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Urethral sphincter insufficiency following radical prostatectomy (RP) is a common cause of non-neurogenic stress urinary incontinence (SUI). Artificial urinary sphincter (AUS) insertion remains the standard of care for fit patients with SUI refractory to non-operative interventions. The proximal urethra is a common location for uncomplicated AUS placement. However, previous failed AUS, urethroplasty, or pelvic radiotherapy (RT) may compromise urethral tissue requiring technique modifications that optimise outcomes. In these situations, transcorporal cuff (TC) placement has been well described to facilitate continence restoration in men where there is no other feasible option other than urinary diversion or permanent incontinence. In the traditional TC approach, the procedure may be complicated by haematoma due to difficulty in completely closing the corporal defects behind the urethra. This narrated video demonstrates the tunical flap (TF) modification for transcorporal AUS implantation via a perineal and penoscrotal approach in patients with prior failed AUS placements secondary to urethral erosion. The TF technique for transcorporal AUS insertion provides circumferential reinforcement with tunica albuginea from the corpora cavernosa. Here, we show how this technique provides additional urethral support for compromised urethral tissue to help prevent cuff erosion. The TF preserves the corporal volume and does not limit candidacy for future penile prosthesis implantation. In our early results, there have been no postoperative haematoma formation with this technique.
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Introduction and Objectives: Patient-centred (PC) and holistic care improves patient satisfaction and health outcomes. We sought to investigate the benefit of utilising a PC pathology report in patients undergoing radical prostatectomy (RP) for prostate cancer (PCa). Our study aimed to evaluate and compare patient understanding of their PCa diagnosis after RP, upon receiving either a standard histopathology report or a personalised and PC report (PCR). Moreover, we evaluated knowledge retention at 4 weeks after the initial consultation. Methods: We invited patients undergoing RP at three metropolitan Urology clinics to participate in our randomised controlled study. Patients were randomised to receive either a PCR or standard pathology report. Patient satisfaction questionnaires (Perceived Efficacy in Patient-Physician Interactions [PEPPI], Consultation and Relational Empathy [CARE] and Communication Assessment Tool [CAT]) and a knowledge test were conducted within 72 h of the initial appointment and again at 4 weeks. Accurate recollection of Gleason grade group (GGG) and extracapsular extension (ECE) were classified as 'correct'. Baseline demographic data included age, education, marital and employment status, pre-op prostate specific antigen (PSA) and clinical stage. Baseline data were tested for differences between groups using the Student's t test, chi-squared test or Fisher's exact test depending on whether data were continuous, categorical or sparse. Comparison of correctly answered 'knowledge' questions was analysed using chi-squared test. A significance level of p ≤ 0.05 was used. Results: Data from 62 patients were analysed (30 standard vs. 32 PCR). No significant differences in baseline demographics were found between groups. Both groups reported high levels of satisfaction with their healthcare experiences in all domains of patient-physician rapport, empathy and communication. There were no significant differences between groups in PEPPI (p = 0.68), CAT (p = 0.39) and CARE (p = 0.66) scores, at baseline and 4 weeks. Ninety-three per cent of patients who received the PCR understood the report while 90% felt the report added to their understanding of their PCa. Regarding patient knowledge, the PCR group had significantly more correct answers on GGG and ECE as compared with the standard report group at baseline and 4 weeks (p < 0.001 and 0.001, respectively). Conclusions: Our findings demonstrate that PC pathology reports improve patient knowledge and understanding of their PCa that is retained for at least 4 weeks after initial receipt of results.
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The review examines the vital role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, and treatment of prostate cancer (PCa). It focuses on the superior diagnostic abilities of PSMA PET/CT for identifying both nodal and distant PCa, and its potential as a prognostic indicator for biochemical recurrence and overall survival. Additionally, we focused on the variability of PSMA's expression and its impact on personalised treatment, particularly the use of [177Lu] Lu-PSMA-617 radioligand therapy. This review emphasises the essential role of PSMA PET/CT in enhancing treatment approaches, improving patient outcomes, and reducing unnecessary interventions, positioning it as a key element in personalised PCa management.
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Finasteride competitively inhibits 5α-reductase (5-AR) isoenzymes, which blocks dihydrotestosterone (DHT) production, thereby reducing DHT. Finasteride is used in the management of benign prostatic hyperplasia (BPH) and androgenic alopecia. Amid patient reports of suicidal ideation (SI), the Post Finasteride Syndrome advocacy group has petitioned for either a stop to selling of the drug or advertisement of stronger warnings. The US Food and Drug Administration recently added SI to the adverse effects listed for finasteride. Here we provide a brief but comprehensive review of the literature on the psychological side effects of 5-AR inhibitors (5-ARIs) to provide an opinion to help in guiding treating urologists. Most of the current evidence, obtained from the literature on dermatology, suggests that 5-ARI users experience a higher rate of depressive symptoms. However, given the lack of comprehensive randomised studies, the causal link between finasteride and SI remains unclear. Urologists prescribing 5-ARIs should be aware of the recent addition of suicide and SI risk to the list of side effects. A mental health screen should be performed and appropriate resources provided to patients commencing treatment. Furthermore, a review should be arranged with the general practitioner to assess new-onset mental health or SI symptoms. Patient summary: We provide recommendations for urologists who prescribe finasteride for the treatment of benign prostate enlargement. Urologists should be aware of the recent addition of suicidal ideation to the list of side effects for this drug. Finasteride prescription should be continued; however, we recommend a detailed medical history to screen for prior mental health and personality disorders, with discontinuation of the medication in patients with new onset of depression or suicidal symptoms. Close liaison with the patient's general practitioner is vital for management of depressive or suicidal symptoms.
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Mutations in ß-catenin, especially at the residues critical for its degradation, render it constitutively active. Here, we show that mutant ß-catenin can be transported via extracellular vesicles (EVs) and activate Wnt signalling pathway in the recipient cells. An integrative proteogenomic analysis identified the presence of mutated ß-catenin in EVs secreted by colorectal cancer (CRC) cells. Follow-up experiments established that EVs released from LIM1215 CRC cells stimulated Wnt signalling pathway in the recipient cells with wild-type ß-catenin. SILAC-based quantitative proteomics analysis confirmed the transfer of mutant ß-catenin to the nucleus of the recipient cells. In vivo tracking of DiR-labelled EVs in mouse implanted with RKO CRC cells revealed its bio-distribution, confirmed the activation of Wnt signalling pathway in tumour cells and increased the tumour burden. Overall, for the first time, this study reveals that EVs can transfer mutant ß-catenin to the recipient cells and promote cancer progression.
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Extracellular vesicles (EVs) are membranous vesicles that are released by cells. In this study, the role of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in the biogenesis of yeast EVs was examined. Knockout of components of the ESCRT machinery altered the morphology and size of EVs as well as decreased the abundance of EVs. In contrast, strains with deletions in cell wall biosynthesis genes, produced more EVs than wildtype. Proteomic analysis highlighted the depletion of ESCRT components and enrichment of cell wall remodelling enzymes, glucan synthase subunit Fks1 and chitin synthase Chs3, in yeast EVs. Interestingly, EVs containing Fks1 and Chs3 rescued the yeast cells from antifungal molecules. However, EVs from fks1∆ or chs3∆ or the vps23∆chs3∆ double knockout strain were unable to rescue the yeast cells as compared to vps23∆ EVs. Overall, we have identified a potential role for yeast EVs in cell wall remodelling.
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Pared Celular/metabolismo , Vesículas Extracelulares/metabolismo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/metabolismo , Antifúngicos/farmacología , Caspofungina/farmacología , Supervivencia Celular/efectos de los fármacos , Pared Celular/efectos de los fármacos , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Vesículas Extracelulares/efectos de los fármacos , Mutación/genética , Proteómica , Saccharomyces cerevisiae/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacosRESUMEN
Exosomes are membranous vesicles that are released by a variety of cells into the extracellular microenvironment and are implicated in intercellular communication. As exosomes contain RNA, proteins and lipids, there is a significant interest in characterizing the molecular cargo of exosomes. Here, we describe ExoCarta (http://www.exocarta.org), a manually curated Web-based compendium of exosomal proteins, RNAs and lipids. Since its inception, the database has been highly accessed (>54,000 visitors from 135 countries). The current version of ExoCarta hosts 41,860 proteins, >7540 RNA and 1116 lipid molecules from more than 286 exosomal studies annotated with International Society for Extracellular Vesicles minimal experimental requirements for definition of extracellular vesicles. Besides, ExoCarta features dynamic protein-protein interaction networks and biological pathways of exosomal proteins. Users can download most often identified exosomal proteins based on the number of studies. The downloaded files can further be imported directly into FunRich (http://www.funrich.org) tool for additional functional enrichment and interaction network analysis.
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Bases de Datos de Compuestos Químicos , Exosomas/química , Exosomas/metabolismo , Lípidos/análisis , Proteoma/análisis , ARN/análisis , InternetRESUMEN
In order to advance our understanding of colorectal cancer (CRC) development and progression, biomedical researchers have generated large amounts of OMICS data from CRC patient samples and representative cell lines. However, these data are deposited in various repositories or in supplementary tables. A database which integrates data from heterogeneous resources and enables analysis of the multidimensional data sets, specifically pertaining to CRC is currently lacking. Here, we have developed Colorectal Cancer Atlas (http://www.colonatlas.org), an integrated web-based resource that catalogues the genomic and proteomic annotations identified in CRC tissues and cell lines. The data catalogued to-date include sequence variations as well as quantitative and non-quantitative protein expression data. The database enables the analysis of these data in the context of signaling pathways, protein-protein interactions, Gene Ontology terms, protein domains and post-translational modifications. Currently, Colorectal Cancer Atlas contains data for >13 711 CRC tissues, >165 CRC cell lines, 62 251 protein identifications, >8.3 million MS/MS spectra, >18 410 genes with sequence variations (404 278 entries) and 351 pathways with sequence variants. Overall, Colorectal Cancer Atlas has been designed to serve as a central resource to facilitate research in CRC.