Organization of the Autonomic Nuclei in the Spinal Cord : Functional Morphology

Disease-associated genes. Complete list of the disease-associated genes for each dataset. (XZ 46 kb

X-ray radiation effects in multilayer epitaxial graphene

International audienceWe characterize multilayer graphene grown on C-face SiC before and after exposure to a total ionizing dose (TID) of 12 Mrad(SiO2) using a 10 keV X-ray source. While we observe the partial peeling of the top graphene layer and the appearance of a modest Raman D-peak, we find that the electrical characteristics (mobility, sheet resistivity, free carrier concentration) of the material are mostly unaffected by radiation exposure. Combined with X-ray photoelectron spectroscopy (XPS) data showing numerous carbon-oxygen bonds after irradiation, we conclude that the primary damage mechanism is through surface etching from reactive oxygen species created by the X-rays

Photodynamic Diagnosis-guided Transurethral Resection of Bladder Tumour in Participants with a First Suspected Diagnosis of Intermediate- or High-risk Non–muscle-invasive Bladder Cancer : Cost-effectiveness Analysis Alongside a Randomised Controlled Trial

Funding/Support and role of the sponsor: The article processing charge was funded by the PHOTO project, which was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (11/142/02). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The funding body had no direct role in the study. Acknowledgments: This study is part of the PHOTO project. We thank the PHOTO team who contributed to the overall research project and are grateful to all the participants and facility staff who took part in the study.Peer reviewedPublisher PD

Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

Time to Turn on the Blue Lights: A Systematic Review and Meta-analysis of Photodynamic Diagnosis for Bladder Cancer.

CONTEXT: White light (WL) cystoscopy and transurethral resection of bladder tumour (TURBT) comprise the current gold standard technique for detecting and grading bladder cancer. However, with WL cystoscopy, recurrence following initial TURBT is high, and identification of smaller tumours and carcinoma in situ is poor. Photodynamic diagnosis (PDD) has been developed to improve the detection of bladder. OBJECTIVE: To assess the effect of PDD-guided TURBT compared with WL on recurrence rates (RRs) in non-muscle-invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION: A systematic review of the literature from inception to April 2020 using Medline, EMBASE, and CENTRAL was undertaken. Randomised control trials comparing TURBT undertaken with PDD to WL that reported RRs of at least 12 mo were included in the analysis. The primary outcomes were RRs at 12 and 24 mo. The secondary outcomes were reported adverse effects. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of the evidence. EVIDENCE SYNTHESIS: Twelve randomised controlled trials (2288 patients) were included for the meta-analysis. PDD was found to reduce RRs at 12 mo (RR 0.73, confidence interval [CI] 0.60-0.88) and 24 mo (RR 0.75, CI 0.62-0.91). There was an increased risk of recurrence for patients undergoing WL at 12 mo (hazard ratio [HR] 1.14, CI 1.05-1.23) and 24 mo (HR 1.25, CI 1.15-1.35). Two studies reported recurrence data at 60 mo showing statistically significant outcomes in favour of PDD: one showed lower RRs for PDD (49% PDD vs 68% WL), whilst the other showed increased recurrence-free survival (68.2% PDD vs 57.3% WL). Adverse effects appeared to be minimal, though poorly reported. A GRADE analysis showed the evidence to be of moderate certainty overall. CONCLUSIONS: This systematic review found that PDD reduced RRs and improved recurrence-free survival compared with WL in NMIBC over at least 2-yr follow-up. These effects may persist up to 5 yr. Further research in a pragmatic study looking at longer-term outcomes beyond 24 mo will help guide recommendations on clinical adoption. PATIENT SUMMARY: This review suggests that photodynamic diagnosis, compared with white light cystoscopy, improves recurrence-free survival in non-muscle-invasive bladder cancer over at least 2 yr of follow-up. However, confirmatory pragmatic studies with longer-term outcomes are required for its clinical adoption

Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts.

Stem cell (SC) dynamics within the human colorectal crypt SC niche remain poorly understood, with previous studies proposing divergent hypotheses on the predominant mode of SC self-renewal and the rate of SC replacement. Here we use age-related mitochondrial oxidative phosphorylation (OXPHOS) defects to trace clonal lineages within human colorectal crypts across the adult life-course. By resolving the frequency and size distribution of OXPHOS-deficient clones, quantitative analysis shows that, in common with mouse, long-term maintenance of the colonic epithelial crypt relies on stochastic SC loss and replacement mediated by competition for limited niche access. We find that the colonic crypt is maintained by ~5 effective SCs. However, with a SC loss/replacement rate estimated to be slower than once per year, our results indicate that the vast majority of individual SC divisions result in asymmetric fate outcome. These findings provide a quantitative platform to detect and study deviations from human colorectal crypt SC niche homeostasis during the process of colorectal carcinogenesis.Wellcome Trus

A core outcome set for localised prostate cancer effectiveness trials

Objective: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Background: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. Subjects and methods: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients. Results: The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. Conclusion: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials

Photodynamic versus white light-guided treatment of non-muscle invasive bladder cancer: a study protocol for a randomised trial of clinical and cost-effectiveness

Bladder cancer is the most frequently occurring tumour of the urinary system. Ta, T1 tumours and carcinoma in situ (CIS) are grouped as non-muscle invasive bladder cancer (NMIBC), which can be effectively treated by transurethral resection of bladder tumour (TURBT). There are limitations to the visualisation of tumours with conventional TURBT using white light illumination within the bladder. Incomplete resections occur from the failure to identify satellite lesions or the full extent of the tumour leading to recurrence and potential risk of disease progression. To improve complete resection, photodynamic diagnosis (PDD) has been proposed as a method that can enhance tumour detection and guide resection. The objective of the current research is to determine whether PDD-guided TURBT is better than conventional white light surgery and whether it is cost-effective.This article is freely available via Open Access. Click on the publisher URL to access the full-text from the publisher's site