Most patients with acute myelogenous leukemia (AML) relapse and die of their disease. Increasing evidence indicates that AML relapse is driven by the inability to eradicate leukemia stem cells (LSC). Thus, it is imperative to identify novel therapies that can ablate LSCs. Using an in silico gene expression-based screen for compounds evoking transcriptional effects similar to the previously described anti-LSC agent parthenolide, we identified AR-42 (OSU-HDAC42), a novel histone deacetylase inhibitor that is structurally similar to phenylbutyrate, but with improved activity at submicromolar concentrations. Here, we report that AR-42 induces NF-kB inhibition, disrupts the ability of Hsp90 to stabilize its oncogenic clients, and causes potent and specific cell death of LSCs but not normal hematopoietic stem and progenitor cells. Unlike parthenolide, the caspasedependent apoptosis caused by AR-42 occurs without activation of Nrf-2-driven cytoprotective pathways. As AR-42 is already being tested in early clinical trials, we expect that our results can be extended to the clinic. Mol Cancer Ther; 13(8); 1979-90. Ó2014 AACR.

Implementation of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains incomplete. Non-cardiovascular hospitalization may present opportunities for GDMT optimization. We assessed the efficacy and durability of a virtual, multidisciplinary 'GDMT Team' on medical therapy prescription for HFrEF.

In 2019, the U.S. Centers for Disease Control and Prevention classified the multidrug-resistant Candida auris as one of five pathogens posing the most urgent threats to public health.

The documentation of lead toxicity (plumbism) dates back to the times when man learnt its various applications. This versatile heavy metal is non-degradable and its ability to get accumulated in the body that goes undiagnosed, makes it a serious environmental health hazard. Lead is now known to affect almost every organ/tissue of the human body. With irreversible effects on neurobiological development of young children and foetus, its toxicity has lasting implications on the human life. Outlining the symptoms, diagnosis and treatment therapy for lead poisoning, the present review elaborates the pathophysiological effects of lead on various organs. This will be of immense help to the health professionals so as to inculcate a better understanding of the lead poisoning which otherwise is asymptomatic. With chelation therapy being the classic path of treatment, new strategies are being explored as additive/adjunct therapy. It is now understood that lead toxicity is completely preventable. In this regard significant efforts are in place in the developed countries whereas much needs to be done in the developing countries. Spreading the awareness amongst the masses by educating them and reducing the usage of lead following stricter industry norms appears to be the only roadmap to prevent lead poisoning. Efforts being undertaken by the Government of India and other organisations are also mentioned.

Dangerousness in the delusional misidentification syndromes is studied by reviewing a sample of 82 cases defined by either verbal threats or physical violence caused by a misidentification delusion. Eighty cases were obtained from a review of the anglophone psychiatric literature in which the patients exhibited some degree of dangerousness, to which we added 2 previously unreported cases.