Thiazole-Based IL-17 Inhibitors Discovered by Scaffold Morphing.

The pro-inflammatory cytokine interleukin-17A (IL-17) plays an important role in the body's defense against bacterial and fungal infections. However, overexpression of IL-17 has been associated with several diseases, including rheumatoid arthritis, asthma, psoriasis, and even cancer. The role of IL-17 in psoriasis has been confirmed by clinical use of IL-17 antibodies, e.

Introducing entrustable professional activities for postgraduate medical training in Switzerland.

Introduction: Graduate medical education is being reformed in many countries, with a focus on the principles of competency-based medical education (CBME). A main novel aspect in this context is the implementation of entrustable professional activities (EPAs). The introduction of EPAs aims to better align training curricula with clinical practice, provide individualized supervision, and enhance the quality of feedback.

Vulcanization Accelerators and Silica Coupling Agents in Polyisoprene Melts.

The achievement of sufficient dispersion of vulcanization accelerators is critical to tailoring superior cross-linked elastomers. Modern recipes rely on multicomponent formulations with silica particles covered by coupling agents. We study the molecular properties of select accelerators in polyisoprene melts and their affinity for functionalized surfaces via extensive all-atom molecular dynamics simulations.

SLC6A19 inhibition facilitates urinary neutral amino acid excretion and lowers plasma phenylalanine.

BACKGROUNDThe toxic accumulation of phenylalanine (Phe) in the brain underlies the neurological presentation of phenylketonuria (PKU). Solute carrier family 6 member 19 (SLC6A19) is the major transporter responsible for the (re)absorption of Phe in the kidney and intestine. Here, we describe the characterization of the first small molecule SLC6A19 inhibitor to enter clinical development for the treatment of PKU.