Ethics takes time, but not that long

© 2007 Hansson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair

A hexanucleotide repeat expansion represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, though the mechanisms by which the expansion cause neurodegeneration are poorly understood. We report elevated levels of DNA/RNA hybrids (R-loops) and double-strand breaks (DSBs) in rodent neurons, human cells, and in C9orf72-ALS patient spinal cord tissues. Accumulation of endogenous DNA damage is concomitant with defective ATM-mediated DNA repair signalling and accumulation of protein-linked DNA breaks. We further reveal that defective ATM-mediated DNA repair is a consequence of p62 accumulation, which impairs H2A ubiquitylation and perturbs ATM signalling. Adeno-associated virus- mediated expression of C9orf72-related RNA and dipeptide repeats in the murine central nervous system causes elevated DSBs, ATM defects, and triggers neurodegeneration. These findings identify R-Loops, DSBs, and defective ATM-mediated repair as pathological consequences of C9orf72 expansions, and suggest that C9orf72-linked neurodegeneration is driven, at least in part, by genomic instability

Ethics, intimate examinations and tomorrow’s doctors

The teaching of vaginal and rectal examinations poses ethical problems for students and educators, and guidelines exist to protect patients from unethical practice. Yvette Coldicott and colleagues report an exploratory survey, whose findings suggest that best practice is not always followed and that in many cases consent has not been given for procedure

Audit and exploration of graduating medical students' opportunities to perform digital rectal examinations as part of their learning

[Extract] Dear Editor, There appears to be a trend indicating a decrease in the number of digital rectal examinations (DREs) performed by medical students over the last few decades.1, 2 Reasons why opportunities to practise have fallen include ethical concerns3 and deterrents such as being told not to by medical staff, embarrassment, refusal by patients and lack of a chaperon