores, controlling for age, disease duration, baseline score, motor improvement, and levodopa-equivalent dose changes. An electric field model was applied to localize the maximal-effect sites for constipation and urinary dysfunction compared with those for motor improvement. Among 74 patients, 23 improved, 28 deteriorated, and 23 remained unchanged for urinary dysfunction; 25 improved, 15 deteriorated, and 34 remained unchanged for constipation. GCA score and age significantly predicted urinary dysfunction follow-up score (R2 = 0.36, p < 0.001). Increased GCA and age were independently associated with worsening urinary symptoms. Disease duration, baseline constipation score, and anterior active electrode contacts in both hemispheres were significant predictors of constipation follow-up score (R2 = 0.31, p < 0.001). Higher baseline constipation score and disease duration were associated with worsening constipation; anterior active contact location was associated with improvement in constipation. Anterior active contact location was associated with improvement in constipation in PD patients after STN DBS. PD patients with greater GCA scores before surgery were more likely to experience urinary deterioration after DBS.

Comparison of the efficiency of transcutaneous electrical nerve stimulation and manual therapy in children with cerebral palsy with lower urinary system dysfunction- a randomized prospective trial

Neurological defects in children with cerebral palsy (CP) not only affect their motor skills but also lead to bladder and bowel problems. Although most children with CP have achieved urinary control, more than 50% of cases experience lower urinary tract symptoms (LUTS). Common LUTS complaints observed in CP include delayed toilet training, urinary incontinence, increased frequency of urination, urgency, urinary hesitancy, and recurrent urinary tract infections. This study aimed to prospectively evaluate and compare the effectiveness of two different physiotherapy approaches, sacral Transcutaneous Electrical Nerve Stimulation (TENS) and massage, on lower urinary tract dysfunction in children with CP. A total of 54 children with CP who had the Dysfunctional Voiding Scoring System (DVISS) of 8.5 or higher were included in the study. Children were randomized to the TENS (TG; n=27) and Manual Therapy (MG; n=27) groups. TENS application was performed 2 sessions in a week for 20min for a total of 12 weeks. The electrodes used during the application were adhered bilaterally to the parasacral region (S2-S4). 4 electrodes of 5×5cm were used. Classical bowel massage was applied to the MG with the friction massage technique twice a week for 12 weeks. Manual therapy applications were performed in the form of abdominal, colon, and friction massage, twice a week for 20min by the physiotherapist. Massage was applied to the abdominal region between the lower subcostal border and the anterior superior iliac spine. Questionnaires were applied before and after treatment interventions: DVISS, functional bladder capacity (FBC), frequency of voiding, and urinary incontinence episodes evaluated by bladder diary, Bristol Gaita Scale, and Pediatric Incontinence Quality of Life Scale (PIN-Q) used. The decrease in the episodes of incontinence was higher in the TG (p=0.037; p<0.05). FBC increased after treatment in both groups, but there was no statistically significant difference between the groups (p=0.683; p>0.05). Manual therapy was more effective in improving constipation symptoms. In both groups, DVISS and PIN-Q values decreased after treatment, but the decrease in TG was statistically significant in the evaluation made between groups (p=0.001; p<0.01). Both parasacral TENS and massage provided a significant improvement in LUTS, constipation, and quality of life but TENS showed a bigger improvement. We suggest adding these interventions to the treatment of bladder and bowel problems in CP children.

Evaluating the Therapeutic Efficacy of L-Lysine Aescinat Supplementation on Neurological Outcomes in Patients with Spinal Fractures and Traumatic Spine Injuries: A Prospective Cohort Study from Tbilisi, Georgia

This prospective study aimed to comprehensively investigate the impact of L-Lysine aescinat supplementation on the neurological outcomes of patients recovering from spinal fractures and traumatic spine injuries. A total of 32 patients were recruited and categorised into two groups: Group A (n=16), receiving L-Lysine aescinat supplementation, and Group B (N=16), serving as the control group without L-Lysine aescinat administration. The primary objective was to assess changes in the Karnofsky performance scale, a functional and well-being neurological assessment tool especially for those undergoing operations or with chronic illness, over a follow up period of one month in order to determine if L-Lysine aescinat had an immediate effect on recovery in the post-operative period. Urinary dysfunction was noted, alongside the location of the fracture, type of surgery and if there were any significant comorbidities.

Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study.

We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at eight centres (seven US-based and one European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB and 23% to MSA). Faster phenoconversion from study enrolment to any diagnosis was associated with urinary and sexual dysfunction [hazard ratio (HR) 5.9, 95% confidence interval (CI): 1.6-22 and HR: 3.6, 95% CI: 1.1-12] followed by subtle motor signs (HR: 2.7, 95% CI: 1.2-6), trouble swallowing (HR 2.5, 95% CI: 1.4-4.5) and changes in speech (HR:2.4, 95% CI:1.1-4.8) at enrolment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95% CI: 1.1-5.9) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95% CI: 1.2-38). Patients with a younger age of PAF onset (HR: 11, 95% CI: 2.6-46), preserved olfaction (HR: 8.7, 95% CI: 1.7-45), anhidrosis (HR: 1.8, 95% CI: 1-3.1, P = 0.042) and severe urinary problems (HR 1.6, 95% CI: 1-2.5, P = 0.033) were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95% CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.

Notoginsenoside Fc, a novel renoprotective agent, ameliorates glomerular endothelial cells pyroptosis and mitochondrial dysfunction in diabetic nephropathy through regulating HMGCS2 pathway

BackgroundDiabetic nephropathy (DN) is the primary cause of end-stage renal disease (ESRD), and the therapeutic strategies for DN are limited. Notoginsenoside Fc (Fc), a novel saponin isolated from Panax Notoginseng (PNG), has been reported to alleviate vascular injury in diabetic rats. However, the protective effects of Fc on DN remain unclear. PurposeTo investigate the beneficial effects and mechanisms of Fc on DN. MethodsDb/db mice were treated with 2.5, 5 and 10 mg·kg−1·d−1 of Fc for 8 weeks. High glucose (HG) induced mouse glomerular endothelial cells (GECs) were treated with 2.5, 5 and 10 μM of Fc for 24 h. ResultsOur data found that Fc ameliorated urinary microalbumin level, kidney dysfunction and histopathological damage in diabetic mice. Moreover, Fc alleviated the accumulation of oxidative stress, the collapse of mitochondrial membrane potential and the expression of mitochondrial fission proteins, such as Drp-1 and Fis1, while increased the expression of mitochondrial fusion protein Mfn2. Fc also decreased pyroptosis-related proteins levels, such as TXNIP, NLRP3, cleaved caspase-1, and GSDMD-NT, indicating that Fc ameliorated GECs pyroptosis. In addition, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) expression was increased in diabetic group, which was partially abrogated by Fc. Our data further proved that knockdown of HMGCS2 could restrain HG-induced GECs mitochondrial dysfunction and pyroptosis. These results indicated that the inhibitory effects of Fc on mitochondrial damage and pyroptosis were associated with the suppression of HMGCS2. ConclusionTaken together, this study clearly demonstrated that Fc ameliorated GECs pyroptosis and mitochondrial dysfunction partly through regulating HMGCS2 pathway, which might provide a novel drug candidate for DN.

The clinical and neuroimaging differences between vascular parkinsonism and Parkinson's disease: a case-control study.

Parkinson's disease (PD) and vascular parkinsonism (VaP) have highly overlapping phenotypes, and different prognosis. This study comprehensively investigated the clinical, brain MRI and transcranial sonography differences between VaP and PD. Forty-eight patients with PD, 27 patients with VaP, and 29 healthy controls were compared. All patients were assessed using the MDS-UPDRS, Berg Balance Scale (BBS), Ten-Meter Walking Test (10-MWT), Time Up and Go Test, and Non-Motor Symptoms Scale. Beck Depression Inventory, PD questionnaire- 39, international urine incontinence scale, cognitive assessment scales, MRI brain and transcranial colour-coded doppler. The study was registered on clinical-Trial.gov (NCT04308135) on 03/12/2020. VaP patients showed significantly older age of onset, shorter disease duration, lower drug doses and levodopa responsiveness, higher On and Off axial scores, On and Off BBS, higher On scores for PIGD, rigidity, bradykinesia and total motor MDS-UPDRS, lower On and Off tremor, lower-half predominance, lower asymmetrical presentation and symmetric index than PD patients. VaP patients had worse non-motor symptoms Scale (NMSS) than controls except for perceptual problems/hallucinations but better symptoms than PD patients except for urinary dysfunction. Quality of life (QoL) was impaired in VaP patients and was correlated with motor function and NMSs. The VaP group had significantly higher white matter lesions and brain atrophy, with lower hyperechogenicity of the substantia nigra and more impaired cerebral vascular resistance and vasoreactivity than the PD group. VaP has a characteristic motor and non-motor profile, with impaired QoL, white matter, and transcranial sonography abnormalities that differentiate it from PD. Further studies are warranted to explore the role of vascular lesions in the pathogenesis of VaP. The registered identifier NCT04308135 on clinical-Trial.gov. Registered on 03/12/2020.

A review on Parkinson’s disease symptoms before and after deep brain stimulation treatment

Introduction: Parkinson’s disease (PD), followed by Alzheimer’s disease, is the most common progressive neurodegenerative disease. Tremors, rigidity, akinesia, and disorders are common PD symptoms. Over the last few decades, deep brain stimulation (DBS) of the subthalamic nucleus has become a standard treatment for advanced PD. The aim of this systematic review paper is to see the difference between the symptoms of PD before and after DBS. Methods: We conducted a literature search using PubMed and Google Scholar. We chose research from the past 10 years. We retrieved 64 papers, and seven duplicated papers were removed. We reviewed the abstract for the remaining 57 papers which led to the selection of 29 papers. After applying inclusion and exclusion criteria for the remaining 29 papers, 23 papers in the English language were chosen for our review. Results: Five Randomized Clinical Trials (RCTs) studied the outcomes of DBS and eight RCTs about effects on posture and motor function. Four RCTs investigated the effects on gait and balance, two on tremors, and the remaining two on posture. The effects of DBS on speech and language were compared in two RCTs. Three studies looked at cognitive performance. One RCT studied sleeping versus awake DBS on PD. These studies showed that with DBS treatment, there was significant improvement in posture, motor function, gait, balance, speech, and language. However, more studies are required for the further analysis on dysphagia and urinary dysfunction. Conclusion: Our study contributed to a better understanding of the advantages of DBS for a range of symptoms, but it concluded that additional RCT on dysphagia and urinary dysfunction was required to reach a reliable conclusion. More research is required to determine the effects of DBS on different motor and non-motor PD symptoms to standardize treatment.

Making bladder management a priority for multiple sclerosis

Multiple sclerosis (MS) can result in uro-neurological dysfunction, leading to a range of different urological problems that are distressing to the patient and costly for the NHS. Sue Thomas outlines why bladder management in MS needs greater focus to alleviate both negative patient experience and the financial burden of urinary dysfunction on the NHS.

Lifelong LUTS: Understanding the bladder's role and implications across transition phases, a comprehensive review.

Lower urinary tract symptoms (LUTSs) are a diverse array of urinary and pelvic dysfunctions that can emerge from childhood, extend through adulthood, and persist into older age. This narrative review aims to provide a comprehensive perspective on the continuum of LUTS and shed light on the underlying mechanisms and clinical implications that span across the lower urinary tract. A panel of five experts from Belgium, the Netherlands, India, Denmark, and the United States participated in an intensive research to explore and pinpoint existing insights into the lifelong concept of LUTS, particularly at the pelvic level. The experts reviewed the existing literature and held a webinar to discuss their findings. Childhood LUTS can persist, resolve, or progress into bladder underactivity, dysfunctional voiding, or pain syndromes. The Lifelong character can be explained by pelvic organ cross-talk facilitated through complex neurological and nonneurological interactions. At the molecular level, the role of vasopressin receptors in the bladder's modulation and their potential relevance to therapeutic strategies for LUTS are explored. Frailty emerges as a parallel concept to lifelong LUTS, with a complex and synergistic relationship. Frailty, not solely an age-related condition, accentuates LUTS severity with insufficient evidence regarding the effectiveness and safety profile of the available therapeutic modalities. Understanding lifelong LUTSs offers insights into genetic, anatomical, neurological, and molecular mechanisms. Further research could identify predictive biomarkers, elucidate the role of clinically translatable elements in pelvic cross-talk, and uncover molecular signatures for personalized management.

Etiology, presentation and management of urinary tract infections in multiple sclerosis patients: A review of the current literature.

Urinary tract infections (UTIs) present a formidable challenge in the care of individuals affected by multiple sclerosis (MS). Lower urinary tract dysfunction is a prevalent issue among MS patients, predisposing them to an elevated risk of UTIs. When left untreated, UTIs can further exacerbate the already compromised quality of life in individuals with MS. The diagnosis and management of UTIs in MS patients necessitate a careful clinical evaluation. The objective of this review is to delineate preventive strategies and current and developing therapeutic approaches for preventing and treating UTIs associated with urinary dysfunction, catheterization, and upper urinary tract infections in patients with MS. Effectively addressing UTIs and urinary tract dysfunction in individuals with multiple sclerosis calls for a comprehensive, interdisciplinary approach.

Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson’s disease autonomic dysfunction

Despite the significant frequency of autonomic dysfunction (AutD) in Parkinson’s disease (PD) patients, its pathogenesis and diagnosis are challenging. Here, we aimed to further explore the mechanism of phosphorylated α-synuclein (p-α-syn) deposited in vagus nerve Schwann cells (SCs) causing SCs damage and PD AutD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was administrated to C57BL/6 mice twice a week for 35 days. Following the final injection, locomotor functions, gastrointestinal symptoms, urine functions, and cardiovascular system functions were evaluated. Meanwhile, we examined p-α-syn deposited in vagus nerve SCs, Toll-like receptor 2 (TLR2) activation, and SCs loss using immunofluorescence, western blot, and Luxol fast blue staining. In vitro, the rat SCs line RSC96 cells were exposed to α-synuclein preformed fibril (α-syn PFF), and cell viability was detected by CCK8. Co-IP was used to identify the interaction between p-α-syn and TLR2. Furthermore, the role of TLR2 in p-α-syn-mediated SCs damage was confirmed by the administration of CU-CPT22, a specific blocker of TLR2. In vivo, apart from dyskinesia, MPTP mice exhibited constipation, urinary dysfunction, and cardiovascular failure, which were associated with the deposition of p-α-syn in vagus nerve SCs, TLR2 activation, and vagus nerve demyelination. In vitro, stimulation of α-syn PFF induced a time-dependent loss of viability, and p-α-syn deposited in RSC96 cells induced a cellular inflammatory response by interacting with TLR2, resulting in cell dysfunction and apoptosis. However, both SCs inflammatory response and cell viability were alleviated after inhibition of TLR2. Furthermore, 1 h fecal pellets and water content, the frequency of 1 h urine, blood pressure, heart rate, and heart rate variability of mice in the MPTP + CU-CPT22 group were also improved. Our results support the perspective that p-α-syn interacts with TLR2 induced SCs damage and is involved in PD AutD, which sheds fresh light on the mechanism of PD AutD and indicates a promising treatment for PD AutD targeting SCs p-α-syn/ TLR2 signaling pathway.

Noradrenergic Pathways Involved in Micturition in an Animal Model of Hydrocephalus-Implications for Urinary Dysfunction.

Hydrocephalus is characterized by enlargement of the cerebral ventricles, accompanied by distortion of the periventricular tissue. Patients with hydrocephalus usually experience urinary impairments. Although the underlying etiology is not fully described, the effects of hydrocephalus in the neuronal network responsible for the control of urination, which involves periventricular areas, including the periaqueductal gray (PAG) and the noradrenergic locus coeruleus (LC). In this study, we aimed to investigate the mechanisms behind urinary dysfunction in rats with kaolin-induced hydrocephalus. For that purpose, we used a validated model of hydrocephalus-the rat injected with kaolin in the cisterna magna-also presents urinary impairments in order to investigate the putative involvement of noradrenergic control from the brain to the spinal cord Onuf's nucleus, a key area in the motor control of micturition. We first evaluated bladder contraction capacity using cystometry. Since our previous characterization of the LC in hydrocephalic animals showed increased levels of noradrenaline, we then evaluated the noradrenergic innervation of the spinal cord's Onuf's nucleus by measuring levels of dopamine β-hydroxylase (DBH). We also evaluated the expression of the c-Fos protooncogene, the most widely used marker of neuronal activation, in the ventrolateral PAG (vlPAG), an area that plays a major role in the control of urination by its indirect control of the LC via pontine micturition center. Hydrocephalic rats showed an increased frequency of bladder contractions and lower minimum pressure. These animals also presented increased DBH levels at the Onuf´s nucleus, along with decreased c-Fos expression in the vlPAG. The present findings suggest that impairments in urinary function during hydrocephalus may be due to alterations in descending noradrenergic modulation. We propose that the effects of hydrocephalus in the decrease of vlPAG neuronal activation lead to a decrease in the control over the LC. The increased availability of noradrenaline production at the LC probably causes an exaggerated micturition reflex due to the increased innervation of the Onuf´s nucleus, accounting for the urinary impairments detected in hydrocephalic animals. The results of the study provide new insights into the neuronal underlying mechanisms of urinary dysfunction in hydrocephalus. Further research is needed to fully evaluate the translational perspectives of the current findings.

Finite Element Analysis of Pelvic Floor Biomechanical Models to Elucidate the Mechanism for Improving Urination and Defecation Dysfunction in Older Adults: Protocol for a Model Development and Validation Study.

The population is constantly aging, and most older adults will experience many potential physiological changes as they age, leading to functional decline. Urinary and bowel dysfunction is the most common obstacle in older people. At present, the analysis of pelvic floor histological changes related to aging has not been fully elucidated, and the mechanism of improving intestinal control ability in older people is still unclear. The purpose of this study is to describehow the finite element method will be usedto understand the mechanical characteristics of and physiological changes in the pelvic cavity during the rehabilitation process, providing theoretical support for the mechanism for improving urination and defecation dysfunction in older individuals. We will collect magnetic resonance imaging (MRI) and computed tomography (CT) data of the pelvic cavity of one male and one female volunteer older than 60 years and use the finite element method to construct a 3D computer simulation model of the pelvic cavity. By simulating different physiological states, such as the Valsalva maneuver and bowel movement, we will verify the accuracy of the constructed model, investigate the effects of different neuromuscular functional changes, and quantify the impact proportions of the pelvic floor muscle group, core muscle group, and sacral nerve. At present, we have registered the study in the Chinese Clinical Trial Registry and collected MRI and CT data for an older male and an older female patient. Next, the construction and analysis of the finite element model will be accomplished according to the study plan. We expect to complete the construction and analysis of the finite element model by July 2024 and publish the research results by October 2025. Our study will build finite element models of the pelvic floor of older men and older women, and we shall elucidate the relationship between the muscles of the pelvic floor, back, abdomen, and hips and the ability of older adults to control bowel movements. The results of this study will provide theoretical support for elucidating the mechanism for improving urination and defecation dysfunction through rehabilitation. Chinese Clinical Trial Registry ChiCTR2400080749; https://www.chictr.org.cn/showproj.html?proj=193428. DERR1-10.2196/56333.

Lateral lymph node dissection can increase overall survival and 5‑year survival rate of rectal cancer patients: A meta‑analysis.

Rectal cancer is one of the most malignant tumors, and postoperative recurrence and metastasis are the main reasons for treatment failure. Lymph node metastasis is the main metastatic pathway of rectal cancer. The present study aimed to investigate the role of lateral lymph node dissection (LLND) in patients with rectal cancer using a meta-analysis. Articles in Chinese and English related to the application of LLND in patients with rectal cancer were retrieved and eligible studies were selected for data analysis. Evaluation indicators included the 5-year survival rate, recurrence rate, urinary system function and operation time. The random-effects model was utilized for the analysis. A total of 10 studies that met the eligibility criteria were selected, comprising 2,272 patients, including 1,101 cases in the LLND group and 1,171 cases in the non-LLND group. No significant difference was found between the two groups in terms of local recurrence rate, 5-year disease-free survival (DFS) rate, and DFS rate at the follow-up. It is noteworthy that cases in the LLND group had no significantly longer overall survival, but had a higher 5-year survival rate. However, cases in the LLND group had a longer operation time and worse urinary dysfunction. The results remained consistent throughout separate analyses for different research quality sources. The present meta-analysis showed that LLND provided a specific advantage in prolonging survival time. However, it was associated with prolonged operation time and an increased incidence of urinary dysfunction.

Management of Urinary Dysfunction in Patients with Multiple Sclerosis

Besides the motor and sensory dysfunction that characterizes multiple sclerosis, during the disease evolution and with the accumulation of new demyelinating lesions in specific areas of the central nervous system, autonomic dysfunction be-comes more prevalent among patients suffering from multiple sclerosis. Although not usually addressed, the complex spectrum of autonomic dysfunction manifestations has the potential of a negative impact on the daily activities of multiple sclerosis patients, needing specific investigations and therapeutic measures destined to alleviate symptoms and increase the quality of life. Since urinary dysfunction is evident from the early stages of multiple sclerosis on urodynamic studies even in patients without urinary complaints, it is indicated to thoroughly screen for urinary tract dysfunction as well as other autonomic dysfunctions in all the multiple sclerosis patients.

External validation of predictive models of sexual, urinary, bowel and hormonal function after surgery in prostate cancer subjects

BackgroundIn 2020, a research group published five linear longitudinal models, predict Expanded Prostate Cancer Index Composite-26 (EPIC-26) scores post-treatment for radical prostatectomy, external beam radiotherapy and active surveillance collectively in US patients with localized prostate cancer.MethodsOur study externally validates the five prediction models for patient reported outcomes post-surgery for localised prostate cancer. The models’ calibration, fit, variance explained and discrimination (concordance-indices) were assessed. Two Australian validation cohorts 1 and 2 years post-prostatectomy were constructed, consisting of 669 and 439 subjects, respectively (750 in total). Patient reported function in five domains post-prostatectomy: sexual, bowel, hormonal, urinary incontinence and other urinary dysfunction (irritation/obstruction). Domain function was assessed using the EPIC-26 questionnaire.Results1 year post-surgery, R2 was highest for the sexual domain (35%, SD = 0.02), lower for the bowel (21%, SD = 0.03) and hormone (15%, SD = 0.03) domains, and close to zero for urinary incontinence (1%, SD = 0.01) and irritation/obstruction (− 5%, SD = 0.04). Calibration slopes for these five models were 1.04 (SD = 0.04), 0.84 (SD = 0.06), 0.85 (SD = 0.06), 1.16 (SD = 0.13) and 0.45 (SD = 0.04), respectively. Calibration-in-the-large values were − 2.2 (SD = 0.6), 2.1 (SD = 0.01), 5.1 (SD = 0.1), 9.6 (SD = 0.9) and 4.0 (SD = 0.2), respectively. Concordance-indices were 0.73, 0.70, 0.70, 0.58 and 0.62, respectively (all had SD = 0.01). Mean absolute error and root mean square error were similar across the validation and development cohorts. The validation measures were largely similar at 2 years post-surgery.ConclusionsThe sexual, bowel and hormone domain models validated well and show promise for accurately predicting patient reported outcomes in a non-US surgical population. The urinary domain models validated poorly and may require recalibration or revision.

The aryl hydrocarbon receptor agonist ITE reduces inflammation and urinary dysfunction in a mouse model of autoimmune prostatitis.

Prostate inflammation is linked to lower urinary tract dysfunction and is a key factor in chronic prostatitis/chronic pelvic pain syndrome. Autoimmunity was recently identified as a driver of prostate inflammation. Agonists of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, have been used to suppress autoimmunity in mouse models of colitis, rhinitis, and dermatitis, but whether AHR agonists suppress prostate autoimmunity has not been examined. Here, we test whether ITE (2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester), an AHR agonist, suppresses inflammation, allodynia, and urinary dysfunction in a mouse model of experimental autoimmune prostatitis (EAP). C57BL/6J adult male mice were immunized with rat prostate antigen to induce EAP or TiterMax Gold® adjuvant (uninflamed control). Mice were also treated with ITE (10 mg/kg/day IP) or DMSO (vehicle, 5 mg/kg/day IP) for 6 days. Using the Nanostring nCounter Inflammation Panel, we evaluated the impact of EAP and ITE on prostatic RNA abundance. We validated EAP and ITE-mediated changes in a subset of RNAs by RT-PCR and RNAScope in situ RNA detection. EAP appeared to heighten histological inflammation in the dorsal prostate, induced tactile allodynia, and appeared to increase the frequency of non-voiding bladder contractions. ITE mitigated some actions of EAP. EAP changed abundance of 40 inflammation-related RNAs, while ITE changed abundance of 28 inflammation-related RNAs. We identified a cluster of RNAs for which ITE protected against EAP-induced changes in the abundance of H2-Ab1, S100a8, and S100a9. ITE also increased the abundance of the AHR-responsive Cyp1a1 RNA. These findings support the hypothesis that ITE activates the AHR in the prostate and reduces autoimmune-mediated prostatitis in mice.

Effect of photobiomodulation on lower urinary tract dysfunction in rat cystitis model.

Photobiomodulation selectively controls the activity of the sensory nervous system associated with A-delta and C fibers. Hypersensitivity involving the afferent A-delta and C fibers occurs in cystitis and decreases urinary function. This study aimed to investigate the effect of photobiomodulation on urinary storage dysfunction and voiding functions in cystitis model rats. We prepared the rat cystitis model. Under anesthesia, a cannula was connected to the bladder via a ventral incision. 0.3% acetic acid or saline was injected into the bladder. Continuous cystometry was performed, measuring bladder pressure and voiding urine volume with rats freely mobile. Laser irradiation was applied to the L6 lumbosacral intervertebral foramen using an 830 nm laser. Residual urine was extracted post-cystometry. In the rat cystitis model groups, there was a significant decrease in the voiding interval and volume compared to the group receiving normal saline infusion. After sham or laser irradiation, only the group with laser irradiation showed a significant increase in voiding interval (217%, p = 0.0002) and voiding volume (192%, p = 0.0012) in the parameters of storage dysfunction. The basal pressure, intravesical pressure, and residual urine volume remained unchanged in all groups before and after irradiation. This study indicates that photobiomodulation may improve urine storage dysfunction without exacerbating voiding function in a rat model of cystitis. Thus, photobiomodulation may be a new treatment option for the hypersensitivity and detrusor overactivity caused by cystitis.

Sex Disparities in Rectal Cancer Surgery: An In-Depth Analysis of Surgical Approaches and Outcomes.

Anatomical and physiological differences exist between sex, leading to variations in how diseases, such as rectal cancer, are prevalence and treatment outcomes of diseases including rectal cancer. In particular, in the case of rectal cancer, anatomical differences may be associated with surgical challenges, and these factors are believed to be important contributors to potential disparities in postoperative recovery, associated complications, and oncological outcomes between male and female patients. However, there is still ongoing debate regarding this matter. Significantly, the male pelvic anatomy is distinguished by its narrower dimensions, which can present surgical challenges and impede visual access during operative procedures, rendering it more complex than surgical interventions in the female pelvis. As a result, this anatomical difference leads to a greater occurrence of postoperative complications, such as anastomotic leakage. Moreover, the pelvis houses nerves that are vital for urinary and genital functions, underscoring the need to assess the potential risks of sexual and urinary dysfunction in rectal cancer surgery. These postoperative complications can significantly impact the quality of life; therefore, it is imperative to perform surgery with an understanding of the structural differences between sexes. Therefore, to address the limitations imposed by anatomical structures, new approaches such as robotic surgery, trans-anal total mesorectal excision, and intraoperative neuromonitoring are being introduced. Furthermore, it is essential to conduct research into fundamental mechanisms that may give rise to differences in surgical outcomes and oncological results between sexes. By comprehending the disparities between males and females, we can advance toward personalized treatments. Consequently, this review outlines variations in surgical approaches, complications, and treatments for rectal cancer in male and female patients.

Validation of a mobile application for adults with neurological lower urinary tract dysfunction.

to validate with experts the content of a mobile application to guide patients with neurological dysfunction of the lower urinary tract. methodological study. For content validation, 81 specialist nurses took part. The data collection instrument was designed in the form of an electronic form, and included assessments of the application's objectives, content, language, relevance, functionality and usability. The data was submitted to descriptive and inferential statistical analysis, based on the measurement of the Content Validity Index. the overall content validity index of the prototype application was 0.98. The lowest item (0.93) was related to the adequacy of the font size, and the highest module (1) was associated with usability, showing ease in handling the application. The experts recommended correcting spelling and grammar, as well as adding and minimizing information, standardizing language, among others. the content of the MeduLar sem Medo ® mobile app was validated with excellence by specialists, and presented important resources for teaching urinary dysfunction control and adherence to rehabilitation. With these results, it is possible to envision the next stages of validation, with application in the populations for which it is intended and incorporation of this care technology into the Unified Health System.