Structure-Guided Discovery of Selective USP7 Inhibitors with In Vivo Activity.

Inhibition of ubiquitin-specific protease 7, USP7, has been proposed as a mechanism to affect many disease processes, primarily those implicated in oncology. The bound crystal structure of a published high-throughput screening hit with low-micromolar affinity for USP7 identified three regions of the compound for structure-guided optimization. Replacing one side of the compound with different aromatic moieties gave little improvement in affinity, and the central piperidine could not be improved.

Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

Purpose: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization.

Effective dose of ephedrine for treatment of hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age: a multicentre randomised, controlled, open label, dose escalation trial.

Background: The recommended dose of ephedrine in adults (0.1 mg kg) frequently fails to treat hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age. The aim of this study was to determine the optimal dose of ephedrine in this population for the treatment of hypotension after induction of general anaesthesia with sevoflurane.