Digital Commons Network^™

Restriction Spectrum Imaging Improves Risk Stratification In Patients With Glioblastoma., A P Krishnan, R Karunamuni, K M Leyden, T M Seibert, R L Delfanti, J M Kuperman, H Bartsch, P Elbe, A Srikant, A M Dale, Santosh Kesari, D E Piccioni, J A Hattangadi-Gluth, N Farid, C R Mcdonald, N S White

Articles, Abstracts, and Reports

BACKGROUND AND PURPOSE: ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC.

MATERIALS AND METHODS: Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, …

Tuberculosis And Risk Of Acute Myocardial Infarction: A Propensity Score-Matched Analysis, Moises A. Huaman, Richard J. Kryscio, Carl J. Fichtenbaum, David Henson, Elizabeth G. Salt, Timothy R. Sterling, Beth A. Garvy

Biostatistics Faculty Publications

Several pathogens have been associated with increased cardiovascular disease (CVD) risk. Whether this occurs with Mycobacterium tuberculosis infection is unclear. We assessed if tuberculosis disease increased the risk of acute myocardial infarction (AMI). We identified patients with tuberculosis index claims from a large de-identified database of ~15 million adults enrolled in a U.S. commercial insurance policy between 2008 and 2010. Tuberculosis patients were 1:1 matched to patients without tuberculosis claims using propensity scores. We compared the occurrence of index AMI claims between the tuberculosis and non-tuberculosis cohorts using Kaplan–Meier curves and Cox Proportional Hazard models. Data on 2026 patients with …

A Pilot Investigation Of Acute Inhibitory Control Training In Cocaine Users, Joseph L. Alcorn, Erika Pike, William W. Stoops, Joshua A. Lile, Craig R. Rush

Behavioral Science Faculty Publications

Background—Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals.

Methods—Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using …

Odd Symptom Network During Preschool, Tess E. Smith, Christine A. Lee, Michelle M. Martel, Marni E. Axelrad

Psychology Faculty Publications

Several different conceptualizations of Oppositional Defiant Disorder (ODD) symptoms have been proposed, including one undivided set of symptoms (DSM-IV-TR; APA 2000); two domains of symptoms subdivided into affective and behavioral; and three domains of symptoms subdivided as angry/irritable, argumentative/defiant, and spiteful. The current study utilizes a novel approach to examining the division of ODD symptoms through use of network analysis. Participants were 109 preschoolers (64 male) between the ages of three and six (M = 4.34 years, SD = 1.08) and their parents and teachers/caregivers, who provided ratings of ODD symptoms. Results are consistent with one-, two-, and three- …

Demographics, Patterns Of Care, And Survival In Pediatric Medulloblastoma, Emily V. Dressler, Therese A. Dolecek, Meng Liu, John L. Villano

Internal Medicine Faculty Publications

We evaluated the American College of Surgeon’s National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency, survival, and patterns of care of pediatric medulloblastoma. We analyzed NCDB 1998–2011 data on medulloblastoma for children ages 0–19 years using logistic and poisson regression, Kaplan–Meier survival estimates, and Cox proportional hazards models. 3647 cases of medulloblastoma in those aged 0–19 years were identified. Chemotherapy was received by 79 and 74% received radiation, with 65% receiving both therapies. Those who received radiation were more likely to be older than four, while those who received chemotherapy were more likely to be age four …

A Phase Ib/Ii Study Of Cabozantinib (Xl184) With Or Without Erlotinib In Patients With Non-Small Cell Lung Cancer., Heather A Wakelee, Scott Gettinger, Jeffrey Engelman, Pasi A Jänne, Howard J. West, Deepa S Subramaniam, Joseph Leach, Michael Wax, Yifah Yaron, Dale R Miles, Primo N Lara

Articles, Abstracts, and Reports

PURPOSE: Cabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib.

METHODS: This was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent …

Sex-Specific Associations Of Maternal Birthweight With Offspring Birthweight In The Omega Study., Collette N Ncube, Amelia R Gavin, Michelle A Williams, Chunfang Qiu, Tanya K Sorensen, Daniel A Enquobahrie

Articles, Abstracts, and Reports

PURPOSE: We investigated nonlinear and offspring sex-specific associations of maternal birthweight (BW) with offspring BW among participants of the Omega study, a pregnancy cohort.

METHODS: Maternal BW was modeled as a continuous variable, linear spline and binary variable indicating low birthweight (LBW;≥2500 grams). Offspring BW was modeled as a continuous and binary variable in regression models. Nonlinearity was assessed using likelihood ratio tests (LRTs) in marginal linear spline models.

RESULTS: For every 100-gram increase of maternal BW, offspring BW increased by 22.29 (95% CI: 17.57, 27.02) or 23.41 (95% CI: 6.87, 39.96) grams among mothers with normal BW or born …

Incidence Of Cns Tumors In Appalachian Children, Bin Huang, Alice Luo, Eric B. Durbin, Ellen Lycan, Thomas Tucker, Quan Chen, Craig Horbinski, John L. Villano

Markey Cancer Center Faculty Publications

Determine whether the risk of astrocytomas in Appalachian children is higher than the national average. We compared the incidence of pediatric brain tumors in Appalachia versus non-Appalachia regions, covering years 2000–2011. The North American Association of Central Cancer Registries (NAACCR) collects population-based data from 55 cancer registries throughout U.S. and Canada. All invasive primary (i.e. non-metastatic tumors), with age at diagnosis 0–19 years old, were included. Nearly 27,000 and 2200 central nervous system (CNS) tumors from non-Appalachia and Appalachia, respectively comprise the cohorts. Age-adjusted incidence rates of each main brain tumor subtype were compared. The incidence rate of pediatric CNS …

The Interactive Effect Of Diabetes Family Conflict And Depression On Insulin Bolusing Behaviors For Youth., Genevieve Maliszewski, Susana R. Patton, L Kurt Midyett, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Adherence to type 1 diabetes management declines as children enter adolescence. For youth, psychosocial variables including mood and interpersonal relationships play a large role in diabetes maintenance. The current study assessed the unique and interactive roles diabetes family conflict and depression have on insulin bolusing behaviors for youth ages 10-16 years.

METHODS: Ninety-one youth-parent dyads completed a survey assessing family conflict and depression. Mean daily blood glucose levels, mealtime insulin bolus scores ( BOLUS), and glycated hemoglobin (HbA1c) were collected from the medical record as outcome variables.

RESULTS: Parent-reported diabetes-related family conflict and youths' endorsed depression both significantly predicted …

Potential Deaths Averted And Serious Adverse Events Incurred From Adoption Of The Sprint (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen In The United States: Projections From Nhanes (National Health And Nutrition Examination Survey), Adam P. Bress, Holly Kramer, Rasha Khatib, Srinivasan Beddhu, Alfred K. Cheung, Rachel Hess, Vinod K. Bansal, Guichan Cao, Jerry Yee, Andrew E. Moran, Ramon Durazo-Arvizu, Paul Muntner, Richard S. Cooper

Nephrology Articles

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal ofmellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults.

METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to …

Functional Human Grin2b Promoter Polymorphism And Variation Of Mental Processing Speed In Older Adults, Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. Mcilwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard J. Kryscio, Robert H. Lipsky

Behavioral Science Faculty Publications

We investigated the role of a single nucleotide polymorphism rs3764030 (G > A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was …

Discovery And Fine-Mapping Of Adiposity Loci Using High Density Imputation Of Genome-Wide Association Studies In Individuals Of African Ancestry: African Ancestry Anthropometry Genetics Consortium, Maggie C. Y. Ng, Mariaelisa Graff, Yingchang Lu, Anne E. Justice, Poorva Mudgal, Ching-Ti Liu, Kristin Young, Lisa R. Yanek, Mary F. Feitosa, Mary K. Wojczynski, Kristin Rand, Jennifer A. Brody, Brian E. Cade, Latchezar Dimitrov, Qing Duan, Xiuqing Guo, Leslie A. Lange, Michael A. Nalls, Hayrettin Okut, Salman M. Tajuddin, Bamidele O. Tayo, Sailaja Vedantam, Jonathan P. Bradfield, Guanjie Chen, Wei-Min Chen, Alessandra Chesi, Marguerite R. Irvin, Badri Padhukasahasram, Jennifer A. Smith, Wei Zheng, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Genome-wide association studies (GWAS) have identified > 300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHR_adjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHR_adjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified …

The Effects Of A Hpv Educational Intervention Aimed At Collegiate Males On Knowledge, Vaccine Intention, And Uptake, Mary A. Knudtson

Evidence-Based Practice Project Reports

Human Papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the United States (US). In 2013, approximately 6% of 19 to 26-year-old males had received at least one dose of the HPV vaccine (Richman, Maddy, Torres, & Goldberg, 2016). Currently there is no known cure for HPV, however a prophylactic vaccination provides an efficacious method for protection against HPV related diseases. The purpose of the evidence-based project was to provide a HPV educational intervention to collegiate males and examine the effects of HPV knowledge, intention to vaccinate, and receipt of vaccination. The Health Belief Model was selected to …

Population Effect Model Identifies Gene Expression Predictors Of Survival Outcomes In Lung Adenocarcinoma For Both Caucasian And Asian Patients, Guoshuai Cai, Feifei Xiao, Chao Cheng, Yafang Li, Christopher I. I. Amos, Michael L. Whitfield

Dartmouth Scholarship

Background: We analyzed and integrated transcriptome data from two large studies of lung adenocarcinomas on distinct populations. Our goal was to investigate the variable gene expression alterations between paired tumor-normal tissues and prospectively identify those alterations that can reliably predict lung disease related outcomes across populations. Methods: We developed a mixed model that combined the paired tumor-normal RNA-seq from two populations. Alterations in gene expression common to both populations were detected and validated in two independent DNA microarray datasets. A 10-gene prognosis signature was developed through a l1 penalized regression approach and its prognostic value was evaluated in a third …

Within-Person Associations Of Young Adolescents' Physical Activity Across Five Primary Locations: Is There Evidence Of Cross-Location Compensation?, Jordan A. Carlson, Tarrah B. Mitchell, Brian E. Saelens, Vincent S. Staggs, Jacqueline Kerr, Lawrence D. Frank, Jasper Schipperijn, Terry L. Conway, Karen Glanz, Jim E. Chapman, Kelli L. Cain, James F. Sallis

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Youth are active in multiple locations, but it is unknown whether more physical activity in one location is associated with less in other locations. This cross-sectional study examines whether on days with more physical activity in a given location, relative to their typical activity in that location, youth had less activity in other locations (i.e., within-person associations/compensation).

METHODS: Participants were 528 adolescents, ages 12 to 16 (M = 14.12, SD = 1.44, 50% boys, 70% White non-Hispanic). Accelerometer and Global Positioning System devices were used to measure the proportion of time spent in moderate-to-vigorous physical activity (MVPA) in five …

Cholinergic, But Not Dopaminergic Or Noradrenergic, Enhancement Sharpens Visual Spatial Perception In Humans, Caterina Gratton, Sahar Yousef, Esther Aarts, Deanna L. Wallace, Mark D'Esposito, Michael A. Silver

Open Access Publications

The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker …

Association Of Magnet Status With Hospitalization Outcomes For Ischemic Stroke Patients., Kimon Bekelis, Symeon Missios, Todd A. Mackenzie

Department of Neurosurgery Faculty Papers

BACKGROUND: It is not clear whether Magnet recognition by the American Nurses Credentialing Center (nursing excellence program) is associated with improved patient outcomes. We investigated whether hospitalization in a Magnet hospital is associated with improved outcomes for patients with ischemic stroke.

METHODS AND RESULTS: We performed a cohort study of patients with ischemic stroke from 2009 to 2013, who were registered in the New York Statewide Planning and Research Cooperative System database. Propensity-score-adjusted multivariable regression models were used to adjust for known confounders, with mixed effects methods to control for clustering at the facility level. An instrumental variable analysis was …

Nicotinamide Phosphoribosyltransferase Promotes Pulmonary Vascular Remodeling And Is A Therapeutic Target In Pulmonary Arterial Hypertension., Jiwang Chen, Justin R Sysol, Sunit Singla, Shuangping Zhao, Aya Yamamura, Daniela Valdez-Jasso, Taimur Abbasi, Krystyna M. Shioura, Sakshi Sahni, Vamsi Reddy, Arvind Sridhar, Hui Gao, Jaime Torres, Sara M. Camp, Haiyang Tang, Shui Q. Ye, Suzy Comhair, Raed Dweik, Paul Hassoun, Jason X-J Yuan, Joe G N Garcia, Roberto F. Machado

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pulmonary arterial hypertension is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT) is a cytozyme that regulates intracellular nicotinamide adenine dinucleotide levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation, and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling and that inhibition of NAMPT could attenuate pulmonary hypertension.

METHODS: Plasma, mRNA, and protein levels of NAMPT were measured in the lungs and isolated pulmonary artery endothelial cells from patients with pulmonary arterial hypertension and in the lungs of rodent models of pulmonary hypertension.Nampt+/- mice were …

Pilot Study Comparing The Childhood Arthritis & Rheumatology Research Alliance (Carra) Systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans., Yukiko Kimura, Sriharsha Grevich, Timothy Beukelman, Esi Morgan, Peter A. Nigrovic, Kelly Mieszkalski, T Brent Graham, Maria Ibarra, Norman Ilowite, Marisa Klein-Gitelman, Karen Onel, Sampath Prahalad, Marilynn Punaro, Sarah Ringold, Dana Toib, Heather Van Mater, Jennifer E. Weiss, Pamela F. Weiss, Laura E. Schanberg, Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry.

METHODS: Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months.

TRIAL REGISTRATION: clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled). …

Psychosocial Factors Related To The Intergenerational Transmission Of Externalizing Behaviors In Early Midlife, Chenshu Zhang, Judith S. Brook, Neo K. Morojele, Mario De La Rosa, Carl G. Leukefeld, David W. Brook

Behavioral Science Faculty Publications

Background: To study the intergenerational transmission of externalizing behaviors. Methods: Participants came from a community-based random sample of residents in two upstate New York counties (N = 548). Data were collected from mothers at mean age 40 and from their children from adolescence (mean age = 14, SD = 2.8) to early midlife (mean age = 43, SD = 2.8) at seven time points. Structural equation modeling (SEM) was used to study the psychosocial factors as related to externalizing behaviors in early midlife. Results: First, maternal externalizing behaviors were indirectly associated with the offspring's externalizing behaviors …

Seroprevalence Of Poliovirus Antibodies In The Kansas City Metropolitan Area, 2012-2013., Gregory S. Wallace, Barbara A. Pahud, William C. Weldon, Aaron T. Curns, M Steven Oberste, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

No indigenous cases of poliomyelitis have occurred in the US since 1979; however the risk of importation persists until global eradication is achieved. The seropositivity rate for different age cohorts with exposures to different poliovirus vaccine types and wild virus in the US are not presently known. A convenience sample was conducted in the Kansas City metropolitan area during 2012-2103 with approximately 100 participants enrolled for each of 5 age cohorts categorized based on vaccine policy changes over time in the US. Immunization records for poliovirus vaccination were required for participants90.7%, 94.4%, and 83.3%, for types 1, 2, and 3, …

Long-Term Outcomes After Autologous Hematopoietic Stem Cell Transplantation For Multiple Sclerosis., Paolo A Muraro, Marcelo Pasquini, Harold L Atkins, James D Bowen, Dominique Farge, Athanasios Fassas, Mark S Freedman, George E Georges, Francesca Gualandi, Nelson Hamerschlak, Eva Havrdova, Vassilios K Kimiskidis, Tomas Kozak, Giovanni L Mancardi, Luca Massacesi, Daniela A Moraes, Richard A Nash, Steven Pavletic, Jian Ouyang, Montserrat Rovira, Albert Saiz, Belinda Simoes, Marek Trnený, Lin Zhu, Manuela Badoglio, Xiaobo Zhong, Maria Pia Sormani, Riccardo Saccardi

Articles, Abstracts, and Reports

Importance: Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies.

Objective: To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.

Design, Setting, and Participants: Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

Evolutionary History Of Tibetans Inferred From Whole-Genome Sequencing., Hao Hu, Nayia Petousi, Gustavo Glusman, Yao Yu, Ryan Bohlender, Tsewang Tashi, Jonathan M Downie, Jared C Roach, Amy M Cole, Felipe R Lorenzo, Alan R Rogers, Mary E Brunkow, Gianpiero Cavalleri, Leroy Hood, Sama M Alpatty, Josef T Prchal, Lynn B Jorde, Peter A Robbins, Tatum S Simonson, Chad D Huff

Articles, Abstracts, and Reports

The indigenous people of the Tibetan Plateau have been the subject of much recent interest because of their unique genetic adaptations to high altitude. Recent studies have demonstrated that the Tibetan EPAS1 haplotype is involved in high altitude-adaptation and originated in an archaic Denisovan-related population. We sequenced the whole-genomes of 27 Tibetans and conducted analyses to infer a detailed history of demography and natural selection of this population. We detected evidence of population structure between the ancestral Han and Tibetan subpopulations as early as 44 to 58 thousand years ago, but with high rates of gene flow until approximately 9 …

Lethal Neonatal Case And Review Of Primary Short-Chain Enoyl-Coa Hydratase (Sceh) Deficiency Associated With Secondary Lymphocyte Pyruvate Dehydrogenase Complex (Pdc) Deficiency., Jirair K Bedoyan, Samuel P Yang, Sacha Ferdinandusse, Rhona M Jack, Alexander Miron, George Grahame, Suzanne D Debrosse, Charles L Hoppel, Douglas S Kerr, Ronald J A Wanders

Articles, Abstracts, and Reports

Mutations in ECHS1 result in short-chain enoyl-CoA hydratase (SCEH) deficiency which mainly affects the catabolism of various amino acids, particularly valine. We describe a case compound heterozygous for ECHS1 mutations c.836T>C (novel) and c.8C>A identified by whole exome sequencing of proband and parents. SCEH deficiency was confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient had a severe neonatal course with elevated blood and cerebrospinal fluid lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine. 2-Methyl-2,3-dihydroxybutyric acid was markedly elevated as were metabolites of the three branched-chain α-ketoacids …

A Compromised Liver Alters Polychlorinated Biphenyl-Mediated Toxicity, Banrida Wahlang, Jordan T. Perkins, Michael C. Petriello, Jessie B. Hoffman, Arnold J. Stromberg, Bernhard Hennig

Superfund Research Center Faculty Publications

Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9 mg/kg) or the …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

Natural History Of Gutter-Related Type Ia Endoleaks After Snorkel/Chimney Endovascular Aneurysm Repair., Brant W Ullery, Kenneth Tran, Nathan K Itoga, Ronald L Dalman, Jason T Lee

Articles, Abstracts, and Reports

OBJECTIVE: Alternative endovascular strategies using parallel or snorkel/chimney (chimney endovascular aneurysm repair [ch-EVAR]) techniques have been developed to address the lack of widespread availability and manufacturing limitations with branched/fenestrated aortic devices for the treatment of complex abdominal aortic aneurysms. Despite high technical success and midterm patency of snorkel stent configurations, concerns remain regarding the perceived increased incidence of early gutter-related type Ia endoleaks. We aimed to evaluate the incidence and natural history of gutter-related type Ia endoleaks following ch-EVAR.

METHODS: Review of medical records and available imaging studies, including completion angiography and serial computed tomographic angiography, was performed for all …

A Randomized Controlled Trial Of Ethyl Glucuronide-Based Contingency Management For Outpatients With Co-Occurring Alcohol Use Disorders And Serious Mental Illness., Michael G Mcdonell, Emily Leickly, Sterling Mcpherson, Jordan Skalisky, Debra Srebnik, Frank Angelo, Roger Vilardaga, Jenny R Nepom, John M Roll, Richard K Ries

Articles, Abstracts, and Reports

OBJECTIVE: The authors examined whether a contingency management intervention using the ethyl glucuronide (EtG) alcohol biomarker resulted in increased alcohol abstinence in outpatients with co-occurring serious mental illnesses. Secondary objectives were to determine whether contingency management was associated with changes in heavy drinking, treatment attendance, drug use, cigarette smoking, psychiatric symptoms, and HIV-risk behavior.

METHOD: Seventy-nine (37% female, 44% nonwhite) outpatients with serious mental illness and alcohol dependence receiving treatment as usual completed a 4-week observation period and were randomly assigned to 12 weeks of contingency management for EtG-negative urine samples and addiction treatment attendance, or reinforcement only for study …

Thin Melanoma With Nodal Involvement: Analysis Of Demographic, Pathologic, And Treatment Factors With Regard To Prognosis., Giorgos Karakousis, Phyllis A Gimotty, Edmund K Bartlett, Myung-Shin Sim, Madalyn G Neuwirth, Douglas Fraker, Brian J Czerniecki, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although only a small proportion of thin melanomas result in lymph node metastasis, the abundance of these lesions results in a relatively large absolute number of patients with a diagnosis of nodal metastases, determined by either sentinel lymph node (SLN) biopsy or clinical nodal recurrence (CNR).

METHODS: Independent cohorts with thin melanoma and either SLN metastasis or CNR were identified at two melanoma referral centers. At both centers, SLN metastasis patients were included. At center 1, the CNR cohort included patients with initial negative clinical nodal evaluation followed by CNR. At center 2, the CNR cohort was restricted to …