Nephrin is a slit diaphragm protein critical for structural and functional integrity of visceral glomerular epithelial cells (podocytes) and is known to be tyrosine phosphorylated by Src family kinases. We studied the role of phosphoinositide 3-kinase (PI3K), activated via the phosphorylation of nephrin, in actin cytoskeletal reorganization of cultured rat podocytes. Phosphorylation of rat nephrin by the Fyn kinase markedly increased its interaction with a regulatory subunit of PI3K. Stable transfection of rat nephrin in the podocytes with podocin led to nephrin tyrosine phosphorylation, PI3K-dependent phosphorylation of Akt, increased Rac1 activity, and an altered actin cytoskeleton with decreased stress fibers and increased lamellipodia. These changes were reversed with an inhibitor of PI3K and not seen when the nephrin-mutant Y1152F replaced wild-type nephrin. Rac1 and Akt1 contributed to lamellipodia formation and decreased stress fibers, respectively. Finally, in the rat model of puromycin aminonucleoside nephrosis, nephrin tyrosine phosphorylation, nephrin-PI3K association, and glomerular Akt phosphorylation were all decreased. Our results suggest that PI3K is involved in nephrin-mediated actin reorganization in podocytes. Disturbed nephrin-PI3K interactions may contribute to abnormal podocyte morphology and proteinuria.

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BackgroundDespite the use of ‘patient ownership’ as an embodiment of professionalism and increasing concerns over its loss among trainees, how its development in residents has been affected by duty hour regulations has not been well described. In this qualitative study, we aim to outline the key features of patient ownership in internal medicine, factors enabling its development, and how these have been affected by the adoption of a night float system to comply with duty hour regulations.MethodsIn this qualitative descriptive study, we interviewed 18 residents and 12 faculty internists at one university centre and conducted a thematic analysis of the data focused on the concept of patient ownership.ResultsWe identified three key features of patient ownership: personal concern for patients, professional capacity for autonomous decision-making, and knowledge of patients’ issues. Within the context of a night float system, factors that facilitate development of patient ownership include improved fitness for duty and more consistent interactions with patients/families resulting from working the same shift over consecutive days (or nights). Conversely, the increase in patient handovers, if done poorly, is a potential threat to patient ownership development. Trainees often struggle to develop ownership when autonomy is not supported with supervision and when role-modelling by faculty is lacking.DiscussionThese features of patient ownership can be used to frame discussions when coaching trainees. Residency programs should be mindful of the downstream effects of shift-based scheduling. We propose strategies to optimize factors that enable trainee development of patient ownership.Electronic supplementary materialThe online version of this article (10.1007/s40037-019-00540-9) contains supplementary material, which is available to authorized users.

Duty hours restrictions, as exemplified by an NF system, have both positive and negative impacts on professionalism. Interventions and training toward effective team-based care are needed to curb emergence of shift-worker mentality.