Innervation pattern of the unclosed detrusor muscle in classic bladder exstrophy: a study of patients with urothelial overexpression of nerve growth factor

Purpose An overexpression of nerve growth factor (NGF) in the urothelium is discussed to lead to neuronal hyperinnervation of the bladder detrusor. The aim was to assess the sensory and sympathetic innervation of the detrusor in unclosed exstrophic bladders patients with known overexpression of NGF in the urothelium. Methods Full-thickness bladder biopsies were prospectively obtained from 34 infants at delayed primary bladder closure between 01/2015 and 04/2020. The bladder biopsies were immunohistochemically stained with antibodies against S100, calcitonin gene-related peptide (anti-CGRP), Neurofilament 200 (anti-NF200), and tyrosine-hydroxylase (anti-TH). Specimens from 6 children with congenital vesicoureterorenal reflux (VUR) served as controls. Results There was no statistically significant difference in nerve fiber density in any of the immunohistochemical assessments (anti-S100 [p = 0.210], anti-CGRP [p = 0.897], anti-NF200 [p = 0.897]), and anti-TH [p = 0.956]) between patients with BE and patients with VUR. However, we observed a trend toward lower nerve fiber densities in exstrophic detrusor. Conclusion Overall our results showed an unharmed innervation pattern in this cohort but a lower density of nerve fibers in the detrusor compared to controls. Further studies in patients after successful primary closure are needed to clarify the potential impact of the urothelial overexpression of NGF modulating the innervation pattern in exstrophic bladders

Cold versus hot snare endoscopic resection of large non-pedunculated colorectal polyps (randomized-controlled German CHRONICLE-trial)

Background and aims Endoscopic mucosal resection (EMR) is standard therapy for non-pedunculated colorectal polyps ≥20mm. Recently, it has been suggested that polyp resection without current (cold resection) may be superior to the standard technique using cutting/coagulation current (hot resection) by reducing adverse events (AE), but evidence from a randomized trial is missing. Methods In this randomized-controlled multicentric trial involving 19 centers, non-pedunculated colorectal polyps ≥20mm were randomly assigned to cold or hot EMR. Primary outcome was major AE (perforation or post-endoscopic bleeding). Among secondary outcomes major AE subcategories, postpolypectomy-syndrome and residual adenoma were most relevant. Results Between 2021 and 2023, 396 polyps in 363 patients (48.2% female) were enrolled for the intention-to-treat analysis. Major AE occurred in 1.0 % in the cold and in 7.9% in the hot group (p=0.001; Odds ratio [OR] 0.12 [95%-CI: 0.03-0.54]). Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group with 0% vs. 3.9% (p=0.007) and 1.0% vs. 4.4% (p=0.040). Postpolypectomy-syndrome occurred with similar frequency (3.1% vs. 4.4%, p=0.490). After cold resection, residual adenoma was found more frequently, with 23.7% vs. 13.8% (p=0.020; OR 1.94 [95%-CI: 1.12-3.38]). In multivariable analysis, lesion diameter of ≥4cm was an independent predictor both for major AE (OR 3.37) and residual adenoma (OR 2.47), and high-grade dysplasia/cancer for residual adenoma (OR 2.92). Conclusion Cold resection of large non-pedunculated colorectal polyps appears considerably safer than hot EMR, however at the cost of a higher residual adenoma rate. Further studies have to confirm to which extent polyp size and histology can determine an individualized approach (Trial number: DRKS00025170)

Persistent urothelial differentiation changes in the reconstructed exstrophic bladder: Congenital or acquired dysfunction of the epithelial barrier?

Background We have previously characterised the urothelium from infants with classic bladder exstrophy (CBE) for the expression of urothelial differentiation associated markers. We found abnormal expression patterns of uroplakin 3a, cytokeratin 13, cytokeratin 20 and claudin 4 in the majority of bladder biopsies taken at the time of primary bladder closure. Abnormal urothelial differentiation results in a compromised urothelial barrier with potential implications on bladder development and the success of reconstructive surgery. Objective To investigate whether the urothelial differentiation changes observed in the unclosed exstrophic bladder persist after successful primary exstrophy repair. Design, setting and participants From 2005 to 2018 bladder biopsies from 115 children with CBE obtained at the time of primary bladder closure (n = 67, median age: 8.1 weeks) and during secondary procedures aimed at achieving continence (n = 48, median age: 6.8 years) were prospectively collected. Following histological assessment immunohistochemistry was used to investigate the expression of uroplakin 3a, cytokeratin 13 and 20 and claudin 4, well characterized markers associated with the terminally-differentiated, fully functional urothelial phenotype. The urothelium from 16 children with VUR and with non-refluxing disorders of the urinary tract served as controls. Results Tissue specimen from 100 children were included in the analysis. Only 32% of bladder specimens from children having undergone successful primary bladder closure in early infancy displayed a fully differentiated urothelial phenotype with regular expression of all 4 markers. The remaining bladders revealed irregular or absent marker expression suggesting abnormal urothelial differentiation. 86% of the samples had inflammatory, proliferative or metaplastic histological changes. Conclusion Our results suggest persisting urothelial differentiation changes in two-thirds of exstrophic bladders following successful bladder closure in early infancy. Despite some limitations, the findings provide a platform for translational studies into the role of the urothelium for the developmental potential of the exstrophic bladder and the success of reconstructive surgery

Influence of bacterial <em>N</em>-acyl-homoserine lactones on growth parameters, pigments, antioxidative capacities and the xenobiotic phase II detoxification enzymes in barley and yam bean.

Bacteria are able to communicate with each other and sense their environment in a population density dependent mechanism known as quorum sensing (QS). N-acyl- homoserine lactones (AHLs) are the QS signaling compounds of Gram-negative bacteria which are frequent colonizers of rhizospheres. While cross-kingdom signaling and AHL- dependent gene expression in plants has been confirmed, the responses of enzyme activities in the eukaryotic host upon AHLs are unknown. Since AHL are thought to be used as so-called plant boosters or strengthening agents, which might change their resistance toward radiation and/or xenobiotic stress, we have examined the plants pigment status and their antioxidative and detoxifying capacities upon AHL treatment. Because the yield of a crop plant should not be negatively influenced, we have also checked for growth and root parameters. We investigated the influence of three different AHLs, namely N-hexanoyl- (C6-HSL), N-octanoyl- (C8-HSL), and N-decanoyl- homoserine lactone (C10-HSL) on two agricultural crop plants. The AHL-effects on Hordeum vulgare (L.) as an example of a monocotyledonous crop and on the tropical leguminous crop plant Pachyrhizus erosus (L.) were compared. While plant growth and pigment contents in both plants showed only small responses to the applied AHLs, AHL treatment triggered tissue- and compound-specific changes in the activity of important detoxification enzymes. The activity of dehydroascorbate reductase in barley shoots after C10-HSL treatment for instance increased up to 384% of control plant levels, whereas superoxide dismutase activity in barley roots was decreased down to 23% of control levels upon C6-HSL treatment. Other detoxification enzymes reacted similarly within this range, with interesting clusters of positive or negative answers toward AHL treatment.In general the changes on the enzyme level were more severe in barley than in yam bean which might be due to the differentabilities of the plants to degrade AHLs to metabolites such as thehy droxy-or keto-form of the original compound

Ultraschall- und Wirbelstromprüfung an Radsatzkomponenten von Hochgeschwindigkeitszügen

Um die Verfügbarkeit der Schienenfahrzeuge sicher zustellen, sowie die Verkehrssicherheit von Schienenfahrzeugen zu gewährleisten, sind u.a. zerstörungsfreie Werkstoffprüfungen, beginnend bei der Herstellung der Radsatzkomponenten (Räder und Radsatzwellen), in bestimmten Intervallen nach nationalen und internationalen Vorschriften durchzuführen! Im Vortrag werden Ultraschall-und Wirbelstromprüfsysteme in Verbindung mit mechanisierten Manipulatorsystemem vorgestellt, die beginnend bei der Herstellung, nach festgelegten Laufzeiten regelmäßig zum Einsatz kommen und so eine kostengünstige Wartung und Instandhaltung von Hochgeschwindigkeitsfahrzeugen ermöglichen