Impact of 'street' benzodiazepines on drug-related deaths in England, Wales and Northern Ireland.

Introduction: 'Street' benzodiazepines (BZD) are structurally and pharmacologically related to BZDs licensed for human use. In this study we investigated how street BZDs contribute to overall BZD use and death prevalences in England, Wales and Northern Ireland.

Methods: Data were analysed from deaths reported to the National Programme on Substance Use Mortality with post-mortem BZD detections (1999-2021), BZDs seized from music festivals (2017-2021) and drug samples with BZD detections submitted to Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) (2017-2021).

Alternate MHC I Antigen Presentation Pathways Allow CD8+ T-cell Recognition and Killing of Cancer Cells in the Absence of β2M or TAP.

MHC I antigen presentation allows CD8+ T cells to detect and eliminate cancerous or virally infected cells. The MHC I pathway is not essential for cell growth and viability, so cancers and viruses can evade control by CD8+ T cells by inactivating antigen presentation. In cancers, two common ways for this evasion are the loss of either the MHC I light chain [β2 microglobulin (β2M)] or the transporter-associated with antigen processing (TAP).

IRF2 loss is associated with reduced MHC I pathway transcripts in subsets of most human cancers and causes resistance to checkpoint immunotherapy in human and mouse melanomas.

Background: In order for cancers to progress, they must evade elimination by CD8 T cells or other immune mechanisms. CD8 T cells recognize and kill tumor cells that display immunogenic tumor peptides bound to MHC I molecules. One of the ways that cancers can escape such killing is by reducing expression of MHC I molecules, and loss of MHC I is frequently observed in tumors.

Making Living-donor Liver Transplantation a Viable Option for Patients With Portopulmonary Hypertension.

Liver transplantation (LT) in patients with significant portopulmonary hypertension (PoPH) is associated with an increased risk of several complications, including graft failure. Graft loss is one of the major reasons. Living donor LT (LDLT) is not routinely performed in the United States in this patient population.