Medicine and Health Sciences Commons^™

One-Step Generation Of Multiple Transgenic Mouse Lines Using An Improved Pronuclear Injection-Based Targeted Transgenesis (I-Pitt)., Masato Ohtsuka, Hiromi Miura, Keiji Mochida, Michiko Hirose, Ayumi Hasegawa, Atsuo Ogura, Ryuta Mizutani, Minoru Kimura, Ayako Isotani, Masahito Ikawa, Masahiro Sato, Channabasavaiah B. Gurumurthy

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: The pronuclear injection (PI) is the simplest and widely used method to generate transgenic (Tg) mice. Unfortunately, PI-based Tg mice show uncertain transgene expression due to random transgene insertion in the genome, usually with multiple copies. Thus, typically at least three or more Tg lines are produced by injecting over 200 zygotes and the best line/s among them are selected through laborious screening steps. Recently, we developed technologies using Cre-loxP system that allow targeted insertion of single-copy transgene into a predetermined locus through PI. We termed the method as PI-based Targeted Transgenesis (PITT). A similar method using PhiC31-attP/B system …

Myocardial Feature Tracking Reduces Observer-Dependence In Low-Dose Dobutamine Stress Cardiovascular Magnetic Resonance., Andreas Schuster, Matthias Paul, Nuno Bettencourt, Shazia T. Hussain, Geraint Morton, Shelby Kutty, Boris Bigalke, Amedeo Chiribiri, Divaka Perera, Eike Nagel, Philipp Beerbaum

Journal Articles: Cardiology

OBJECTIVES: To determine whether quantitative wall motion assessment by CMR myocardial feature tracking (CMR-FT) would reduce the impact of observer experience as compared to visual analysis in patients with ischemic cardiomyopathy (ICM).

METHODS: 15 consecutive patients with ICM referred for assessment of hibernating myocardium were studied at 3 Tesla using SSFP cine images at rest and during low dose dobutamine stress (5 and 10 μg/kg/min of dobutamine). Conventional visual, qualitative analysis was performed independently and blinded by an experienced and an inexperienced reader, followed by post-processing of the same images by CMR-FT to quantify subendocardial and subepicardial circumferential (Eccendo and …

The Human Motor System Alters Its Reaching Movement Plan For Task-Irrelevant, Positional Forces., Joshua G A Cashaback, Heather R Mcgregor, Paul L Gribble

Brain and Mind Institute Researchers' Publications

The minimum intervention principle and the uncontrolled manifold hypothesis state that our nervous system only responds to force perturbations and sensorimotor noise if they affect task success. This idea has been tested in muscle and joint coordinate frames and more recently using workspace redundancy (e.g., reaching to large targets). However, reaching studies typically involve spatial and or temporal constraints. Constrained reaches represent a small proportion of movements we perform daily and may limit the emergence of natural behavior. Using more relaxed constraints, we conducted two reaching experiments to test the hypothesis that humans respond to task-relevant forces and ignore task-irrelevant …

True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring., Debra A Benator, Angelo Elmi, Manuel D Rodriguez, Howard B Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires

Medicine Faculty Publications

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 …

Transcatheter Aortic Valve Implantation Despite Challenging Vascular Access, Angelo Nascimbene, Federico Azpurua, James J Livesay, R David Fish, Zvonimir Krajcer

The Texas Heart Institute Journal

We describe transcatheter aortic valve implantation in a patient who had severe peripheral artery disease. The patient's vascular condition required additional preliminary peripheral intervention to enable adequate vascular access.

A 78-year-old man with severe aortic stenosis, substantial comorbidities, and severe heart failure symptoms was referred for aortic valve replacement. The patient's 20-mm aortic annulus necessitated the use of a 23-mm Edwards Sapien valve inserted through a 22F sheath, which itself needed a vessel diameter of at least 7 mm for percutaneous delivery. The left common femoral artery was selected for valve delivery. The left iliac artery and infrarenal aorta underwent …

Regression Of Left Ventricular Mass After Implantation Of The Sutureless 3f Enable Aortic Bioprosthesis, Giovanni Concistrè, Antonio Miceli, Federica Marchi, Francesca Chiaramonti, Mattia Glauber, Marco Solinas

The Texas Heart Institute Journal

Left ventricular hypertrophy in aortic stenosis is considered a compensatory response for the maintenance of systolic function but a risk factor for cardiac morbidity and death. We investigated the degree of left ventricular mass regression after implantation of the sutureless Medtronic 3f Enable® Aortic Bioprosthesis.

We studied 19 patients who, from May 2010 through July 2011, underwent isolated aortic valve replacement with the 3f Enable bioprosthetic valve, with clinical and echocardiographic follow-up at 6 months. The mean age was 77.1 ± 5.1 years (range, 68–86 yr); 14 patients were women (73.7%); and the mean logistic EuroSCORE was 15.4% ± 11.8%. …

Effects Of Periodontal Therapy On White Blood Cell Count And Levels Of Transforming Growth Factor Beta In Serum Of Subjects With Severe Periodontitis, A. C. E. Leite, V. M. A. Carneiro, Ana Carolina Morandini, Erivan Schnaider Ramos-Junior, M. C. M. Guimarães

All Dugoni School of Dentistry Faculty Articles

This study aimed to investigate the effects of nonsurgical periodontal therapy on white blood cell (WBC) count and levels of transforming growth factor beta (TGF—β) in serum from subjects with severe periodontitis. Serum from 28 subjects with periodontitis (mean age: 34.36±6.24; 32% men) and 27 healthy controls (mean age: 33.18±6.42; 33% men) were collected prior to therapy. Blood samples were obtained from 23 subjects who completed therapy (9—12 months). A well—controlled periodontal treatment protocol was established in three stages: mechanical periodontal therapy (scaling and root planning), reinstrumentation of dental sites, and supportive periodontal therapy. Periodontal and systemic parameters such as …

A Cost-Reducing Extracorporeal Membrane Oxygenation (Ecmo) Program Model: A Single Institution Experience., Nicholas C. Cavarocchi, S Wallace, E Y. Hong, A Tropea, J Byrne, Harrsion Pitcher, Hitoshi Hirose

Department of Surgery Faculty Papers

BACKGROUND: The worldwide demand for ECMO support has grown. Its provision remains limited due to several factors (high cost, complicated technology, lack of expertise) that increase healthcare cost. Our goal was to assess if an intensive care unit (ICU)-run ECMO model without continuous bedside perfusionists would decrease costs while maintaining patient safety and outcomes.

METHOD: A new ECMO program was implemented in 2010, consisting of dedicated ICU multidisciplinary providers (ICU-registered nurses, mid-level providers and intensivists). In year one, we introduced an education platform, new technology and dedicated space. In year two, continuous bedside monitoring by perfusionists was removed and new …

Unlocking The Mysteries Of Tdp-43, Keith A. Josephs, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

Mitochondria-Associated Micrornas In Rat Hippocampus Following Traumatic Brain Injury, Wang-Xia Wang, Nishant P. Visavadiya, Jignesh D. Pandya, Peter T. Nelson, Patrick G. Sullivan, Joe E. Springer

Sanders-Brown Center on Aging Faculty Publications

Traumatic brain injury (TBI) is a major cause of death and disability. However, the molecular events contributing to the pathogenesis are not well understood. Mitochondria serve as the powerhouse of cells, respond to cellular demands and stressors, and play an essential role in cell signaling, differentiation, and survival. There is clear evidence of compromised mitochondrial function following TBI; however, the underlying mechanisms and consequences are not clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally, and function as important mediators of neuronal development, synaptic plasticity, and neurodegeneration. Several miRNAs show altered expression following TBI; however, the …

Changes In Speckle Tracking Echocardiography Measures Of Ventricular Function After Percutaneous Implantation Of The Edwards Sapien Transcatheter Heart Valve In The Pulmonary Position., Shahryar M. Chowdhury, Ziyad M. Hijazi, John F. Rhodes, Saibal Kar, Raj Makkar, Michael Mullen, Qi-Ling Cao, Lazar Mandinov, Jason Buckley, Nicholas P. Pietris, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with free pulmonary regurgitation or mixed pulmonary stenosis and regurgitation and severely dilated right ventricles (RV) show little improvement in ventricular function after pulmonary valve replacement when assessed by traditional echocardiographic markers. We evaluated changes in right and left ventricular (LV) function using speckle tracking echocardiography in patients after SAPIEN transcatheter pulmonary valve (TPV) placement.

METHODS: Echocardiograms were evaluated at baseline, discharge, 1 and 6 months after TPV placement in 24 patients from 4 centers. Speckle tracking measures of function included peak longitudinal strain, strain rate, and early diastolic strain rate. RV fractional area change, tricuspid annular plane …

Clinical Outcomes Of Splenectomy In Children: Report Of The Splenectomy In Congenital Hemolytic Anemia Registry., Henry E. Rice, Brian R. Englum, Jennifer Rothman, Sarah Leonard, Audra Reiter, Courtney Thornburg, Mary Brindle, Nicola Wright, Matthew M. Heeney, Charles Smithers, Rebeccah L. Brown, Theodosia Kalfa, Jacob C. Langer, Michaela Cada, Keith T. Oldham, J Paul Scott, Shawn D. St Peter, Mukta Sharma, Andrew M. Davidoff, Kerri Nottage, Kathryn Bernabe, David B. Wilson, Sanjeev Dutta, Bertil Glader, Shelley E. Crary, Melvin S. Dassinger, Levette Dunbar, Saleem Islam, Manjusha Kumar, Fred Rescorla, Steve Bruch, Andrew Campbell, Mary Austin, Robert Sidonio, Martin L Blakely, Splenectomy In Congenital Hemolytic Anemia (Sicha) Consortium

Manuscripts, Articles, Book Chapters and Other Papers

The outcomes of children with congenital hemolytic anemia (CHA) undergoing total splenectomy (TS) or partial splenectomy (PS) remain unclear. In this study, we collected data from 100 children with CHA who underwent TS or PS from 2005 to 2013 at 16 sites in the Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium using a patient registry. We analyzed demographics and baseline clinical status, operative details, and outcomes at 4, 24, and 52 weeks after surgery. Results were summarized as hematologic outcomes, short-term adverse events (AEs) (≤30 days after surgery), and long-term AEs (31-365 days after surgery). For children with hereditary spherocytosis, …

Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation In Calyx-Bearing Vestibular Afferents, J. Chris Holt, Kevin Kewin, Paivi M. Jordan, Peter Cameron, Marcin Klapczynski, J. Michael Mcintosh, Peter A. Crooks, Linda P. Dwoskin, Anna Lysakowski

Pharmaceutical Sciences Faculty Publications

Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the peripheral vestibular system implicate most of the known nAChR subunits, specific information about those contributing to efferent-mediated excitation of CD afferents is lacking. We sought to identify the nAChR subunits that underlie the rapid excitation of CD afferents and whether they differ from α9α10 nAChRs on type II hair cells that drive efferent-mediated inhibition in adjacent bouton …

Belief About Nicotine Selectively Modulates Value And Reward Prediction Error Signals In Smokers, Xiaosi Gu, Terry Lohrenz, Ramiro Salas, Philip R. Baldwin, Alireza Soltani

Dartmouth Scholarship

Little is known about how prior beliefs impact biophysically described processes in the presence of neuroactive drugs, which presents a profound challenge to the understanding of the mechanisms and treatments of addiction. We engineered smokers' prior beliefs about the presence of nicotine in a cigarette smoked before a functional magnetic resonance imaging session where subjects carried out a sequential choice task. Using a model-based approach, we show that smokers' beliefs about nicotine specifically modulated learning signals (value and reward prediction error) defined by a computational model of mesolimbic dopamine systems. Belief of "no nicotine in cigarette" (compared with "nicotine in …

Scoliosis Related Information On The Internet In China: Can Patients Benefit From This Information?, Hongda Bao, Feng Zhu, Fei Wang, Zhen Liu, Mike H. Bao, Shouyu He, Zezhang Zhu, Yong Qiu

Dartmouth Scholarship

Background: There has been an increasing popularity of searching health related information online in recent years. Despite that considerable amount of scoliosis patients have shown interest in obtaining scoliosis information through Internet, previous studies have demonstrated poor quality of online information. However, this conclusion may vary depending on region and culture. Since China has a restricted Internet access outside of its borders, the aim of this study is to evaluate the quality of scoliosis information available online using recognized scoring systems and to analyze the Internet as a source of health information in China.

Methods: A survey-based questionnaire was distributed …

Novel Actions Of Next-Generation Taxanes Benefit Advanced Stages Of Prostate Cancer., Renée De Leeuw, Lisa D. Berman-Booty, Matthew J. Schiewer, Stephen J Ciment, Robert Den, Adam P. Dicker, William Kelly, Edouard J. Trabulsi, Costas D. Lallas, Leonard G. Gomella, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond.

EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro …

Shbg Gene Polymorphism (Rs1799941) Associates With Metabolic Syndrome In Children And Adolescents, Marquitta J. White, Fatih Eren, Deniz Agirbasli, Scott M. Williams, Mehmet Agirbasli

Dartmouth Scholarship

Background: Metabolic syndrome (MetS) is a complex disorder characterized by coexistence of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD). The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents.

Methods: Genetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs), previously shown to modulate lipid or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish …

Efficacy Of Transoral Fundoplication Vs Omeprazole For Treatment Of Regurgitation In A Randomized Controlled Trial., John G. Hunter, Peter J. Kahrilas, Reginald C.W. Bell, Erik B. Wilson, Karim S. Trad, James P. Dolan, Kyle A. Perry, Brant K. Oelschlager, Nathaniel J. Soper, Brad E. Snyder, Miguel A. Burch, William Scott Melvin, Kevin M. Reavis, Daniel G. Turgeon, Eric S. Hungness, Brian S. Diggs

Surgery Faculty Publications

Background

The aim of this randomized, crossover study was to determine if transoral fundoplication (TF) could further improve clinical outcomes in partial responders to high-dose (HD) proton-pump inhibitor (PPI) therapy and to evaluate durability of TF.

Methods

In seven United States centers, patients with hiatal hernia ≤2 cm and abnormal esophageal acid exposure (EAE) were randomized to TF (n = 40) or HD PPIs (n = 23) group. At 6-month follow-up, PPI patients underwent crossover. We assessed clinical outcomes 6-month post TF in crossover patients (COP), as compared to 6-month of HD PPI therapy, and 12-month outcomes in patients initially …

Cytometric Characterization Of Circulating Tumor Cells Captured By Microfiltration And Their Correlation To The Cellsearch(®) Ctc Test., Daniel L Adams, Steingrimur Stefansson, Christian Haudenschild, Stuart S Martin, Monica Charpentier, Saranya Chumsri, Massimo Cristofanilli, Cha-Mei Tang, R Katherine Alpaugh

Pathology Faculty Publications

Recent studies reporting hundreds, to thousands, of circulating tumor cells (CTCs) in the blood of cancer patients have raised questions regarding the prevalence of CTCs, as enumerated by the CellSearch(®) CTC Test. Although CellSearch has been shown to consistently detect clinically relevant CTCs; the ability to only capture EpCAM positive cells has led to speculation that it captures limited subsets of CTCs. In contrast, alternative approaches to CTC isolation are often cited as capturing large numbers of CTCs from patient blood. Not surprisingly the number of cells isolated by alternative approaches show poor correlations when compared to CellSearch, even when …

African American Men With Low-Grade Prostate Cancer Have Increased Disease Recurrence After Prostatectomy Compared With Caucasian Men., Kosj Yamoah, Curtiland Deville, Neha Vapiwala, Elaine Spangler, Charnita M. Zeigler-Johnson, Bruce Malkowicz, David I Lee, Michael Kattan, Adam P. Dicker, Timothy R. Rebbeck

Department of Radiation Oncology Faculty Papers

PURPOSE: To explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP).

METHODS: The overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and …

Improved Systemic Saturation After Ventricular Assist Device Implantation In A Patient With Decompensated Dextro-Transposition Of The Great Arteries After The Fontan Procedure, Ali Abdul Jabbar, Wayne J Franklin, Leo Simpson, Andrew B Civitello, Reynolds M Delgado, O H Frazier

The Texas Heart Institute Journal

We report the successful implantation of a HeartMate II left ventricular assist device after a failed Fontan procedure in a patient with dextro-transposition of the great arteries. The patient had developed significant intrapulmonary arteriovenous shunting. Despite the theoretical risk of worsening intrapulmonary shunting due to the decrease in systemic vascular resistance after device implantation, our patient did well. He was discharged from the hospital in stable condition and had better oxygen saturation than before the device was implanted. To our knowledge, ours is the 2nd report of the use of a ventricular assist device after the failure of a Fontan …

Echocardiographic Versus Histologic Findings In Marfan Syndrome, Xiaoyan Gu, Yihua He, Zhian Li, Jiancheng Han, Jian Chen, J V Ian Nixon

The Texas Heart Institute Journal

This retrospective study attempted to establish the prevalence of multiple-valve involvement in Marfan syndrome and to compare echocardiographic with histopathologic findings in Marfan patients undergoing valvular or aortic surgery.

We reviewed echocardiograms of 73 Marfan patients who underwent cardiovascular surgery from January 2004 through October 2009. Tissue histology was available for comparison in 29 patients.

Among the 73 patients, 66 underwent aortic valve replacement or the Bentall procedure. Histologic findings were available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients with moderate or severe aortic regurgitation as determined by echocardiography, 4 had thickened aortic valves. The …

Impact And Predictors Of Noncircular Left Ventricular Outflow Tract Shapes On Estimating Aortic Stenosis Severity By Means Of Continuity Equations, Nirmanmoh Bhatia, Buddhadeb Dawn, Tariq S Siddiqui, Marcus F Stoddard

The Texas Heart Institute Journal

Determining aortic stenosis (AS) severity is clinically important. Calculating aortic valve (AV) area by means of the continuity equation assumes a circular left ventricular outflow tract (LVOT). The full impact of this assumption in calculating AV area is unknown. Predictors of noncircular LVOT shape in patients with AS are undefined.

In 109 adult patients with AS who underwent multiplanar transesophageal echocardiography, we calculated AV area by means of the standard continuity method and by a modified method involving planimetric LVOT area.

We found 54 circular, 37 horizontal-oval, 8 vertical-oval, and 10 irregular LVOTs. Area derived by direct planimetry correlated better …

On Voxel-By-Voxel Accumulated Dose For Prostate Radiation Therapy Using Deformable Image Registration., Jialu Yu, Nicholas Hardcastle, Kyoungkeun Jeong, Edward T. Bender, Mark A. Ritter, Wolfgang A. Tomé

Department of Radiation Oncology Faculty Papers

Since delivered dose is rarely the same with planned, we calculated the delivered total dose to ten prostate radiotherapy patients treated with rectal balloons using deformable dose accumulation (DDA) and compared it with the planned dose. The patients were treated with TomoTherapy using two rectal balloon designs: five patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM balloon (balloon B). Prostate and rectal wall contours were outlined on each pre-treatment MVCT for all patients. Delivered fractional doses were calculated using the MVCT taken immediately prior to delivery. Dose grids were accumulated to the last MVCT using …

Underlying Construct Of Empathy, Optimism, And Burnout In Medical Students., Mohammadreza Hojat, Michael Vergare, Gerald A. Isenberg, Mitchell Cohen, John Spandorfer

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE: This study was designed to explore the underlying construct of measures of empathy, optimism, and burnout in medical students.

METHODS: Three instruments for measuring empathy (Jefferson Scale of Empathy, JSE); Optimism (the Life Orientation Test-Revised, LOT-R); and burnout (the Maslach Burnout Inventory, MBI, which includes three scales of Emotional Exhaustion, Depersonalization, and Personal Accomplishment) were administered to 265 third-year students at Sidney Kimmel (formerly Jefferson) Medical College at Thomas Jefferson University. Data were subjected to factor analysis to examine relationships among measures of empathy, optimism, and burnout in a multivariate statistical model.

RESULTS: Factor analysis (principal component with oblique …

Designer Receptors Enhance Memory In A Mouse Model Of Down Syndrome, Ashley M. Fortress, Eric D. Hamlett, Elena M. Vazey, Gary Aston-Jones, Wayne A. Cass, Heather A. Boger, Ann-Charlotte E. Granholm

Neuroscience Faculty Publications

Designer receptors exclusively activated by designer drugs (DREADDs) are novel and powerful tools to investigate discrete neuronal populations in the brain. We have used DREADDs to stimulate degenerating neurons in a Down syndrome (DS) model, Ts65Dn mice. Individuals with DS develop Alzheimer's disease (AD) neuropathology and have elevated risk for dementia starting in their 30s and 40s. Individuals with DS often exhibit working memory deficits coupled with degeneration of the locus coeruleus (LC) norepinephrine (NE) neurons. It is thought that LC degeneration precedes other AD-related neuronal loss, and LC noradrenergic integrity is important for executive function, working memory, and attention. …

Experimentally-Derived Fibroblast Gene Signatures Identify Molecular Pathways Associated With Distinct Subsets Of Systemic Sclerosis Patients In Three Independent Cohorts, Michael E. Johnson, J. Matthew Mahoney, Jaclyn Taroni, Jennifer L. Sargent, Eleni Marmarelis, Ming-Ru Wu, John Varga, Monique E. Hinchcliff, Michael L. Whitfield

Dartmouth Scholarship

Genome-wide expression profiling in systemic sclerosis (SSc) has identified four ‘intrinsic’ subsets of disease (fibroproliferative, inflammatory, limited, and normal-like), each of which shows deregulation of distinct signaling pathways; however, the full set of pathways contributing to this differential gene expression has not been fully elucidated. Here we examine experimentally derived gene expression signatures in dermal fibroblasts for thirteen different signaling pathways implicated in SSc pathogenesis. These data show distinct and overlapping sets of genes induced by each pathway, allowing for a better understanding of the molecular relationship between profibrotic and immune signaling networks. Pathway-specific gene signatures were analyzed across a …

Continuing To Confront Copd International Surveys: Comparison Of Patient And Physician Perceptions About Copd Risk And Management, Ana M. Menezes, Sarah H. Landis, Meilan K. Han, Hana Muellerova, Zaurbek Aisanov, Thys Van Der Molen, Yeon-Mok Oh, Masakazu Ichinose, David M. Mannino, Kourtney J. Davis

Preventive Medicine and Environmental Health Faculty Publications

PURPOSE: Using data from the Continuing to Confront COPD International Physician and Patient Surveys, this paper describes physicians' attitudes and beliefs regarding chronic obstructive pulmonary disease (COPD) prognosis, and compares physician and patient perceptions with respect to COPD.

METHODS: In 12 countries worldwide, 4,343 patients with COPD were identified through systematic screening of population samples, and 1,307 physicians who regularly saw patients with COPD were sampled from in-country professional databases. Both patients and physicians completed surveys about their COPD knowledge, beliefs, and perceptions; physicians answered further questions about diagnostic methods and treatment choices for COPD.

RESULTS: Most physicians (79%) responded …

Zhx2 Enhances The Cytotoxicity Of Chemotherapeutic Drugs In Liver Tumor Cells By Repressing Mdr1 Via Interfering With Nf-Ya, Hongxin Ma, Xuetian Yue, Lifen Gao, Xiaohong Liang, Wenjiang Yan, Zhenyu Zhang, Haixia Shan, Hualin Zhang, Brett T. Spear, Chunhong Ma

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated …

Cohort Of Birth Modifies The Association Between Fto Genotype And Bmi, James Niels Rosenquist, Steven F. Lehrer, A. James O'Malley, Alan M. Zaslavsky, Jordan W. Smoller, Nicholas A. Christakis

Dartmouth Scholarship

A substantial body of research has explored the relative roles of genetic and environmental factors on phenotype expression in humans. Recent research has also sought to identify gene-environment (or g-by-e) interactions, with mixed success. One potential reason for these mixed results may relate to the fact that genetic effects might be modified by changes in the environment over time. For example, the noted rise of obesity in the United States in the latter part of the 20th century might reflect an interaction between genetic variation and changing environmental conditions that together affect the penetrance of genetic influences. To evaluate this …