Venetoclax with decitabine or azacitidine in relapsed or refractory acute myeloid leukemia.

Relapsed or refractory acute myeloid leukemia (AML) is associated with poor outcomes and resistance to therapy. The addition of venetoclax, a BCL-2 antagonist, to lower-intensity therapies results in improved survival in the first-line setting compared to monotherapy with a hypomethylating agent or low-dose cytarabine. Despite this, much remains unknown about the performance of venetoclax with a hypomethylating agent following the first-line setting.

Venetoclax with decitabine or azacitidine in the first-line treatment of acute myeloid leukemia.

Treatment paradigms for acute myeloid leukemia (AML) have evolved at a rapid pace in recent years. The combination of venetoclax with a hypomethylating agent prolonged survival in clinical trials when compared to hypomethylating agent monotherapy. However, little is known about the performance of venetoclax-based regimens outside of clinical trials, given conflicting safety and efficacy data.

The kappa-opioid receptor agonist, nalfurafine, blocks acquisition of oxycodone self-administration and oxycodone's conditioned rewarding effects in male rats.

Mu-opioid receptor (MOR) agonists are highly efficacious for the treatment of pain but have significant abuse liability. Recently, we reported that nalfurafine, when combined with oxycodone at a certain ratio, reduced the reinforcing effects of oxycodone in rats while producing additive antinociceptive effects. Questions remain, however, including if the combination will function as a reinforcer in drug-naïve rats, and if the combination produces aversive effects that could explain nalfurafine's ability to reduce oxycodone self-administration? In the present study, we investigated nalfurafine's ability to reduce acquisition of oxycodone self-administration when the two were self-administered as a mixture in drug-naïve rats and nalfurafine's ability to attenuate a conditioned place preference (CPP) induced by oxycodone.

High Levels of the Xenorhabdus nematophila Transcription Factor Lrp Promote Mutualism with the Steinernema carpocapsae Nematode Host.

bacteria are mutualistic symbionts of nematodes and pathogens of insects. The global regulator Lrp controls the expression of many genes involved in both mutualism and pathogenic activities, suggesting a role in the transition between the two host organisms. We previously reported that natural populations of exhibit various levels of Lrp expression and that cells expressing relatively low levels of Lrp are optimized for virulence in the insect The adaptive advantage of the high-Lrp-expressing state was not established.