Selective RET Inhibitors (SRIs) in Cancer: A Journey from Multi-Kinase Inhibitors to the Next Generation of SRIs.

RET is a receptor tyrosine kinase that plays an important role in the development of neurons and kidneys. The gene encoding the rearranged-during-transfection () receptor tyrosine kinase was first discovered in the 1980s. Activating mutations and rearrangements have since been identified as actionable drivers of oncogenesis in numerous cancer types and are most prevalent in thyroid and non-small-cell lung cancer.

Implementation of a Proactive Pilot Health Plan-Driven Opioid Tapering Program to Decrease Chronic Opioid Use for Conditions of the Back and Spine in a Medicaid Population.

Background: In 2016, the Oregon Health Authority and the Health Evidence Review Commission implemented guidance for Oregon Medicaid members who were taking opioids for chronic pain related to conditions of the back and spine. This guidance required that an individualized taper plan be developed and initiated by January 1, 2017, and a discontinuation date for all chronic opioid therapy of January 1, 2018.

Program Description: This program evaluated the effect of a proactive and voluntary health plan-driven opioid tapering program on morphine equivalent daily dose (MEDD) before the implementation of governmental guidance.

Continuous-flow injection microfluidic thrombin assays: The effect of binding kinetics on observed enzyme inhibition.

A microfluidic assay for monitoring the inhibition of thrombin peptidase activity was developed. The system, which utilised soluble reagents in continuous-flow injection mode, was configured so as to allow inhibitor titrations via gradient formation. This microfluidic continuous-flow injection titration assay (CFITA) enabled the potency of a set of small-molecule serine peptidase inhibitors (SPIs) to be evaluated.

Epidemiology of Anorectal Melanoma in the United States: 1992 to 2011.

Background: Anorectal melanoma is a rare type of malignant melanoma and thus the epidemiology of patients with this tumor has been poorly defined.

Objective: To describe the epidemiology of anorectal melanoma in the United States.

Methods And Materials: We obtained case and population data from the Surveillance, Epidemiology, and End Results 13 Registries Database (SEER 13) between 1992 and 2011 using rectal diagnostic codes C20.

Subungual abscess caused by Staphylococcus lugdunensis.

Although Staphylococcus lugdunensis is a constituent of the normal human skin flora, it does have pathogenic potential. Infections can range from severe (eg, endocarditis, osteomyelitis) to less invasive skin and soft-tissue infections. We report a case of a subungual abscess in a patient with S lugdunensis infection.

Genes, molecules and patients--emerging topics to guide clinical pain research.

This review selectively explores some areas of pain research that, until recently, have been poorly understood. We have chosen four topics that relate to clinical pain and we discuss the underlying mechanisms and related pathophysiologies contributing to these pain states. A key issue in pain medicine involves crucial events and mediators that contribute to normal and abnormal pain signaling, but remain unseen without genetic, biomarker or imaging analysis.

High throughput discovery of heteroaromatic-modifying enzymes allows enhancement of novobiocin selectivity.

Glycosylated analogues of novobiocin, discovered using a broad library of enzymes, have 100-fold improved activity against breast, brain, pancreatic, lung and ovarian cancers and ablated associated off-target activity leading to an up to 2.7 × 10(4) fold increase in selectivity.

Systemic blockade of P2X3 and P2X2/3 receptors attenuates bone cancer pain behaviour in rats.

Pain remains an area of considerable unmet clinical need, and this is particularly true of pain associated with bone metastases, in part because existing analgesic drugs show only limited efficacy in many patients and in part because of the adverse side effects associated with these agents. An important issue is that the nature and roles of the algogens produced in bone that drive pain-signalling systems remain unknown. Here, we tested the hypothesis that adenosine triphosphate is one such key mediator through actions on P2X3 and P2X2/3 receptors, which are expressed selectively on primary afferent nocioceptors, including those innervating the bone.