Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax.

Artemisinins are active against human leukemia cell lines and have low clinical toxicity in worldwide use as antimalarials. Because multiagent combination regimens are necessary to cure fully evolved leukemias, we sought to leverage our previous finding that artemisinin analogs synergize with kinase inhibitors, including sorafenib (SOR), by identifying additional synergistic antileukemic drugs with low toxicity. Screening of a targeted antineoplastic drug library revealed that B-cell lymphoma 2 (BCL2) inhibitors synergize with artemisinins, and validation assays confirmed that the selective BCL2 inhibitor, venetoclax (VEN), synergized with artemisinin analogs to inhibit growth and induce apoptotic cell death of multiple acute leukemia cell lines in vitro.

Outcome measures of risk and recovery in Broadmoor High Secure Forensic Hospital: stratification of care pathways and moves to medium secure hospitals.

Background: Placements within high secure forensic hospitals consist of wards providing various different levels of relational security. They should form a coherent pathway through secure care, based on individual patient risks and needs. Moves to less secure wards within high secure forensic hospitals and moves on to lower secure hospital settings have rarely been systematically studied.

Stereospecific anti SE2' fluorination of allenylsilanes: synthesis of enantioenriched propargylic fluorides.

The electrophilic fluorodesilylation of enantioenriched allenylsilanes proceeds with efficient transfer of chirality. The silylation-fluorination of propargylic alcohols occurs with overall retention of stereochemistry, a result consistent with a stereospecific anti S(E)2' mechanism for the fluorination step.