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Chondronikola M.,University of Texas Medical Branch | Sidossis L.S.,Shriners Hospitals for Children | Sidossis L.S.,Institute for Translational science | Richardson L.M.,Shriners Hospitals for Children | And 3 more authors.
Journal of Burn Care and Research | Year: 2013

Burn injury deformities and obesity have been associated with social integration difficulty and body image dissatisfaction. However, the combined effects of obesity and burn injury on social integration difficulty and body image dissatisfaction are unknown. Adolescent and young adult burn injury survivors were categorized as normal weight (n = 47) or overweight and obese (n = 21). Burn-related and anthropometric information were obtained from patients' medical records, and validated questionnaires were used to assess the main outcomes and possible confounders. Analysis of covariance and multiple linear regressions were performed to evaluate the objectives of this study. Obese and overweight burn injury survivors did not experience increased body image dissatisfaction (12 ± 4.3 vs 13.1 ± 4.4; P = .57) or social integration difficulty (17.5 ± 6.9 vs 15.5 ± 5.7; P = .16) compared with normal weight burn injury survivors. Weight status was not a significant predictor of social integration difficulty or body image dissatisfaction (P = .19 and P = .24, respectively). However, mobility limitations predicted greater social integration difficulty (P = .005) and body image dissatisfaction (P < .001), whereas higher weight status at burn was a borderline significant predictor of body image dissatisfaction (P = .05). Obese and overweight adolescents and young adults, who sustained major burn injury as children, do not experience greater social integration difficulty and body image dissatisfaction compared with normal weight burn injury survivors. Mobility limitations and higher weight status at burn are likely more important factors affecting the long-term social integration difficulty and body image dissatisfaction of these young people. © 2013 by the American Burn Association. Source


Fang L.,University of Texas Medical Branch | Choudhary S.,University of Texas Medical Branch | Choudhary S.,301 University Blvd | Zhao Y.,University of Texas Medical Branch | And 7 more authors.
Nucleic Acids Research | Year: 2014

Ataxia-telangiectasia mutated (ATM), a member of the phosphatidylinositol 3 kinase-like kinase family, is a master regulator of the double strand DNA break-repair pathway after genotoxic stress. Here, we found ATM serves as an essential regulator of TNF-induced NF-kB pathway. We observed that TNF exposure of cells rapidly induced DNA double strand breaks and activates ATM. TNF-induced ROS promote nuclear IKKγ association with ubiquitin and its complex formation with ATM for nuclear export. Activated cytoplasmic ATM is involved in the selective recruitment of the E3-ubiquitin ligase β-TrCP to phospho-IκBα proteosomal degradation. Importantly, ATM binds and activates the catalytic subunit of protein kinase A (PKAc), ribosmal S6 kinase that controls RelA Ser 276 phosphorylation. In ATM knockdown cells, TNF-induced RelA Ser 276 phosphorylation is significantly decreased. We further observed decreased binding and recruitment of the transcriptional elongation complex containing cyclin dependent kinase-9 (CDK9; a kinase necessary for triggering transcriptional elongation) to promoters of NF-κB-dependent immediate-early cytokine genes, in ATM knockdown cells. We conclude that ATM is a nuclear damage-response signal modulator of TNF-induced NF-κB activation that plays a key scaffolding role in IκBα degradation and RelA Ser 276 phosphorylation. Our study provides a mechanistic explanation of decreased innate immune response associated with A-T mutation. © 2014 The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. Source


Finnerty C.C.,Shriners Hospitals for Children | Finnerty C.C.,Institute for Translational science | Finnerty C.C.,University of Texas Medical Branch | Herndon D.N.,Shriners Hospitals for Children
Expert Opinion on Pharmacotherapy | Year: 2012

Introduction: The worldwide occurrence of burn injuries remains high despite efforts to reduce injury incidence through public awareness campaigns and improvements in living conditions. In 2004, almost 11 million people experienced burns severe enough to warrant medical treatment. Advances over the past several decades in aggressive resuscitation, nutrition, excision and grafting have reduced morbidity and mortality. Incorporation of pharmacotherapeutics into treatment regimens may further reduce complications of severe burn injuries. Areas covered: Severe burn injuries, as well as other forms of stress and trauma, trigger a hypermetabolic response that, if left untreated, impedes recovery. In the past two decades, use of anabolic agents, β-adrenergic receptor antagonists and anti-hyperglycemic agents has successfully counteracted post-burn morbidities including catabolism, the catecholamine-mediated response and insulin resistance. Here, the authors review the most up-to-date information on currently used pharmacotherapies in the treatment of these sequelae of severe burns and the insights that have expanded the understanding of the pathophysiology of severe burns. Expert opinion: Existing drugs offer promising advances in the care of burn injuries. Continued gains in the understanding of the molecular mechanisms driving the hypermetabolic response will enable the application of additional existing drugs to be broadened to further attenuate the hypermetabolic response. © Informa UK, Ltd. Source


Caldwell B.J.,New York University | Caldwell B.J.,Institute for Translational science | Trew M.L.,University of Auckland | Pertsov A.M.,New York University
Circulation: Arrhythmia and Electrophysiology | Year: 2015

Background - The electric response of myocardial tissue to periodic field stimuli has attracted significant attention as the basis for low-energy antifibrillation pacing, potentially more effective than traditional single high-energy shocks. In conventional models, an electric field produces a highly nonuniform response of the myocardial wall, with discrete excitations, or hot spots (HS), occurring at cathodal tissue surfaces or large coronary vessels. We test this prediction using novel 3-dimensional tomographic optical imaging. Methods and Results - Experiments were performed in isolated coronary perfused pig ventricular wall preparations stained with near-infrared voltage-sensitive fluorescent dye DI-4-ANBDQBS. The 3-dimensional coordinates of HS were determined using alternating transillumination. To relate HS formation with myocardial structures, we used ultradeep confocal imaging (interrogation depths, >4 mm). The peak HS distribution is located deep inside the heart wall, and the depth is not significantly affected by field polarity. We did not observe the strong colocalization of HS with major coronary vessels anticipated from theory. Yet, we observed considerable lateral displacement of HS with field polarity reversal. Models that de-emphasized lateral intracellular coupling and accounted for resistive heterogeneity in the extracellular space showed similar HS distributions to the experimental observations. Conclusions - The HS distributions within the myocardial wall and the significant lateral displacements with field polarity reversal are inconsistent with standard theories of defibrillation. Extended theories based on enhanced descriptions of cellular scale electric mechanisms may be necessary. The considerable lateral displacement of HS with field polarity reversal supports the hypothesis of biphasic stimuli in low-energy antifibrillation pacing being advantageous. © 2015 American Heart Association, Inc. Source


Ju H.,University of Texas Medical Branch | Ju H.,Institute for Translational science | Brasier A.R.,Sealy Center for Molecular Medicine | Brasier A.R.,Institute for Translational science
BMC Research Notes | Year: 2013

Background: The choice of selection methods to identify important variables for binary classification modeling is critical to produce stable models that are interpretable, that generate accurate predictions and have minimum bias. This work is motivated by data on clinical and laboratory features of severe dengue infections (dengue hemorrhagic fever, DHF) obtained from 51 individuals enrolled in a prospective observational study of acute human dengue infections. Results: We carry out a comprehensive performance comparison using several classification models for DHF over the dengue data set. We compared variable selection results by Multivariate Adaptive Regression Splines, Learning Ensemble, Random Forest, Bayesian Moving Averaging, Stochastic Search Variable Selection, and Generalized Regularized Logistics Regression. Model averaging methods (bagging, boosting and ensemble learners) have higher accuracy, but the generalized regularized regression model has the highest predictive power because the linearity assumptions of candidate predictors are strongly satisfied via deviance chi-square testing procedures. Bootstrapping applications for evaluating predictive regression coefficients in regularized regression model are performed. Conclusions: Feature reduction methods introduce inherent biases and therefore are data-type dependent. We propose that these limitations can be overcome using an exhaustive approach for searching feature space. Using this approach, our results suggest that IL-10, platelet and lymphocyte counts are the major features for predicting dengue DHF on the basis of blood chemistries and cytokine measurements. © 2013 Ju and Brasier; licensee BioMed Central Ltd. Source

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