Digital Commons Network^™

Discovery And Validation Of Autosomal Dominant Alzheimer's Disease Mutations, Simon Hsu, Brian A Gordon, Russ Hornbeck, Joanne B Norton, Denise Levitch, Adia Louden, Ellen Ziegemeier, Robert Laforce, Jasmeer Chhatwal, Gregory S Day, Eric Mcdade, John C Morris, Anne M Fagan, Tammie L S Benzinger, Alison M Goate, Carlos Cruchaga, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Celeste M Karch

Open Access Publications

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. Mutations in amyloid-β precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the pathogenic cause of autosomal dominant AD (ADAD). However, polymorphisms also exist within these genes.

METHODS: In order to distinguish polymorphisms from pathogenic mutations, the DIAN Expanded Registry has implemented an algorithm for determining ADAD pathogenicity using available information from multiple domains, including genetic, bioinformatic, clinical, imaging, and biofluid measures and in vitro analyses.

RESULTS: We propose that PSEN1 M84V, PSEN1 A396T, PSEN2 R284G, and APP T719N are likely pathogenic …

Dysregulation Of Nad+ Metabolism Induces A Schwann Cell Dedifferentiation Program, Yo Sasaki, Amber R. Hackett, Sungsu Kim, Amy Strickland, Jeffrey Milbrandt

Open Access Publications

The Schwann cell (SC) is the major component of the peripheral nervous system (PNS) that provides metabolic and functional support for peripheral axons. The emerging roles of SC mitochondrial function for PNS development and axonal stability indicate the importance of SC metabolism in nerve function and in peripheral neuropathies associated with metabolic disorders. Nicotinamide adenine dinucleotide (NAD

Co-Expression Of Cd39 And Cd103 Identifies Tumor-Reactive Cd8 T Cells In Human Solid Tumors., Thomas Duhen, Rebekka Duhen, Ryan Montler, Jake Moses, Tarsem Moudgil, Noel F De Miranda, Cheri P Goodall, Tiffany C Blair, Bernard A Fox, Jason E Mcdermott, Shu-Ching Chang, Gary Grunkemeier, Rom Leidner, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies of CD103+CD39+ CD8 …

Association Of Inferior Vena Cava Filter Placement For Venous Thromboembolic Disease And A Contraindication To Anticoagulation With 30-Day Mortality, Tyson E. Turner, Mohammed J. Saeed, Eric Novak, David L. Brown

Open Access Publications

Importance: Despite the absence of data from randomized clinical trials, professional societies recommend inferior vena cava (IVC) filters for patients with venous thromboembolic disease (VTE) and a contraindication to anticoagulation therapy. Prior observational studies of IVC filters have suggested a mortality benefit associated with IVC filter insertion but have often failed to adjust for immortal time bias, which is the time before IVC filter insertion, during which death can only occur in the control group.

Objective: To determine the association of IVC filter placement with 30-day mortality after adjustment for immortal time bias.

Design, Setting, and Participants: This comparative effectiveness, …

Epigenomics And Metabolomics Reveal The Mechanism Of The Apoa2-Saturated Fat Intake Interaction Affecting Obesity, Chao-Qiang Lai, Caren E Smith, Laurence D Parnell, Yu-Chi Lee, Dolores Corella, Paul Hopkins, Bertha A Hidalgo, Stella Aslibekyan, Michael A Province, Devin Absher, Donna K Arnett, Katherine L Tucker, Jose M Ordovas

Open Access Publications

Background: The putative functional variant -265T>C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity.

Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction.

Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (<22 g/d) or high-SFA diet (≥22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, and blood metabolites.

Results: In the BPRHS, we identified methylation site cg04436964 as exhibiting significant differences between CC and TT participants consuming a high-SFA diet, but not among those consuming low-SFA. Similar …

Transcription Factor Gata4 Associates With Mesenchymal-Like Gene Expression In Human Hepatoblastoma Cells, Tea Soini, Katja Eloranta, Marjut Pihlajoki, Antti Kyrönlahti, Oyediran Akinrinade, Noora Andersson, Jouko Lohi, Mikko P Pakarinen, David B Wilson, Markku Heikinheimo

2010-2019 OA Pubs

GATA4, a transcription factor crucial for early liver development, has been implicated in the pathophysiology of hepatoblastoma, an embryonal tumor of childhood. However, the molecular and phenotypic consequences of GATA4 expression in hepatoblastoma are not fully understood. We surveyed GATA4 expression in 24 hepatoblastomas using RNA in situ hybridization and immunohistochemistry. RNA interference was used to inhibit GATA4 in human HUH6 hepatoblastoma cells, and changes in cell migration were measured with wound healing and transwell assays. RNA microarray hybridization was performed on control and GATA4 knockdown HUH6 cells, and differentially expressed genes were validated by quantitative polymerase chain reaction or …

Hepatic Ketogenic Insufficiency Reprograms Hepatic Glycogen Metabolism And The Lipidome, D. André D'Avignon, Patrycja Puchalska, Baris Ercal, Yingju Chang, Shannon E. Martin, Mark J. Graham, Gary J. Patti, Xianlin Han, Peter A. Crawford

Open Access Publications

While several molecular targets are under consideration, mechanistic underpinnings of the transition from uncomplicated nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) remain unresolved. Here we apply multiscale chemical profiling technologies to mouse models of deranged hepatic ketogenesis to uncover potential NAFLD driver signatures. Use of stable-isotope tracers, quantitatively tracked by nuclear magnetic resonance (NMR) spectroscopy, supported previous observations that livers of wild-type mice maintained long term on a high-fat diet (HFD) exhibit a marked increase in hepatic energy charge. Fed-state ketogenesis rates increased nearly 3-fold in livers of HFD-fed mice, a greater proportionate increase than that observed for …

Ursodeoxycholic Acid Versus Phenobarbital For Cholestasis In The Neonatal Intensive Care Unit., Tamorah Lewis, Simisola Kuye, Ashley Sherman

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Although neonates and young infants with cholestasis are commonly treated with either phenobarbital or ursodeoxycholic acid (ursodiol), there is no evidence that phenobarbital is effective for this indication. Our objective was to compare the effectiveness of ursodiol and phenobarbital for the treatment of cholestasis in a diverse NICU population.

METHODS: This is a retrospective cohort study including infants with cholestasis who were admitted to a Level IV NICU between January 2010 and December 2015. Drug courses of phenobarbital and ursodiol were identified within the medical record, and medical, demographic, and drug information were extracted. The primary outcome was reduction …

Altered Expression Of Genes Involved In Ganglioside Biosynthesis In Substantia Nigra Neurons In Parkinson's Disease., Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Reduced expression of GM1 and other major brain gangliosides GD1a, GD1b and GT1b have been reported in Parkinson's disease (PD) brain. Mechanisms underlying these changes are unclear but may be due to a deficit in the ganglioside biosynthetic process. The present study examined the extent to which deficits in gene expression of key biosynthetic enzymes involved in synthesis of GM1 and GD1b (B3galt4) and GD1a and GT1b (St3gal2) exist in neuromelanin-containing neurons in the PD substantia nigra (SN). In situ hybridization histochemistry was used to examine gene expression of B3GALT4 and ST3GAL2 in neuromelanin-containing neurons in the SN in 8 …

The Zinc Transporter Zipt-7.1 Regulates Sperm Activation In Nematodes, Yanmei Zhao, Chieh-Hsiang Tan, Amber Krauchunas, Andrea Scharf, Nicholas Dietrich, Kurt Warnhoff, Zhiheng Yuan, Marina Druzhinina, Sam Guoping Gu, Long Miao, Andrew Singson, Ronald E Ellis, Kerry Kornfeld

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sperm activation is a fascinating example of cell differentiation, in which immotile spermatids undergo a rapid and dramatic transition to become mature, motile sperm. Because the sperm nucleus is transcriptionally silent, this transition does not involve transcriptional changes. Although Caenorhabditis elegans is a leading model for studies of sperm activation, the mechanisms by which signaling pathways induce this transformation remain poorly characterized. Here we show that a conserved transmembrane zinc transporter, ZIPT-7.1, regulates the induction of sperm activation in Caenorhabditis nematodes. The zipt-7.1 mutant hermaphrodites cannot self-fertilize, and males reproduce poorly, because mutant spermatids are defective in responding to activating …

Multinational Comparative Cross-Sectional Survey Of Views Of Medical Students About Acceptable Terminology And Subgroups In Schizophrenia, Shanaya Rathod, Muhammad Irfan, Rachna Bhargava, Narsimha Pinninti, Joseph Scott, Haifa Mohammad Algahtani, Zhihua Guo, Rishab Gupta, Pallavi Nadkarni, Farooq Naeem, Fleur Howells, Katherine Sorsdahi, Kerensa Thorne, Victoria Osman-Hicks, Sasee Pallikadavath, Peter Phiri, Hannah Carr, Lizi Graves, David Kingdon

Rowan-Virtua School of Osteopathic Medicine Departmental Research

AIM: The aim of this study was to inform thinking around the terminology for 'schizophrenia' in different countries.

OBJECTIVES: The objective of this study was to investigate: (1) whether medical students view alternative terminology (psychosis subgroups), derived from vulnerability-stress models of schizophrenia, as acceptable and less stigmatising than the term schizophrenia; (2) if there are differences in attitudes to the different terminology across countries with different cultures and (3) whether clinical training has an impact in reducing stigma.

DESIGN: This is a cross-sectional survey that examined the attitudes of medical students towards schizophrenia and the alternative subgroups.

SETTING: The study …

Agreement Between Clinician-Rated Versus Patient-Reported Outcomes In Huntington Disease, Noelle E Carlozzi, Nicholas R Boileau, Joel S Perlmutter, Kelvin L Chou, Julie C Stout, Jane S Paulsen, Michael K Mccormack, David Cella, Martha A Nance, Jin-Shei Lai, Praveen Dayalu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Clinician-rated measures of functioning are often used as primary endpoints in clinical trials and other behavioral research in Huntington disease. As study costs for clinician-rated assessments are not always feasible, there is a question of whether patient self-report of commonly used clinician-rated measures may serve as acceptable alternatives in low risk behavioral trials.

AIM: The purpose of this paper was to determine the level of agreement between self-report and clinician-ratings of commonly used functional assessment measures in Huntington disease.

DESIGN: 486 participants with premanifest or manifest Huntington disease were examined. Total Functional Capacity, Functional Assessment, and Independence Scale assessments …

Additive Drug-Specific And Sex-Specific Risks Associated With Co-Use Of Marijuana And Tobacco During Pregnancy: Evidence From 3 Recent Developmental Cohorts (2003-2015)., Suena H Massey, Daniel K Mroczek, David Reiss, Emily S Miller, Jessica A Jakubowski, Eileen K Graham, Shannon M Shisler, Meaghan Mccallum, Marilyn A. Huestis, Jody M Ganiban, Daniel S Shaw, Leslie D Leve, Rina D Eiden, Laura R Stroud, Jenae M Neiderhiser

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Methodologic challenges related to the concomitant use (co-use) of substances and changes in policy and potency of marijuana contribute to ongoing uncertainty about risks to fetal neurodevelopment associated with prenatal marijuana use. In this study, we examined two biomarkers of fetal neurodevelopmental risk-birth weight and length of gestation-associated with prenatal marijuana use, independent of tobacco (TOB), alcohol (ALC), other drug use (OTH), and socioeconomic risk (SES), in a pooled sample (N = 1191) derived from 3 recent developmental cohorts (2003-2015) with state-of-the-art substance use measures. We examined differential associations by infant sex, and multiplicative effects associated with co-use of …

Use Of International Classification Of Diseases, Ninth Revision Codes For Obesity: Trends In The United States From An Electronic Health Record-Derived Database., Michelle Mocarski, Ye Tian, B. Gabriel Smolarz, John Mcana, Albert Crawford

College of Population Health Faculty Papers

Obesity is a potentially modifiable risk factor for many diseases, and a better understanding of its impact on health care utilization, costs, and medical outcomes is needed. The ability to accurately evaluate obesity outcomes depends on a correct identification of the population with obesity. The primary objective of this study was to determine the prevalence and accuracy of International Classification of Diseases, Ninth Revision (ICD-9) coding for overweight and obesity within a US primary care electronic health record (EHR) database compared against actual body mass index (BMI) values from recorded clinical patient data; characteristics of patients with obesity who did …

Age Adjusted Hematopoietic Stem Cell Transplant Comorbidity Index Predicts Survival In A T-Cell Depleted Cohort, Hayder Saeed, Swati Yalamanchi, Meng Liu, Emily Van Meter, Zartash Gul, Gregory Monohan, Dianna Howard, Gerhard C. Hildebrandt, Roger Herzig

Markey Cancer Center Faculty Publications

Objectives: Allogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria.

Methods: A retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was …

Palladin Is A Neuron-Specific Translational Target Of Mtor Signaling That Regulates Axon Morphogenesis, Yusuke Umegaki, Antonio Martínez Brotons, Yui Nakanishi, Zhongyue Luo, Hanlu Zhang, Azad Bonni, Yoshiho Ikeuchi

Open Access Publications

The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein palladin, which is localized within the cell body and axons in hippocampal neurons. Knockdown of palladin eliminated supernumerary axons induced by suppression of the tuberous sclerosis complex protein TSC1 in neurons, demonstrating that palladin regulates …

Analysis Of The Immunological Biomarker Profile During Acute Zika Virus Infection Reveals The Overexpression Of Cxcl10, A Chemokine Linked To Neuronal Damage., Felipe Gomes Naveca, Gemilson Soares Pontes, Aileen Yu-Hen Chang, George Allan Villarouco Da Silva, Valdinete Alves Do Nascimento, Dana Cristina Da Silva Monteiro, +Several Additional Authors

Medicine Faculty Publications

BACKGROUND: Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis.

OBJECTIVES: To define the immunologic biomarkers that correlate with acute ZIKV infection.

METHODS: We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining.

FINDINGS: ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite …

Parabiosis And Single-Cell Rna Sequencing Reveal A Limited Contribution Of Monocytes To Myofibroblasts In Kidney Fibrosis, Rafael Kramann, Flavia Machado, Haojia Wu, Tetsuro Kusaba, Konrad Hoeft, Rebekka K Schneider, Benjamin D Humphreys

Open Access Publications

Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney …

Population-Specific Genetic Modification Of Huntington's Disease In Venezuela., Michael J Chao, Kyung-Hee Kim, Jun Wan Shin, Diane Lucente, Vanessa C Wheeler, Hong Li, Jared C Roach, Leroy Hood, Nancy S Wexler, Laura B Jardim, Peter Holmans, Lesley Jones, Michael Orth, Seung Kwak, Marcy E Macdonald, James F Gusella, Jong-Min Lee

Articles, Abstracts, and Reports

Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers. The main Venezuelan HD family inherits HTT haplotype hap.03, which differs subtly at the sequence level from European HD hap.03, suggesting a different ancestral origin …

Amylin And Diabetic Cardiomyopathy – Amylin-Induced Sarcolemmal Ca2+ Leak Is Independent Of Diabetic Remodeling Of Myocardium, Miao Liu, Amanda Hoskins, Nirmal Verma, Donald M. Bers, Sanda Despa, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Amylin is a pancreatic β-cell hormone co-secreted with insulin, plays a role in normal glucose homeostasis, and forms amyloid in the pancreatic islets of individuals with type-2 diabetes. Aggregated amylin is also found in blood and extra-pancreatic tissues, including myocardium. Myocardial amylin accumulation is associated with myocyte Ca²⁺ dysregulation in diabetic rats expressing human amylin. Whether deposition of amylin in the heart is a consequence of or a contributor to diabetic cardiomyopathy remains unknown. We used amylin knockout (AKO) mice intravenously infused with either human amylin (i.e, the aggregated form) or non-amyloidogenic (i.e., monomeric) rodent amylin to test the …

Neural Mechanisms Of The Rejection-Aggression Link, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

Social rejection is a painful event that often increases aggression. However, the neural mechanisms of this rejection–aggression link remain unclear. A potential clue may be that rejected people often recruit the ventrolateral prefrontal cortex’s (VLPFC) self-regulatory processes to manage the pain of rejection. Using functional MRI, we replicated previous links between rejection and activity in the brain’s mentalizing network, social pain network and VLPFC. VLPFC recruitment during rejection was associated with greater activity in the brain’s reward network (i.e. the ventral striatum) when individuals were given an opportunity to retaliate. This retaliation-related striatal response was associated with greater levels of …

Patterns Of Tobacco Use In The United Arab Emirates Healthy Future (Uaehfs) Pilot Study, Mohammed Al-Houqani, Andrea Leinberger-Jabari, Abdullah Al Naeemi, Abdullah Al Junaibi, Eiman Al Zaabi, Naima Oumeziane, Marina Kazim, Fatima Al Maskari, Ayesha Al Dhaheri, Leila Abdel Wareth, Wael Al Mahmeed, Habiba Alsafar, Fatme Al Anouti, Abdishakur Abdulle, Claire K. Inman, Aisha Al Hamiz, Muna Haji, Jiyoung Ahn, Tomas Kirchhoff, Richard B. Hayes, Ravichandran Ramasamy, Ann Marie Schmidt, Omar El Shahawy, Michael Weitzman, Raghib Ali, Scott Sherman

All Works

© 2018 Al-Houqani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Self-reported tobacco use in the United Arab Emirates is among the highest in the region. Use of tobacco products other than cigarettes is widespread, but little is known about specific behavior use patterns. There have been no studies that have biochemically verified smoking status. Methods The UAE Healthy Future Study (UAEHFS) seeks to understand the causes of non-communicable diseases through …

Validation Of A Novel Scoring System For Changes In Skeletal Manifestations Of Hypophosphatasia In Newborns, Infants, And Children: The Radiographic Global Impression Of Change Scale, Michael P Whyte, Kenji P Fujita, Scott Moseley, David D Thompson, William H Mcalister

Open Access Publications

Hypophosphatasia (HPP) is the heritable metabolic disease characterized by impaired skeletal mineralization due to low activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. Although HPP during growth often manifests with distinctive radiographic skeletal features, no validated method was available to quantify them, including changes over time. We created the Radiographic Global Impression of Change (RGI-C) scale to assess changes in the skeletal burden of pediatric HPP. Site-specific pairs of radiographs of newborns, infants, and children with HPP from three clinical studies of asfotase alfa, an enzyme replacement therapy for HPP, were obtained at baseline and during treatment. Each pair was …

Bilateral Carotid Artery Stenosis Causes Unexpected Early Changes In Brain Extracellular Matrix And Blood-Brain Barrier Integrity In Mice, Jill M. Roberts, Michael E. Maniskas, Gregory J. Bix

Neuroscience Faculty Publications

Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology. Here, C57Bl/6 mice underwent BCAS or sham surgeries …

A Behavioral Lifestyle Intervention Enhanced With Multiple-Behavior Self-Monitoring Using Mobile And Connected Tools For Underserved Individuals With Type 2 Diabetes And Comorbid Overweight Or Obesity: Pilot Comparative Effectiveness Trial, Jing Wang, Chunyan Cai, Nikhil Padhye, Philip Orlander, Mohammad Zare

Faculty, Staff and Student Publications

BACKGROUND: Self-monitoring is a cornerstone of behavioral lifestyle interventions for obesity and type 2 diabetes mellitus. Mobile technology has the potential to improve adherence to self-monitoring and patient outcomes. However, no study has tested the use of a smartphone to facilitate self-monitoring in overweight or obese adults with type 2 diabetes mellitus living in the underserved community.

OBJECTIVE: The aim of this study was to examine the feasibility of and compare preliminary efficacy of a behavioral lifestyle intervention using smartphone- or paper-based self-monitoring of multiple behaviors on weight loss and glycemic control in a sample of overweight or obese adults …

Genetic Variants In Hsd17b3, Smad3, And Ipo11 Impact Circulating Lipids In Response To Fenofibrate In Individuals With Type 2 Diabetes, Daniel M. Rotroff, Sonja S. Pijut, Skylar W. Marvel, John R. Jack, Tammy M. Havener, Aurora Pujol, Agatha Schluter, Gregory A. Graf, Henry N. Ginsberg, Hetal S. Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C. Mychaleckyi, Howard L. Mcleod, John B. Buse, Michael J. Wagner, Alison A. Motsinger-Reif, Accord/Accordion Investigators

Pharmaceutical Sciences Faculty Publications

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin‐treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed‐up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10^‐6). Rare variant and gene expression changes …

A Test Of Multisession Automatic Action Tendency Retraining To Reduce Alcohol Consumption Among Young Adults In The Context Of A Human Laboratory Paradigm., Robert F Leeman, Christine Nogueira, Reinout W Wiers, Janna Cousijn, Kelly Serafini, Kelly S Demartini, John A Bargh, Stephanie S O'Malley

Articles, Abstracts, and Reports

BACKGROUND: Young adult heavy drinking is an important public health concern. Current interventions have efficacy but with only modest effects, and thus, novel interventions are needed. In prior studies, heavy drinkers, including young adults, have demonstrated stronger automatically triggered approach tendencies to alcohol-related stimuli than lighter drinkers. Automatic action tendency retraining has been developed to correct this tendency and consequently reduce alcohol consumption. This study is the first to test multiple iterations of automatic action tendency retraining, followed by laboratory alcohol self-administration.

METHODS: A total of 72 nontreatment-seeking, heavy drinking young adults ages 21 to 25 were randomized to automatic …

Early Relapse After Autologous Hematopoietic Cell Transplantation Remains A Poor Prognostic Factor In Multiple Myeloma But Outcomes Have Improved Over Time, Shaji K. Kumar, Angela Dispenzieri, Raphael Fraser, Fei Mingwei, Gorgun Akpek, Robert Cornell, Mohamed Kharfan-Dabaja, Cesar Freytes, Shahrukh Hashmi, Gerhard C. Hildebrandt, Leona Holmberg, Robert Kyle, Hillard Lazarus, Cindy Lee, Jospeh Mikhael, Taiga Nishihori, Jason Tay, Saad Usmani, David Vesole, Ravi Vij, Baldeep Wirk, Amrita Krishnan, Cristina Gasparetto, Tomer Mark, Yago Nieto, Parameswaran Hari, Anita D'Souza

Internal Medicine Faculty Publications

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (< 24 months), and to identify factors predicting for early vs late relapses (24−48 months post-AHCT). Over three periods (2001–2004, 2005–2008, 2009–2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35–38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky < 90, stage III, > 1 line of induction and lack of maintenance. Post-AHCT early relapse remains …

Blood Rheological Abnormalities In Sickle Cell Anemia., Philippe Connes, Céline Renoux, Marc Romana, Manouk Abkarian, Philippe Joly, Cyril Martin, Marie-Dominique Hardy-Dessources, Samir K. Ballas

Department of Medicine Faculty Papers

This review focuses on the contribution of abnormal blood rheology in the pathophysiology of sickle cell anemia (SCA). SCA is characterized by a reduction of red blood cell (RBC) deformability but this reduction is very heterogeneous among patients. Recent works have shown that patients with the lowest RBC deformability (measured by ektacytometry) have enhanced hemolysis and would be more prone to develop several complications such as priapism, leg ulcers and glomerulopathy. In contrast, patients with the highest deformability, and not under hydroxyurea therapy, seem to develop more frequently vaso-occlusive like events. Although less studied, RBC aggregation properties are very different …

Walking Speed Differentially Alters Spinal Loads In Persons With Traumatic Lower Limb Amputation, Brad D. Hendershot, Iman Shojaei, Julian C. Acasio, Christopher L. Dearth, Babak Bazrgari

Biomedical Engineering Faculty Publications

Persons with lower limb amputation (LLA) perceive altered motions of the trunk/pelvis during activities of daily living as contributing factors for low back pain. When walking (at a singular speed), larger trunk motions among persons with vs. without LLA are associated with larger spinal loads; however, modulating walking speed is necessary in daily life and thus understanding the influences of walking speed on spinal loads in persons with LLA is of particular interest here. Three-dimensional trunk-pelvic kinematics, collected during level-ground walking at self-selected (SSW) and two controlled speeds (~1.0 and ~1.4 m/s), were obtained for seventy-eight participants: 26 with transfemoral …