Le Bonheur Childrens Hospital

Memphis, TN, United States

Le Bonheur Childrens Hospital

Memphis, TN, United States
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Khazaee A.,University of Bojnord | Ebrahimzadeh A.,Babol Noshirvani University of Technology | Babajani-Feremi A.,University of Tennessee Health Science Center | Babajani-Feremi A.,Le Bonheur Childrens Hospital
Behavioural Brain Research | Year: 2017

Brain network alterations in patients with Alzheimer's disease (AD) has been the subject of much investigation, but the biological mechanisms underlying these alterations remain poorly understood. Here, we aim to identify the changes in brain networks in patients with AD and mild cognitive impairment (MCI), and provide an accurate algorithm for classification of these patients from healthy control subjects (HC) by using a graph theoretical approach and advanced machine learning methods. Multivariate Granger causality analysis was performed on resting-state functional magnetic resonance imaging (rs-fMRI) data of 34 AD, 89 MCI, and 45 HC to calculate various directed graph measures. The graph measures were used as the original feature set for the machine learning algorithm. Filter and wrapper feature selection methods were applied to the original feature set to select an optimal subset of features. An accuracy of 93.3% was achieved for classification of AD, MCI, and HC using the optimal features and the naïve Bayes classifier. We also performed a hub node analysis and found that the number of hubs in HC, MCI, and AD were 12, 10, and 9, respectively, suggesting that patients with AD experience disturbance of critical communication areas in their brain network as AD progresses. The findings of this study provide insight into the neurophysiological mechanisms underlying MCI and AD. The proposed classification method highlights the potential of directed graph measures of rs-fMRI data for identification of the early stage of AD. © 2016 Elsevier B.V.

Babajani-Feremi A.,University of Tennessee Health Science Center | Babajani-Feremi A.,Le Bonheur Childrens Hospital
Brain Topography | Year: 2017

Comprehension of narratives constitutes a fundamental part of our everyday life experience. Although the neural mechanism of auditory narrative comprehension has been investigated in some studies, the neural correlates underlying this mechanism and its heritability remain poorly understood. We investigated comprehension of naturalistic speech in a large, healthy adult population (n = 429; 176/253 M/F; 22–36 years of age) consisting of 192 twin pairs (49 monozygotic and 47 dizygotic pairs) and 237 of their siblings. We used high quality functional MRI datasets from the Human Connectome Project (HCP) in which a story-based paradigm was utilized for the auditory narrative comprehension. Our results revealed that narrative comprehension was associated with activations of the classical language regions including superior temporal gyrus (STG), middle temporal gyrus (MTG), and inferior frontal gyrus (IFG) in both hemispheres, though STG and MTG were activated symmetrically and activation in IFG were left-lateralized. Our results further showed that the narrative comprehension was associated with activations in areas beyond the classical language regions, e.g. medial superior frontal gyrus (SFGmed), middle frontal gyrus (MFG), and supplementary motor area (SMA). Of subcortical structures, only the hippocampus was involved. The results of heritability analysis revealed that the oral reading recognition and picture vocabulary comprehension were significantly heritable (h2 > 0.56, p < 10− 13). In addition, the extent of activation of five areas in the left hemisphere, i.e. STG, IFG pars opercularis, SFGmed, SMA, and precuneus, and one area in the right hemisphere, i.e. MFG, were significantly heritable (h2 > 0.33, p < 0.0004). The current study, to the best of our knowledge, is the first to investigate auditory narrative comprehension and its heritability in a large healthy population. Referring to the excellent quality of the HCP data, our results can clarify the functional contributions of linguistic and extra-linguistic cortices during narrative comprehension. © 2017 Springer Science+Business Media New York

Dong C.,St Jude Childrens Research Hospital | Dong C.,University of Tennessee Health Science Center | Anand K.J.S.,University of Tennessee Health Science Center | Anand K.J.S.,Le Bonheur Childrens Hospital
Toxicology Letters | Year: 2013

Ketamine is widely used as an anesthetic, analgesic, and sedative in pediatric clinical practice and it is also listed as an illicit drug by most countries. Recent in vivo and in vitro animal studies have confirmed that ketamine can induce neuronal cell death in the immature brain, resulting from widespread neuronal apoptosis. These effects can disturb normal development further altering the structure and functions of the brain. Our recent studies further indicate that ketamine can alter neurogenesis from neural stem progenitor cells in the developing brain. Taken together, these findings identify a novel complication associated with ketamine use in premature infants, term newborns, and pregnant women. Recent data on the developmental neurotoxicity of ketamine are reviewed with proposed future directions for evaluating the safety of ketamine in these patient populations. © 2013 Elsevier Ireland Ltd.

De Vincenzo J.P.,University of Tennessee Health Science Center | De Vincenzo J.P.,Le Bonheur Childrens Hospital
Antiviral Therapy | Year: 2012

Advances in the understanding of RNA biological processing and control are leading to new concepts in human therapeutics with practical implications for many human diseases, including antiviral therapy of respiratory viruses. So-called 'non-coding RNA' exerts specific and profound functional control on regulation of protein production and indeed controls the expression of all genes through processes collectively known as RNA interference (RNAi). RNAi is a naturally occurring intracellular process that regulates gene expression through the silencing of specific messenger RNAs (mRNAs). Methods are being developed that allow the catalytic degradation of targeted mRNAs using specifically designed complementary small interfering RNAs (siRNA). siRNAs are now being chemically modified and packaged into advanced delivery systems so as to acquire drug-like properties and the ability to deliver their effects systemically. Recent in vivo studies have provided proofs of the concept that RNAi may be useful therapeutically. Much of the design of these siRNAs can be accomplished bioinformatically, thus potentially expediting drug discovery and opening new avenues of therapy for many uncommon, orphan, or emerging diseases. Theoretically, any disease that can be ameliorated through knockdown of any endogenous or exogenous protein is a potential therapeutic target for RNAi-based therapeutics. Lung diseases in general are attractive targets for RNAi therapeutics, since the location of affected cells increases their accessibility to topical administration of siRNA, and respiratory viral infections are particularly attractive targets for RNAi-based drug discovery and development. RNAi therapeutics have been shown to exert potent antiviral effects against respiratory syncytial virus (RSV), parainfluenza, influenza, coronaviruses, measles and human metapneumoviruses in vitro and in vivo. Recently, a double-blind placebo-controlled clinical trial of an RNAi-based therapeutic against RSV demonstrated that this technology has therapeutic activity, representing the first proof-of-concept test of efficacy for RNAi's therapeutic effect in humans. This review discusses the science behind RNAi and the potential practical issues in applying this technology to various respiratory viral diseases. © 2012 International Medical Press.

We evaluate the clinical performance of the Luminex xTAG gastrointestinal (GI) pathogen in vitro diagnostic (IVD) assay in a comparison between clinical and public health laboratories. The site reproducibility study showed 98.7% sensitivity with high positive and negative agreement values (96.2% and 99.8%, respectively), while assay performance against confirmatory methods resulted in 96.4% sensitivity with similar positive and negative agreement values (90.1% and 99.5%, respectively). High-throughput detection of multiple GI pathogens improved turnaround time, consolidated laboratory workflow, and simplified stool culture practices, thus reducing the overall cost and number of specimens processed. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Parvaneh N.,Tehran University of Medical Sciences | Casanova J.-L.,Rockefeller University | Casanova J.-L.,University of Paris Descartes | Notarangelo L.D.,Harvard University | And 2 more authors.
Journal of Allergy and Clinical Immunology | Year: 2013

The characterization of primary immunodeficiencies (PIDs) in human subjects is crucial for a better understanding of the biology of the immune response. New achievements in this field have been possible in light of collaborative studies; attention paid to new phenotypes, infectious and otherwise; improved immunologic techniques; and use of exome sequencing technology. The International Union of Immunological Societies Expert Committee on PIDs recently reported on the updated classification of PIDs. However, new PIDs are being discovered at an ever-increasing rate. A series of 19 novel primary defects of immunity that have been discovered after release of the International Union of Immunological Societies report are discussed here. These new findings highlight the molecular pathways that are associated with clinical phenotypes and suggest potential therapies for affected patients. © 2013 American Academy of Allergy, Asthma & Immunology.

Khazaee A.,Babol Noshirvani University of Technology | Ebrahimzadeh A.,Babol Noshirvani University of Technology | Babajani-Feremi A.,University of Tennessee Health Science Center | Babajani-Feremi A.,Le Bonheur Childrens Hospital
Clinical Neurophysiology | Year: 2015

Objective: Study of brain network on the basis of resting-state functional magnetic resonance imaging (fMRI) has provided promising results to investigate changes in connectivity among different brain regions because of diseases. Graph theory can efficiently characterize different aspects of the brain network by calculating measures of integration and segregation. Method: In this study, we combine graph theoretical approaches with advanced machine learning methods to study functional brain network alteration in patients with Alzheimer's disease (AD). Support vector machine (SVM) was used to explore the ability of graph measures in diagnosis of AD. We applied our method on the resting-state fMRI data of twenty patients with AD and twenty age and gender matched healthy subjects. The data were preprocessed and each subject's graph was constructed by parcellation of the whole brain into 90 distinct regions using the automated anatomical labeling (AAL) atlas. The graph measures were then calculated and used as the discriminating features. Extracted network-based features were fed to different feature selection algorithms to choose most significant features. In addition to the machine learning approach, statistical analysis was performed on connectivity matrices to find altered connectivity patterns in patients with AD. Results: Using the selected features, we were able to accurately classify patients with AD from healthy subjects with accuracy of 100%. Conclusion: Results of this study show that pattern recognition and graph of brain network, on the basis of the resting state fMRI data, can efficiently assist in the diagnosis of AD. Significance: Classification based on the resting-state fMRI can be used as a non-invasive and automatic tool to diagnosis of Alzheimer's disease. © 2015 International Federation of Clinical Neurophysiology.

Jacobs J.D.,University of Tennessee Health Science Center | Jacobs J.D.,Le Bonheur Childrens Hospital | Foster M.,University of Tennessee Health Science Center | Wan J.,University of Tennessee Health Science Center | And 2 more authors.
Pediatrics | Year: 2014

BACKGROUND: Research suggests that hypertonic saline (HS) may improve mucous flow in infants with acute bronchiolitis. Data suggest a trend favoring reduced length of hospital stay and improved pulmonary scores with increasing concentration of nebulized solution to 3% and 5% saline as compared with 0.9% saline mixed with epinephrine. To our knowledge, 7% HS has not been previously investigated. METHODS: We conducted a prospective, double-blind, randomized controlled trial in 101 infants presenting with moderate to severe acute bronchiolitis. Subjects received either 7% saline or 0.9% saline, both with epinephrine. Our primary outcome was a change in bronchiolitis severity score (BSS), obtained before and after treatment, and at the time of disposition from the emergency department (ED). Secondary outcomes measured were hospitalization rate, proportion of admitted patients discharged at 23 hours, and ED and inpatient length of stay. RESULTS: At baseline, study groups were similar in demographic and clinical characteristics. The decrease in mean BSS was not statistically significant between groups (2.6 vs 2.4 for HS and control groups, respectively). The difference between the groups in proportion of admitted patients (42% in HS versus 49% in normal saline), ED or inpatient length of stay, and proportion of admitted patients discharged at 23 hours was not statistically significant. CONCLUSIONS: In moderate to severe acute bronchiolitis, inhalation of 7% HS with epinephrine does not appear to confer any clinically significant decrease in BSS when compared with 0.9% saline with epinephrine. Copyright © 2014 by the American Academy of Pediatrics.

Bridges D.,University of Tennessee Health Science Center | Bridges D.,Le Bonheur Childrens Hospital | Saltiel A.R.,University of Michigan
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2015

Abstract Phosphoinositides are key players in many trafficking and signaling pathways. Recent advances regarding the synthesis, location and functions of these lipids have dramatically improved our understanding of how and when these lipids are generated and what their roles are in animal physiology. In particular, phosphoinositides play a central role in insulin signaling, and manipulation of PtdIns(3,4,5)P3 levels in particular, may be an important potential therapeutic target for the alleviation of insulin resistance associated with obesity and the metabolic syndrome. In this article we review the metabolism, regulation and functional roles of phosphoinositides in insulin signaling and the regulation of energy metabolism. This article is part of a Special Issue entitled Phosphoinositides. © 2014 Elsevier B.V. All rights reserved.

Hoberman A.,University of Pittsburgh | Greenfield S.P.,Children's Hospital of Buffalo | Mattoo T.K.,Wayne State University | Keren R.,Children's Hospital of Philadelphia | And 7 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial. METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance. RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group. CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring. Copyright © 2014 Massachusetts Medical Society.

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