Medicine and Health Sciences Commons^™

A Pilot Clinical Trial Of Intravesical Mitomycin-C And External Deep Pelvic Hyperthermia For Non-Muscle-Invasive Bladder Cancer., Brant A Inman, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Mark W Dewhirst, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: This paper aims to evaluate the safety and heating efficiency of external deep pelvic hyperthermia combined with intravesical mitomycin C (MMC) as a novel therapy for non-muscle-invasive bladder cancer (NMIBC).

MATERIALS AND METHODS: We enrolled subjects with bacillus Calmette-Guérin (BCG) refractory NMIBC to an early phase clinical trial of external deep pelvic hyperthermia (using a BSD-2000 device) combined with MMC. Bladders were heated to 42 °C for 1 h during intravesical MMC treatment. Treatments were given weekly for 6 weeks, then monthly for 4 months. Heating parameters, treatment toxicity, and clinical outcomes were systematically measured.

RESULTS: Fifteen patients were …

Performance Of The Oraquick Hcv Rapid Antibody Test For Screening Exposed Patients In A Hepatitis C Outbreak Investigation, Fengxiang Gao, Elizabeth A. Talbot, Carol H. Loring, Jill J. Power, Jodie Dionne-Odom

Dartmouth Scholarship

During a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site, and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordant results between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative predictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an outbreak investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms.

A Device For Performing Automated Balloon Catheter Inflation Ischemia Studies, Silas Leavesley, Whitley Ledkins, Petra Rocic

NYMC Faculty Publications

Coronary collateral growth (arteriogenesis) is a physiological adaptive response to transient and repetitive occlusion of major coronary arteries in which small arterioles (native collaterals) with minimal to no blood flow remodel into larger conduit arteries capable of supplying adequate perfusion to tissue distal to the site of occlusion. The ability to reliably and reproducibly mimic transient, repetitive coronary artery occlusion (ischemia) in animal models is critical to the development of therapies to restore coronary collateral development in type II diabetes and the metabolic syndrome. Current animal models for repetitive coronary artery occlusion implement a pneumatic occluder (balloon) that is secured …

Diagnosis Of Pancreatic Neoplasms Using A Novel Method Of Dna Methylation Analysis Of Mucin Expression In Pancreatic Juice., Seiya Yokoyama, Sho Kitamoto, Michiyo Higashi, Yuko Goto, Taro Hara, Dai Ikebe, Taketo Yamaguchi, Yoshifumi Arisaka, Toru Niihara, Hiroto Nishimata, Sadao Tanaka, Kyoichi Takaori, Surinder K. Batra, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (MUC1, MUC2 and MUC4) expression in cancer cell line was regulated by DNA methylation. …

Modeling The Natural History And Detection Of Lung Cancer Based On Smoking Behavior, Xing Chen, Millennia Foy, Marek Kimmel, Olga Y. Gorlova

Dartmouth Scholarship

In this study, we developed a method for modeling the progression and detection of lung cancer based on the smoking behavior at an individual level. The model allows obtaining the characteristics of lung cancer in a population at the time of diagnosis. Lung cancer data from Surveillance, Epidemiology and End Results (SEER) database collected between 2004 and 2008 were used to fit the lung cancer progression and detection model. The fitted model combined with a smoking based carcinogenesis model was used to predict the distribution of age, gender, tumor size, disease stage and smoking status at diagnosis and the results …

Effector-Independent Motor Sequence Representations Exist In Extrinsic And Intrinsic Reference Frames., Tobias Wiestler, Sheena Waters-Metenier, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences …

Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian

Journal Articles: Pathology and Microbiology

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have …

Characterization Of A Far-Red Analog Of Ghrelin For Imaging Ghs-R In P19-Derived Cardiomyocytes., Gregory A F Douglas, Rebecca Mcgirr, Carlie L Charlton, Dov B Kagan, Lisa M Hoffman, Leonard G Luyt, Savita Dhanvantari

Medical Biophysics Publications

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as …

The Impact Of Salsalate Treatment On Serum Levels Of Advanced Glycation End Products In Type 2 Diabetes., Joshua I Barzilay, Kathleen A. Jablonski, Vivian Fonseca, Steven E Shoelson, Allison B Goldfine, Christopher Strauch, Vincent M Monnier, Tinsal-T2d Research Consortium.

GW Biostatistics Center

OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine …

Comparative Analysis Of Gingival Tissue Antigen Presentation Pathways In Ageing And Periodontitis, Octavio A. Gonzalez, Michael John Novak, Sreenatha S. Kirakodu, Luis Orraca, Kuey-Chu Chen, Arnold J. Stromberg, Janis Gonzalez-Martinez, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

AIM: Gingival tissues of periodontitis lesions contribute to local elevations in mediators, including both specific T cell and antibody immune responses to oral bacterial antigens. Thus, antigen processing and presentation activities must exist in these tissues to link antigen-presenting cells with adaptive immunity. We hypothesized that alterations in the transcriptome of antigen processing and presentation genes occur in ageing gingival tissues and that periodontitis enhances these differences reflecting tissues less capable of immune resistance to oral pathogens.

MATERIALS AND METHODS: Rhesus monkeys (n = 34) from 3 to 23 years of age were examined. A buccal gingival sample from healthy …

A Long-Term Study Of The Effects Of Antiviral Therapy On Survival Of Patients With Hbv-Associated Hepatocellular Carcinoma (Hcc) Following Local Tumor Ablation., Hie-Won Hann, Robert Coben, Daniel Brown, Laurence Needleman, Ernest Rosato, Albert Min, Richard Hann, Kyong Bin Park, Stephen Dunn, Anthony J. Dimarino

Department of Medicine Faculty Papers

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed …

Exploration And Confirmation Of The Latent Variable Structure Of The Jefferson Scale Of Empathy., Mohammadreza Hojat, Marianna Lanoue

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE: To reaffirm the underlying components of the JSE by using exploratory factor analysis (EFA), and to confirm its latent variable structure by using confirmatory factor analysis (CFA).

METHODS: Research participants included 2,612 medical students who entered Jefferson Medical College between 2002 and 2012. This sample was divided into two groups: Matriculants between 2002 and 2007 (n=1,380) and be-tween 2008 and 2012 (n=1,232). Data for 2002-2007 matriculants were subjected to EFA (principal component factor extraction), and data for matriculants of 2008-2012 were used for CFA (structural equation modeling, and root mean square error for approximation.

RESULTS: The EFA resulted in …

Wandering Acute Myocardial Infarction., Kamal R. Joshi, D Lynn Morris, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Incorrect electrode placement or cable connection during electrocardiographic (ECG) recording can significantly alter the ECG morphology. We report a case of ST-segment elevation myocardial infarction causing a diagnostic dilemma due to cable interchange.

Bisphenol A Increases Atherosclerosis In Pregnane X Receptor-Humanized Apoe Deficient Mice, Yipeng Sui, Se-Hyung Park, Robert N. Helsley, Manjula Sunkara, Frank J. Gonzalez, Andrew J. Morris, Changcheng Zhou

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. …

Metformin Inhibits Androgen-Induced Igf-Ir Up-Regulation In Prostate Cancer Cells By Disrupting Membrane-Initiated Androgen Signaling., Roberta Malaguarnera, Antonella Sacco, Alaide Morcavallo, Sebastiano Squatrito, Antimo Migliaccio, Andrea Morrione, Marcello Maggiolini, Antonino Belfiore

Department of Urology Faculty Papers

We have previously demonstrated that, in prostate cancer cells, androgens up-regulate IGF-I receptor (IGF-IR) by inducing cAMP-response element-binding protein (CREB) activation and CREB-dependent IGF-IR gene transcription through androgen receptor (AR)-dependent membrane-initiated effects. This IGF-IR up-regulation is not blocked by classical antiandrogens and sensitizes cells to IGF-I-induced biological effects. Metformin exerts complex antitumoral functions in various models and may inhibit CREB activation in hepatocytes. We, therefore, evaluated whether metformin may affect androgen-dependent IGF-IR up-regulation. In the AR(+) LNCaP prostate cancer cells, we found that metformin inhibits androgen-induced CRE activity and IGF-IR gene transcription. CRE activity requires the formation of a CREB-CREB …

Emergent Surgical Pulmonary Embolectomy In A Pregnant Woman: Case Report And Literature Review, Giovanni Saeed, Michael Möller, Jörg Neuzner, Rainer Gradaus, Werner Stein, Uwe Langebrake, Thomas Dimpfl, Meradjoddin Matin, Ali Peivandi

The Texas Heart Institute Journal

Acute pulmonary embolism is a leading cause of death during pregnancy and delivery in the United States. We describe the case of a 25-year-old woman who presented in cardiogenic shock in week 38 of her first pregnancy. After the emergent cesarean delivery of a healthy male neonate, the mother underwent immediate surgical pulmonary embolectomy. We confirmed the diagnosis of pulmonary embolism intraoperatively by means of transesophageal echocardiography and removed large clots from the patient's pulmonary arteries. Mother and child were doing well, 27 months later. In addition to presenting our patient's case, we discuss the other relevant reports and the …

Serum Levels Of Soluble Icam-1 In Children With Pulmonary Artery Hypertension, Melahat Melek Oguz, Ayse Deniz Oguz, Cihat Sanli, Ayhan Cevik

The Texas Heart Institute Journal

This prospective cross-sectional study attempted to determine both the usefulness of the serum intercellular adhesion molecule-1 (ICAM-1) as a biomarker for pulmonary artery hypertension secondary to congenital heart disease and the nature of this marker's association with catheter angiographic findings.

Our study included a total of 70 male and female children, comprising 30 patients with both pulmonary artery hypertension and congenital heart disease, 20 patients with congenital heart disease alone, and 20 healthy control subjects. Levels of ICAM-1 in plasma samples from all groups were measured by the enzyme-linked immunosorbent assay method. Cardiac catheterization was also performed in all patients. …

Variability Of M-Mode Versus Two-Dimensional Echocardiography Measurements In Children With Dilated Cardiomyopathy., Caroline K. Lee, Renee Margossian, Lynn A. Sleeper, Charles E. Canter, Shan Chen, Lloyd Y. Tani, Girish S. Shirali, Anita Szwast, Elif Seda Selamet Tierney, M Jay Campbell, Fraser Golding, Yanli Wang, Karen Altmann, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

M-mode and 2-dimensional (2D) echocardiographic imaging are routinely used to quantify left-ventricular (LV) size and function in pediatric patients with dilated cardiomyopathy (DCM). The reproducibility of and correlation between these techniques are unknown. This analysis sought to compare interreader, intrareader, and interacquisition reproducibility of M-mode versus 2D measurements in pediatric DCM patients. The Ventricular Volume Variability study of the Pediatric Heart Network is a multicenter, prospective, observational study assessing the course of chronic DCM in children. Two sonographers performed baseline image acquisitions locally, and two readers performed measurements at the echocardiographic core laboratory. One reader repeated measurements 1 month later. …

Aging Aggravates Nitrate-Mediated Ros/Rns Changes., Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, Jing Hua Liu

Department of Emergency Medicine Faculty Papers

Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50  μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress …

Patterns And Predictors Of Self-Medication In Northern Uganda., Moses Ocan, Freddie Bwanga, Godfrey S. Bbosa, Danstan Bagenda, Paul Waako, Jasper Ogwal-Okeng, Celestino Obua

Journal Articles: Epidemiology

Self-medication with antimicrobial agents is a common form of self-care among patients globally with the prevalence and nature differing from country to country. Here we assessed the prevalence and predictors of antimicrobial self-medication in post-conflict northern Uganda. A cross-sectional study was carried out using structured interviews on 892 adult (≥18 years) participants. Information on drug name, prescriber, source, cost, quantity of drug obtained, and drug use was collected. Households were randomly selected using multistage cluster sampling method. One respondent who reported having an illness within three months in each household was recruited. In each household, information was obtained from only …

Cryo Surgery Of The Prostate: An Effective, Minimally Invasive Cancer Therapy With Superior Health-Related Quality-Of-Life Outcomes, Martyn A. Vickers Jr

Oncology

What is the best treatment for localized, aggressive prostate cancer? One option is Cryo Surgery, a primary option that utilizes localized freezing to destroy diseased tissue. If you or your patients wish to consider Cryo Surgery, be sure to discuss this option with an urologist who performs Cryo Surgery of the prostate. Many urologists have not observed or been trained in the performance of this procedure. Prostate cancer allows you time to carefully consider all treatment options. Make an educated decision!

New Malignancies After Squamous Cell Carcinoma And Melanomas: A Population-Based Study From Norway, Trude E. Robsahm, Margaret R. Karagas, Judy R. Rees, Astri Syse

Dartmouth Scholarship

Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers.

Prevalence Of Small-For-Gestational Age And Its Mortality Risk Varies By Choice Of Birth-Weight-For-Gestation Reference Population, Joanne D. Katz, Lauren A. Wu, Luke C. Mullany, Christian L. Coles, Anne C.C. Lee, Naoko Kozuki, James M. Tielsch

Global Health Faculty Publications

Background

We use data from rural Nepal and South India to compare the prevalence of small-for-gestational-age (SGA) and neonatal mortality risk associated with SGA using different birth-weight-for-gestation reference populations.

Methods

We identified 46 reference populations in low-, middle-, and high-income countries, of which 26 met the inclusion criteria of being commonly cited and having numeric 10th percentile cut points published. Those reference populations were then applied to populations from two community-based studies to determine SGA prevalence and its relative risk of neonatal mortality.

Results

The prevalence of SGA ranged from 10.5% to 72.5% in Nepal, and 12.0% to 78.4% in …

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …

Influence Of The X-Chromosome On Neuroanatomy: Evidence From Turner And Klinefelter Syndromes., David S Hong, Fumiko Hoeft, Matthew J Marzelli, Jean-Francois Lepage, David Roeltgen, Judith L. Ross, Allan L Reiss

Department of Psychiatry and Human Behavior Faculty Papers

Studies of sex effects on neurodevelopment have traditionally focused on animal models investigating hormonal influences on brain anatomy. However, more recent evidence suggests that sex chromosomes may also have direct upstream effects that act independently of hormones. Sex chromosome aneuploidies provide ideal models to examine this framework in humans, including Turner syndrome (TS), where females are missing one X-chromosome (45X), and Klinefelter syndrome (KS), where males have an additional X-chromosome (47XXY). As these disorders essentially represent copy number variants of the sex chromosomes, investigation of brain structure across these disorders allows us to determine whether sex chromosome gene dosage effects …

Investigating The Relation Between Striatal Volume And Iq., Penny A Macdonald, Hooman Ganjavi, D Louis Collins, Alan C Evans, Sherif Karama

Brain and Mind Institute Researchers' Publications

The volume of the input region of the basal ganglia, the striatum, is reduced with aging and in a number of conditions associated with cognitive impairment. The aim of the current study was to investigate the relation between the volume of striatum and general cognitive ability in a sample of 303 healthy children that were sampled to be representative of the population of the United States. Correlations between the WASI-IQ and the left striatum, composed of the caudate nucleus and putamen, were significant. When these data were analyzed separately for male and female children, positive correlations were significant for the …

High-Speed Optical Coherence Tomography As A Reliable Adjuvant Tool To Grade Ocular Anterior Chamber Inflammation., Ann O. Igbre, Mario C. Rico, Sunir Garg

Wills Eye Hospital Papers

PURPOSE: To evaluate the high-speed anterior segment optical coherence tomography (AS-OCT) grading of the AS inflammation in patients with ocular inflammation.

METHODS: A retrospective consecutive case series study. Patients with clinically visible AS inflammation in at least one eye underwent AS-OCT (Visante; Zeiss Meditec) with three to eight line scans per eye, performed by a trained masked examiner. The images were reviewed for hyperreflective spots, noise, and artifact, and these were correlated to clinical examination.

RESULTS: Seventy-eight eyes of 41 patients were imaged. Forty-seven eyes had anterior chamber cells on clinical examination, and 68 had hyperreflective spots visible on AS-OCT. …

Headstrong Intervention For Pediatric Migraine Headache: A Randomized Clinical Trial., Michael A. Rapoff, Mark Connelly, Jennifer Bickel, Scott W. Powers, Andrew D. Hershey, Janelle R. Allen, Cynthia W. Karlson, Catrina C. Litzenburg, John M. Belmont

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The purpose of this study was to evaluate the efficacy of a self-guided CD-ROM program ("Headstrong") containing cognitive-behavioral self-management strategies versus an educational CD-ROM program for treating headaches, headache-related disability, and quality of life.

METHODS: Participants were 35 children ages 7-12 years with migraine recruited from one university medical center and two children's hospital headache clinics. Participants were randomly assigned to complete the Headstrong or educational control CD-ROM program over a 4-week period. Data on headache frequency, duration, and severity, migraine-related disability, and quality of life (QOL) were obtained at baseline, post-intervention, and 3-months post-intervention.

RESULTS: At post-intervention, Headstrong …

Attention Deficit Associated With Early Life Interictal Spikes In A Rat Model Is Improved With Acth, Amanda E. Hernan, Abigail Alexander, Pierre-Pascal Lenck-Santini, Rod C. Scott

Dartmouth Scholarship

Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some of these children, particularly those with epilepsies classified as Landau-Kleffner Syndrome or continuous spike and wave during sleep, have infrequent seizure activity but frequent focal epileptiform activity. This frequent epileptiform activity is thought to be detrimental to cognitive development; however, it is also possible that these IIS events initiate pathophysiological pathways in the developing brain that may be independently associated with cognitive deficits. These …

Irf8 Suppresses Pathological Cardiac Remodelling By Inhibiting Calcineurin Signalling., Ding-Sheng Jiang, Xiang Wei, Xiao-Fei Zhang, Yu Liu, Yan Zhang, Ke Chen, Lu Gao, Heng Zhou, Xue-Hai Zhu, Peter P. Liu, Wayne Bond Lau, Xin-Liang Ma, Yunzeng Zou, Xiao-Dong Zhang, Guo-Chang Fan, Hongliang Li

Department of Emergency Medicine Faculty Papers

Interferon regulatory factor 8 (IRF8) is known to affect the innate immune response, for example, by regulating the differentiation and function of immune cells. However, whether IRF8 can influence cardiac hypertrophy is unknown. Here we show that IRF8 levels are decreased in human dilated/hypertrophic cardiomyopathic hearts and in murine hypertrophic hearts. Mice overexpressing Irf8 specifically in the heart are resistant to aortic banding (AB)-induced cardiac hypertrophy, whereas mice lacking IRF8 either globally or specifically in cardiomyocytes develop an aggravated phenotype induced by pressure overload. Mechanistically, we show that IRF8 directly interacts with NFATc1 to prevent NFATc1 translocation and thus inhibits …