Pediatr Qual Saf
December 2021
Unlabelled: The Centers for Disease Control and Prevention recommends tracking risk-adjusted antimicrobial prescribing. Prior studies have used prescribing variation to drive quality improvement initiatives without adjusting for severity of illness. The present study aimed to determine the relationship between antimicrobial prescribing and risk-adjusted ICU mortality in the Pediatric Health Information Systems (PHIS) database, assessed by IBM-Watson risk of mortality.
View Article and Find Full Text PDFThe aging brain is shaped by many structural and functional alterations. Recent cross-disciplinary efforts have uncovered powerful and integrated adaptive mechanisms that promote brain health and prevent functional decline during aging. Here, we review some of the most robust adaptive mechanisms and how they can be engaged to protect, and restore the aging brain.
View Article and Find Full Text PDFAim: We aimed to describe changes in invasive pneumococcal disease (IPD) hospitalisations after introduction of the pneumococcal conjugate vaccine (PCV13).
Methods: This was a retrospective analysis of the Pediatric Health Information System (PHIS) database, including children with IPD pre-PCV13 (2004-2009) and post-PCV13 (2012-2017). Healthy children and those with chronic conditions were analysed separately.
Background: Hyperglycemia is a complication of induction chemotherapy in 10%-50% of pediatric patients with acute lymphoblastic leukemia (ALL). Though hyperglycemia in ALL patients is usually transient, it may be associated with adverse health outcomes. However, the risk factors for and consequences of hyperglycemia are poorly understood.
View Article and Find Full Text PDFThe mechanisms that extend lifespan in humans are poorly understood. Here we show that extended longevity in humans is associated with a distinct transcriptome signature in the cerebral cortex that is characterized by downregulation of genes related to neural excitation and synaptic function. In Caenorhabditis elegans, neural excitation increases with age and inhibition of excitation globally, or in glutamatergic or cholinergic neurons, increases longevity.
View Article and Find Full Text PDFObjectives: This study compared the safety and diagnostic yield of a selective referral strategy using coronary computed tomographic angiography (CCTA) compared with a direct referral strategy using invasive coronary angiography (ICA) as the index procedure.
Background: Among patients presenting with signs and symptoms suggestive of coronary artery disease (CAD), a sizeable proportion who are referred to ICA do not have a significant, obstructive stenosis.
Methods: In a multinational, randomized clinical trial of patients referred to ICA for nonemergent indications, a selective referral strategy was compared with a direct referral strategy.
Neurostimulant medications are commonly prescribed following traumatic brain injury (TBI) in adults; little is known about their use in children with TBI. Our objective was to analyze neurostimulant prescribing practices from 2005 to 2015 in children admitted to the intensive care unit (ICU) with TBI. We hypothesized that neurostimulant prescriptions have increased over time and are associated with older age and injury severity.
View Article and Find Full Text PDFDysfunctional endothelial cells are an essential contributor to the progression of diverse chronic cardiovascular, renal, and metabolic diseases. It manifests in impairment of nitric oxide-dependent vasorelaxation, vascular permeability, and leukocytes deterrent. While endothelial glycocalyx is known to regulate these functions, glycocalyx has been shown to be impaired in pathologic settings leading to endothelial dysfunction.
View Article and Find Full Text PDFNephrol Dial Transplant
February 2018
After briefly discussing endothelial glycocalyx and its role in vascular physiology and renal disease, this overview focuses on its degradation very early in the course of microbial sepsis. We describe our recently proposed mechanism for glycocalyx degradation induced by exocytosis of lysosome-related organelles and release of their cargo. Notably, an intermediate in nitric oxide synthesis, NG-hydroxy-l-arginine, shows efficacy in curtailing exocytosis of these organelles and improvement in animal survival.
View Article and Find Full Text PDFBackgroundLow birth weight (LBW) neonates have impaired kidney development that leaves them susceptible to kidney disease and hypertension during adulthood. The study here identifies events that blunt nephrogenesis and kidney development in the murine LBW neonate.MethodsWe examined survival, kidney development, GFR, gene expression, and cyto-/chemokines in the LBW offspring of malnourished (caloric and protein-restricted) pregnant mice.
View Article and Find Full Text PDFEndothelial glycocalyx (EG) is disintegrated during sepsis. We have previously shown that this occurs very early in the course of sepsis and its prevention improves the survival of mice with sepsis. Here, we sought to investigate the possibility of pharmacologically accelerating the restoration of disintegrated EG in sepsis.
View Article and Find Full Text PDFPearly penile papules (PPP) present as dome-shaped papules of no more than 3 mm in diameter that line the base of the glans of the penis. These benign lesions affect between 14.3 and 48 % of men.
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2016
Peritubular capillary (PTC) rarefaction along with tissue fibrosis is a hallmark of chronic kidney disease (CKD). However, molecular mechanisms of PTC loss have been poorly understood. Previous studies have demonstrated that functional loss of endothelial sirtuin 1 (SIRT1) impairs angiogenesis during development and tissue damage.
View Article and Find Full Text PDFSepsis is a systemic inflammatory syndrome induced by bacterial infection that can lead to multiorgan failure. Endothelial surface glycocalyx (ESG) decorating the inner wall of blood vessels is a regulator of multiple vascular functions. Here, we tested a hypothesis that patchy degradation of ESG occurs early in sepsis and is a result of exocytosis of lysosome-related organelles.
View Article and Find Full Text PDFUnlabelled: : We previously reported the delivery of endothelial progenitor cells (EPCs) embedded in hyaluronic acid-based (HA)-hydrogels protects renal function during acute kidney injury (AKI) and promotes angiogenesis. We attempted to further ameliorate renal dysfunction by coembedding EPCs with renal mesenchymal stem cells (MSCs), while examining their paracrine influence on cytokine/chemokine release and proinflammatory macrophages. A live/dead assay determined whether EPC-MSC coculturing improved viability during lipopolysaccharide (LPS) treatment, and HA-hydrogel-embedded delivery of cells to LPS-induced AKI mice was assessed for effects on mean arterial pressure (MAP), renal blood flow (RBF), circulating cytokines/chemokines, serum creatinine, proteinuria, and angiogenesis (femoral ligation).
View Article and Find Full Text PDFProstaglandins Other Lipid Mediat
July 2015
We are witnessing the emergence of a novel type of biological regulation, namely, the communication between cells via their secreted substances, the secretome. This brief overview is based on the available published data and our own experience. We discuss three vignettes illustrating the importance of communication via the secretome: (1) the secretome of stem cells and its effects in sepsis and systemic inflammatory response; (2) the profibrotic secretomes partially responsible for development of fibrotic complications; and (3) the contribution of senescence-associated secretory products to the propagation of the senescence phenotype.
View Article and Find Full Text PDFWe sought to characterize a minor renal cryoinjury that allows investigation into renal damage processes and subsequent endogenous repair mechanisms. To achieve this, we induced a small cryoinjury to mice, in which the transient superficial application of a liquid nitrogen-cooled cryoprobe to the exposed kidney induces a localized lesion that did not impair renal function. The resulting cryoinjury was examined by immunohistochemistry and Laser-Doppler flowmetry.
View Article and Find Full Text PDFExcessive TGF-β signaling in epithelial cells, pericytes, or fibroblasts has been implicated in CKD. This list has recently been joined by endothelial cells (ECs) undergoing mesenchymal transition. Although several studies focused on the effects of ablating epithelial or fibroblast TGF-β signaling on development of fibrosis, there is a lack of information on ablating TGF-β signaling in the endothelium because this ablation causes embryonic lethality.
View Article and Find Full Text PDFHuman neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease.
View Article and Find Full Text PDFA large fraction of the mammalian genome is organized into inactive chromosomal domains along the nuclear lamina. The mechanism by which these lamina associated domains (LADs) are established remains to be elucidated. Using genomic repositioning assays, we show that LADs, spanning the developmentally regulated IgH and Cyp3a loci contain discrete DNA regions that associate chromatin with the nuclear lamina and repress gene activity in fibroblasts.
View Article and Find Full Text PDFPurpose: To measure the neutron dose equivalent per therapeutic proton dose (H/D) in a passive scattering proton therapy system and study its dependence on the proton energy, aperture-to-isocenter distance, spread-out Bragg peak (SOBP) width, and field size.
Methods And Materials: We performed four experiments of varying proton energies, aperture-to-isocenter distances, SOBP widths, and field sizes. Etched track detectors were used to measure the neutron dose equivalent at both an in-field (isocenter, beyond the protons' range) and out-of-field (30 cm lateral to the isocenter) location in air.
In the region of high-dose gradients at the end of the proton range, the stopping power ratio of the protons undergoes significant changes, allowing for a broad spectrum of proton energies to be deposited within a relatively small volume. Because of the potential linear energy transfer dependence of LiF TLD-100 (thermolumescent dosimeter), dose measurements made in the distal fall-off region of a proton beam may be less accurate than those made in regions of low-dose gradients. The purpose of this study is to determine the accuracy and precision of dose measured using TLD-100 for a pristine Bragg peak, particularly in the distal fall-off region.
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