Digital Commons Network^™

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 …

The Efficacy And Safety Of Apremilast, Etanercept And Placebo In Patients With Moderate-To-Severe Plaque Psoriasis: 52-Week Results From A Phase Iiib, Randomized, Placebo-Controlled Trial (Liberate)., K Reich, M Gooderham, L Green, A Bewley, Z Zhang, I Khanskaya, R M Day, J Goncalves, K Shah, V Piguet, J Soung

Dermatology Faculty Publications

BACKGROUND: Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis.

OBJECTIVE: Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299).

METHODS: Two hundred and fifty patients were randomized to placebo (n = 84), apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at …

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 …

Habituation Of Distress And Craving During Treatment As Predictors Of Change In Ptsd Symptoms And Substance Use Severity, Christal L. Badour, Julianne C. Flanagan, Daniel F. Gros, Therese Killeen, Irene Pericot-Valverde, Kristina J. Korte, Nicholas P. Allan, Sudie E. Back

Psychology Faculty Publications

Objective—Increasing evidence supports the efficacy of trauma-focused exposure therapy in the treatment of posttraumatic stress disorder (PTSD) and co-occurring substance use disorders. Little is known, however, about the mechanisms of change in treatment for patients with PTSD and co-occurring substance use disorders. The aim of the present study was to examine whether within- and between-session habituation of distress and substance craving during imaginal exposure relates to treatment outcomes among U.S. military veterans with PTSD and a co-occurring substance use disorder (N = 54).

Method—Veterans received Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure, a manualized …

Faster Self-Paced Rate Of Drinking For Alcohol Mixed With Energy Drinks Versus Alcohol Alone, Cecile A. Marczinski, Mark T. Fillmore, Sarah F. Maloney, Amy L. Stamates

Psychology Faculty Publications

The consumption of alcohol mixed with energy drinks (AmED) has been associated with higher rates of binge drinking and impaired driving when compared with alcohol alone. However, it remains unclear why the risks of use of AmED are heightened compared with alcohol alone even when the doses of alcohol consumed are similar. Therefore, the purpose of this laboratory study was to investigate if the rate of self-paced beverage consumption was faster for a dose of AmED versus alcohol alone using a double-blind, within-subjects, placebo-controlled study design. Participants (n = 16) of equal gender who were social drinkers attended 4 separate …

Otolith Dysfunction In Persons With Both Diabetes And Benign Paroxysmal Positional Vertigo., Linda J. DʼSilva, Hinrich Staecker, James Lin, Christy Maddux, John Ferraro, Hongying Dai, Patricia M. Kluding

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Vestibular dysfunction is a well-recognized complication of type 2 diabetes (DM) that may contribute to increased fall risk. The prevalence of benign paroxysmal positional vertigo (BPPV) is higher in people with DM. The impact of DM on the otolith organs of the vestibular system in people with BPPV is unknown. The purpose of this study was to analyze otolith function using vestibular-evoked myogenic potential (VEMP) tests in people with DM and concurrent BPPV (BPPV + DM), and to examine the relationships between VEMP variables and diabetes-related variables.

STUDY DESIGN: Prospective, cross-sectional study.

SETTING: Tertiary academic medical center.

SUBJECTS AND …

Metabolomic Biomarkers As Strong Correlates Of Parkinson Disease Progression, Peter A. Lewitt, Jia Li, Mei Lu, Lining Guo, Peggy Auinger

Neurology Articles

OBJECTIVE: To determine whether a Parkinson disease (PD)-specific biochemical signature might be found in the total body metabolic milieu or in the CSF compartment, especially since this disorder has systemic manifestations beyond the progressive loss of dopaminergic nigrostriatal neurons.

METHODS: Our goal was to discover biomarkers of PD progression. Using ultra-high-performance liquid chromatography linked to gas chromatography and tandem mass spectrometry, we measured concentrations of small-molecule (≤1.5 kDa) constituents of plasma and CSF from 49 unmedicated, mildly affected patients with PD (mean age 61.4 years; mean duration of PD 11.4 months). Specimens were collected twice (baseline and final) at intervals …

The Influence Of Tumor Regression, Solar Elastosis, And Patient Age On Pathologists' Interpretation Of Melanocytic Skin Lesions., Linda Titus, Raymond L Barnhill, Jason P Lott, Michael W Piepkorn, David E Elder, Paul D Frederick, Heidi D Nelson, Patricia A Carney, Stevan R Knezevich, Martin A Weinstock, Joann G Elmore

Articles, Abstracts, and Reports

It is not known whether patient age or tumor characteristics such as tumor regression or solar elastosis influence pathologists' interpretation of melanocytic skin lesions (MSLs). We undertook a study to determine the influence of these factors, and to explore pathologist's characteristics associated with the direction of diagnosis. To meet our objective, we designed a cross-sectional survey study of pathologists' clinical practices and perceptions. Pathologists were recruited from diverse practices in 10 states in the United States. We enrolled 207 pathologist participants whose practice included the interpretation of MSLs. Our findings indicated that the majority of pathologists (54.6%) were influenced toward …

Placental Genetic Variations In Vitamin D Metabolism And Birthweight., Tsegaselassie Workalemahu, Sylvia E Badon, Michal Dishi-Galitzky, Chunfang Qiu, Michelle A Williams, Tanya Sorensen, Daniel A Enquobahrie

Articles, Abstracts, and Reports

INTRODUCTION: Vitamin D has pleiotropic functions that regulate fetal growth and development. We investigated associations of common placental genetic variations in vitamin D metabolism with birthweight.

METHODS: The study was conducted among participants (506 maternal-infant pairs) of a pregnancy cohort study. Data were collected using interviewer-administered questionnaires and post-delivery medical record abstraction. DNA, extracted from placental samples collected at delivery, was genotyped for eight single nucleotide polymorphisms (SNPs) in five vitamin D metabolism genes (CUBN, LRP2, VDR, GC, and CYP2R1). Linear and logistic regression models were used to evaluate associations of SNPs with birthweight and risk of low birthweight, respectively. …

Age-Dependent Absolute Abundance Of Hepatic Carboxylesterases (Ces1 And Ces2) By Lc-Ms/Ms Proteomics: Application To Pbpk Modeling Of Oseltamivir In Vivo Pharmacokinetics In Infants., Mikael Boberg, Marc Vrana, Aanchal Mehrotra, Robin E. Pearce, Andrea Gaedigk, Deepak Kumar Bhatt, J Steven Leeder, Bhagwat Prasad

Manuscripts, Articles, Book Chapters and Other Papers

The age-dependent absolute protein abundance of carboxylesterase (CES) 1 and CES2 in human liver was investigated and applied to predict infant pharmacokinetics (PK) of oseltamivir. The CES absolute protein abundance was determined by liquid chromatography-tandem mass spectrometry proteomics in human liver microsomal and cytosolic fractions prepared from tissue samples obtained from 136 pediatric donors and 35 adult donors. Two surrogate peptides per protein were selected for the quantification of CES1 and CES2 protein abundance. Purified CES1 and CES2 protein standards were used as calibrators, and the heavy labeled peptides were used as the internal standards. In hepatic microsomes, CES1 and …

Surrogate Pregnancy After Prenatal Diagnosis Of Spina Bifida., Lynnette J. Mazur, Mary Kay Kisthardt, Helen H. Kim, Laura M. Rosas, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Some pregnancies today involve infertile individuals or couples who contract with a fertile woman to carry a pregnancy for them. The woman who carries the pregnancy is referred to as a "gestational carrier." The use of such arrangements is increasing. Most of the time, these arrangements play out as planned; sometimes, however, problems arise. This article discusses a case in which a fetal diagnosis of spina bifida led the infertile couple to request that the gestational carrier terminate the pregnancy, and the gestational carrier did not wish to do so. Experts in the medical and legal issues surrounding surrogacy discuss …

Reliability And Validity Of The Hd-Pro-Triadtm, A Health-Related Quality Of Life Measure Designed To Assess The Symptom Triad Of Huntington's Disease., Nicholas R Boileau, Julie C Stout, Janes S Paulsen, David Cella, Michael K Mccormack, Martha A Nance, Samuel Frank, Jin-Shei Lai, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Huntington's disease (HD), is a neurodegenerative disorder that is associated with cognitive, behavioral, and motor impairments that diminish health related quality of life (HRQOL). The HD-PRO-TRIADTM is a quality of life measure that assesses health concerns specific to individuals with HD. Preliminary psychometric characterization was limited to a convenience sample of HD participants who completed measures at home so clinician-ratings were unavailable.

OBJECTIVES: The current study evaluates the reliability and validity of the HD-PRO-TRIADTM in a well-characterized sample of individuals with HD.

METHODS: Four-hundred and eighty-two individuals with HD (n = 192 prodromal, n = 193 early, and n …

Reduced Microrna-503 Expression Augments Lung Fibroblast Vegf Production In Chronic Obstructive Pulmonary Disease, Jun Ikari, Amy J. Nelson, Jannah Obaid, Alvaro Giron-Martinez, Kumiko Ikari, Fumihiko Makino, Shunichiro Iwasawa, Yoko Gunji, Maha Farid, Xingqi Wang, Hesham Basma, Dawn Demeo, Carol Feghali-Bostwick, Olaf Holz, Klaus Rabe, Xiangde Liu, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis. In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release. Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined. The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD. Primary adult lung fibroblasts were isolated from patients with or without COPD. MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without …

Desynchronization Of Autonomic Response And Central Autonomic Network Connectivity In Posttraumatic Stress Disorder, Janine Thome, Maria Densmore, Paul A Frewen, Margaret C Mckinnon, Jean Théberge, Andrew A Nicholson, Julian Koenig, Julian F Thayer, Ruth A Lanius

Department of Medicine Publications

OBJECTIVES: Although dysfunctional emotion regulatory capacities are increasingly recognized as contributing to posttraumatic stress disorder (PTSD), little work has sought to identify biological markers of this vulnerability. Heart rate variability (HRV) is a promising biomarker that, together with neuroimaging, may assist in gaining a deeper understanding of emotion dysregulation in PTSD. The objective of the present study was, therefore, to characterize autonomic response patterns, and their related neuronal patterns in individuals with PTSD at rest.

METHODS: PTSD patients (N = 57) and healthy controls (N = 41) underwent resting-state fMRI. Connectivity patterns of key regions within the central autonomic network …

Variability In Objective And Subjective Measures Affects Baseline Values In Studies Of Patients With Copd, Wayne H. Anderson, Jae Wook Ha, David J. Couper, Wanda K. O'Neal, R. Graham Barr, Eugene R. Bleecker, Elizabeth E. Carretta, Christopher B. Cooper, Claire M. Doerschuk, M. Bradley Drummond, Meilan K. Han, Nadia N. Hansel, Victor Kim, Eric C. Kleerup, Fernando J. Martinez, Stephen I. Rennard, Donald Tashkin, Prescott G. Woodruff, Robert Paine, Jeffrey L. Curtis, Richard W. Kanner, Spiromics Research Group

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety.

OBJECTIVES: Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes.

METHODS: Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same …

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …

Body Mass Index Change In Gastrointestinal Cancer And Chronic Obstructive Pulmonary Disease Is Associated With Dedicator Of Cytokinesis 1, Merry-Lynn Noelle Mcdonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.

METHODS: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years …

Astrocytes Promote Progression Of Breast Cancer Metastases To The Brain Via A Kiss1-Mediated Autophagy., Natalya Kaverina, Anton V Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs, Ilya V Ulasov

Articles, Abstracts, and Reports

Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12. The latter was found in this study to downregulate KISS1 expression at the post-transcriptional level …

Bone-Specific Alkaline Phosphatase And Bone Turnover In African American Hemodialysis Patients, Lenar Yessayan, Carol L. Moore, Mei Lu, Jerry Yee

Nephrology Articles

INTRODUCTION: Noninvasive measures of bone activity include intact parathyroid hormone (iPTH) and bone-specific alkaline phosphatase (BSAP). Whether BSAP measurement alone or in combination with other biochemical data provides more reliable information about bone turnover than iPTH alone in African Americans on hemodialysis is unknown.

METHODS: This cross-sectional study aimed to determine the optimal predictor and cutoff points for BSAP, iPTH, calcium and phosphorus in classifying bone biopsy findings. Forty-three African American hemodialysis patients were available for analysis. Biochemical data on the day of biopsy across a spectrum of qualitative histologic bone features were compared. Classification and regression tree analysis was …

Micrornas Regulating Cluster Of Differentiation 46 (Cd46) In Cardioembolic And Non-Cardioembolic Stroke, J.R. Tan, K.S. Tan, F.L. Yong, A. Armugam, C.W. Wang, K. Jeyaseelan, P.T.H. Wong

Research Publications (2016 to 2020)

Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting cluster of differentiation 46 (CD46), a potential biomarker for cardioembolic stroke. CD46 mRNA level was shown to be differentially expressed (p < 0.001) between cardioembolic stroke (median = 1.32) and non-cardioembolic stroke subtypes (large artery stroke median = 5.05; small vessel stroke median = 6.45). Bioinformatic search showed that miR-19a, -20a, -185 and -374b were found to target CD46 mRNA and further verified by luciferase reporter assay. The levels of miRNAs targeting CD46 were significantly reduced (p < 0.05) in non-cardioembolic stroke patients (large artery stroke median: miR-19a = 0.63, miR-20a = 0.42, miR-185 = 0.32, miR-374b = 0.27; small artery stroke median: miR-19a = 0.07, miR-20a = 0.06, miR-185 = 0.07, miR-374b = 0.05) as compared to cardioembolic stroke patients (median: miR-19a = 2.69, miR-20a = 1.36, miR-185 = 1.05, miR-374b = 1.23). ROC curve showed that the miRNAs could distinguish cardioembolic stroke from non-cardioembolic stroke with better AUC value as compared to CD46. Endogenous expression of CD46 in Human Umbilical Vein Endothelial Cells (HUVECs) were found to be regulated by miR-19a and miR-20a. Thus implicating that miR-19a and -20a may play a role in pathogenesis of cardioembolic stroke, possibly via the endothelial cells.

Utilization Of Free Medication Samples In The United States In A Nationally Representative Sample: 2009-2013, Joshua D. Brown, Pratik A. Doshi, Jeffery C. Talbert

Institute for Pharmaceutical Outcomes and Policy Faculty Publications

Background—Manufacturers provide free sample medications as a means to increase use of branded medications. Sample use varies year-to-year as branded product patents expire and new products come to market.

Objective—This study sought to describe the use of sample medications during 2009–2013 and assess individual characteristics associated with sample use.

Methods—Data from the 2009–2013 U.S. Medical Expenditure Panel Survey (MEPS) were used. MEPS asks participants whether they received each medication they are taking as a sample. The top 10 medications and medication classes used each year by volume were identified as well as the proportion of people who …

Network-Based Analysis Reveals Novel Gene Signatures In Peripheral Blood Of Patients With Chronic Obstructive Pulmonary Disease, Ma'en Obeidat, Yunlong Nie, Virginia Chen, Casey P. Shannon, Anand Kumar Andiappan, Bernett Lee, Olaf Rotzschke, Peter J. Castaldi, Craig P. Hersh, Nick Fishbane, Raymond T. Ng, Bruce Mcmanus, Bruce E. Miller, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death and there is a huge unmet clinical need to identify disease biomarkers in peripheral blood. Compared to gene level differential expression approaches to identify gene signatures, network analyses provide a biologically intuitive approach which leverages the co-expression patterns in the transcriptome to identify modules of co-expressed genes.

METHODS: A weighted gene co-expression network analysis (WGCNA) was applied to peripheral blood transcriptome from 238 COPD subjects to discover co-expressed gene modules. We then determined the relationship between these modules and forced expiratory volume in 1 s (FEV …

Risk Of Glucose Intolerance And Gestational Diabetes Mellitus In Relation To Maternal Habitual Snoring During Early Pregnancy., Chunfang Qiu, Wayne Lawrence, Bizu Gelaye, Lee Stoner, Ihunnaya O Frederick, Daniel A Enquobahrie, Tanya K Sorensen, Michelle A Williams

Articles, Abstracts, and Reports

BACKGROUND: Obstructive sleep apnea (OSA) or habitual snoring is known to be associated with impaired glucose tolerance and type 2 diabetes among both men and non-pregnant women. We examined the association of habitual snoring during early pregnancy with risk of impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM).

METHODS: A cohort of 1,579 women was interviewed during early pregnancy. We collected information about snoring frequency during early pregnancy. Results from screening and diagnostic tests for IGT and GDM were abstracted from medical records. Multivariate logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% …

Development And Validation Of An Adult Diet And Physical Activity Program In Primary Care Setting, Christiana Chinyere Keke-Ekekwe

Walden Dissertations and Doctoral Studies

Obesity is a national health problem with serious medical, psychological, and economic outcomes. Nurses and nurse practitioners (NPs) are frequently the first point of patient contact and play an essential role in the management of obesity. The current literature noted that practitioners working in primary care settings demonstrate inadequate knowledge related to evidence based practice (EBP) strategies to treat obesity, including diet modification and physical activity. The purpose of this DNP project was to develop and validate an EBP provider educational module related to diet modification and physical activity education for adult patients diagnosed with obesity in a primary care …

Novel Hla-Dp Region Susceptibility Loci Associated With Severe Acute Gvhd., Rakesh K. Goyal, S J. Lee, T Wang, M Trucco, M Haagenson, S R. Spellman, M Verneris, R E. Ferrell

Manuscripts, Articles, Book Chapters and Other Papers

Despite HLA allele matching, significant acute GvHD remains a major barrier to successful unrelated donor BMT. We conducted a genome-wide association study (GWAS) to identify recipient and donor genes associated with the risk of acute GvHD. A case-control design (grade III-IV versus no acute GvHD) and pooled GWA approach was used to study European-American recipients with hematological malignancies who received myeloablative conditioning non-T-cell-depleted first transplantation from HLA-A, -B, -C, -DRB1, -DQB1 allele level (10/10) matched unrelated donors. DNA samples were divided into three pools and tested in triplicate using the Affymetrix Genome-wide SNP Array 6.0. We identified three novel susceptibility …

Protective Behavioral Strategies As A Context-Specific Mediator: A Multilevel Examination Of Within- And Between-Person Associations Of Daily Drinking, Abby L. Braitman, Ashley N. Linden-Carmichael, James M. Henson

Psychology Faculty Publications

Research indicates that a drinker’s environmental and social context can be differentially associated with drinking outcomes. Further, although many researchers have identified that more frequent use of protective behavioral strategies (PBS) is associated with lower alcohol consumption and negative consequences, scant research has examined how one’s drinking context may promote or hinder PBS use. The present study examined how the context of drinking each day (i.e., where and with whom) is associated with level of consumption and reported alcohol-related problems among n = 284 college drinkers (69.0% female) directly, as well as indirectly through the use of PBS. Two different …

Rural Adults In Education: Why Don't They Come? A Curriculum Addressing Dispositional Barriers To Participation, Erica A. Silver

Cal Poly Humboldt theses and projects

Rural adults participate in education at lower rates than their urban counterparts. If rural communities and their residents are to compete and stay viable in a global economy that demands life-long learning, it is imperative to increase adult motivation to engage in education. Non- participation by rural adults will be examined through an investigation of the concept of rural, rural education, participants and non-participants, and barriers to and motivations for participation. Lastly, Wlodkowski’s (2008) Motivational Framework for Culturally Responsive Teaching will be explored as a framework to present a learning-to-learn curriculum addressing local barriers to rural adult non-participation and promoting …

Genomics Of Primary Chemoresistance And Remission Induction Failure In Paediatric And Adult Acute Myeloid Leukaemia., Fiona C. Brown, Paolo Cifani, Esther Drill, Jie He, Eric Still, Shan Zhong, Sohail Balasubramanian, Dean Pavlick, Bahar Yilmazel, Kristina M. Knapp, Todd A. Alonzo, Soheil Meshinchi, Richard M. Stone, Steven M. Kornblau, Guido Marcucci, Alan S. Gamis, John C. Byrd, Mithat Gonen, Ross L. Levine, Alex Kentsis

Manuscripts, Articles, Book Chapters and Other Papers

Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in paediatric and adult AML.

A Novel Approach To Identifying A Neuroimaging Biomarker For Patients With Serious Mental Illness, Alok Madan, J Christopher Fowler, Michelle A Patriquin, Ramiro Salas, Philip R Baldwin, Kenia M Velasquez, Humsini Viswanath, David L Molfese, Carla Sharp, Jon G Allen, Susan Hardesty, John M Oldham, B Christopher Frueh

Staff and Researcher Publications

Serious mental illness (SMI) is disabling, and current interventions are ineffective for many. This exploratory study sought to demonstrate the feasibility of applying topological data analysis (TDA) to resting-state functional connectivity data obtained from a heterogeneous sample of 235 adult inpatients to identify a biomarker of treatment response. TDA identified two groups based on connectivity between the prefrontal cortex and striatal regions: patients admitted with greater functional connectivity between these regions evidenced less improvement from admission to discharge than patients with lesser connectivity between them. TDA identified a potential biomarker of an attenuated treatment response among inpatients with SMI. Insofar …

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 …