Putting students at the center: moving beyond time-variable one-size-fits-all medical education to true individualization.

Medical education has undergone a wave of creative innovation over the last decade, with new curricular structures, pedagogy, content, and team-based approaches. Augmenting these changes, integration of clinical and scientific principles increasingly occurs across all years of training. Given success in innovation and integration, as well as recent interest and national pilots in time-variable (competency-based) education, we propose the next important step in medical education evolution is individualization.

Influence of early life events on health and diseases.

The transition from the fetal to the extrauterine environment is associated with complex physiological adjustments and involves numerous cardiovascular, pulmonary, and metabolic adjustments to ensure successful adaptation to the postnatal life. While such changes are in response to the altered environment in which the newborn finds itself, external changes affecting the fetal environment could impact the integrity of these mechanisms and increase susceptibility to diseases later in life. The present article reviews some of the mechanisms involved in the transition from fetal to postnatal life and focuses of how our health as adults is dependent on the conditions we experienced in-utero.

G protein-coupled receptor kinase 4 gene variants in human essential hypertension.

Essential hypertension has a heritability as high as 30-50%, but its genetic cause(s) has not been determined despite intensive investigation. The renal dopaminergic system exerts a pivotal role in maintaining fluid and electrolyte balance and participates in the pathogenesis of genetic hypertension. In genetic hypertension, the ability of dopamine and D(1)-like agonists to increase urinary sodium excretion is impaired. A defective coupling between the D(1) dopamine receptor and the G protein/effector enzyme complex in the proximal tubule of the kidney is the cause of the impaired renal dopaminergic action in genetic rodent and human essential hypertension. We now report that, in human essential hypertension, single nucleotide polymorphisms of a G protein-coupled receptor kinase, GRK4gamma, increase G protein-coupled receptor kinase (GRK) activity and cause the serine phosphorylation and uncoupling of the D(1) receptor from its G protein/effector enzyme complex in the renal proximal tubule and in transfected Chinese hamster ovary cells. Moreover, expressing GRK4gammaA142V but not the wild-type gene in transgenic mice produces hypertension and impairs the diuretic and natriuretic but not the hypotensive effects of D(1)-like agonist stimulation. These findings provide a mechanism for the D(1) receptor coupling defect in the kidney and may explain the inability of the kidney to properly excrete sodium in genetic hypertension.