Life Sciences Commons^™

Physical Aggressiveness And Gray Matter Deficits In Ventromedial Prefrontal Cortex, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

What causes individuals to hurt others? Since the famous case of Phineas Gage, lesions of the ventromedial prefrontal cortex (VMPFC) have been reliably linked to physically aggressive behavior. However, it is unclear whether naturally-occurring deficits in VMPFC, among normal individuals, might have widespread consequences for aggression. Using voxel based morphometry, we regressed gray matter density from the brains of 138 normal female and male adults onto their dispositional levels of physical aggression, verbal aggression, and sex, simultaneously. Physical, but not verbal, aggression was associated with reduced gray matter volume in the VMPFC and to a lesser extent, frontopolar cortex. Participants …

Common Tdp1 Polymorphisms In Relation To Survival Among Small Cell Lung Cancer Patients: A Multicenter Study From The International Lung Cancer Consortium, Pawadee Lohavanichbutr, Lori C. Sakoda, Christopher I. Amos, Susanne M. Arnold, David C. Christiani, Michael P. A. Davies, John K. Field, Eric B. Haura, Rayjean J Hung, Takashi Kohno, Maria Teresa Landi, Geoffrey Liu, Yi Liu, Michael W. Marcus, Grainne M. O'Kane, Matthew B. Schabath, Kouya Shiraishi, Stacey A. Slone, Adonina Tardón, Ping Yang, Kazushi Yoshida, Ruyang Zhang, Xuchen Zong, Gary E. Goodman, Noel S. Weiss, Chu Chen

Internal Medicine Faculty Publications

Background—DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients.

Methods—Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan–Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …

Influence Of Dietary Salt Knowledge, Perceptions, And Beliefs On Consumption Choices After Stroke In Uganda, Martin N. Kaddumukasa, Elly Katabira, Martha Sajatovic, Svetlana Pundik, Mark Kaddumukasa, Larry B. Goldstein

Neurology Faculty Publications

Background

Previous research on Uganda's poststroke population revealed that their level of dietary salt knowledge did not lead to healthier consumption choices.

Purpose

Identify barriers and motivators for healthy dietary behaviors and evaluate the understanding of widely accepted salt regulation mechanisms among poststroke patients in Uganda.

Methods

Convergent parallel mixed methods triangulation design comprised a cross-sectional survey (n = 81) and 8 focus group discussions with 7-10 poststroke participants in each group. We assessed participant characteristics and obtained insights into their salt consumption attitudes, perceptions, and knowledge. Qualitative responses were analyzed using an inductive approach with thematic analytic procedures. Relationships …

Cerebral Amyloid Angiopathy In Down Syndrome And Sporadic And Autosomal-Dominant Alzheimer's Disease, María Carmona-Iragui, Mircea Balasa, Bessy Benejam, Daniel Alcolea, Susana Fernández, Laura Videla, Isabel Sala, María Belén Sánchez-Saudinós, Estrella Morenas-Rodriguez, Roser Ribosa-Nogué, Ignacio Illán-Gala, Sofía Gonzalez-Ortiz, Jordi Clarimón, Frederick A. Schmitt, David K. Powell, Beatriz Bosch, Albert Lladó, Michael S. Rafii, Elizabeth Head, José Luis Molinuevo, Rafael Blesa, Sebastián Videla, Alberto Lleó, Raquel Sánchez-Valle, Juan Fortea

Sanders-Brown Center on Aging Faculty Publications

Introduction—We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]).

Methods—Neuroimaging features of CAA, APOE, and cerebrospinal fluid-Aβ40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68).

Results—CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. …

Clinically Silent Alzheimer's And Vascular Pathologies Influence Brain Networks Supporting Executive Function In Healthy Older Adults, Brian T. Gold, Christopher A. Brown, Jonathan G. Hakun, Leslie M. Shaw, John Q. Trojanowski, Charles D. Smith

Neuroscience Faculty Publications

Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer’s disease (AD) pathology and cerebral white matter hyperintensities (WMHs). Twenty-nine younger adults and thirty-four cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Older adults further underwent lumbar cerebrospinal fluid (CSF) draw for assessment of AD pathology and FLAIR imaging for assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked …

Increased Birth Weight Is Associated With Altered Gene Expression In Neonatal Foreskin, Leryn J. Reynolds, Rebecca I. Pollack, Richard J. Charnigo, Cetewayo S. Rashid, Arnold J. Stromberg, Shu Shen, John O'Brien, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n = 7) v. the remainder of the cohort (n = 40). Multivariate linear regression models were fit to relate expression levels on differentially …

A Meta-Analysis To Determine The Impact Of Restaurant Menu Labeling On Calories And Nutrients (Ordered Or Consumed) In U.S. Adults, Thaisa M Cantu-Jungles, Lacey A. Mccormack, James E Slaven, Maribeth Slebodnik, Heather A Eicher-Miller

Health and Nutritional Sciences Faculty Publications

A systematic review and meta-analysis determined the effect of restaurant menu labeling on calories and nutrients chosen in laboratory and away-from-home settings in U.S. adults. Cochrane-based criteria adherent, peer-reviewed study designs conducted and published in the English language from 1950 to 2014 were collected in 2015, analyzed in 2016, and used to evaluate the effect of nutrition labeling on calories and nutrients ordered or consumed. Before and after menu labeling outcomes were used to determine weighted mean differences in calories, saturated fat, total fat, carbohydrate, and sodium ordered/consumed which were pooled across studies using random effects modeling. Stratified analysis for …

Multimodality Therapy Improves Survival In Intramedullary Spinal Cord Metastasis Of Lung Primary, Hayder Saeed, Reema Patel, Jigisha Thakkar, Lames Hamoodi, Li Chen, John L. Villano

Internal Medicine Faculty Publications

Background: Most metastatic spinal cord lesions are located either in the intradural, extramedullary, or in the epidural compartments. Intramedullary spinal cord metastasis (ISCM) is a rare central nervous system spread of cancer. The aim of this report was to evaluate ISCM in the published literature.

Methods: A literature review of PubMed from 1960 to 2016 was undertaken for the publications having demographic, clinical, histological, and outcome data.

Results: A total of 59 relevant papers were identified, showing 128 cases of intramedullary metastasis from lung cancer. The incidence of lung cancer as the primary malignancy with intramedullary metastasis was 56%. The …

Whole-Genome Dna Methylation Status Associated With Clinical Ptsd Measures Of Oif/Oef Veterans., R Hammamieh, N Chakraborty, A Gautam, S Muhie, R Yang, D Donohue, R Kumar, B J Daigle, Y Zhang, D A Amara, S-A Miller, S Srinivasan, J Flory, R Yehuda, L Petzold, O M Wolkowitz, S H Mellon, L Hood, F J Doyle, C Marmar, M Jett

Articles, Abstracts, and Reports

Emerging knowledge suggests that post-traumatic stress disorder (PTSD) pathophysiology is linked to the patients' epigenetic changes, but comprehensive studies examining genome-wide methylation have not been performed. In this study, we examined genome-wide DNA methylation in peripheral whole blood in combat veterans with and without PTSD to ascertain differentially methylated probes. Discovery was initially made in a training sample comprising 48 male Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans with PTSD and 51 age/ethnicity/gender-matched combat-exposed PTSD-negative controls. Agilent whole-genome array detected ~5600 differentially methylated CpG islands (CpGI) annotated to ~2800 differently methylated genes (DMGs). The majority (84.5%) of these CpGIs …

College Students' Health Behavior Clusters: Differences By Sex., Sarah E. Colby, Wenjun Zhou, Morgan F F. Sowers, Karla Shelnutt, Melissa D. Olfert, Jesse Morrell, Mallory Koenings, Tandalayo Kidd, Tanya M. Horacek, Geoffrey W. Greene, Melissa D. Olfert, Adrienne A. White, Sharon L Hoerr, Carol Byrd-Bredbenner, Kendra Kattelmann

Health and Nutritional Sciences Faculty Publications

OBJECTIVE: The study purpose was to identify clusters of weight-related behaviors by sex in a college student populations.

METHODS: We conducted secondary data analysis from online surveys and physical assessments collected in Project Young Adults Eating and Active for Health (YEAH) with a convenience sample of students on 13 college campuses in the United States. We performed 2-step cluster analysis by sex to identify subgroups with homogeneous characteristics and behaviors. We used 8 derivation variables: healthy eating; eating restraints; external cues; stress; fruit/vegetable intake; calories from fat; calories from sugar-sweetened beverages; and physical activity. Contribution of derivation variables to clusters …

Meta-Analysis Of Five Genome-Wide Association Studies Identifies Multiple New Loci Associated With Testicular Germ Cell Tumor., Zhaoming Wang, Katherine A Mcglynn, Ewa Rajpert-De Meyts, D Timothy Bishop, Charles C Chung, Marlene D Dalgaard, Mark H Greene, Ramneek Gupta, Tom Grotmol, Trine B Haugen, Robert Karlsson, Kevin Litchfield, Nandita Mitra, Kasper Nielsen, Louise C Pyle, Stephen M Schwartz, Vésteinn Thorsson, Saran Vardhanabhuti, Fredrik Wiklund, Clare Turnbull, Stephen J Chanock, Peter A Kanetsky, Katherine L Nathanson

Articles, Abstracts, and Reports

The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5 × 10

Cross-Talk Between Clinical And Host-Response Parameters Of Periodontitis In Smokers, Radha Nagarajan, Craig S. Miller, Dolph R. Dawson Iii, Mohanad Al-Sabbagh, Jeffrey L. Ebersole

Institute for Biomedical Informatics Faculty Publications

Background and Objective

Periodontal diseases are a major public health concern leading to tooth loss and have also been shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for the development of numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies regarding susceptibility to disease associated with smoking. This investigation focused on identifying differences in four broad sets of variables, consisting of: (i) host‐response molecules; (ii) periodontal clinical parameters; (iii) antibody responses to periodontal pathogens …

Down Syndrome: Age-Dependence Of Pib Binding In Postmortem Frontal Cortex Across The Lifespan, Harry Levine Iii, H. Peter Spielmann, Sergey V. Matveev, Francesca Macchiavello Cauvi, M. Paul Murphy, Tina L. Beckett, Katie Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh Compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro ³H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (N=25) and DS (N=39). In DS, ³H-PiB binding …

Rod-Shaped Microglia Morphology Is Associated With Aging In 2 Human Autopsy Series, Adam D. Bachstetter, Eseosa T. Ighodaro, Yasmin Hassoun, Danah Aldeiri, Janna H. Neltner, Ela Patel, Erin L. Abner, Peter T. Nelson

Spinal Cord and Brain Injury Research Center Faculty Publications

A subtype of microglia is defined by the morphological appearance of the cells as rod-shaped. Little is known about this intriguing cell type, as there are only a few case reports describing rod-shaped microglia in the neuropathological literature. Rod-shaped microglia were shown recently to account for a substantial proportion of the microglia cells in the hippocampus of both demented and cognitively intact aged individuals. We hypothesized that aging could be a defining feature in the occurrence of rod-shaped microglia. To test this hypothesis, two independent series of autopsy cases (total n=168 cases), which covered the adult lifespan from 20 – …

Cpt1a Methylation Is Associated With Plasma Adiponectin, S. Aslibekyan, A. N. Do, H. Xu, S. Li, M. R. Irvin, D Zhi, H. K. Tiwari, D. M. Absher, A. R. Shuldiner, T. Zhang, W. Chen, K. Tanner, C. Hong, B. D. Mitchell, G. Berenson, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background and Aims—Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood.

Methods and Results—We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n= 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression …

Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt

Electrical and Computer Engineering Faculty Publications

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion.

Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure …

Integrated Biomarker Profiling Of Smokers With Periodontitis, Radhakrishnan Nagarajan, Mohanad Al-Sabbagh, Dolph Dawson Iii, Jeffrey L. Ebersole

Institute for Biomedical Informatics Faculty Publications

Background

In the context of precision medicine, understanding patient‐specific variation is an important step in developing targeted and patient‐tailored treatment regimens for periodontitis. While several studies have successfully demonstrated the usefulness of molecular expression profiling in conjunction with single classifier systems in discerning distinct disease groups, the majority of these studies do not provide sufficient insights into potential variations within the disease groups.

Aim

The goal of this study was to discern biological response profiles of periodontitis and non‐periodontitis smoking subjects using an informed panel of biomarkers across multiple scales (salivary, oral microbiome, pathogens and other markers).

Material & Methods …

Nephrotoxicity During Vancomycin Therapy In Combination With Piperacillin-Tazobactam Or Cefepime, Wilbur Cliff Rutter, Jessica N. Cox, Craig A. Martin, Donna R. Burgess, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in …

Safety And Improvement Of Movement Function After Stroke With Atomoxetine: A Pilot Randomized Trial, Andrea Ward, Cheryl Carrico, Elizabeth Powell, Philip M. Westgate, Laurie Nichols, Anne Fleischer, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

Background: Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention.

Objective: Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke.

Methods: In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, …

Impact Of Age On Cerebrovascular Dilation Versus Reactivity To Hypercapnia., Nicole S Coverdale, Mark B Badrov, J Kevin Shoemaker

Kinesiology Publications

This study quantified the effect of age on cerebrovascular reactivity and cerebrovascular conductance while accounting for differences in grey matter volume in younger (YA: n = 12; 24 ± 4 years, six females) and older adults (OA: n = 10; 66 ± 7 years; five females). Cerebral blood flow velocity (CBFV; transcranial Doppler) in the middle cerebral artery (MCA), MCA cross-sectional area (CSA), intracranial volumes (magnetic resonance imaging), and mean arterial pressure (MAP; Finometer), were measured under normocapnic and hypercapnic (6% carbon dioxide) conditions. Cerebral blood flow (CBF) was quantified from CBFV and MCA CSA and normalized to grey matter …

Individual Fluid Plans Versus Ad Libitum On Hydration Status In Minor Professional Ice Hockey Players, Dawn M. Emerson, Toni Torres-Mcgehee, Charles C. Emerson, Teri L. Lasalle

Faculty Publications

BACKGROUND: Despite exercising in cool environments, ice hockey players exhibit several dehydration risk factors. Individualized fluid plans (IFPs) are designed to mitigate dehydration by matching an individual's sweat loss in order to optimize physiological systems and performance. METHODS: A randomized control trial was used to examine IFP versus ad libitum fluid ingestion on hydration in 11 male minor professional ice hockey players (mean age = 24.4 ± 2.6 years, height = 183.0 ± 4.6 cm, weight = 92.9 ± 7.8 kg). Following baseline measures over 2 practices, participants were randomly assigned to either control (CON) or intervention (INT) for 10 …

The Rs16906252:C>T Snp Is Not Associated With Increased Overall Survival Or Temozolomide Response In A Han-Chinese Glioma Cohort., Kuo-Chen Wei, Chia-Yuan Chen, Li-Ying Feng, Wei-Tzu Huang, Chia-Hua Chen, Peng-Wei Hsu, Kai Wang, Leroy Hood, Leslie Y Chen

Articles, Abstracts, and Reports

The methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST) and the response to temozolomide (TMZ) treatment. However, these findings haven't been systematically investigated in the Han-Chinese population. We analyzed the relevance between rs16906252 polymorphisms, the MGMT methylation status, and the OST in 72 Han-Chinese gliomas patients. The MGMT promoter methylation was measured by bisulfite conversion followed by pyro-sequencing, while rs16906252 was measured by restriction endonuclease …