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White D.L.,Baylor College of Medicine | White D.L.,Center for Innovations in Quality | White D.L.,Center for Translational Research in Inflammatory Diseases | Thrift A.P.,Baylor College of Medicine | And 6 more authors.
Gastroenterology | Year: 2017

Background & Aims The incidence and mortality of hepatocellular carcinoma (HCC) have been reported to be plateauing in the United States. The United States has large racial, ethnic, and regional variation; we collected data from all 50 states to better analyze changes in HCC incidence in the entire United States. Methods We collected data from the US Cancer Statistics registry, which covers 97% of the population, and calculated adjusted incidence rates. We assessed annual trends among sociodemographic and geographic subgroups using joinpoint analysis. Results HCC incidence increased from 4.4/100,000 in 2000 to 6.7/100,000 in 2012, increasing by 4.5% (95% confidence interval [CI], 4.3%–4.7%) annually between 2000 and 2009, but only by 0.7% annually (95% CI, –0.2% to 1.6%) from 2010 through 2012. The average annual percentage change (AAPC) between 2000 and 2012 was higher in men (increase, 3.7%) than in women (increase, 2.7%), and highest in 55- to 59-year-old individuals (AAPC, 8.9%; 95% CI, 7.1%–10.7%) and 60- to 64-year-old individuals (AAPC, 6.4%; 95% CI, 4.7%–8.2%). By 2012, rates in Hispanics surpassed those in Asians, and rates in Texas surpassed those in Hawaii (9.71/100,000 vs 9.68/100,000). Geographic variation within individual race and ethnic groups was observed, but rates were highest in all major race and ethnic groups in Texas. Conclusions In an analysis of the incidence of HCC in all 50 US states, we found the rate of increase in HCC to have slowed from 2010 through 2012. However, incidence is increasing in subgroups such as men ages 55 to 64 years old—especially those born in the peak era of hepatitis C virus infection and among whites/Caucasians. Rates in Hispanics have surpassed those in Asian Americans. We observed geographic differences, with Texas having the highest age-adjusted HCC rates nationwide. © 2017 AGA Institute

Jalilov A.S.,Rice University | Nilewski L.G.,Rice University | Berka V.,University of Houston | Zhang C.,Rice University | And 6 more authors.
ACS Nano | Year: 2017

Here we show that the active portion of a graphitic nanoparticle can be mimicked by a perylene diimide (PDI) to explain the otherwise elusive biological and electrocatalytic activity of the nanoparticle construct. Development of molecular analogues that mimic the antioxidant properties of oxidized graphenes, in this case the poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs), will afford important insights into the highly efficient activity of PEG-HCCs and their graphitic analogues. PEGylated perylene diimides (PEGn-PDI) serve as well-defined molecular analogues of PEG-HCCs and oxidized graphenes in general, and their antioxidant and superoxide dismutase-like (SOD-like) properties were studied. PEGn-PDIs have two reversible reduction peaks, which are more positive than the oxidation peak of superoxide (O2 •-). This is similar to the reduction peak of the HCCs. Thus, as with PEG-HCCs, PEGn-PDIs are also strong single-electron oxidants of O2 •-. Furthermore, reduced PEGn-PDI, PEGn-PDI•-, in the presence of protons, was shown to reduce O2 •- to H2O2 to complete the catalytic cycle in this SOD analogue. The kinetics of the conversion of O2 •- to O2 and H2O2 by PEG8-PDI was measured using freeze-trap EPR experiments to provide a turnover number of 133 s-1 the similarity in kinetics further supports that PEG8-PDI is a true SOD mimetic. Finally, PDIs can be used as catalysts in the electrochemical oxygen reduction reaction in water, which proceeds by a two-electron process with the production of H2O2, mimicking graphene oxide nanoparticles that are otherwise difficult to study spectroscopically. © 2017 American Chemical Society.

Samuel E.L.G.,Rice University | Marcano D.C.,Rice University | Berka V.,University of Houston | Wu G.,University of Houston | And 7 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Many diseases are associated with oxidative stress, which occurs when the production of reactive oxygen species (ROS) overwhelms the scavenging ability of an organism. Here, we evaluated the carbon nanoparticle antioxidant properties of poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs) by electron paramagnetic resonance (EPR) spectroscopy, oxygen electrode, and spectrophotometric assays. These carbon nanoparticles have 1 equivalent of stable radical and showed superoxide (O2 •-) dismu-tase-like properties yet were inert to nitric oxide (NO•) as well as peroxynitrite (ONOO-). Thus, PEG-HCCs can act as selective antioxidants that do not require regeneration by enzymes. Our steadystate kinetic assay using KO2 and direct freeze-trap EPR to follow its decay removed the rate-limiting substrate provision, thus enabling determination of the remarkable intrinsic turnover numbers of O2 •-to O2 by PEG-HCCs at >20,000 s-1 . Themajor products of this catalytic turnover are O2 and H 2 O 2, making the PEG-HCCs a biomimetic superoxide dismutase.

Lo N.C.,Rice University | Turner N.A.,Rice University | Cruz M.A.,Baylor College of Medicine | Cruz M.A.,Center for Translational Research in Inflammatory Diseases | Moake J.,Rice University
Journal of Biological Chemistry | Year: 2013

Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli causes diarrhea-associated hemolytic-uremic syndrome (DHUS), a severe renal thrombotic microangiopathy. We investigated the interaction between Stx and von Willebrand Factor (VWF), a multimeric plasma glycoprotein that mediates platelet adhesion, activation, and aggregation. Stx bound to ultra-large VWF (ULVWF) secreted from and anchored to stimulated human umbilical vein endothelial cells, as well as to immobilized VWF-rich human umbilical vein endothelial cell supernatant. This Stx binding was localized to the A1 and A2 domain of VWF monomeric subunits and reduced the rate of ADAMTS- 13-mediated cleavage of the Tyr1605- Met1606 peptide bond in the A2 domain. Stx-VWF interaction and the associated delay in ADAMTS-13-mediated cleavage of VWF may contribute to the pathophysiology of DHUS. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Samuel E.L.G.,Rice University | Duong M.T.,Rice University | Bitner B.R.,Baylor College of Medicine | Marcano D.C.,Rice University | And 4 more authors.
Trends in Biotechnology | Year: 2014

Oxidative stress reflects an excessive accumulation of reactive oxygen species (ROS) and is a hallmark of several acute and chronic human pathologies. Although many antioxidants have been investigated, most have demonstrated poor efficacy in clinical trials. Here we discuss the limitations of current antioxidants and describe a new class of nanoparticle antioxidants, poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs). PEG-HCCs show high capacity to annihilate ROS such as superoxide (O2•-) and the hydroxyl (HO•) radical, show no reactivity toward the nitric oxide radical (NO•), and can be functionalized with targeting moieties without loss of activity. Given these properties, we propose that PEG-HCCs offer an exciting new area of study for the treatment of numerous ROS-induced human pathologies. © 2014.

Kanwal F.,Center for Innovations in Quality | Kanwal F.,Baylor College of Medicine | Kramer J.R.,Center for Innovations in Quality | Kramer J.R.,Baylor College of Medicine | And 8 more authors.
Clinical Gastroenterology and Hepatology | Year: 2016

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States. However, few data are available on recent trends in the incidence and prevalence of NAFLD in the U.S. Methods: We analyzed the national Veterans Administration databases from 2003 to 2011 and calculated the age-adjusted prevalence and incidence of NAFLD for the overall sample of patients and by demographic subgroups. We used a previously validated algorithm to define NAFLD, which was based on persistent increases in levels of liver enzymes in the absence of positive results from tests for hepatitis C or hepatitis B or evidence of excessive alcohol use. Results: Of the 9,784,541 patients with at least 1 visit to the Veterans Administration between 2003 and 2011, 1,330,600 patients (13.6%) had NAFLD. The annual incidence rates of NAFLD remained stable (from 2.2% to 3.2%) during the study duration. The prevalence of NAFLD increased from 6.3% in 2003 (95% confidence interval, 6.26%-6.3%) to 17.6% in 2011 (95% confidence interval, 17.58%-17.65%), a 2.8-fold increase. The incidence and prevalence increased at significantly greater rates in patients younger than 45 years vs older patients. Conclusions: In a U.S. population, the annual incidence of NAFLD ranges from 2% to 3%. The prevalence of NAFLD more than doubled from 2003 through 2011; it is likely to continue to increase because of a steady overall incidence coupled with a rising incidence in younger individuals. © 2016 AGA Institute.

Da Q.,Baylor College of Medicine | Behymer M.,Baylor College of Medicine | Correa J.I.,Baylor College of Medicine | Vijayan K.V.,Baylor College of Medicine | And 3 more authors.
Blood | Year: 2014

The interaction between platelet receptor glycoprotein Iba and the A1 domain of von Willebrand factor (VWF) mediates tethering/translocationof platelets to sites of vascular injury. Unexpectedly, we observed platelets translocating over A1A2A3 domains protein slower than on A1 domain at high shear stress. This observation suggests an additional interaction between A domains and an adhesive receptor. We investigated vimentin because we have data showing the interaction of vimentin with the A2 domain of VWF. Moreover, vimentin is expressed on the platelet surface. This novel interaction was analyzed by using purified VWF, recombinant proteins, anti-vimentin antibodies, parallel flow chamber adhesion assays, flow cytometry, and vimentin-deficient murine platelets. The active form of VWF bound to vimentin, and the purified A2 domain blocked that binding. The interaction of a gain-of-function A1A2A3 mutant with platelet was reduced using anti-vimentin antibody. Platelet adhesion to wild-type (WT) A1A2A3 protein, collagen, and fibrin(ogen) was inhibited (32-75%) by anti-vimentin antibody under high shear stress. Compared with WT mice, platelets from vimentin-deficient mice had a reduced flow-dependent adhesion to both collagen and purified murine VWF. Last, the vimentin knockout mice had a prolonged tail bleeding time. The results describe that platelet vimentin engages VWF during platelet adhesion under high shear stress. © 2014 by The American Society of Hematology.

Kosten T.A.,Baylor College of Medicine | Kosten T.A.,Research Service Line 151 | Shen X.Y.,Research Service Line 151 | Shen X.Y.,Baylor College of Medicine | And 7 more authors.
American Journal on Addictions | Year: 2014

Background and Objectives Immunotherapy for drug addiction is being investigated in several laboratories but most studies are conducted in animals of one sex. Yet, women show heightened immune responses and are more likely to develop autoimmune diseases than men. The purpose of this study was to compare the effects of an active anti-cocaine vaccine, succinyl-norcocaine conjugated to keyhole limpet hemocyanin, for its ability to elicit antibodies and alter cocaine-induced ambulatory activity in male versus female mice. Methods Male and female BALB/c mice were vaccinated (n-=-44) or served as non-vaccinated controls (n-=-34). Three weeks after initial vaccination, a booster was given. Ambulatory activity induced by cocaine (20-mg/kg) was assessed at 7 weeks and plasma obtained at 8 weeks to assess antibody levels. Results High antibody titers were produced in mice of both sexes. The vaccine reduced ambulatory activity cocaine-induced but this effect was greater in female compared to male mice. Discussion and Conclusions The efficacy of this anti-cocaine vaccine is demonstrated in mice of both sexes but its functional consequences are greater in females than males. Scientific Significance Results point to the importance of testing animals of both sexes in studies of immunotherapies for addiction. (Am J Addict 2014;23:604-607) © American Academy of Addiction Psychiatry.

Mandava P.,Michael bakey Va Medical Center | Mandava P.,Baylor College of Medicine | Shah S.D.,Baylor College of Medicine | Sarma A.K.,Baylor College of Medicine | And 3 more authors.
Translational Stroke Research | Year: 2015

Most early phase trials in stroke and brain trauma have failed in phase 3, including efforts to improve acute ischemic stroke outcomes beyond that achieved by intravenous recombinant tissue plasminogen activator (t-PA) (IVT). With the exception of more recent stent retriever trials, most subsequent phase 3 trials failed. We previously showed that baseline imbalances, non-linear relationships of these factors to outcome, and unrepresentative control populations invalidate traditional statistical analysis in early trials of heterogeneous diseases such as stroke. We developed an alternative approach using a pooled outcome model derived from control arms of randomized clinical trial (RCTs). This model then permits comparing treatment trials to an expected outcome of a pooled population. Here, we hypothesized we could develop such a model for IVT and tested it against outcomes without IVT. We surveyed literature for all trials involving one arm with IVT reporting baseline National Institute Stroke Scale (NIHSS), age, and outcome. A non-linear fit was performed including multi-dimensional statistical intervals (±95 %) permitting visual comparison of outcomes at their own baselines. We compared models derived from non-IVT control arms. Models from 24 IVT RCTs representing 3195 subjects were successfully generated for functional outcome, modified Rankin Scale (mRS) 0–2 (r2 = 0. 83, p < 0.001), and mortality (r2 = 0.54; p = 0.001). We confirmed better outcomes compared to no IVT and mixed use IVT models across the range of baseline factors. It was possible to generate an expected outcome model for IVT from existing literature. We confirmed benefit compared to placebo. This model should be useful to compare to new agents without the need for statistical manipulation. © 2015, Springer Science+Business Media New York (Outside the USA).

Engineer D.R.,Center for Translational Research in Inflammatory Diseases | Engineer D.R.,Baylor College of Medicine | Engineer D.R.,St Lukes Episcopal Hospital | Burney B.O.,Center for Translational Research in Inflammatory Diseases | And 3 more authors.
Translational Oncology | Year: 2013

BACKGROUND: Advanced colon cancer is associated with weight loss and decreased survival. Studies suggest that angiotensin and β-adrenergic blockade decrease colon cancer progression and ameliorate weight loss. This study aims to determine whether exposure to β-adrenoceptor blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) is associated with decreased mortality, tumor progression, number of hospitalizations, or weight loss in colorectal cancer. METHODS: Retrospective chart review included patients with advanced colorectal cancer. Survival, stage, hospitalization, cancer progression, cancer treatment, and body weight history were collected. RESULTS: Two hundred sixty-two of 425 new stage III to IV colorectal cancer cases reviewed met the study criteria. Those exposed to ACEI/ARB, BB, or both were more likely to have diabetes, hypertension, and stage III colorectal cancer. Adjusting for age, presence of hypertension and diabetes, and stage, ACEI/ARB + BB exposure was associated with decreased mortality compared to unexposed individuals [hazard ratio (HR) = 0.5, confidence interval (CI) = 0.29-0.85; Cox regression, P =.01]. Fewer total and cancer-related hospitalizations and decreased cancer progression in the ACEI/ARB + BB group versus the unexposed group (HR = 0.59, CI = 0.36-0.99, P =.047) were seen. Exposure did not affect weight changes; furthermore, body weight changes from both prediagnosis and at diagnosis to 6, 12, 18, and 24 months postdiagnosis predicted survival. CONCLUSIONS: We have observed an association between exposure to a combination of ACEI/ ARB + BB and increased survival, decreased hospitalizations, and decreased tumor progression in advanced colorectal cancer. Future studies will be needed to replicate these results and generalize them to broader populations. Determination of causality will require a randomized controlled trial. © 2013 Neoplasia Press, Inc. All rights reserved.

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