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Background: Neurogenic bladder (NB) is a form of neurological bladder dysfunction characterized by excessive contraction of the bladder detrusor. Protein kinase A (PKA) signaling is involved in the contraction of the detrusor muscle. Aims: To investigate whether PKA signaling mediates the effect of electroacupuncture (EA) on the excessive contraction of the bladder detrusor in NB. Methods: Sixty rats were randomly divided into control, sham, NB, NB + EA, and NB + EA + H89 (a PKA receptor antagonist) groups. The modified Hassan Shaker spinal cord transection method was used to generate a NB model. After EA intervention for one week, urodynamic tests were used to evaluate bladder function, hematoxylin and eosin staining was conducted to assess morphological changes, enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentration of PKA, and Western blotting was conducted to measure the protein levels of phosphorylated myosin light chain kinase (p-MLCK)/p-MLC. Results: The results showed that NB resulted in morphological disruption, impairment of urodynamics, and decreases in the concentration of PKA and the protein levels of p-MLCK/p-MLC. EA reversed the changes induced by NB dysfunction. However, the improvement in urodynamics and the increases in the concentration of PKA and the protein levels of p-MLCK/p-MLC were inhibited by H89. Conclusion: Our findings indicate that the PKA signaling pathway mediates the beneficial effect of EA on excessive contraction of the bladder detrusor in a rat model of NB. [ABSTRACT FROM AUTHOR]

Deterioration of neurovascular conditions can be rapid in patients with spontaneous subarachnoid haemorrhage (SAH) and often lead to poor clinical outcomes. Therefore, it is crucial to promptly assess and continually track the progression of the disease. This study incorporated baseline clinical conditions, repeatedly measured neurological grades and haematological biomarkers for dynamic outcome prediction in patients with spontaneous SAH. Neurological intervention, mainly aneurysm clipping and endovascular embolisation, was also incorporated as an intermediate event in developing a neurological intervention transition (NIT) joint model. A retrospective cohort study was performed on 701 patients in spontaneous SAH with a study period of 14 days from the MIMIC-IV dataset. A dynamic prognostic model predicting outcome of patients was developed based on combination of Cox model and piecewise linear mixed-effect models to incorporate different types of prognostic information. Clinical baseline covariates, including cerebral oedema, cerebral infarction, respiratory failure, hydrocephalus and vasospasm, as well as repeated measured Glasgow Coma Scale (GCS), glucose and white blood cell (WBC) levels were covariates contributing to the optimal model. Incorporation of neurological intervention as an intermediate event increases the prediction performance compared with baseline joint modelling approach. The average AUC of the optimal model proposed in this study is 0.7783 across different starting points of prediction and prediction intervals. The model proposed in this study can provide dynamic prognosis for spontaneous SAH patients and significant potential benefits in critical care management. [ABSTRACT FROM AUTHOR]

The prognosis for patients who achieve a pathologic complete response in bladder cancer is excellent, but the association between their prognosis and the tumor microenvironment is unclear. We investigated the tumor immune microenvironment of those with pathological complete response after platinum-based neoadjuvant chemotherapy for cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. Our retrospective study included 12 patients with pathological complete response who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. We assessed the density of several immune cell types in pretreatment and posttreatment tissues via multiplex fluorescence immunohistochemical analysis. The median age was 67 years; 10 patients were male. Nine (75%) and 3 (25%) patients were cT2 and cT3, respectively. The 5-year progression-free and overall survivals were 90% and 100%, respectively. The densities of regulatory T cells (Treg; CD3+CD4+FoxP3+ cell) were significantly decreased and almost disappeared in the tumor microenvironment of posttreatment tissue compared with pretreatment tissue. Other immune cells, such as effector T cells or M2 macrophages, were not significantly changed between posttreatment and pretreatment tissues. In pathological complete response, Tregs in the tumor immune microenvironment were significantly decreased after platinum-based chemotherapy for muscle-invasive bladder cancer. The temporary arresting of immune response in the tumor microenvironment may reflect a favorable prognosis due to the decrease of Tregs with tumor shrinkage and improve the host tumor immune response. [ABSTRACT FROM AUTHOR]

Simple Summary: This review introduces different methods for estimating the age of vertebrates for professionals in related fields and evaluates the accuracy of each method. Firstly, the degree of damage to vertebrates at the time of sample collection is classified. Then, the sample types and their applications are introduced, the most commonly used methods are listed, and methodological recommendations regarding accuracy are presented. Finally, the methods that will be used for vertebrate age estimation in the future, taking into account the current level of research and requirements, are predicted. This review is essential for promoting animal conservation and guiding the successful implementation of conservation management plans. Age is a core metric in vertebrate management, and the correct estimation of the age of an individual plays a principal role in comprehending animal behavior, identifying genealogical information, and assessing the potential reproductive capacity of populations. Vertebrates have a vertebral column and a distinct head containing a developed brain; they have played an important role in the study of biological evolution. However, biological age estimations constantly exhibit large deviations due to the diversity of vertebrate taxon species, sample types, and determination methods. To systematically and comprehensively understand age estimation methods in different situations, we classify the degree of damage to vertebrates during sample collection, present the sample types and their applications, list commonly applied methods, present methodological recommendations based on the combination of accuracy and implementability, and, finally, predict future methods for vertebrate age assessments, taking into account the current level of research and requirements. Through comprehensive data gathering and compilation, this work serves as an introduction and summary for those who are eager to catch up on related fields and facilitates the rapid and accurate selection of an evaluation method for researchers engaged in related research. This is essential to promote animal conservation and guide the smooth implementation of conservation management plans. [ABSTRACT FROM AUTHOR]

Background: Hunner-type interstitial cystitis (HIC) is a chronic inflammatory condition of the bladder. However, it remains unclear whether there is a causal relationship between the presence of Hunner lesions and seemingly normal-appearing areas in the bladder (non-Hunner lesions). This study aimed to investigate the fundamental aspects of HIC by examining potential genetic differences between Hunner and non-Hunner lesions and elucidate their role as potential markers in the progression and suppression of the disease. Methods: This cross-sectional study enrolled patients with HIC (n = 10) who underwent supratrigonal cystectomy along with augmentation cystoplasty. Full-thickness bladder tissue was collected from Hunner and non-Hunner lesions in the same patient. Normal bladder tissue biopsies were also obtained as controls. Whole transcriptome analysis was performed to analyze the gene expression patterns and immune cell populations. Results: The mucosal layers of patients exhibited similar pathway dysregulation across Hunner and non-Hunner lesions, with immunerelated pathways being prominently affected. In the mucosal layer, genes related to anti-inflammatory and immune suppression were downregulated in Hunner lesions compared to non-Hunner lesions. Moreover, in Hunner lesions, genes related to macrophage differentiation and polarization, such as VSIG4, CD68, MAFB, and LIRB4, were downregulated. The cell fraction of M2 macrophages was found to decrease in Hunner lesions. Immunohistochemical staining revealed an elevated fraction of M1 macrophages and a reduced fraction of M2 macrophages in Hunner lesions compared to those in non-Hunner lesions. In the muscular layer, transcriptomic evidence of muscle thickness was observed in both Hunner and non-Hunner lesions; however, the difference was not significant. Conclusion: Hunner lesions showed a reduced expression of anti-inflammatory and immunosuppressive factors compared to non-Hunner lesions, along with alterations in immune cell populations. This study suggests the possibility that macrophage polarization is related to the progression from non-Hunner lesions to Hunner lesions, suggesting its relevance to the characteristics of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Diabetic cystopathy (DCP) is a prevalent etiology of bladder dysfunction in individuals with longstanding diabetes, frequently leading to bladder interstitial fibrosis. Research investigating the initial pathological alterations of DCP is notably scarce. To comprehend the development of fibrosis and find effective biomarkers for its diagnosis, we prepared streptozotocin-induced long-term diabetic SD rats exhibiting a type 1 diabetes phenotype and bladder fibrosis in histology detection. After observing myofibroblast differentiation from rats' primary bladder fibroblasts with immunofluorescence, we isolated fibroblasts derived exosomes and performed exosomal miRNA sequencing. The co-differentially expressed miRNAs (DEMis) (miR-16-5p and let-7e-5p) were screened through a joint analysis of diabetic rats and long-term patients' plasma data (GES97123) downloaded from the GEO database. Then two co-DEMis were validated by quantitative PCR on exosomes derived from diabetic rats' plasma. Following with a series of analysis, including target mRNAs and transcription factors (TFs) prediction, hubgenes identification, protein–protein interaction (PPI) network construction and gene enrichment analysis, a miRNA-mediated genetic regulatory network consisting of two miRNAs, nine TFs, and thirty target mRNAs were identified in relation to fibrotic processes. Thus, circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of DCP, and the crucial genes in regulatory network might hold immense significance in studying the pathogenesis and molecular mechanisms of fibrosis, which deserves further exploration. [ABSTRACT FROM AUTHOR]

Uropathogenic Escherichia coli (UPEC) is the primary causative agent of urinary tract infections (UTIs) in humans. Moreover, as one of the most common bacterial pathogens, UPEC imposes a substantial burden on healthcare systems worldwide. Epithelial cells and macrophages are two major components of the innate immune system, which play critical roles in defending the bladder against UPEC invasion. Yet, the routes of communication between these cells during UTI pathogenesis are still not fully understood. In the present study, we investigated the role of membrane-bound nanovesicles (exosomes) in the communication between bladder epithelial cells and macrophages during UPEC infection, using an array of techniques such as flow cytometry, miRNA profiling, RNA sequencing, and western blotting. Moreover, our in vitro findings were validated in a mouse model of UPEC-induced cystitis. We found that UPEC infection induced the bladder epithelial MB49 cell line to secrete large numbers of exosomes (MB49-U-Exo), which were efficiently absorbed by macrophages both in vivo and in vitro. Assimilation of MB49-U-Exo induced macrophages to produce proinflammatory cytokines, including tumor necrosis factor (TNF)α. Exposure of macrophages to MB49-U-Exo reduced their phagocytic activity (by downregulating the expression of phagocytosis-related genes) and increased their rate of apoptosis. Mechanistically, we showed that MB49-U-Exo were enriched in miR-18a-5p, which induced TNFα expression in macrophages by targeting PTEN and activating the MAPK/JNK signaling pathway. Moreover, administration of the exosome secretion inhibitor GW4869 or a TNFα-neutralizing antibody alleviated UPEC-mediated tissue damage in mice with UPEC-induced cystitis by reducing the bacterial burden of the bladder and dampening the associated inflammatory response. Collectively, these findings suggest that MB49-U-Exo regulate macrophage function in a way that exacerbates UPEC-mediated tissue impairment. Thus, targeting exosomal -release or TNFα signaling during UPEC infection may represent promising non-antibiotic strategies for treating UTIs. Author summary: Urinary tract infections, which are typically caused by uropathogenic Escherichia coli (UPEC), affect over 150 million people each year, worldwide. Because the incidence of antibiotic resistance among UPEC strains is on the rise, urinary tract infections are becoming increasingly challenging to treat using this standard treatment method. Moreover, although the host immune response against UPEC has been intensively studied, the mechanism of communication between bladder epithelial cells and macrophages during UPEC infection remains largely unexplored. Here, we characterized the exosomes released from bladder epithelial cells following UPEC infection and evaluated their impact on macrophages. We demonstrated that bladder tissue destruction following excessive innate immune cell activation during UPEC infection may be driven by exosomes secreted from bladder epithelial cells. We further showed that pharmacologically inhibiting exosomal release from epithelial cells limited macrophage-associated inflammation, innate immune cell infiltration, and histopathological injuries in a mouse model of UPEC-induced cystitis. Collectively, our findings suggest that modulating exosome release represents a promising non-antibiotic therapy for UTIs. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a chronic granulomatous disease of unknown cause characterized by the presence of non-caseating granulomas. The disease can affect any organ including the nervous system. Neurosarcoidosis occurs in about 5% patients with sarcoidosis. The clinical presentation of neurosarcoidosis is varied, and it can involve the brain, spinal cord and peripheral nervous system, separately or in different combinations. The diagnosis of neurosarcoidosis is challenging, as biopsies from the nervous system are not readily available. Anti-TNFα agents are becoming one of the cornerstone treatments for neurosarcoidosis. In this case-based review, we discuss two cases of neurosarcoidosis with different clinical presentations. The first patient presented with confusion, while the second presented with walking difficulty and neurogenic bladder. Both patients were treated with methylprednisolone pulse therapy with rapid, but non-complete, improvement. Therefore, infliximab was initiated in both cases with subsequent improvement in the clinical manifestations and imaging findings, emphasizing the effectiveness and safety of infliximab in cases of severe neurosarcoidosis. In conclusion, the goal of neurosarcoidosis management is to prevent organ system damage and minimize the toxic cumulative adverse effects of glucocorticoid use. In this case-based review we discuss the various presentations, the diagnosis and the treatment of neurosarcoidosis. [ABSTRACT FROM AUTHOR]

Human Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent antimicrobial activity toward uropathogenic bacteria. The RNASE6 gene is heterogeneous in humans due to the presence of single nucleotide polymorphisms (SNPs). RNASE6 rs1045922 is the most common non-synonymous SNP, resulting in a G to A substitution that determines an arginine (R) to glutamine (Q) transversion at position 66 in the protein sequence. By structural analysis we observed that R66Q substitution significantly reduces the positive electrostatic charge at the protein surface. Here, we generated both recombinant RNase 6-R66 and -Q66 protein variants and determined their antimicrobial activity toward uropathogenic Escherichia coli (UPEC), the most common cause of UTI. We found that the R66 variant, encoded by the major SNP rs1045922 allele, exhibited superior bactericidal activity in comparison to the Q66 variant. The higher bactericidal activity of R66 variant correlated with an increase in the protein lipopolysaccharide binding and bacterial agglutination abilities, while retaining the same enzymatic efficiency. These findings encourage further work to evaluate RNASE6 SNP distribution and its impact in UTI susceptibility. [ABSTRACT FROM AUTHOR]

Although the intravesical instillation of Bacillus Calmette-Guerin (BCG) is widely used as adjuvant treatment for nonmuscle-invasive bladder cancers, the clinical benefit is variable across patients, and the molecular mechanisms underlying the sensitivity to BCG administration and disease progression are poorly understood. To establish the molecular signatures that predict the responsiveness and disease progression of bladder cancers treated with BCG, we performed transcriptome sequencing (RNA-seq) for 13 treatment-naïve and 22 post-treatment specimens obtained from 14 bladder cancer patients. To overcome disease heterogeneity, we used non-negative matrix factorization to identify the latent molecular features associated with drug responsiveness and disease progression. At least 12 molecular features were present, among which the immune-related feature was associated with drug responsiveness, indicating that pre-treatment anti-cancer immunity might dictate BCG responsiveness. We also identified disease progression-associated molecular features indicative of elevated cellular proliferation in post-treatment specimens. The progression-associated molecular features were validated in an extended cohort of BCG-treated bladder cancers. Our study advances understanding of the molecular mechanisms of BCG activity in bladder cancers and provides clinically relevant gene markers for evaluating and monitoring patients. [ABSTRACT FROM AUTHOR]

Aims The aims of the present study were to assess the efectiveness of transcutaneous tibial nerve stimulation (TTNS) on overactive bladder (OAB) symptoms and on urodynamic parameters in patients with multiple sclerosis (PwMS) and to seek predictive factors of satisfaction. Methods All PwMS who performed 12–24 weeks of TTNS and who underwent urodynamic assessment before and after treatment between June 2020 and October 2022 were included retrospectively. Data collected were bladder diaries, symptoms assessed with Urinary Symptoms Profle (USP), and urodynamic parameters (bladder sensations, detrusor overactivity, and voiding phase). Patients with improvement rated as very good or good on Patient Global Impression of Improvement (PGI-I) score were considered as responders. Results Eighty-two patients were included (mean age: 47.1±11.5 years, 67 (82%) were women). The mean USP OAB sub-score decreased from 7.7±3.5 to 6.0±3.4 (p<0.0001). On bladder diaries, voided volumes, void frequency, and the proportion of micturition done at urgent need to void signifcantly improved with TTNS (p<0.05). No signifcant change was found in urodynamic parameters. According to the PGI-I, 34 (42.5%) patients were good responders. The only parameter associated with higher satisfaction was the percentage of micturition done at urgent need to void before the initiation of the treatment (39.8%±30.5 in the responder group vs 25.1%±25.6 in the low/no responder group; p=0.04). Conclusion TTNS improves OAB symptoms in PwMS, without signifcant changes on urodynamics. A high rate of strong or urgent need to void in daily life was associated with higher satisfaction [ABSTRACT FROM AUTHOR]

Purpose: Spinal cord injury (SCI) leads to sensorimotor impairments; however, it can also be complicated by significant autonomic dysfunction, including cardiovascular and lower urinary tract (LUT) dysfunctions. Autonomic dysreflexia (AD) is a dangerous cardiovascular complication of SCI often overlooked by healthcare professionals. AD is characterized by a sudden increase in blood pressure (BP) that can result in severe cardiovascular and cerebrovascular complications. In this review, we provide an overview on the clinical manifestations, risk factors, underlying mechanisms, and current approaches in prevention and management of AD. Methods: After conducting a literature research, we summarized relevant information regarding the clinical and pathophysiological aspects in the context of urological clinical practice Conclusions: The most common triggers of AD are those arising from LUT, such as bladder distention and urinary tract infections. Furthermore, AD is commonly observed in individuals with SCI during urological procedures, including catheterization, cystoscopy and urodynamics. Although significant progress in the clinical assessment of AD has been made in recent decades, effective approaches for its prevention and treatment are currently lacking. [ABSTRACT FROM AUTHOR]

A recent development in cancer chemotherapy is to use cytotoxics to induce tumor-specific immune response through immunogenic cell death (ICD). In ICD, calreticulin is translocated from endoplasmic reticulum to cell membrane (ecto-CRT) which serves as the 'eat-me-signal' to antigen-presenting cells. Ecto-CRT measurements, e.g., by ecto-CRT immunostaining plus flow cytometry, can be used to study the pharmacodynamics of ICD in single cells, whereas ICD studies in intact 3-dimensional tissues such as human tumors require different approaches. The present study described a method that used (a) immunostaining with fluorescent antibodies followed by confocal microscopy to obtain the spatial locations of two molecules-of-interest (CRT and a marker protein WGA), and (b) machine-learning (trainable WEKA segmentation) and additional image processing tools to locate the target molecules, remove the interfering signals in the nucleus, cytosol and extracellular space, enable the distinction of the inner and outer edges of the cell membrane and thereby identify the cells with ecto-CRT. This method, when applied to 3-dimensional human bladder cancer cell spheroids, yielded drug-induced ecto-CRT measurements that were qualitatively comparable to the flow cytometry results obtained with single cells disaggregated from spheroids. This new method was applied to study drug-induced ICD in short-term cultures of surgical specimens of human patient bladder tumors. [Display omitted] • Calreticulin translocation to membrane is a key event in immunogenic cell death. • Tumor microenvironment regulates immune response. • Pharmacodynamic studies in intact tumors are likely to be clinically relevant. • Machine-learning/imaging tools to quantify membrane calreticulin in 3D tumors. [ABSTRACT FROM AUTHOR]

Objective: This systematic review was done to critically appraise the various evidence available in the literature for the presenting symptoms, diagnosis, and management modalities for primary bladder neck obstruction diagnosed on invasive urodynamics in young adult men 18-50 years of age. Methods: A search was conducted on PubMed, Embase, and Cochrane Central Register of Controlled Trials databases until July 2022 to find English-language studies relevant to the topic. Results: A total of 10 studies were included. The estimated difference in International Prostate Symptom Score between baseline and 3 months in the subgroup of medical and surgical treatment was found to be -8.82 and -11.25, respectively (P = .37), and after 12 months, it was found to be -7.69 and -17.70 respectively (P < .001). The pooled estimate for the difference in Qmax between baseline and 3 months after medical and surgical treatments in the subgroup was found to be 2.92 and 7.03, respectively (P = .18), and after 12 months, it was found to be 4.54 and 7.74, respectively (P < .001). The pooled estimate of the difference in post-void residue before and after 3 months of medical and surgical treatments in a subgroup was found to be -31.15 and -70, respectively (P < .001), and after 12 months, it was found to be -31.49 and -156.00, respectively (P < .001). Quality of life scores improved in both subgroups. Conclusion: The alpha-blockers are effective in managing primary bladder neck obstruction in the short term, while bladder neck incision is preferred for better longterm outcomes. [ABSTRACT FROM AUTHOR]

Background/Aims: Bladder cancer is considered one of the most aggressive neoplasms due to its recurrence and progression profile, and even with the improvement in diagnosis and treatment methods, the mortality rate has not shown a declining trend in recent decades. From this perspective, the search and development of more effective and safer therapeutic alternatives are necessary. Phytochemicals are excellent sources of active principles with therapeutic potential. [6]-Shogaol is a phenolic compound extracted from the ginger rhizomes that has shown antitumor effects in a wide variety of cancer models. However, there is no record in the literature of studies reporting these effects in models of bladder cancer. Thus, this study aimed to investigate the in vitro cytotoxic and pro-apoptotic potential of [6]-Shogaol against murine bladder cancer urothelial cells (MB49). Methods: The cytotoxic effects of [6]-Shogaol on cell viability (MTT method), cell morphology (light microscopy), alteration of proliferative processes (clonogenic assay), oxidative stress pathway (levels of reactive oxygen species) and the induction of apoptotic events (flow cytometry and high-resolution epifluorescence imaging) were evaluated in murine urothelial bladder cancer cell lines (MB49), relative to non-tumor murine fibroblasts (L929). Results: The results showed that [6]-Shogaol was able to induce concentration-dependent cytotoxic effects, which compromised cell viability, exhibiting an inhibitory concentration of 50% of cells (IC50) of 146.8 µM for MB49 tumor cells and 236.0 µM for L929 non-tumor fibroblasts. In addition to inhibiting and altering the proliferative processes if colony formation, it presented pro-apoptotic activity identified through a quantitative analysis and the observation of apoptotic phenotypes, events apparently mediated by the induction of nuclear fragmentation. Conclusion: The data presented suggest that [6]-Shogaol has a higher concentration-dependent cytotoxic and apoptosis-inducing potential in MB49 cells than in L929 fibroblasts. These results may contribute to the development of therapeutic alternatives for bladder cancer. [ABSTRACT FROM AUTHOR]

The aim of motorway networks is to ensure smooth, high volume road traffic. The problem of anomalies in the system has been a longstanding concern for researchers, and with the widespread use of motorway networks a series of studies have been published on the subject. Speed limitation is one of the most important tools of mitigating disturbances. This study is looking for a solution to the problem known as the "shock wave effect". The research is based on a simulation method in a PTV VISSIM environment. The software can be used to examine certain traffic conditions, and then apply dynamic speed limitation based on these conditions. The Built Environment Information Platform (BENIP) is based on the idea that the built environment, the traffic, and the flow of information between them are closely related. The relevance of the study lies in the fact that a point-based notification of speed limits can be used for vehicles - a technology that is available in most cases at the infrastructure level on motorways - thus, improving road capacity and traffic safety. [ABSTRACT FROM AUTHOR]

Introduction To investigate the role of trans-labial ultrasound study in detection of female urethral stenosis (FUS) compared to former cysto-urethroscopy as the currently available definitive diagnostic modality. Material and methods In this cross-sectional study, 60 consecutive patients with bladder outlet obstruction diagnosed by clinical symptoms and urodynamic study, were included from 2019 to 2022. For additional assessment, all these patients underwent gel-Infused trans-labial ultrasound (GITLUS) and cystourethroscopy. Trans-labial real-time ultrasonography was performed following the insertion of 20 ml steady stream viscous jelly into the urethral meatus to assess the length of the urethra and exact location and length of the probable narrowing, as well as the presence of peri-urethral fibrosis (PUF). Results In GITLUS evaluation, urethral stricture was found in 27 patients. Mean urethral length and stricture length were 35.63 ±4.78 and 17.04 ±10.59, respectively. All these stenosis were confirmed via cysto-urethroscopy. PUF was found in 20 of 27 patients. In cysto-urethroscopy, urethral stricture was confirmed in 40 patients: 13 in urethral meatus and 27 in other parts or pan-urethra. GITLUS could not reveal urethral stricture in 13 patients with meatal stenosis, confirmed with cystoscopy. GITLUS detected FUS less accurately when it involves pure distal urethra compared to other parts of urethra or pan-urethral stenosis (p value = 0.002). Conclusions GITLUS is a safe, non-invasive, and valuable technique for detecting FUS. The location and the length of the stricture and probable peri-urethral fibrosis can be identified by this method. However, in meatal or pure short-length distal urethral strictures, this method should be used with caution. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study was to assess the detrusor underactivity (DUA) prevalence of females with symptomatic anterior pelvic organ prolapse (POP) and to evaluate the relationship between DUA and POP stage. Material and methods This was a prospective study recruiting women with symptomatic anterior POP. Patients with symptomatic stage 2-4 POP quantification system (POP-Q) who underwent urodynamics (UD) between January 2018 and April 2021 were included. Results Data on 330 women (mean age 63.7 ±18.4 years old) with anterior vaginal wall defect were enrolled. Concomitant apical defect (uterine/vaginal vault) requiring surgical correction was diagnosed in 38 women (11.5%). DUA was found in 166 females (50.3%). In DUA women, POP-Q stage 2 was found in 45.2%, stage 3 in 50.9% and stage 4 in 76.5%. Only stage POP-Q stage 4 showed a statistically significant difference between DUA and non-DUA females (p 0.006). Conclusions In women with symptomatic POP, regardless of the POP-Q stage, the chance of DUA occurrence was high. DUA was diagnosed in approximately half of the women undergoing UD for symptomatic POP, and it was three-fold higher in cases of POP-Q stage 4. Due to the high incidence of DUA in POP-Q 4 stage, it may be advantageous to identify and treat prolapse before they progress to stage 4. [ABSTRACT FROM AUTHOR]

Introduction It is still uncertain whether detrusor underactivity (DUA) influences the outcomes of women undergoing surgery for stress urinary incontinence (SUI). Even less evidence is available about women with complicated stress urinary incontinence (C-SUI). The aim of the study was to assess outcomes of middle urethral sling (MUS) placement according to the type of SUI, and the impact of DUA on uncomplicated SUI (U-SUI) and C-SUI functional and surgical results. Material and methods The study was conducted among patients undergoing MUS. The population was divided into 4 groups: 1: C-SUI with DUA; 2: C-SUI without DUA; 3: U-SUI with DUA; and 4: U-SUI without DUA. Women were qualified for the DUA group if they met one of the Jeong, Abarbanel and Marcus, BVE, and PIP1 Griffiths criteria. Post-operative functional outcomes and differences in POUR rate, de novo overactive bladder syndrome (OAB), and SUI recurrence were examined. Results 142 women took part in the study, of whom 97 completed the 2-year follow-up. DUA was found in 54.6% (53/97) of patients. C-SUI was prevalent also in the no-DUA group (59.1%). Post-operative ICIQ-FLUTS improved more in the no-DUA patients compared to the DUA women. Post-operative Qmax was statistically significant higher the in no-DUA than in the DUA population. After surgery, neither the PVR nor the PVR ratio differed in the DUA and the no-DUA patients. C-SUI and U-SUI patients showed a POUR rate of 15.6%-12.1%, de novo OAB 12.5%-3%, tape incision 3.1%-3%, and SUI recurrence 4.6%-3%, respectively. Conclusions The impact of pre-operative DUA on the outcomes of patients undergoing MUS was negligible, even in C-SUI cases. DUA women with SUI, even if complicated, should not be excluded from this kind of surgery. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Physical Medicine & Rehabilitation Sciences is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Chilena de Urologia is the property of Sociedad Chilena de Urologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Men with detrusor underactivity (DUA) and concomitant bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE) may present poorer functional outcomes after surgical desobstruction. This study aimed to evaluate the safety and efficacy of BPE surgery in men with DUA compared with those with normal detrusor contractility (NC). Materials and Methods: This review was performed according to the 2020 PRISMA framework. A comprehensive literature search was performed until May 7, 2023, using MEDLINE, EMBASE, and Cochrane Database. No date limits were imposed. Only comparative studies were accepted. The primary endpoint was to assess if there was any difference in short‐ and long‐term functional outcomes after BPE surgery in men with DUA and NC. The secondary endpoint was to evaluate the differences in perioperative outcomes and postoperative complications between the two groups. Meta‐analysis was performed using Review Manager (RevMan) software. Results: There were 5 prospective nonrandomized studies and 12 retrospective studies, including 1701 DUA and 1993 NC patients. Regarding surgical procedures, there were eight TURP (transurethral resection of the prostate) studies, four GreenLight PVP (photoselective vaporization of the prostate) studies, two HoLEP (Holmium laser enucleation of the prostate) studies, one GreenLight PVP/HoLEP study, one Holmium laser incision of the prostate study, and one study did not report the type of surgery. We did not find a statistically significant difference between the two groups in terms of perioperative outcomes, including postoperative catheterization time, hospitalization time, urinary retention, need to recatheterization, transfusion rate, or urinary tract infections. Also, we found no significant differences in long‐term complications, such as bladder neck stenosis or urethral stenosis. Posttreatment bladder recatheterization and retreatment rate for BPE regrowth could not be evaluated properly, because only one study reported these findings. When we analyzed functional outcomes at 3 months, those with NC had lower International Prostatic Symptom Score (IPSS), lower quality‐of‐life (QoL) score, better maximum flow rate (Qmax), and lower post‐voiding residual (PVR) of urine. These results were maintained at 6 months postoperatively, with exception of PVR that showed no difference. However, at 12 and more than 12 months the functional outcomes became similar regarding IPSS and QoL. There were few data about Qmax and PVR at longer follow‐up. Conclusion: In this meta‐analysis, data suggest that BOO surgical treatment in patients with concomitant BPE and DUA appears to be safe. Despite patients with DUA may present worse functional outcomes in the short postoperative term compared with the NC population, IPSS and QoL scores become comparable again after a longer follow‐up period after surgery. [ABSTRACT FROM AUTHOR]

Objectives: We examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI). Methods: SCI was induced by Th8−9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6‐S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme‐linked immunosorbent assay. Results: Sex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice. Conclusions: We demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6‐S1 DRG and NGF in the bladder could be involved in SCI‐induced lower urinary tract dysfunction in both sexes of mice. [ABSTRACT FROM AUTHOR]

Objective: To establish a normal reference value of postvoid residual (PVR) urine volume in "healthy" adults. Methods: Adults were recruited to undergo uroflowmetry and PVR. Those with neurological disorders, malignancy, diabetes, known lower urinary tract dysfunction, and urinary tract infection within the previous 3 months, were excluded from the study. Constipation was defined as Rome IV ≥ 2. Results: Of the 883 adults enrolled in this study, 194 (22.3%) did not complete the questionnaires or perform the uroflowmetry, 103 (11.7%) met ≥1 exclusion criteria and thus were excluded. In addition, 30 and 38 uroflowmetry were excluded due to artifacts and low bladder volume (BV) (<100 mL), respectively. Finally, 515 uroflowmetry and PVR data from adults aged 36–89 (mean: 59.0 ± 9.5) were examined. There was a significant nonlinear relationship between BV and PVR (p < 0.05), with PVR significantly increased when BV was around 528 mL. Women had lower PVR than men (p < 0.05). PVR also increased as the International Prostatic Symptom Score (IPSS) increased. PVR was unaffected by age and functional constipation. A multivariate analysis revealed that BV (p < 0.05) and IPSS (p < 0.05) had significant influence on PVR, but age, gender, and Rome IV score did not. The 90th and 95th percentiles of PVR for men were 73.2 mL (25% of BV) and 102.6 mL (30% of BV), respectively, while for women they were 60.5 mL (21% of BV) and 93.8 mL (27% of BV), respectively. Conclusion: Women had lower PVR than men. The 90th percentile or 95th percentile of normal adults' PVR may serve as the upper limit of normal PVR, and readings above this level may necessitate additional evaluation and treatment. Further studies are required to substantiate these recommendations. [ABSTRACT FROM AUTHOR]

We developed a high‐resolution and noninvasive multichannel urodynamic system combined with a novel signal‐processing algorithm tailored to extract electromyographic (EMG) activity from the urinary bladder. We utilized a flexible noninvasive biopotential recording system to collect an array of EMG signals from the urinary bladder of human subjects. This study also presents the use of an existing artifact rejection methodology to autonomously extract an EMG signal from an environment prone to motion artifacts. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

Lower urinary tract dysfunction not only interferes with the health-related quality of life of patients but may also lead to acute kidney injury and infections. To assess the bladder, urodynamic studies (UDS) have been implemented but the use of catheters leads to discomfort for the patient. Catheter-free long-term UDS would be useful and a potential solution could be ambulatory wireless devices that communicate via telemetry. Such sensors can detect pressure or volume. Numerous types of potential catheter-free sensors have been proposed for bladder monitoring. Despite substantial innovation in the manufacturing of implantable biomedical electronic systems, such sensors have remained at the laboratory stage due to a number of critical challenges. These challenges primarily concern hermeticity and biocompatibility, sensitivity and artifacts, drift, telemetry, and energy management. Having overcome these challenges, catheter-free ambulatory urodynamic monitoring could combine a synchronized intravesical pressure sensor with a volume analyzer but only the steps of cystometry and volume measurement are currently sufficiently reproducible to simulate UDS results. The measurement of volume by infrared optical sensors, in the form of abdominal patches, appears to be promising and studies are underway to market a telemetric ambulatory urodynamic monitoring system that includes an intravesical pressure sensor. There has been considerable progress in wearable and conformable electronics on many fronts, and continued collaboration between engineers and urologists could quickly overcome current challenges. In addition, to the diagnosis of UDS, such sensors could be useful in the development of a long-term closed-loop neuromodulation system. In this review, we explore the various types of catheter-free bladder sensors, inherent challenges and solutions to overcome these challenges, and the clinical potential of such long-term implantable sensors. [ABSTRACT FROM AUTHOR]

Introduction: The bladder is believed to be acontractile due to the phase of spinal shock and there is a lack of data on the detrusor function within the first few days after spinal cord injury (SCI). This study intended to assess the detrusor function with invasive urodynamics (UDS) during the first 15 days of SCI. Methods: This prospective observational study was carried out from January 2020 to June 2021 and consecutive stable patients older than 18 years of age who had a history of traumatic SCI within the past 15 days were screened for inclusion. For each patient, the International Standards for Neurological Classification of SCI Worksheet was filled. All patients underwent bedside invasive UDS within 15 days of injury. Results: There were a total of 41 patients with a mean age of 35 years. The thoracic cord was most commonly involved (46.3%) with Type A AISA grade being the most common (68.2%). The mean duration of injury at the time of UDS was 6 days. Abnormality in the filling phase could be identified in six patients. Three patients had neurogenic detrusor overactivity (NDO), with one having a high-pressure phasic NDO and one having a sustained NDO. Two patients had poor compliance and one had borderline poor compliance. None of the patients generated any detrusor pressure during voiding cystometry. Conclusions: In patients with SCI, 14.5% of the patients had abnormal findings during the filling phase on the UDS performed within 15 days of the injury. These findings are in stark contrast to the traditional understanding that the detrusor is acontractile during the early phase of the SCI and merit further evaluation. [ABSTRACT FROM AUTHOR]

Background:: Overactive Bladder Syndrome (OAB) affects individuals across all ages and genders, reducing quality of life. Although Transcutaneous Posterior Tibial Nerve Stimulation (TTNS) is an effective treatment, its acute effects on OAB remain underexplored. Objectives:: This study aimed to assess the acute effects of TTNS on OAB through invasive urodynamics (UDI), using an intermittent, on-demand approach; with a focus on urinary urgency as the central axis for its application. Methods:: A proof-of-concept trial was conducted involving patients with OAB symptoms and no previous treatment. An initial urodynamic evaluation (UDI DG) identified patients with detrusor overactivity (DO) associated with urgency, who then received on-demand TTNS during a second urodynamic study (UDI TENS). Parameters measured included the number of involuntary detrusor contractions (IDC), episodes of urge urinary incontinence (UUI), and maximum cystometric capacity (MCC). Statistical significance was assessed using Student’s t-test and Wilcoxon test, with a p-value ≤ 0.05 chosen as significance threshold. Results:: Of the initial twenty-nine participants, 12 completed the study. UDI DG measurements showed an average of 3.33 ± 1.3 IDCs, 0.67 ± 0.98 UUI episodes, and MCC of 235 ± 79 ml. During UDI TENS results demonstrated a significant reduction in IDCs to 0.08 ± 0.29 (p ≤ 0.001), an absence of UUI episodes, and an increase in MCC to 315 ± 83 ml (p = 0.00012). Conclusions:: Our findings suggest that an acute, on-demand TTNS protocol is effective for managing OAB symptoms and improvement of UDI parameters. However, the limited number of participants and absence of a control group highlight the need for further research through larger, controlled studies.

Introduction and Objectives:: The International Continence Society (ICS) has published essential documents standardizing urodynamic technique and reporting. Currently, no consensus exists regarding patient prompts for bladder sensation, particularly in the setting of impaired bladder sensation (e.g. spinal cord injury) (SCI). Similarly, no published standardization exists for the reporting of rectal contractions or duration and amplitude of involuntary detrusor contractions (IDCs). We evaluated current practice patterns among ICS urodynamicists regarding sensation prompts, mention of rectal contractions, and the extent to which involuntary detrusor contractions are described. Methods:: A Qualtrics urodynamic testing survey was distributed via email to all ICS members twice over a 2 week period. The survey included 18 questions regarding provider and practice characteristics, urodynamic practice patterns, coaching prompts given to patients regarding sensation during urodynamic testing, and documentation of rectal and involuntary detrusor contractions (IDCs). Data were analyzed using descriptive statistics. Results:: Of 2859 ICS members, 614 (21%) returned surveys. Of these, 35 did not perform urodynamic testing and 142 surveys were incomplete. Thus, 437/614 (71%) surveys were included in our analysis. Participants were most commonly fellowship-trained female functional urologists (40%) and practiced in a government service hospital (46.4%). Half of the providers (56%) are present for the study 100% of the time. Most participants instructed patients on how to report sensation during testing (57%). First Sensation (86%), First Desire (85%), Strong Desire (93%), and Urgency (86%) were the parameters most utilized. Various prompts for each of the UDS sensation parameters were reported including repeating ICS definitions and real-life analogies. 45% of respondents altered instructions for patients with impaired sensation (e.g. SCI), 59% commented on the presence or absence of rectal contraction, and 70% characterized the amplitude and duration of involuntary detrusor contractions in their reports. Conclusion:: Although most survey participants report they standardize urodynamic instructions, there is no consensus for sensation prompts within ICS urodynamic practice publications. Urodynamic testing practice patterns vary widely among ICS urodynamicists with respect to sensation prompts, modified instructions for those with impaired sensation, and reporting of rectal contractions and involuntary detrusor contractions. Opportunity exists for further standardization of good urodynamic practice in published guidelines.

IntroductionBladder profile in boys with Posterior Urethral Valves can be very varied with a spectrum going from high pressure, unstable, hypocompliant small bladders to hypercompliant, large acontractile bladders, with some being near-normal. Our question was whether appearance, specifically of the bladder, on initial VCUG was correlated to prenatal features and whether it could predict early postnatal outcome.MethodWe used a prospectively gathered database of boys with prenatally suspected PUV. We analyzed whether the appearance, specifically of the bladder, was related to date of prenatal diagnosis, presence of a megacystis on prenatal ultrasound, presence of vesico-ureteral reflux (VUR), presence of abnormal DMSA scan, nadir creatinine or presence of febrile urinary tract infection (fUTI) during the first two years of life.ResultsThe database comprised 90 cystograms. 15% of bladders were judged normal/regular, 54 % were small/diverticular and 31% were large/diverticular. Bladder appearance was not associated with presence of prenatal megacystis, abnormal DMSA scan, VUR, nor rate of fUTI. The only significant associations were normal/regular bladder and early prenatal diagnosis (p = 0.04) and normal/regular bladder and elevated nadir creatinine (>75µmol/l) (p = 0.01).DiscussionWe believe that when focusing solely on the appearance of the bladder, excluding information about the urethra and presence of reflux, the cystogram alone is insufficient to inform on future bladder function. This could be used as an argument in favor of performing early urodynamics in this population.

Mixed urinary incontinence (UI) is common in women. This study aimed to assess the efficacy of anti-incontinence surgery in female patients with equally severe stress UI (SUI) and urge UI (UUI). All patients had equal severity of SUI and UUI. The postoperative cure rate was categorized into the cure group (CG) and failure group (FG). Postoperative satisfaction was categorized into the satisfaction group (SG) and the dissatisfaction group (DG). Statistical significance was set at P

Lower urinary tract dysfunction is clinically relevant because it may cause urinary tract infections, mainly due to accumulation of residual urine, adversely affect renal function, and may cause urine incontinence that strongly affects the child’s quality of life. The function of the lower urinary tract is closely associated with that of the bowel, as constipation is commonly associated with bladder dysfunction. Detrusor overactivity, a benign but socially harmful condition, is the leading cause of daytime urinary incontinence in child-hood and needs to be differentiated from more severe conditions such as neurogenic bladder dysfunction or urethral obstruction. Voiding dysfunction, a habitual sphincter con-traction during voiding, is common in children with detrusor overactivity and may be self-limiting but may also result in residual urine and urinary tract infections. It may resemble, in severe cases, the neurogenic bladder dysfunction, most often caused by spinal dysraphism, which is characterized by several subtypes of lower urinary tract dysfunction. This condition very often leads to recurrent urinary tract infections and high intravesical pressures, threatening kidney function. A voiding diary is crucial in the initial evaluation of lower uri-nary tract function in children.

Buffering agents have not been comprehensively profiled in terms of their capacity to influence water retention prior to exercise. The purpose of this investigation was to profile the fluid retention characteristics of sodium bicarbonate (BIC) and sodium citrate (CIT) to determine the efficacy of these buffering mediums as hyperhydrating agents. Nineteen volunteers (13 males and six females; age = 28.3 ± 4.9 years) completed three trials (randomized and cross-over design). For each trial, a baseline measurement of body mass, capillary blood, and urine was collected prior to ingestion of their respective condition (control condition [CON] = 25 ml/kg artificially sweetened water; BIC condition = CON + 7.5 g/L of sodium in the form of BIC; CIT condition = CON + 7.5 g/L of sodium in the form of CIT). The fluid loads were consumed in four equal aliquots (0, 20, 40 and 60 min; fluid intake was 1.972 ± 361 ml [CON]; 1.977 ± 360 ml [BIC]; 1.953 ± 352 ml [CIT]). Samples were recorded at 20 (body mass and urine) and 60 min (blood) intervals for 180 min. Blood buffering capacity (HCO3−) was elevated (p <.001) in both BIC (32.1 ± 2.2 mmol/L) and CIT (28.9 ± 3.8 mmol/L) at 180 min compared with CON (25.1 ± 1.8 mmol/L). Plasma volume expansion was greater (p <.001) in both BIC (8.1 ± 1.3%) and CIT (5.9 ± 1.8%) compared with CON (−1.1 ± 1.4%); whereas, total urine production was lower in BIC and CIT at 180 min (BIC vs. CON, mean difference of 370 ± 85 ml; p <.001; CIT vs. CON, mean difference of 239 ± 102 ml; p =.05). There were no increases observed in body mass (p =.9). Under resting conditions, these data suggest BIC and CIT induce a greater plasma hypervolemic response as compared with water alone. [ABSTRACT FROM AUTHOR]

[Display omitted] Nuclear factor kappa-B (NF-κB), a pivotal transcriptional regulator, plays a crucial role in modulating downstream genes implicated in tumor drug resistance. We establish a programmable system within bladder cancer cells to tailor drug responses by employing a synthetic clustered regularly interspaced short palindromic repeats (CRISPR)-based expression strategy that emulates natural transcriptional regulators. Our investigation uncovers the functional significance of Opa-interacting protein 5 (OIP5), upregulated upon NF-κB activation, as a key regulator governing drug-resistance to vincristine (VCR) treatment in bladder cancer. Through engineered guide RNAs (sgRNAs) targeting OIP5 to integrate NF-κB aptamers, we construct a modular scaffold RNA that encodes both the target locus and regulatory functionality. This engineered CRISPR scaffold RNA effectively responds to VCR stimulus by binding with activated NF-κB. Intriguingly, it redirects NF-κB to attenuate OIP5 expression—a reversal of its original role—while concurrently obstructing multiple NF-κB-mediated drug resistance pathways. This dual action thwarts drug resistance development. Further enhancing therapeutic potential, we develop a versatile nanoparticle system capable of co-delivering CRISPR scaffold RNAs and VCR. This synergistic approach demonstrates potent anti-tumor effects in both in vitro and in vivo settings. Our nanoparticle-mediated combination presents a compelling proof-of-concept, showcasing the utility of engineered CRISPR-based synthetic expression programs to reconfigure cellular drug responses and heighten tumor cell susceptibility to chemotherapy. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is a prevalent causative agent that causes trichomoniasis leading to uropathogenic inflammation in the host. The crucial role of the actin cytoskeleton in T. vaginalis cytoadherence has been established but the associated signaling has not been fully elucidated. The present study revealed that the T. vaginalis second messenger PIP2 is located in the recurrent flagellum of the less adherent isolate and is more abundant around the cell membrane of the adherent isolates. The T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) with conserved activity phosphorylating PI(4)P to PI(4, 5)P2 was highly expressed in the adherent isolate and partially colocalized with PIP2 on the plasma membrane but with discrete punctate signals in the cytoplasm. Plasma membrane PIP2 degradation by phospholipase C (PLC)-dependent pathway concomitant with increasing intracellular calcium during flagellate-amoeboid morphogenesis. This could be inhibited by Edelfosine or BAPTA simultaneously repressing parasite actin assembly, morphogenesis, and cytoadherence with inhibitory effects similar to the iron-depleted parasite, supporting the significance of PIP2 and iron in T. vaginalis colonization. Intriguingly, iron is required for the optimal expression and cell membrane trafficking of TvPI4P5K for in situ PIP2 production, which was diminished in the iron-depleted parasites. TvPI4P5K-mediated PIP2 signaling may coordinate with iron to modulate T. vaginalis contact-dependent cytolysis to influence host cell viability. These observations provide novel insights into T. vaginalis cytopathogenesis during the host-parasite interaction. Author summary: Signal transduction in T. vaginalis pathogenesis remains elusive despite elucidation of the distinctive actin-based cytoadherence of the adherent isolates. Herein, we identified a T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) which converts PI(4)P into PI(4, 5)P2. Differential TvPI4P5K expression and specific PIP2 localization in the T. vaginalis isolates with distinct cytoadherence suggest a potential link underlying PIP2 signaling and cytoskeleton behaviors in this parasite. In the parasite transforming from the flagellate into an amoeboid trophozoite, the plasma membrane PIP2 signal may be cleaved by a phospholipase C (PLC)-like pathway, thereafter increasing intracellular calcium, both of which are required for parasite actin assembly, morphogenesis, and cytoadherence. Moreover, environmental iron elicited TvPI4P5K and PIP2 expression and triggered TvPI4P5K translocation to the plasma membrane. PIP2 signaling also modulated the extracellular cytopathic effectors from the parasite to lyse host cells. Our study reveals the biological significance of PIP2 signal transduction in regulating T. vaginalis pathogenesis, which may be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

The International Continence Society recommends the supine empty stress test (SEST) as an accessory test in the evaluation of women with urinary incontinence, especially for the presence of intrinsic sphincter deficiency (ISD). The aim of this study was to investigate the relationship between the SEST and clinical findings in women diagnosed with stress urinary incontinence with single voiding cycle ambulatory urodynamics (AUM). AUM tracings of patients with lower urinary tract symptoms (LUTS = Lower urinary tract symptoms) (n = 513) were retrospectively reviewed, and 364 charts with urodynamic SUI were analyzed. Demographics, examination findings, scores of the Sandvik Incontinence Severity Index and validated questionnaires, and AUM findings were compared between SEST-positive and -negative groups. Additionally, the diagnostic accuracy of the SEST in the diagnosis of low abdominal leak point pressure (ALPP ≤ 60 cm H2O) in women with pure urodynamic SUI was calculated. The SEST was positive in 41.8% (n = 152) of the cohort. Women with a positive SEST had higher scores on the Sandvik severity index (9.2 ± 3.6 vs. 7.5 ± 3.8, p = 0.003) and lower ALPP (79.6 ± 29.3 vs. 98.4 ± 31.3, p < 0.001). The negative predictive value of the SEST for ISD was found to be 92.4%. Thus, the SEST seems to be an objective clinical test reflecting urinary incontinence severity while excluding the presence of ISD. [ABSTRACT FROM AUTHOR]

Bladder cancer is becoming one of the most common malignancies across the world. Although treatment strategy has been continuously improved, which has led to cisplatin-based chemotherapy becoming the standard medication, cancer recurrence and metastasis still occur in a high proportion of patients because of drug resistance. The high efficacy of regorafenib, a broad-spectrum kinase inhibitor, has been evidenced in treating a variety of advanced cancers. Hence, this study investigated whether regorafenib could also effectively antagonize the survival of cisplatin-resistant bladder cancer and elucidate the underlying mechanism. Two types of cisplatin-resistant bladder cancer cells, T24R1 and T24R2, were isolated from T24 cisplatin-sensitive bladder cancer cells. These cells were characterized, and T24R1- and T24R2-xenografted tumor mice were created to examine the therapeutic efficacy of regorafenib. T24R1 and T24R2 cells exhibited higher expression levels of epithelial–mesenchymal transition (EMT) and stemness markers compared to the T24 cells, and regorafenib could simultaneously inhibit the viability and the expression of EMT/stemness markers of both T24R1 and T24R2 cells. Moreover, regorafenib could efficiently arrest the cell cycle, promote apoptosis, and block the transmigration/migration capabilities of both types of cells. Finally, regorafenib could significantly antagonize the growth of T24R1- and T24R2-xenografted tumors in mice. These results demonstrated the therapeutic efficacy of regorafenib in cisplatin-resistant bladder cancers. This study, thus, provides more insights into the mechanism of action of regorafenib and demonstrates its great potential in the future treatment of cisplatin-resistant advanced bladder cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: The main function of the urinary tract is to form an impermeable barrier against urinary solutes and bacteria. However, this barrier can be compromised by urinary tract infections, most commonly caused by uropathogenic Escherichia coli (UPEC). This can result in damage to the epithelial barrier, leading to decreased epithelial thickness, loss of tight junctions, loss of epithelial integrity, and apoptosis. Due to the rise in antimicrobial resistance, there is worldwide interest in exploring non-antibiotic agents as alternative therapy. Methods: Using the Madin-Darby canine kidney (MDCK) cell line, a widely accepted epithelial cell model for the urinary tract, and the UPEC strain UTI89, this paper aimed to investigate the impact of UPEC on cell integrity, permeability, and barrier functions, and determine whether cranberry, D-mannose and ibuprofen could counteract the effects induced by UPEC. Furthermore, the study examined the protective potential of these agents against UPEC-induced increase in reactive oxygen species (ROS) production and programmed death-ligand 1 (PD-L1) expression. Results: The results demonstrated that UTI89 caused a marked reduction in cell viability and monolayer integrity. Cranberry (3mg/mL) was protective against these changes. In addition, cranberry exhibited protective effects against UPEC-induced damage to cell barrier integrity, escalation of oxidative stress, and UPEC/TNFa-triggered PDL1 expression. However, no effect was observed for D-mannose and ibuprofen in alleviating UPEC-induced cell damage and changes in ROS and PD-L1 levels. Conclusion: Overall, cranberry, but not D-mannose or ibuprofen, has a protective influence against UPEC associated damage in urinary epithelial cells. [ABSTRACT FROM AUTHOR]

This document contains summaries of various research studies conducted in India on topics related to neuroscience and cognitive functioning. The studies explore different aspects of these topics, including the effects of interventions such as transcranial direct current stimulation (tDCS), aerobic exercise, mindfulness meditation, and music therapy on cognitive function, sensory-motor function, stress levels, psychological well-being, mood, and quality of life. The findings suggest that these interventions may have potential benefits for individuals with mild cognitive impairment, chronic pain, depression, and older adults. These studies contribute to our understanding of neuroscience and may have implications for the development of new treatments and interventions. [Extracted from the article]

Bladder exstrophy is a rare congenital condition of the pelvis, bladder, and lower abdomen that opens the bladder against the abdominal wall, produces aberrant growth, short penis, upward curvature during erection, wide penis, and undescended testes. Exstrophy affects 1/30,000 newborns. The bladder opens against the abdominal wall in bladder exstrophy, a rare genitourinary condition. This study is vital to provide appropriate therapy choices as a basis to improve patient outcomes. This study may explain bladder exstrophy and provide treatment. Epispadias, secretory placenta, cloacal exstrophy, and other embryonic abnormalities comprise the exstrophy-spades complex. The mesenchymal layer does not migrate from the ectoderm and endoderm layers in the first trimester, affecting the cloacal membrane. Embryological problems define the exstrophy-aspidistra complex, which resembles epimedium, classic bladder, cloacal exstrophy, and other diseases. Urogenital ventral body wall anomalies expose the bladder mucosa, causing bladder exstrophy. Genetic mutations in the Hedgehog cascade pathway, Wnt signal, FGF, BMP4, Alx4, Gli3, and ISL1 cause ventral body wall closure and urinary bladder failure. External factors such as high maternal age, smoking moms, and high maternal body mass index have also been associated to bladder exstrophy. Valproic acid increases bladder exstrophy risk; chemicals and pollutants during pregnancy may increase bladder exstrophy risk. Bladder exstrophy has no identified cause despite these risk factors. Exstrophy reconstruction seals the bladder, improves bowel function, reconstructs the vaginal region, and restores urination. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the bladder and urethral activity and nitric oxide (NO)-related molecular changes in aging rats. Rats were divided into two groups: Group Y (young rats; 12 wk) and Group A (aging rats; 15 mo). A 24-h voiding assay was performed, and the urodynamic parameters were evaluated using awake cystometry (CMG) and urethral perfusion pressure (UPP) recordings under urethane anesthesia. The mRNA expression levels of NO-, ischemia-, and inflammation-related markers in urethra and bladder tissues and cGMP levels in the urethra were assessed. Body weight was significantly higher in Group A than in Group Y. Voiding assay results (24 h) were insignificant. In the CMG, the number of non-voiding contractions per voiding cycle and post-void residual volume were significantly higher in Group A than in Group Y; voiding efficiency was significantly lower in Group A than in Group Y. In the UPP recordings, the urethral pressure reduction and high-frequency oscillation (HFO) amplitude were significantly lower in Group A than in Group Y. The mRNA expression levels of Hif-1α, Vegf-a, and Tgf-β1 in the bladder were significantly higher in Group A than in Group Y. The mRNA expression levels of Nos1 and Prkg1 and the cGMP concentrations in the urethra were significantly lower in Group A than in Group Y. Aging rats can be useful models for studying the natural progression of age-related lower urinary tract dysfunctions, for which impaired NO-mediated transmitter function is likely to be an important mechanism. NEW & NOTEWORTHY Aging rats can be useful models for studying the natural progression of age-related lower urinary tract dysfunctions, for which impaired nitric oxide-mediated transmitter function is likely to be an important mechanism. [ABSTRACT FROM AUTHOR]

Background Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN. Methods Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis–mass spectrometry at baseline (IgAN237-1, n  = 103) and at follow-up (IgAN237-2, n  = 89). Patients were categorized as "non-progressors" (IgAN237 ≤0.38) and "progressors" (IgAN237 >0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio slopes were calculated. Results Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71–531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P  < .001). Twenty-eight percent and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with chronic eGFR slopes (rho = –0.278, P  = .02 for score-1; rho = –0.409, P  = .002 for score-2) and with ±180 days eGFR slopes (rho = –0.31, P  = .009 and rho = –0.439, P  = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median –5.98 versus –1.22 mL/min/1.73 m2 per year for IgAN237-1, P  < .001; –3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P  = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (P  = .001). Conclusion The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner. [ABSTRACT FROM AUTHOR]

Aim: The rapidly increasing prevalence of gynecological diseases worldwide brings minimally invasive surgical procedures to the fore. This study was conducted to evaluate the urinary system changes of laparoscopic and vaginal hysterectomy types, which are minimally invasive surgical methods. Materials and Method: A total of 86 participants who underwent hysterectomy for benign reasons between 2017 and 2021 in a tertiary hospital were selected and divided into two groups. Group I included 43 participants treated with vaginal hysterectomy, while group II included 43 participants treated with laparoscopic hysterectomy. The Lower Urinary Tract Symptoms in Women questionnaire was used, and statistical analysis was performed to determine flow rate, voiding time, and other factors in both groups. Results: The results from this study showed that there was no change in the initial sensory context in both groups (p = 3.63). Bladder capacity also did not differ in both groups. However, postoperatively, excessive activity in the detrusor muscle was observed in 8 participants (18.6%) in group I, while it was observed in 2 participants (4.6%) in group II (p=0.021). Urine flow rate and residual urine volume were in similar ranges in both groups. Conclusion: This study emphasizes that minimally invasive surgical methods for patients with gynecological diseases may have similar results in the urinary system. In this sense, the study will be useful in terms of predicting and managing post-operative period urinary system changes. [ABSTRACT FROM AUTHOR]

A role of Yes1-associated transcriptional regulator (YAP) and WW domain-containing transcription regulator 1 (TAZ) in vascular and gastrointestinal contractility due to control of myocardin (Myocd) expression, which in turn activates contractile genes, has been demonstrated. Whether this transcriptional hierarchy applies to the urinary bladder is unclear. We found that YAP/TAZ are expressed in human detrusor myocytes and therefore exploited the Itga8-CreERT2 model for the deletion of YAP/TAZ. Recombination occurred in detrusor, and YAP/TAZ transcripts were reduced by >75%. Bladder weights were increased (by ≈22%), but histology demonstrated minimal changes in the detrusor, while arteries in the mucosa were inflamed. Real-time quantitative reverse transcription PCR (RT-qPCR) using the detrusor demonstrated reductions of Myocd (-79 ± 18%) and serum response factor (Srf) along with contractile genes. In addition, the cholinergic receptor muscarinic 2 (Chrm2) and Chrm3 were suppressed (-80 ± 23% and -80 ± 10%), whereas minute increases of Il1b and Il6 were seen. Unlike YAP/TAZ-deficient arteries, SRY (sex-determining region Y)-box 9 (Sox9) did not increase, and no chondrogenic differentiation was apparent. Reductions of smooth muscle myosin heavy chain 11 (Myh11), myosin light-chain kinase gene (Mylk), and Chrm3 were seen at the protein level. Beyond restraining the smooth muscle cell (SMC) program of gene expression, YAP/TAZ depletion silenced SMC-specific splicing, including exon 2a of Myocd. Reduced contractile differentiation was associated with weaker contraction in response to myosin phosphatase inhibition (-36%) and muscarinic activation (reduced by 53% at 0.3 µM carbachol). Finally, short-term overexpression of constitutively active YAP in human embryonic kidney 293 (HEK293) cells increased myocardin (greater than eightfold) along with archetypal target genes, but contractile genes were unaffected or reduced. YAP and TAZ thus regulate myocardin expression in the detrusor, and this is important for SMC differentiation and splicing as well as for contractility. [ABSTRACT FROM AUTHOR]

Kidney stones and Escherichia coli bacterial particles are mineral aggregates found inside the kidney and bladder that cause urinary tract infections and complications during urination. Therefore, it is essential to understand that how such stones create the obstruction in the urine flow and what are the possible solutions to remove them from the urinary system? In view of the complications in the urinary system due to bacteria and CaOx, the major objectives of this study are to investigate (a) how electro-osmosis modulates the urine flow and helps in the removal of CaOx particles and bacteria via urine flow and (b) how diameter and density of the particles will affect the motion of the particles via urine flow? An electrolyte solution with Newtonian model for the urine and a moving wavy channel with time and axial displacement for urinary track are considered. Basset–Boussinesq–Oseen equation is employed to analyze the motion of CaOx and bacteria. Poisson–Boltzmann equation is considered to examine the distribution of the electric potential in urine. Analytical solutions are derived under the suitable assumptions and suitable boundary conditions for the present biophysical model. The results showed that (a) backward motion of bacterial particles was observed via urine flow and (b) the large size of CaOx particle covers fewer trajectories with slower velocity through urine flow, which may be the reasons of obstructions/infections in the urine flow. It is further concluded that the axial electric field increases the trajectory and velocity of the CaOx particle and bacterial particles, which will help in proper functioning of the urine flow and in the removal of such particles. [ABSTRACT FROM AUTHOR]

We studied the influence of medium composition and aeration on the hemolytic activity of uropathogenic Morganella morganii strain MM 190. The maximum level of hemolysis was observed in LB (59%), DMEM supplemented with fetal bovine serum (62%), and urine (53%) under aeration conditions during the exponential growth phase. The presence of 2% urea in the medium suppressed hemolysin synthesis. Moreover, addition of bacterial culture fluid containing hemolysin to a monolayer of T-24 bladder carcinoma and OKP-GS kidney carcinoma cells led to 25 and 42% cell death, respectively. We found that the maximum expression of the hemolysin gene hlyA was observed in 2-h culture in LB medium, which correlated with the hemolytic activity of the bacteria in this medium and indicated the predominance of the short hlyCA transcript in the cells. [ABSTRACT FROM AUTHOR]

• Neurogenic bladder dysfunction negatively impacts quality of life in children with SCI. • Strengthening spared neurocircuitry through activity-dependent plasticity. • Children with SCI may experience improved bladder and bowel function through ABR-LT. • Implications of enhanced bladder and bowel control include reduced medication dependence. Bladder dysfunction and associated complications of the urinary system negatively impact the quality of life in children living with spinal cord injury (SCI). Pediatric lower urinary tract deficits include bladder over-activity, inefficient emptying, decreased compliance, and incontinence. Recent evidence in adults with SCI indicates significant improvements in bladder capacity and detrusor pressure following participation in an activity-based recovery locomotor training (ABR-LT) rehabilitative program. Additionally, anecdotal self-reports from parents in our Pediatric NeuroRecovery Program reference changes in bladder function, ranging from awareness of bladder fullness to gains in voluntary control while undergoing ABR-LT. In a within-subjects repeated measures study, we investigated the effect of ABR-LT on bladder function in three children (ages: 2.5, 3, and 6 years) who sustained upper motor neuron SCI. Each child received at least 60 sessions of ABR-LT (5x/week) for 12–14 weeks. Bladder function was assessed via urodynamics and the Common Data Elements questionnaires. Awareness of bladder filling during cystometry was present in all children and detrusor leak point pressure (LPP) was reduced post-ABR-LT relative to pre-training. A decrease in LPP after locomotor training was observed in all three participants. One out of the three participants had substantial improvements in bladder capacity post-ABR-LT and experienced less bowel incontinence following training. Like our evidence in adults, the changes in bladder function suggest an interaction between lumbosacral networks regulating spinal reflex control of bladder filling, voiding, and afferent input (including potential descending supraspinal commands) and those activated by ABR-LT. Locomotor training may be associated with increased bladder capacity, enhanced perception of bladder filling, and decreased LPP as well as improvements in bowel control in pediatric SCI. This research suggests that children and adolescents with traumatic SCI could experience dynamic improvements in bladder and bowel function with the aid of various therapies. Studies assessing the durability of training on the recovery of bladder and bowel dysfunction in children with SCI are needed. [ABSTRACT FROM AUTHOR]