BackgroundThe secreted ligand Reelin is believed to regulate the translocation of prospective layer 6 (L6) neocortical neurons into the preplate, a loose layer of pioneer neurons that overlies the ventricular zone. Recent studies have also suggested that Reelin controls neuronal orientation and polarized dendritic growth during this period of early cortical development. To explicitly characterize and quantify how Reelin controls this critical aspect of neurite initiation and growth we used a new ex utero explant model of early cortical development to selectively label a subset of L6 cortical neurons for complete 3-D reconstruction.ResultsThe total neurite arbor sizes of neurons in Reelin-deficient (reeler mutant) and Dab1-deficient (Reelin-non-responsive scrambler mutant) cortices were quantified and unexpectedly were not different than control arbor lengths (p = 0.51). For each mutant, however, arbor organization was markedly different: mutant neurons manifested more primary processes (neurites emitted directly from the soma) than wild type, and these neurites were longer and displayed less branching. Reeler and scrambler mutant neurites extended tangentially rather than radially, and the Golgi apparatus that normally invests the apical neurite was compact in both reeler and scrambler mutants. Mutant cortices also exhibited a neurite “exclusion zone” which was relatively devoid of L6 neuron neurites and extended at least 15 μm beneath the pial surface, an area corresponding to the marginal zone (MZ) in the wild type explants. The presence of an exclusion zone was also indicated in the orientation of mutant primary neurite and neuronal somata, which failed to adopt angles within ~20˚ of the radial line to the pial surface. Injection of recombinant Reelin to reeler, but not scrambler, mutant cortices fully rescued soma orientation, Golgi organization, and dendritic projection defects within four hrs.ConclusionsThese findings indicate Reelin promotes directional dendritic growth into the MZ, an otherwise exclusionary zone for L6 neurites.

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Background: It is unknown to what extent the clinical benefits of PCI outweigh the risks and costs in patients with vs. without cancer and within each cancer type. We performed the first known nationally representative propensity score analysis of PCI mortality and cost among all eligible adult inpatients by cancer and its types.Methods: This multicenter case-control study used machine learning–augmented propensity score–adjusted multivariable regression to assess the above outcomes and disparities using the 2016 nationally representative National Inpatient Sample.Results: Of the 30,195,722 hospitalized patients, 15.43% had a malignancy, 3.84% underwent an inpatient PCI (of whom 11.07% had cancer and 0.07% had metastases), and 2.19% died inpatient. In fully adjusted analyses, PCI vs. medical management significantly reduced mortality for patients overall (among all adult inpatients regardless of cancer status) and specifically for cancer patients (OR 0.82, 95% CI 0.75–0.89; p < 0.001), mainly driven by active vs. prior malignancy, head and neck and hematological malignancies. PCI also significantly reduced cancer patients' total hospitalization costs (beta USD$ −8,668.94, 95% CI −9,553.59 to −7,784.28; p < 0.001) independent of length of stay. There were no significant income or disparities among PCI subjects.Conclusions: Our study suggests among all eligible adult inpatients, PCI does not increase mortality or cost for cancer patients, while there may be particular benefit by cancer type. The presence or history of cancer should not preclude these patients from indicated cardiovascular care.

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Hypertension is the most common disease affecting humans and imparts a significant cardiovascular and renal risk to patients. Extensive research over the past few decades has enhanced our understanding of the underlying mechanisms in hypertension. However, in most instances, the cause of hypertension in a given patient continues to remain elusive. Nevertheless, achieving aggressive blood pressure goals significantly reduces cardiovascular morbidity and mortality, as demonstrated in the recently concluded SPRINT trial. Since a large proportion of patients still fail to achieve blood pressure goals, knowledge of novel pathophysiologic mechanisms and mechanism based treatment strategies is crucial. The following chapter will review the novel pathophysiological mechanisms in hypertension, with a focus on role of immunity, inflammation and vascular endothelial homeostasis. The therapeutic implications of these mechanisms will be discussed where applicable.