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Brown R.H.,Atlanta Veterans Administration Medical Center | Zhong L.,University of Miami | Lynch M.G.,Emory University
Journal of Cataract and Refractive Surgery | Year: 2014

Cataract surgery has been demonstrated to lower intraocular pressure (IOP) in eyes with glaucoma. The evidence is strong in angle-closure patients that cataract surgery improves IOP and dramatically reduces the future risk for IOP spikes and acute attacks. Randomized controlled trials (RCTs) have shown that cataract surgery may be preferable to laser iridotomy or phacotrabeculectomy. The data are so convincing that an RCT has been undertaken to assess whether clear lens extraction may be appropriate following acute attacks and in cases of uncontrolled IOP. The case favoring cataract surgery in open-angle glaucoma (OAG) is more controversial. Impressive IOP reduction has been shown in OAG patients when the patients are stratified by preoperative IOP. The patients with the highest preoperative IOPs have pressure reductions up to 8.5 mm Hg. However, these findings have been criticized for methodological weaknesses. Combining cataract surgery with microinvasive glaucoma surgery in phaco-plus procedures provides further options for lens-based glaucoma surgery. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. © 2014 ASCRS and ESCRS. Source

Gray W.D.,Georgia Institute of Technology | Gray W.D.,Emory University | French K.M.,Georgia Institute of Technology | Ghosh-Choudhary S.,Georgia Institute of Technology | And 7 more authors.
Circulation Research | Year: 2015

RATIONALE:: Myocardial infarction is a leading cause of death in developed nations, and there remains a need for cardiac therapeutic systems that mitigate tissue damage. Cardiac progenitor cells (CPCs) and other stem cell types are attractive candidates for treatment of myocardial infarction; however, the benefit of these cells may be as a result of paracrine effects. OBJECTIVE:: We tested the hypothesis that CPCs secrete proregenerative exosomes in response to hypoxic conditions. METHODS AND RESULTS:: The angiogenic and antifibrotic potential of secreted exosomes on cardiac endothelial cells and cardiac fibroblasts were assessed. We found that CPC exosomes secreted in response to hypoxia enhanced tube formation of endothelial cells and decreased profibrotic gene expression in TGF-β-stimulated fibroblasts, indicating that these exosomes possess therapeutic potential. Microarray analysis of exosomes secreted by hypoxic CPCs identified 11 miRNAs that were upregulated compared with exosomes secreted by CPCs grown under normoxic conditions. Principle component analysis was performed to identify miRNAs that were coregulated in response to distinct exosome-generating conditions. To investigate the cue-signal-response relationships of these miRNA clusters with a physiological outcome of tube formation or fibrotic gene expression, partial least squares regression analysis was applied. The importance of each up-or downregulated miRNA on physiological outcomes was determined. Finally, to validate the model, we delivered exosomes after ischemia-reperfusion injury. Exosomes from hypoxic CPCs improved cardiac function and reduced fibrosis. CONCLUSIONS:: These data provide a foundation for subsequent research of the use of exosomal miRNA and systems biology as therapeutic strategies for the damaged heart. © 2014 American Heart Association, Inc. Source

Carr C.W.,Emory University | Veledar E.,Emory University | Chen S.C.,Emory University | Chen S.C.,Atlanta Veterans Administration Medical Center
JAMA Dermatology | Year: 2014

Importance Chronic pruritus is a common problem with a deleterious effect on quality of life. The factors mediating the relationship between chronic pruritus and quality of life are poorly understood. Objective To determine the factors that mediate the impact of chronic pruritus on quality of life. Design, Setting, And Participants Cross-sectional study based on a nationwide telephone survey of US military veterans sampled from the Veterans Hospital Patient Database. Participants were veterans who agreed to participate and were found to have chronic pruritus. Main Outcomes And Measures Statistical significance of predictor variables (characteristics of patients and their chronic pruritus) in multivariate analysis using ItchyQoL scores as response variables. Results Of 6000 veterans telephoned, 1075 consented to participate; 405 of these had chronic pruritus. Factors that mediated the impact of chronic pruritus on quality of life were demographic characteristics (age [P = .007], race [P = .05], marital status [P = .04]), personality (extroversion [P = .03], neuroticism [P = .01]), pruritus characteristics (severity [P < .001], duration [P = .01], frequency [P 7 .001], location [P = .005]), and possible etiology (cutaneous vs systemic [P = .03]). Notable factors not found significant include sex (P = .98) and socioeconomic variables (education level [P > .99], employment status [P = .53], income [P = .62]). Conclusions And Relevance The multitude of factors that significantly influence the impact of chronic pruritus on quality of life demonstrates the complex nature of this relationship. A better appreciation of these factors will improve the clinical evaluation and treatment of chronic pruritus. © 2014 American Medical Association. All rights reserved. Source

Weber M.,Emory University | Baker M.B.,Emory University | Moore J.P.,Emory University | Searles C.D.,Emory University | Searles C.D.,Atlanta Veterans Administration Medical Center
Biochemical and Biophysical Research Communications | Year: 2010

Mechanical forces associated with blood flow play an important role in regulating vascular signaling and gene expression in endothelial cells (ECs). MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. miRNAs are known to have an important role in modulating EC biology, but their expression and functions in cells subjected to shear stress conditions are unknown. We sought to determine the miRNA expression profile in human ECs subjected to unidirectional shear stress and define the role of miR-21 in shear stress-induced changes in EC function. TLDA array and qRT-PCR analysis performed on HUVECs exposed to prolonged unidirectional shear stress (USS, 24 h, 15 dynes/cm2) identified 13 miRNAs whose expression was significantly upregulated (p < 0.05). The miRNA with the greatest change was miR-21; it was increased 5.2-fold (p = 0.002) in USS-treated versus control cells. Western analysis demonstrated that PTEN, a known target of miR-21, was downregulated in HUVECs exposed to USS or transfected with pre-miR-21. Importantly, HUVECs overexpressing miR-21 had decreased apoptosis and increased eNOS phosphorylation and nitric oxide (NO{radical dot}) production. These data demonstrate that shear stress forces regulate the expression of miRNAs in ECs, and that miR-21 influences endothelial biology by decreasing apoptosis and activating the NO{radical dot} pathway. These studies advance our understanding of the mechanisms by which shear stress forces modulate vascular homeostasis. Source

Baker M.B.,Emory University | Bao G.,Georgia Institute of Technology | Searles C.D.,Emory University | Searles C.D.,Atlanta Veterans Administration Medical Center
Nucleic Acids Research | Year: 2012

MicroRNAs (miRNAs), a class of non-coding RNAs, have become a major focus of molecular biology research because of their diverse genomic origin and ability to regulate an array of cellular processes. Although the biological functions of miRNA are yet to be fully understood, tissue levels of specific miRNAs have been shown to correlate with pathological development of disease. Here, we demonstrate that molecular beacons can readily distinguish mature- and pre-miRNAs, and reliably quantify miRNA expression. We found that molecular beacons with DNA, RNA and combined locked nucleic acid (LNA)-DNA backbones can all detect miRNAs of low (<1nM) concentrations in vitro, with RNA beacons having the highest detection sensitivity. Furthermore, we found that molecular beacons have the potential to distinguish miRNAs that have slight variations in their nucleotide sequence. These results suggest that the molecular beacon-based approach to assess miRNA expression and distinguish mature and precursor miRNA species is quite robust, and has the promise for assessing miRNA levels in biological samples. non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. © The Author(s) 2011. Published by Oxford University Press. Source

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