TDP1 mutation causing SCAN1 neurodegenerative syndrome hampers the repair of transcriptional DNA double-strand breaks.

TDP1 removes transcription-blocking topoisomerase I cleavage complexes (TOP1ccs), and its inactivating H493R mutation causes the neurodegenerative syndrome SCAN1. However, the molecular mechanism underlying the SCAN1 phenotype is unclear. Here, we generate human SCAN1 cell models using CRISPR-Cas9 and show that they accumulate TOP1ccs along with changes in gene expression and genomic distribution of R-loops.

Transcription-associated DNA breaks and cancer: A matter of DNA topology.

Transcription is an essential cellular process but also a major threat to genome integrity. Transcription-associated DNA breaks are particularly detrimental as their defective repair can induce gene mutations and oncogenic chromosomal translocations, which are hallmarks of cancer. The past few years have revealed that transcriptional breaks mainly originate from DNA topological problems generated by the transcribing RNA polymerases.

[Assessment before surgical treatment for pelvic organ prolapse: Clinical practice guidelines].

Introduction: The issue addressed in this chapter of recommendations is: What is the clinical and para-clinical assessment to achieve in women with genital prolapse and for whom surgical treatment has been decided. What are the clinical elements of the examination that must be taken into account as a risk factor of failure or relapse after surgery, in order to anticipate and evaluate possible surgical difficulties, and to move towards a preferred surgical technique?

Material And Methods: This work is based on a systematic review of the literature (PubMed, Medline, Cochrane Library, Cochrane Database of Systemactic Reviews, EMBASE) for meta-analyzes, randomized trials, registries, literature reviews, controlled studies and major not controlled studies, published on the subject. Its implementation has followed the methodology of the HAS on the recommendations for clinical practice, with a scientific argument (with the level of evidence, NP) and a recommendation grade (A, B, C, and professional agreement [AP]).

Educational tool-kit on diet and exercise: survey of prostate cancer patients about to receive androgen deprivation therapy.

Objectives: To test a tool-kit designed to improve well-being in patients with prostate cancer. Lifestyle changes might lessen the metabolic, cardiovascular, and osseous side effects of androgen deprivation therapy (ADT) in prostate cancer patients.

Methods: Urologists supplied 10 consecutive patients initiating ADT with a tool-kit (information brochure, practical guidance on diet and exercise, recipe booklet, and lifestyle diary).

Transobturator male sling TOMS for the treatment of stress post-prostatectomy incontinence, initial experience and results with one year's experience.

Purpose: Post-prostatectomy incontinence remains a problem, even in minor or moderate degrees. In order to minimize surgical morbidity and costs, sling procedures have been proposed. The authors have developed a new transobturator male sling procedure and report their results after one-year experience.