Ambulatory blood pressure monitoring in children: A retrospective single-center study

Objectives(1) Compare 24-hour ambulatory blood pressure monitoring (ABPM) diagnoses in a pediatric population with the new 2022 guidelines to the original diagnoses with the 2014 guidelines. (2) Determine whether findings of hypertension from ABPM could be predicted from prior patient data. (3) Determine whether ABPM readings could predict left ventricular mass index (LVMI) in patients who obtained an echocardiogram (ECHO).Study designSingle-center retrospective study on patients referred to Pediatric Nephrology Clinic for evaluation of elevated blood pressure who underwent ABPM from 2015 to 2018. Predictions of hypertension were obtained using a logistic regression model, and predictions of LVMI were performed using regression models including (a) the wake systolic and diastolic BP indices, or (b) additionally including the standard deviation (SD) of wake SBP and DBP.ResultsWith the change in 2022 to new ABPM guidelines from the AHA, comparing the old and new guidelines led to 70% of previous pre-hypertensive diagnoses now meeting criteria for diagnosis of hypertension, and a rise from 21% of the ABPMs meeting criteria for hypertension to 51% now meeting criteria. In a logistic regression model, prior patient data were not predictive of a diagnosis of hypertension from ABPM (Nagelkerke's R2 = 0.04). Among the individual variables studied, none were statistically significant. For prediction of LVMI, the SD of wake SBP and DBP were significantly associated with increased LVMI, but the wake SBP and DBP indices were not.ConclusionsIn our patient population, the new ABPM guidelines led to a significant increase in diagnoses of hypertension. Prior patient data was not sufficient to predict a diagnosis of hypertension by ABPM, supporting the need for evaluation by ABPM as the gold standard. Our analysis of the relationship between ABPM readings and LVMI supports the hypothesis that BP variability contributes to increased LVMI. These data are consistent with growing evidence in the adult literature that BP variability detected by ABPM is associated with left-ventricular hypertroph

Functional Integration of Grafted Neural Stem Cell-Derived Dopaminergic Neurons Monitored by Optogenetics in an In Vitro Parkinson Model

Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D2 autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD

Characterization of an Epitope-Tagged Form of the D2 Dopamine Receptor

Peer reviewe

Translational approaches to medication development

Alcohol accounts for major disability worldwide and available treatments are insufficient. A massive growth in the area of addiction neuroscience over the last several decades has not resulted in a corresponding expansion of treatment options available to patients. In this chapter, we describe our experience with building translational research programs aimed at developing novel pharmacotherapies for alcoholism. The narrative is based on experience and considerations made in the course of building these programs, and work on four mechanisms targeted by our libraries: cholinergic nicotine receptors, receptors for corticotropin-releasing hormone (CRH), neurokinin 1 (NK1) receptors for substance P (SP) and hypocretin/orexin receptors. Around this experience, we discuss issues we believe to be critical for successful translation of basic addiction neuroscience into treatments, and complementarities between academic and other actors that in our assessment need to be harnessed in order to bring treatments to the clinic