Medicine and Health Sciences Commons^™

Study Of Potential Risk Of Dengue Disease Outbreak In Sri Lanka Using Gis And Statistical Modelling, Sumith Pathirana, Masato Kawabata, Rohitha Goonatilake

Adjunct Associate Professor Sumith Pathirana

The increasing incidence of dengue fever has become a priority health issue for Sri Lanka. Recent dengue outbreaks in Sri Lanka show two trends: yearly increase of total number of dengue incidence and increasing dengue outbreaks outside the endemic urbanised areas in the south and the west. Identification of factors responsible for dengue outbreaks and the mapping of potential risk areas in Sri Lanka are long overdue. This study examines the association between weekly rainfall patterns and dengue outbreaks in the western province between 2000 and 2004. Methods: The study develops a model to quantitatively assess the relationship between rainfall …

Erbeta Regulation Of Nf-Kb Activation In Prostate Cancer Is Mediated By Hif-1, Paul Mak, Jiarong Li, Sanjoy Samanta, Arthur M. Mercurio

Arthur M. Mercurio

We examined the regulation of NF-kappaB in prostate cancer by estrogen receptor beta (ERbeta) based on the inverse correlation between p65 and ERbeta expression that exists in prostate carcinomas and reports that ERbeta can inhibit NF-kappaB activation, although the mechanism is not known. We demonstrate that ERbeta functions as a gate-keeper for NF-kappaB p65 signaling by repressing its expression and nuclear translocation. ERbeta regulation of NF-kappaB signaling is mediated by HIF-1. Loss of ERbeta or hypoxia stabilizes HIF-1alpha, which we found to be a direct driver of IKKbeta transcription through a hypoxia response element present in the promoter of the …

Biography, Julie Elaine N. Irish

Julie Elaine Irish

Alkali Therapy In Lactic Acidosis, Zeid J. Khitan, Md, Deepak Malhotra, Md, Dominic S. Raj, Md, Antonios H. Tzamaloukas, Md, Joseph I. Shapiro, Md

Zeid J. Khitan

This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate.

Feasibility And Compliance With Daily Home Ecg Monitoring Of The Qt Interval In Heart Transplant Recipients, Erik V. Carter, Kathleen T. Hickey, David M. Pickham, Lynn V. Doering, Belinda Chen, Patricia Harris, Barbara J. Drew

Patricia Harris

Background: Recent evidence suggests that acute allograft rejection after heart transplantation causes an increased QT interval on electrocardiogram (ECG). The aims of this pilot study were to (1) determine whether heart transplant recipients could achieve compliance in transmitting a 30-second ECG every day for 1 month using a simple ECG device and their home telephone, (2) evaluate the ease of device use and acceptability by transplant recipients, and (3) evaluate the quality of transmitted ECG tracings for QT-interval measurement. Methods: A convenience sample of adult heart transplant recipients were recruited and trained to use the device (HeartOne, Aerotel Medical Systems, …

Prognostic Value Of Heart Rate Turbulence For Risk Assessment In Patients With Unstable Angina And Non-St Elevation Myocardial Infarction, Patricia R.E. Harris, Phyllis K. Stein, Gordon L. Fung, Barbara J. Drew

Patricia Harris

Background: We sought to examine the prognostic value of heart rate turbulence derived from electrocardiographic recordings initiated in the emergency department for patients with non-ST elevation myocardial infarction (NSTEMI) or unstable angina. Methods: Twenty-four-hour Holter recordings were started in patients with cardiac symptoms approximately 45 minutes after arrival in the emergency department. Patients subsequently diagnosed with NSTEMI or unstable angina who had recordings with ≥18 hours of sinus rhythm and sufficient data to compute Thrombolysis In Myocardial Infarction (TIMI) risk scores were chosen for analysis (n = 166). Endpoints were emergent re-entry to the cardiac emergency department and/or death at …

Heart Rate Variability Measured Early In Patients With Evolving Acute Coronary Syndrome And 1-Year Outcomes Of Rehospitalization And Mortality, Patricia R.E. Harris, Phyllis K. Stein, Gordon L. Fung, Barbara J. Drew

Patricia Harris

Objective: This study sought to examine the prognostic value of heart rate variability (HRV) measurement initiated immediately after emergency department presentation for patients with acute coronary syndrome (ACS). Background: Altered HRV has been associated with adverse outcomes in heart disease, but the value of HRV measured during the earliest phases of ACS related to risk of 1-year rehospitalization and death has not been established. Methods: Twenty-four-hour Holter recordings of 279 patients with ACS were initiated within 45 minutes of emergency department arrival; recordings with �18 hours of sinus rhythm were selected for HRV analysis (number [N] �193). Time domain, frequency …

Type I Diabetes In Children And Vitamin D, Ashley B. Litchfield, Rebecca M. Hayes, Franklin D. Shuler Md, Phd, Susan L. Flesher Md

Franklin D. Shuler

Vitamin D deficiency is associated with multiple childhood diseases including type 1 diabetes mellitus (T1DM). T1DM in children is becoming more prevalent, with a 23% increase nationally from 2001 to 2009. Similarly, West Virginia has had an 8.1% increase in children with type 1Diabetes from 2008/2009 to 2010/2011. This article highlights the association between vitamin D and type 1 diabetes and discusses vitamin D’s potential role in the reduction and management of T1DM in children.

Plasma Micrornas Are Associated With Atrial Fibrillation (The Mirhythm Study) And Change After Catheter-Ablation, David D. Mcmanus, Kahraman Tanriverdi, Honghuang Lin, Nada Esa, Menhel Kinno, Rosalind Lee, Divakar Mandapati, Stanley Tam, Patrick T. Ellinor, John F. Keaney, Emelia J. Benjamin, Victor R. Ambros, Jane E. Freedman

Victor R. Ambros

Background: Atrial fibrillation (AF) is the most common dysrhythmia in the U.S. and Europe. Few biomarkers exist to identify individuals at risk for AF. Cardiac microRNAs (miRNAs) have been implicated in susceptibility to AF and are detectable in the circulation. Nevertheless, data are limited on how circulating levels of miRNAs relate to AF or change over time after catheter- ablation. Methods: In 211 miRhythm participants (112 with paroxysmal or persistent AF; 99 without AF), we quantified plasma expression of 86 miRNAs associated with cardiac remodeling or disease by high-throughput quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We used qRT-PCR to examine …

Circulating Micrornas Are Associated With Paroxysmal Or Persistent Atrial Fibrillation, David D. Mcmanus, Jeanine Ward, Amir Y. Shaikh, Khushleen Jaggi, Victor R. Ambros, Jane Freedman, John F. Keaney Jr.

Victor R. Ambros

Introduction: Novel methods of identifying individuals at risk for atrial fibrillation (AF) are needed. MicroRNAs (MiRNAs) regulate gene expression in a number of cardiovascular diseases, including AF. It is unknown, however, if key circulating, cardiac-specific miRNAs differ between individuals with paroxysmal or persistent AF and those in sinus rhythm. Methods: 17 individuals with a history of AF were recruited prior to catheter ablation. 24 hospitalized patients in normal sinus rhythm and no history of AF comprised the control group. 94 plasma miRNAs were selected based on a priori associations with processes implicated in AF for evaluation using the TaqMan miRNA …

Circulating Cell And Plasma Microrna Profiles Differ Between Non-St-Segment And St-Segment-Elevation Myocardial Infarction, Jeanine Ward, Nada Esa, Rahul Pidikiti, Jane E. Freedman, John F. Keaney, Kahraman Tanriverdi, Olga Vitseva, Victor R. Ambros, Rosalind Lee, David D. Mcmanus

Victor R. Ambros

BACKGROUND: Differences in plasma and whole blood expression microRNAs (miRNAs) in patients with an acute coronary syndrome (ACS) have been determined in both in vitro and in vivo studies. Although most circulating miRNAs are located in the cellular components of whole blood, little is known about the miRNA profiles of whole blood subcomponents, including plasma, platelets and leukocytes in patients with myocardial ischemia. METHODS: Thirteen patients with a ST-segment-elevation (STEMI) or non-ST-segment elevation (NSTEMI) myocardial infarction were identified in the University of Massachusetts Medical Center Emergency Department (ED) or cardiac catheterization laboratory between February and June of 2012. Whole blood …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Adjunctive Metformin Therapy In Overweight/Obese Youth With Type 1 Diabetes, Benjamin U. Nwosu, Louise Maranda, Karen Cullen, Lisa Greenman, Jody Fleshman, Nancy Mcshea, Bruce A. Barton, Mary M. Lee

Mary M. Lee

CONTEXT: Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.

OBJECTIVE: To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D.

HYPOTHESIS: Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D.

DESIGN, SETTING, AND PARTICIPANTS: A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Adjunctive Metformin Therapy In Overweight/Obese Youth With Type 1 Diabetes, Benjamin U. Nwosu, Louise Maranda, Karen Cullen, Lisa Greenman, Jody Fleshman, Nancy Mcshea, Bruce A. Barton, Mary M. Lee

Benjamin U. Nwosu

CONTEXT: Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.

OBJECTIVE: To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D.

HYPOTHESIS: Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D.

DESIGN, SETTING, AND PARTICIPANTS: A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of …

Incidence And Predictors Of Permanent Pacemaker Implantation After Valve Surgery – A Single Center Experience, Justin L. Guthier Do, Bilal Ayub Md, Yassir Nawaz Md, Hassam Saif Md, Robert F. Malacoff Md, Facc, Michael J. Weiss Mph, Theodore G. Phillips Md, James K. Wu Md, Raymond L. Singer Md, Sanjay M. Mehta Md, Gary W. Szydlowski Md, Ronald S. Freudenberger Md

Raymond L Singer MD

No abstract provided.

Increased Number Of Circulating Exosomes And Their Microrna Cargos Are Potential Novel Biomarkers In Alcoholic Hepatitis, Fatemeh Momen-Heravi, Banishree Saha, Karen Kodys, Donna Catalano, Abhishek Satishchandran, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: It has been well documented that alcohol and its metabolites induce injury and inflammation in the liver. However, there is no potential biomarker to monitor the extent of liver injury in alcoholic hepatitis patients. MicroRNAs (miRNAs) are a class of non-coding RNAs that are involved in various physiologic and pathologic processes. In the circulation, a great proportion of miRNAs is associated with extracellular vesicles (EVs)/exosomes. Here, we hypothesized that the exosome-associated miRNAs can be used as potential biomarkers in alcoholic hepatitis (AH).

METHODS: Exosomes were isolated from sera of alcohol-fed mice or pair-fed mice, and plasma of alcoholic hepatitis …

Progression Of Non-Alcoholic Steatosis To Steatohepatitis And Fibrosis Parallels Cumulative Accumulation Of Danger Signals That Promote Inflammation And Liver Tumors In A High Fat-Cholesterol-Sugar Diet Model In Mice, Michal Ganz, Terence N. Bukong, Timea Csak, Banishree Saha, Jin-Kyu Park, Aditya Ambade, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming a pandemic. While multiple 'hits' have been reported to contribute to NAFLD progression to non-alcoholic steatohepatitis (NASH), fibrosis and liver cancer, understanding the natural history of the specific molecular signals leading to hepatocyte damage, inflammation and fibrosis, is hampered by the lack of suitable animal models that reproduce disease progression in humans. The purpose of this study was first, to develop a mouse model that closely mimics progressive NAFLD covering the spectrum of immune, metabolic and histopathologic abnormalities present in human disease; and second, to characterize the temporal relationship between sterile/exogenous danger …

Evaluation Of Cardiac Involvement In Children With Dengue By Serial Echocardiographic Studies, Tawatchai Kirawittaya, In-Kyu Yoon, Sineewanlaya Wichit, Sharone Green, Francis A. Ennis, Robert V. Gibbons, Stephen J. Thomas, Alan L. Rothman, Siripen Kalayanarooj, Anon Srikiatkhachorn

Sharone Green

BACKGROUND: Infection with dengue virus results in a wide range of clinical manifestations from dengue fever (DF), a self-limited febrile illness, to dengue hemorrhagic fever (DHF) which is characterized by plasma leakage and bleeding tendency. Although cardiac involvement has been reported in dengue, the incidence and the extent of cardiac involvement are not well defined. METHODS AND PRINCIPAL FINDINGS: We characterized the incidence and changes in cardiac function in a prospective in-patient cohort of suspected dengue cases by serial echocardiography. Plasma leakage was detected by serial chest and abdominal ultrasonography. Daily cardiac troponin-T levels were measured. One hundred and eighty …

Prognostic Value Of Heart Rate Turbulence For Risk Assessment In Patients With Unstable Angina And Non-St Elevation Myocardial Infarction, Patricia R.E. Harris, Phyllis K. Stein, Gordon L. Fung, Barbara J. Drew

Patricia Harris

Background: We sought to examine the prognostic value of heart rate turbulence derived from electrocardiographic recordings initiated in the emergency department for patients with non-ST elevation myocardial infarction (NSTEMI) or unstable angina. Methods: Twenty-four-hour Holter recordings were started in patients with cardiac symptoms approximately 45 minutes after arrival in the emergency department. Patients subsequently diagnosed with NSTEMI or unstable angina who had recordings with ≥18 hours of sinus rhythm and sufficient data to compute Thrombolysis In Myocardial Infarction (TIMI) risk scores were chosen for analysis (n = 166). Endpoints were emergent re-entry to the cardiac emergency department and/or death at …

Septal Myectomy In Obstructive Hypertrophic Cardiomyopathy High Risk Patients, Heather Geist, Matthew W. Martinez Md, James K. Wu Md

James K. Wu, M.D.

No abstract provided.

Incidence And Predictors Of Permanent Pacemaker Implantation After Valve Surgery – A Single Center Experience, Justin L. Guthier Do, Bilal Ayub Md, Yassir Nawaz Md, Hassam Saif Md, Robert F. Malacoff Md, Facc, Michael J. Weiss Mph, Theodore G. Phillips Md, James K. Wu Md, Raymond L. Singer Md, Sanjay M. Mehta Md, Gary W. Szydlowski Md, Ronald S. Freudenberger Md

James K. Wu, M.D.

No abstract provided.

Septal Myectomy In Obstructive Hypertrophic Cardiomyopathy High Risk Patients, Heather Geist, Matthew W. Martinez Md, James K. Wu Md

Matthew W Martinez MD

No abstract provided.

Microrna-155 Deficiency Attenuates Liver Steatosis And Fibrosis Without Reducing Inflammation In A Mouse Model Of Steatohepatitis, Timea Csak, Shashi Bala, Dora Lippai, Karen Kodys, Donna Catalano, Arvin Iracheta-Vellve, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIM: MicroRNAs (miRs) regulate hepatic steatosis, inflammation and fibrosis. Fibrosis is the consequence of chronic tissue damage and inflammation. We hypothesized that deficiency of miR-155, a master regulator of inflammation, attenuates steatohepatitis and fibrosis.

METHODS: Wild type (WT) and miR-155-deficient (KO) mice were fed methionine-choline-deficient (MCD) or -supplemented (MCS) control diet for 5 weeks. Liver injury, inflammation, steatosis and fibrosis were assessed.

RESULTS: MCD diet resulted in steatohepatitis and increased miR-155 expression in total liver, hepatocytes and Kupffer cells. Steatosis and expression of genes involved in fatty acid metabolism were attenuated in miR-155 KO mice after MCD feeding. …

Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor

Janet M. Stavnezer

Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown. Unlike the BRCA-FA pathway, the MMR pathway is not essential for cells to survive toxic DNA interstrand crosslinks (ICLs), although MMR proteins bind ICLs and other DNA structures that form at stalled replication forks. We hypothesized that MMR proteins corrupt ICL repair in cells that lack crosstalk between BRCA-FA and MMR pathways. Here, we show that ICL sensitivity of cells lacking the interaction between FANCJ and the MMR protein MLH1 is …

Understanding Multifactorial Influences On The Continuum Of Maternal Weight Trajectories In Pregnancy And Early Postpartum: Study Protocol, And Participant Baseline Characteristics, Tiffany A. Moore Simas, Silvia Corvera, Mary M. Lee, Ningning Zhang, Katherine Leung, Barbara C. Olendzki, Bruce A. Barton, Milagros C. Rosal

Mary M. Lee

BACKGROUND: Maternal and offspring immediate and long-term health are affected by pregnancy weight gain and maternal weight. This study was designed to determine feasibility of: 1) recruiting a socio-economically and racially/ethnically diverse sample of pregnant women into a longitudinal observational study, including consenting the women for serial biologic specimen evaluations; 2) implementing comprehensive assessments (including biologic, anthropometric, behavioral, cognitive/psychosocial and socio-demographic, and cultural measures) at multiple time points over the study period, including collecting biologic specimens at planned and unplanned pregnancy delivery times; and 3) retaining the sample for one year into the postpartum period. Additionally, the study will provide …

The Spatial Dynamics Of Dengue Virus In Kamphaeng Phet, Thailand, Piraya Bhoomiboonchoo, Robert V. Gibbons, Angkana Huang, In-Kyu Yoon, Darunee Buddhari, Ananda Nisalak, Natkamol Chansatiporn, Mathuros Thipayamongkolgul, Siripen Kalanarooj, Timothy Endy, Alan L. Rothman, Anon Srikiatkhachorn, Sharone Green, Mammen P. Mammen, Derek A. Cummings, Henrik Salje

Sharone Green

BACKGROUND: Dengue is endemic to the rural province of Kamphaeng Phet, Northern Thailand. A decade of prospective cohort studies has provided important insights into the dengue viruses and their generated disease. However, as elsewhere, spatial dynamics of the pathogen remain poorly understood. In particular, the spatial scale of transmission and the scale of clustering are poorly characterized. This information is critical for effective deployment of spatially targeted interventions and for understanding the mechanisms that drive the dispersal of the virus.

METHODOLOGY/PRINCIPAL FINDINGS: We geocoded the home locations of 4,768 confirmed dengue cases admitted to the main hospital in Kamphaeng Phet …

Preliminary Evaluation Of Near Infrared Spectroscopy As A Method To Detect Plasma Leakage In Children With Dengue Hemorrhagic Fever, Babs R. Soller, Anon Srikiatkhachorn, Fengmei Zou, Alan L. Rothman, In-Kyu Yoon, Robert V. Gibbons, Siripen Kalayanarooj, Stephen J. Thomas, Sharone Green

Sharone Green

BACKGROUND: Dengue viral infections are prevalent in the tropical and sub-tropical regions of the world, resulting in substantial morbidity and mortality. Clinical manifestations range from a self-limited fever to a potential life-threatening plasma leakage syndrome (dengue hemorrhagic fever). The objective of this study was to assess the utility of near infrared spectroscopy (NIRS) measurements of muscle oxygen saturation (SmO2) as a possible continuous measure to detect plasma leakage in children with dengue.

METHODS: Children ages 6 months to 15 years of age admitted with suspected dengue were enrolled from the dengue ward at Queen Sirikit National Institute for Child Health. …

Sequential Dengue Virus Infections Detected In Active And Passive Surveillance Programs In Thailand, 1994-2010, Piraya Bhoomiboonchoo, Ananda Nisalak, Natkamol Chansatiporn, In-Kyu Yoon, Siripen Kalayanarooj, Mathuros Thipayamongkolgul, Timothy Endy, Alan L. Rothman, Sharone Green, Anon Srikiatkhachorn, Darunee Buddhari, Mammen P. Mammen, Robert V. Gibbons

Sharone Green

BACKGROUND: The effect of prior dengue virus (DENV) exposure on subsequent heterologous infection can be beneficial or detrimental depending on many factors including timing of infection. We sought to evaluate this effect by examining a large database of DENV infections captured by both active and passive surveillance encompassing a wide clinical spectrum of disease.

METHODS: We evaluated datasets from 17 years of hospital-based passive surveillance and nine years of cohort studies, including clinical and subclinical DENV infections, to assess the outcomes of sequential heterologous infections. Chi square or Fisher's exact test was used to compare proportions of infection outcomes such …

Free-Roaming Dogs In Developing Countries: The Benefits Of Capture, Neuter, And Return Programs, Jennifer Jackman, Andrew N. Rowan

Jennifer Jackman, Ph.D.

This chapter provides an overview of animal welfare and public health problems associated with free-roaming dog populations and strategies to resolve these problems. Placing CNR programs in the context of earlier dog and rabies control methods, the chapter explores CNR’s potential to overcome some of the shortcomings of earlier approaches and to improve animal welfare, reduce dog population growth, and prevent the spread of rabies and other canine-transmitted diseases. Constraints and current debates on current implementation of CNR programs are also examined.

Conformational Changes And Translocation Of Tissue-Transglutaminase To The Plasma Membranes: Role In Cancer Cell Migration, Ambrish Kumar, Jianjun Hu, Holly A. Lavoie, Kenneth B. Walsh, Donald J. Dipette, Ugra S. Singh

Jianjun Hu

Background Tissue-transglutaminase (TG2), a dual function G-protein, plays key roles in cell differentiation and migration. In our previous studies we reported the mechanism of TG2-induced cell differentiation. In present study, we explored the mechanism of how TG2 may be involved in cell migration. Methods To study the mechanism of TG2-mediated cell migration, we used neuroblastoma cells (SH-SY5Y) which do not express TG2, neuroblastoma cells expressing exogenous TG2 (SHYTG2), and pancreatic cancer cells which express high levels of endogenous TG2. Resveratrol, a natural compound previously shown to inhibit neuroblastoma and pancreatic cancer in the animal models, was utilized to investigate the …

Expert–Novice Differences In Mental Models Of Viruses, Vaccines, And The Causes Of Infectious Disease, Benjamin D. Jee, David H. Uttal, Amy N. Spiegel, Judy Diamond

Amy N. Spiegel

Humans are exposed to viruses everywhere they live, play, and work. Yet people’s beliefs about viruses may be confused or inaccurate, potentially impairing their understanding of scientific information. This study used semi-structured interviews to examine people’s beliefs about viruses, vaccines, and the causes of infectious disease. We compared people at different levels of science expertise: middle school students, teachers, and professional virologists. The virologists described more entities involved in microbiological processes, how these entities behaved, and why. Quantitative and qualitative analyses revealed distinctions in the cognitive organization of several concepts, including infection and vaccination. For example, some students and teachers …