Medicine and Health Sciences Commons^™

Genome-Wide Association Study Identifies Loci Influencing Concentrations Of Liver Enzymes In Plasma, John C. Chambers, Weihua Zhang, Joban Sehmi, Xinzhong Li, Mark N. Wass, Pim Van Der Harst, Hilma Holm, Serena Sanna, Maryam Kavousi, Chun Xu

Health & Biomedical Sciences Faculty Publications

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10−8 to P = 10−190). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A …

Unique Phenotype In A Patient With Charge Syndrome., Shobhit Jain, Hyung-Goo Kim, Felicitas Lacbawan, Irene Meliciani, Wolfgang Wenzel, Ingo Kurth, Josefina Sharma, Morris Schoeneman, Svetlana Ten, Lawrence C. Layman, Elka Jacobson-Dickman

Manuscripts, Articles, Book Chapters and Other Papers

CHARGE is a phenotypically heterogeneous autosomal dominant disorder recognized as a cohesive syndrome since the identification of CHD7 as a genetic etiology. Classic features include: Coloboma, Heart defects, Atresia choanae, Retarded growth and development, Genitourinary abnormalities, and Ear anomalies and/or deafness. With greater accessibility to genetic analysis, a wider spectrum of features are emerging, and overlap with disorders such as DiGeorge syndrome, Kallmann syndrome, and Hypoparathyroidism Sensorineural Deafness and Renal Disease syndrome, is increasingly evident. We present a patient with a unique manifestation of CHARGE syndrome, including primary hypoparathyroidism and a limb anomaly; to our knowledge, he is also the …

Calcium-Mediated Mechanisms Of Cystic Expansion, Shakila Abdul-Majeed, Surya M. Nauli

Pharmacy Faculty Articles and Research

In this review, we will discuss several well-accepted signaling pathways toward calcium-mediated mechanisms of cystic expansion. The second messenger calcium ion has contributed to a vast diversity of signal transduction pathways. We will dissect calcium signaling as a possible mechanism that contributes to renal cyst formation. Because cytosolic calcium also regulates an array of signaling pathways, we will first discuss cilia-induced calcium fluxes, followed by Wnt signaling that has attributed to much-discussed planar cell polarity. We will then look at the relationship between cytosolic calcium and cAMP as one of the most important aspects of cyst progression. The signaling of …

Bdnf And ‘Neurobics’: Building A ‘Beautiful Mind’ Against Huntington's, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Neuroprotective Effects Of Bilobalide Are Accompanied By A Reduction Of Ischemia-Induced Glutamate Release In Vivo, Dorothee Lang, Cornelia Kiewert, Alexander Mdzinarishvili, Tina Maria Schwarzkopf, Rachita K. Sumbria, Joachim Hartmann, Jochen Klein

Pharmacy Faculty Articles and Research

Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 h of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40–50% when given at 10 mg/kg 1 h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the …

Making Sense Of Huntington’S Organizations, And A Call For Unity, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Comparative Immunogenicity Of Na-Gst-1 Human Hookworm Vaccine With Synthetic Glucopyranosyl Lipid Adjuvant (Gla) In Balb/C Mice, Amar R. Jariwala, Brian Keegan, Jordan L. Plieskatt, Maria Elena Bottazzi, Peter J. Hotez, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Posters and Presentations

More than 740 million people worldwide are infected with Hookworm. Hookworm infection is most prevalent in the poorest of the poor populations of the world, and has serious health effects. Hookworm infection causes blood loss leading to iron deficiency anemia and protein energy malnutrition, which results in a compromised immune response. Consequently, the target human population suffers from an increased susceptibility to infectious diseases including hookworm infection. We have developed recombinant adult hookworm vaccines against hookworm infection to break this vicious cycle. Toll-like receptor (TLR) 4 agonist are known to boost immune response in healthy and immunocompromised individuals. We believe …

We Are… Bridging Medicine And Science Vol. 1, Issue 1, Fall 2011, Marshall University Biomedical Sciences

We Are... Bridging Medicine Science

No abstract provided.

Transgenic C. Elegans Dauer Larvae Expressing Hookworm Phospho Null Daf-16/Foxo Exit Dauer, Verena Gelmedin, Thomas Brodigan, Xin Gao, Michael Krause, Zhu Wang, John M. Hawdon

Research Center for Neglected Diseases of Poverty

Parasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3) in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from …

Frequency Of Silent Myocardial Ischaemia In Diabetics: A Single Centre Study, Adil Sheikh, Syed Shah Faisal, Abdul Jabbar

Section of Diabetes, Endocrinology and Metabolism

OBJECTIVE: To find the frequency of silent myocardial ischaemia in diabetics as compared to non-diabetics.

METHODS: This was a cross sectional study conducted between November 2008 and March 2010. Two hundred subjects were recruited by convenience sampling after informed consent. All were subjected to an exercise stress test. Electrocardiographic changes were noted for silent Ischaemia Descriptive Statistics were applied for significance.

RESULT: Of the 200 subjects included in the study, 31 had diabetes and 1 69 were non-diabetics. The mean age was 46 +/- 10 years. Twenty eight subjects tested positive for silent ischaemia, of whom six were diabetics (19%) …

Executive Summary: The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: Clinical Practice Guidelines By The Pediatric Infectious Diseases Society And The Infectious Diseases Society Of America., John S. Bradley, Carrie L. Byington, Samir S. Shah, Brian Alverson, Edward R. Carter, Christopher Harrison, Sheldon L. Kaplan, Sharon E. Mace, George H. Mccracken, Matthew R. Moore, Shawn D. St Peter, Jana A. Stockwell, Jack T. Swanson, Pediatric Infectious Diseases Society And The Infectious Diseases Society Of America

Manuscripts, Articles, Book Chapters and Other Papers

Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.

Age At Diagnosis Of Diabetes In Appalachia, Lawrence Barker, Robert Gerzoff, Richard Crespo, Molly Shrewsberry

Family and Community Health

Background

Appalachia is a region of the United States noted for the poverty and poor health outcomes of its residents. Residents of the poorest Appalachian counties have a high prevalence of diabetes and risk factors (obesity, low income, low education, etc.) for type 2 diabetes. However, diabetes prevalence exceeds what these risk factors alone explain. Based on this, the history of poor health outcomes in Appalachia, and personally observed high rates of childhood obesity and lack of concern about prediabetes, we speculated that people in Appalachia with diagnosed diabetes might tend to be diagnosed younger than their non-Appalachian counterparts.

Methods …

Functional Plasticity Of Central Trpv1 Receptors In Brainstem Dorsal Vagal Complex Circuits Of Streptozotocin-Treated Hyperglycemic Mice, Andrea Zsombok, Muthu D. Bhaskaran, Hong Gao, Andrei V. Derbenev, Bret N. Smith

Physiology Faculty Publications

Emerging data indicate that central neurons participate in diabetic processes by modulating autonomic output from neurons in the dorsal motor nucleus of the vagus (DMV). We tested the hypothesis that synaptic modulation by transient receptor potential vanilloid type 1 (TRPV1) receptors is reduced in the DMV in slices from a murine model of type 1 diabetes. The TRPV1 agonist capsaicin robustly enhanced glutamate release onto DMV neurons by acting at preterminal receptors in slices from intact mice, but failed to do so in slices from diabetic mice. TRPV1 receptor protein expression in the vagal complex was unaltered. Brief insulin preapplication …

Waiting For Symptoms: How Long Can I Hang On?, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

How Does Socioeconomic Development Affect Copd Mortality? An Age-Period-Cohort Analysis From A Recently Transitioned Population In China, Jing Chen, Mary Schooling, Janice Mary Johnston, Anthony Johnson Hedley, Sarah Morag Mcghee

Publications and Research

Background
Chronic obstructive pulmonary disease (COPD) is a leading cause of death, particularly in developing countries. Little is known about the effects of economic development on COPD mortality, although economic development may potentially have positive and negative influences over the life course on COPD. We took advantage of a unique population whose rapid and recent economic development is marked by changes at clearly delineated and identifiable time points, and where few women smoke, to examine the effect of macro-level events on COPD mortality.

Methods
We used Poisson regression to decompose sex-specific COPD mortality rates in Hong Kong from 1981 to …

Differences Between Trypanosoma Brucei Gambiense Groups 1 And 2 In Their Resistance To Killing By Trypanolytic Factor 1, Paul Capewell, Nicola J. Veitch, C. Michael R. Turner, Jayne Raper, Matthew Berriman, Stephen L. Hajduk, Annette Macleod

Publications and Research

Background: The three sub-species of Trypanosoma brucei are important pathogens of sub-Saharan Africa. T. b. brucei is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. T. b. rhodesiense and T. b. gambiense are able to resist lysis by TLF. There are two distinct sub-groups of T. b. gambiense that differ genetically and by human serum resistance phenotypes. Group 1 T. b. gambiense have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 T. b. gambiense are resistant to TLF-1 due in-part to reduced …

Mast Cell Activation And Clinical Outcome In Pediatric Cholelithiasis And Biliary Dyskinesia., Craig A. Friesen, Nancy Neilan, James F. Daniel, Kim Radford, Jennifer Verrill Schurman, Ding-You Li, Linda Andre, Shawn D. St Peter, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The current study was undertaken to determine the degree of activation of gallbladder mucosal mast cells, whether mast cell (MC) density or activation differ between patients with and without a positive clinical response to cholecystectomy, and whether either density or activation correlate with gallbladder emptying.

RESULTS: Fifteen biliary dyskinesia (BD) and 13 symptomatic cholelithiasis (CL) patients undergoing cholecystectomy were prospectively enrolled. Gallbladder wall MC density (by immunohistochemistry) and activation (by electron microscopy) were determined. Clinical response was evaluated 30 days post-cholecystectomy on a 5-point Likert-type scale. A complete or nearly complete clinical response was seen in 100% of CL …

Tropical Medicine: A Clinical Text, 8th Edition, Revised And Expanded, Kevin M. Cahill, M.D.

Institute of International Humanitarian Affairs

The history of tropical medicine is as dramatic as the story of humankind. It has its own myths and legends, including tales of epidemics that destroyed whole civilizations. Today, with silent stealth, tropical diseases still claim more lives than all the current wars combined. Having had the privilege of working throughout Africa, Asia, and Latin America, as well as in the great medical centers of Europe and the United States, the author presents the details essential for understanding pathogenesis, clinical manifestations, therapy, and prevention of the major tropical diseases. The text, now in its eighth edition, has been used for …

One Man's Story: Entering The Light, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Deletion Of Rb Accelerates Pancreatic Carcinogenesis By Oncogenic Kras And Impairs Senescence In Pre-Malignant Lesions, Catherine Carrière, A. Jesse Gore, Alixanna M. Norris, Jason R. Gunn, Alison Young, Daniel Longnecker, Murray Korc

Dartmouth Scholarship

Rb1 encodes a cell-cycle regulator that is functionally disrupted in most human cancers. Pancreatic ductal adenocarcinomas (PDACs) have a high frequency of mutations in KRAS and INK4A/CDKN2A that might allow cells to bypass the regulatory actions of retinoblastoma (RB). To determine the role of loss of RB function in PDAC progression, we investigated the effects of Rb disruption during pancreatic malignant transformation initiated by oncogenic Kras.We generated mice with pancreas-specific disruption of Rb, in the absence or presence of oncogenic Kras, to examine the role of RB in pancreatic carcinogenesis.

Autoimmune Responses To Atherosclerotic Lipids: A Study In Murine Models Of Atherosclerosis And Obesity, Hanjing Wu

Dissertations and Theses (Open Access)

Atherosclerosis is a chronic, complex arterial disease characterized by intimal lipid accumulation and inflammation. A unique lipid-binding molecule, namely cluster of differentiation 1d (CD1d), may impact atherosclerosis. Structurally, CD1d acts as a nonpolymorphic cell-surface receptor, resembling the major histocompatibility complex-I (MHC-I). While MHC-I restricts peptide antigen presentation to T cells, CD1d presents lipid antigens to T cells named CD1d-restrictedd T cells. Although increased expression of CD1d has been found in human plaques, the exact nature of CD1d-recognized lipids in atherosclerosis remains to be determined. Three groups of lipids may undergo oxidation in atherosclerosis producing atherogenic lipids: phospholipids, fatty acids, and …

Identifying And Co-Managing The Hiv-Infected Adult: A Guidebook For Primary Care Clinicians, Jason Leider, Susan F. Lelacheur, Julie G. Stewart Dnp, Mph

Nursing Faculty Publications

This guidebook was designed to help primary care clinicians improve their performance in terms of HIV identification and co-management. Surmounting barriers to opt-out screening, making an HIV diagnosis, and preventing transmission and opportunistic infections will be discussed, as will selection of initial therapy and considerations for patients receiving antiretroviral therapy (ART).

Use Of Optimal Control Models To Predict Treatment Time For Managing Tick-Borne Disease, Holly D. Gaff, Elsa Schaefer, Suzanne Lenhart

Biological Sciences Faculty Publications

Tick-borne diseases have been on the rise recently, and correspondingly, there is an increased interest in implementing control measures to decrease the risk. Optimal control provides an ideal tool to identify the best method for reducing risk while accounting for the associated costs. Using a previously published model, a variety of frameworks are assessed to identify the key factors influencing mitigation strategies. The level and duration of tick-reducing efforts are key metrics for understanding the successful reduction in tick-borne disease incidence. The results show that the punctuated nature of the tick's life history plays a critical role in reducing risk …

The 2007 Rift Valley Fever Outbreak In Sudan, Osama Ahmed Hassan, Clas Ahlm, Rosemary Sang, Magnus Evander

All Peer-Reviewed Publications

Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of animals. The virus is transmitted through bites from mosquitoes and exposure to viremic blood, body fluids, or tissues of infected animals. During 2007 a large RVF outbreak occurred in Sudan with a total of 747 confirmed human cases including 230 deaths (case fatality 30.8%); although it has been estimated 75,000 were infected. It was most severe in White Nile, El Gezira, and Sennar states near …

Left Ventricular Assist Devices: Engineering Design Considerations, Marwan A. Simaan, Eduardo Divo, George Faragallah, Yu Wang

Publications

Patients with end-stage congestive heart failure awaiting heart transplantation often wait long periods of time (300 days or more on the average) before a suitable donor heart becomes available. The medical community has placed increased emphasis on the use of Left Ventricular Assist Devices or LVADs that can substitute for, or enhance, the function of the natural heart while the patient is waiting for the heart transplant (Poirier, 1997; Frazier & Myers, 1999). Essentially, a rotary LVAD is a pump that operates continuously directing blood from the left ventricle into the aorta by avoiding the aortic valve. Generally speaking, the …

Do-Or-Die Time For Huntington’S Clinical Trials, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Combination Of Virb Binding Site Mutations To Evaluate Collective Impact On Icsp Promoter Activity In Shigella Flexneri, Pashtana Usufuzy, Juan C. Duhart, Maria I. Castellanos, Helen Wing

Undergraduate Research Opportunities Program (UROP)

Shigella flexneri is a gram-negative, invasive bacterial pathogen that afflicts the human colonic epithelium, causing shigellosis, an illness triggering severe dysentery. The World Health Organization cites the disease burden of shigellosis near 90 million episodes and 108,000 deaths per year.

The motility and spread of Shigella is modulated by icsP, a virulence gene. The transcription factor VirB positively regulates many virulence genes encoded by the Shigella virulence plasmid. Two distal binding sites of VirB have been shown to regulate the promoter activity of icsP, despite their location of more than 1 kb upstream of the transcription start site. Five VirB …

Aids/Hiv Denialism: Patients' Privacy Rights, Fadia Abdullah, Guadalupe Medrano

Undergraduate Research Opportunities Program (UROP)

HIV is a sexually transmitted disease that develops into AIDS. There is no cure for it, only treatment. In this poster, we look at the pros and cons of disclosing this type of information. People who decide to disclose their HIV status may have various reasons for doing so, but most do it for emotional support and for prevention of spreading the disease. Those who decide to keep it private primarily do it to not face rejection, discrimination, degradation, and loss of respect. (Petronio Page 72) The problem with creating a public database is that many organizations are against the …

Regulation Of The Shigella Flexneri Icsp Gene And H-Ns Dependent Repression, Rosa Ojeda, Amanda Wigley, Dustin Harrison, Helen Wing

Undergraduate Research Opportunities Program (UROP)

The gram negative bacterium Shigella flexneri is known to cause dysentery in humans and primates. In order to help prevent the spread of shigellosis, gene regulation must be understood. Studies show that the virulence genes in S .flexneri are thermo regulated. At 30°C histone-like nucleoid structuring protein (H-NS) represses transcription of virulence genes and at 37°C VirB derepresses virulence genes. One of the genes that contribute to the virulence of S. flexneri is icsP. My project focuses on the regulation of the S. flexneri icsP gene and has two main goals. The first is to identify the sequence of H-NS …

Defining The Role Of Nras In Melanoma Maintenance, Sravya T. Challa, Sheri L. Holmen

Undergraduate Research Opportunities Program (UROP)

The incidence of melanoma has increased 600 percent over the last four decades; it is the most rapidly increasing malignancy among young people in the United States and is currently the leading cause of cancer death in women aged 25- 29. If detected early, the disease is easily treated; however, once the disease has metastasized it is largely refractory to conventional therapies and is associated with a high mortality rate. The development of cancer from a pre-malignant primary tumor to a metastatic cancer that develops at secondary sites is a multi-step process, thought to require many genetic and epigenetic events …