Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial.

Importance: Psoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies.

Objective: To evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis.

Design, Setting, And Participants: The GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis.

Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.

CD4(+) T helper lymphocytes that express interleukin-17 (T(H)17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also influence inflammatory processes in humans. Genome-wide association studies in humans have linked genes involved in T(H)17 cell differentiation and function with susceptibility to Crohn's disease, rheumatoid arthritis and psoriasis. Thus, the pathway towards differentiation of T(H)17 cells and, perhaps, of related innate lymphoid cells with similar effector functions, is an attractive target for therapeutic applications.

TCR-dependent differentiation of thymic Foxp3+ cells is limited to small clonal sizes.

Numerous studies have highlighted the importance of high-affinity interactions between T cell receptors (TCRs) and their ligands in the selection of Foxp3(+) regulatory T cells (T reg cells). To determine the role of the TCR in directing T cells into the Foxp3(+) lineage, we generated transgenic (Tg) mice expressing TCRs from Foxp3(+) cells. Initial analyses of the TCR Tg mice crossed with RAG-deficient mice showed that the percentage of Foxp3(+) cells was very low.

Effects of flecainide on atrial and ventricular refractoriness in rabbits in vitro and in vivo.

This study compared the in vitro versus in vivo effects of flecainide on effective refractory period (ERP) in atrial and ventricular tissue in rabbits. Flecainide (a class 1c agent) was chosen, on the basis of its known pharmacological profile and antiarrhythmic actions, to provide a reference compound for investigating models that suitably predict the clinical effects of antiarrhythmics. The rabbit models used were those previously described by Lowe et al.

Effects of E4031 and quinidine on atrial and ventricular refractoriness in rabbits in vivo.

This study assessed the effects of E4031 and quinidine on refractoriness (ERP) in a new in vivo model in rabbits. Following sinoatrial (SAN) and atrioventricular node (AVN) ablation ERP was determined in atria and ventricles with the shortest S1-S2 interval eliciting a second electrogram defined as the ERP. The effects of E4031 and quinidine (dose ranges 1-8 micromol/kg) were compared.