Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition.

Acquired drug resistance prevents cancer therapies from achieving stable and complete responses. Emerging evidence implicates a key role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. The persister cell pool constitutes a reservoir from which drug-resistant tumours may emerge. Targeting persister cells therefore presents a therapeutic opportunity to impede tumour relapse. We previously found that cancer cells in a high mesenchymal therapy-resistant cell state are dependent on the lipid hydroperoxidase GPX4 for survival. Here we show that a similar therapy-resistant cell state underlies the behaviour of persister cells derived from a wide range of cancers and drug treatments. Consequently, we demonstrate that persister cells acquire a dependency on GPX4. Loss of GPX4 function results in selective persister cell ferroptotic death in vitro and prevents tumour relapse in mice. These findings suggest that targeting of GPX4 may represent a therapeutic strategy to prevent acquired drug resistance

Establishing A Continuum of Care to Improve Follow-Up Rates for Survivors of Sexual Assault

Introduction. In 2011 there were over 1000 reported sexual assaults in Vermont. Current recommendations suggest that survivors of sexual assault (survivors) receive follow- up care within two weeks after an initial Sexual Assault Nurse Examiner (SANE) exam, but fewer than 15% receive documented follow-up. A published report has demonstrated increased follow-up to over 80% when appointments are scheduled prior to discharge from the emergency department (ED).https://scholarworks.uvm.edu/comphp_gallery/1082/thumbnail.jp

Acute nongonococcal infectious arthritis

A retrospective analysis of 71 nongonococcal joint infections in 63 patients in reported. Staphylococcus aureus was isolated from 59% of the patients. Five patients died as a result of infections. The outcome in Gram-n egative joint infections was similar to the overall outcome in the entire series of patients. All 11 joints with infected prostheses ultimately required removal of the prostheses. All patients were treated with appropriate parenteral antibiotics, and surgical intervention was used in 40 joints. Six patients underwent surgical treatment because of inability to sterilize the joint with antibiotics and because of repeated joint aspirations. The outcome with surgical intervention was good only in patients younger than 16 years of age. Medical therapy (parenteral antibiotics and frequent joint aspirations) led to good results in 74% of the patients. Outcome of joint infection was also influenced by factors which contribute to imparied host resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37749/1/1780230803_ftp.pd

The commodification of human reproductive materials.

This essay develops a framework for thinking about the moral basis for the commnodification of human reproductive nmaterials. It argues that selling and buyinlg gametes and genes is morally acceptable although there should not be a market for zygotes, embryos, or genomes. Also a market in gametes and genes shouild be regutlated in order to address concerns about the adverse social consequences of conmmodification. Originally published Journal of Medical Ethics, Vol. 24, No. 6, Dec 199