Distal Biceps Brachii Tendon Transfer for Re-establishing Extrinsic Finger Function: Feasibility Study in Cadavers.

Purpose: To determine the anatomic feasibility of transferring the biceps brachii tendon into either the extensor digitorum communis (EDC) or flexor digitorum profundus (FDP), determine the excursion imparted to EDC and FDP tendons after transfer, and compare the work capacity of the cadaver biceps to previously published data on the biceps as well as the recipient muscles by calculating the physiologic cross-sectional area (PCSA).

Methods: Four fresh-frozen cadaver shoulder-elbow-wrist specimens were used to measure tendon excursion that can be obtained with transfer of the distal biceps tendon into either the EDC or FDP. Two cadavers had distal biceps-to-EDC transfer performed, and the other 2 had distal biceps-to-FDP performed.

Multivalent Small-Molecule Pan-RAS Inhibitors.

Design of small molecules that disrupt protein-protein interactions, including the interaction of RAS proteins and their effectors, may provide chemical probes and therapeutic agents. We describe here the synthesis and testing of potential small-molecule pan-RAS ligands, which were designed to interact with adjacent sites on the surface of oncogenic KRAS. One compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear magnetic resonance spectroscopy, and isothermal titration calorimetry and to exhibit lethality in cells partially dependent on expression of RAS proteins.

Small Molecule that Reverses Dexamethasone Resistance in T-cell Acute Lymphoblastic Leukemia (T-ALL).

Glucocorticoids are one of the most utilized and effective therapies in treating T-cell acute lymphoblastic leukemia. However, patients often develop resistance to glucocorticoids, rendering these therapies ineffective. We screened 9517 compounds, selected for their lead-like properties, chosen from among 3 372 615 compounds, against a dexamethasone-resistant T-ALL cell line to identify small molecules that reverse glucocorticoid resistance.

Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis.

Exchange of extracellular cystine for intracellular glutamate by the antiporter system xc (-) is implicated in numerous pathologies. Pharmacological agents that inhibit system xc (-) activity with high potency have long been sought, but have remained elusive. In this study, we report that the small molecule erastin is a potent, selective inhibitor of system xc (-).

Regulation of ferroptotic cancer cell death by GPX4.

Ferroptosis is a form of nonapoptotic cell death for which key regulators remain unknown. We sought a common mediator for the lethality of 12 ferroptosis-inducing small molecules. We used targeted metabolomic profiling to discover that depletion of glutathione causes inactivation of glutathione peroxidases (GPXs) in response to one class of compounds and a chemoproteomics strategy to discover that GPX4 is directly inhibited by a second class of compounds.

Modulatory profiling identifies mechanisms of small molecule-induced cell death.

Cell death is a complex process that plays a vital role in development, homeostasis, and disease. Our understanding of and ability to control cell death is impeded by an incomplete characterization of the full range of cell death processes that occur in mammalian systems, especially in response to exogenous perturbations. We present here a general approach to address this problem, which we call modulatory profiling.

Privileged scaffolds for library design and drug discovery.

This review explores the concept of using privileged scaffolds to identify biologically active compounds through building chemical libraries. We hope to accomplish three main objectives: to provide one of the most comprehensive listings of privileged scaffolds; to reveal through four selected examples the present state of the art in privileged scaffold library synthesis (in hopes of inspiring new and even more creative approaches); and also to offer some thoughts on how new privileged scaffolds might be identified and exploited.

Anatomic reconstruction of thumb metacarpophalangeal joint ulnar collateral ligament using an interference screw docking technique.

Complete rupture of the ulnar collateral ligament injury of the thumb metacarpophalangeal (MCP) joint can be a debilitating injury resulting in decreased grip and pinch strength. The spectrum of injury to this ligament varies from simple strain to complete rupture of both proper and accessory ligaments. Generally, this is a result of an abduction force transmitted across the thumb MCP joint.

Comparison of radiation exposure in lumbar pedicle screw placement with fluoroscopy vs computer-assisted image guidance with intraoperative three-dimensional imaging.

Background/objective: Little is known about the long-term effects of chronic exposure to ionizing radiation. Studies have shown that spine surgeons may be exposed to significantly more radiation than that observed in surgery on the appendicular skeleton. Computer-assisted image guidance systems have been shown in preliminary studies to enable accurate instrumentation of the spine.