Diseases Commons^™

Muscle-Specific Loss Of Bmal1 Leads To Disrupted Tissue Glucose Metabolism And Systemic Glucose Homeostasis, Brianna D. Harfmann, Elizabeth Schroder, Maureen T. Kachman, Brian A. Hodge, Xiping Zhang, Karyn Esser

Center for Muscle Biology Faculty Publications

Background: Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglycemia and glucose intolerance and symptoms caused by failure to produce and/or respond to insulin. The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 % of postprandial glucose. To address the role of the skeletal muscle molecular clock to insulin sensitivity and glucose tolerance, we generated an inducible skeletal muscle-specific Bmal1 ^−/− mouse (iMSBmal1 ^−/−).

Results: Progressive changes in body composition (decreases in …

Global Engagement: Problem Solving And Information Exchange, Vinaya Manchaiah, Brenda Louw

ETSU Faculty Works

This interactive session provides opportunities (1) to share ideas for infusing global perspectives and goals into CAPCSD projects, conferences, and the work of committees and task forces; (2) to discuss ways to collaborate in an ongoing global engagement projects and help include content for 2017 conference; and (3) to create how-to guides for ethical and culturally attuned translational research, and clinical education, and service learning.

Metabolomics Reveals New Mechanisms For Pathogenesis In Barth Syndrome And Introduces Novel Roles For Cardiolipin In Cellular Function, Yana Sandlers, Kelly Mercier, Wimal Pathmasiri, Jim Carlson, Susan Mcritchie, Susan Sumner, Hilary J. Vernon

Chemistry Faculty Publications

Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via ¹H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of …

Conditional Screening For Ultra-High Dimensional Covariates With Survival Outcomes, Hyokyoung Grace Hong, Jian Kang, Yi Li

The University of Michigan Department of Biostatistics Working Paper Series

Identifying important biomarkers that are predictive for cancer patients' prognosis is key in gaining better insights into the biological influences on the disease and has become a critical component of precision medicine. The emergence of large-scale biomedical survival studies, which typically involve excessive number of biomarkers, has brought high demand in designing efficient screening tools for selecting predictive biomarkers. The vast amount of biomarkers defies any existing variable selection methods via regularization. The recently developed variable screening methods, though powerful in many practical setting, fail to incorporate prior information on the importance of each biomarker and are less powerful in …

'Refractory Epilepsy': What Lies Beneath?, Syedah Saira Bokhari, Satwat Hashmi

Section of Internal Medicine

A 30-year-old woman presented to the emergency room with recurrent seizures for 5 days. She had been diagnosed with epilepsy 2 years previously but stopped treatment due to the side effects of her medications. She was now experiencing episodes every 15-30 min. While undergoing a brain MRI to investigate for structural central nervous system pathology, she experienced another episode, preceded by prodromal symptoms. Polymorphic ventricular tachycardia was noted during the event. Further investigation revealed a normal QT interval, normal electrolyte panel, normal coronaries and severe left ventricular systolic dysfunction. Cardiac MRI revealed non-ischaemic cardiomyopathy. The patient was managed with heart …

Billboards: An Old – But Also New – Way Of Projecting The Huntington's Cause, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

A Dataset To Assess Providers׳ Knowledge And Attitudes Towards The 2013 American College Of Cardiology/American Heart Association Cholesterol Management Guideline, Yashashwi Pokharel, Lynne Steinberg, Winston Chan, Julia M. Akeroyd, Peter H. Jones, Vijay Nambi, Khurram Nasir, Laura Petersen, Christie M. Ballantyne, Salim S. Virani

Office of the Provost

We previously examined provider׳s understanding of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol management guideline (DOI: http://dx.doi.org/10.1016/j.jacl.2015.11.002)(Virani et al., 2013) [1], and also assessed whether a case-based educational intervention could improve providers׳ knowledge gaps and attitudes towards the guideline (DOI: 10.1016/j.atherosclerosis.2015.12.044) (Pokharel, et al., 2016) [2]. Here we describe the dataset that we used to examine our objectives.

Expression Of Complement And Toll-Like Receptor Pathway Genes Is Associated With Malaria Severity In Mali: A Pilot Case Control Study, Rafal S. Sobota, Antoine Dara, Jessica E. Manning, Amadou Niangaly

Dartmouth Scholarship

Background: The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood.

Methods: To identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case–control study in Bandiagara, Mali. Microarrays were used to obtain expression …

Huntington's Disease--A Review, Christen Dunn

The Kabod

Huntington’s disease is degenerative and effects both cognitive and motor functioning, beginning in the 20s and continuing a decline for about two decades until death. In this disease, the huntingtin gene on chromosome four codes for an abnormally elongated repeating CAG polypeptide sequence. This mutation causes an atrophy in the brain that translates into decreasing control of movements and other aspects of cognition. To date, there is no cure for Huntington’s disease, but there are treatments for many symptoms that accompany the disease. Even still, there are promising new methods that may be more beneficial to patients in the future.

Relationship Of Optimism And Suicidal Ideation In Three Groups Of Patients At Varying Levels Of Suicide Risk, Jeff C. Huffman, Julia K. Boehm, Scott R. Beach, Eleanor E. Beale, Christina M. Dubois, Brian C. Healy

Psychology Faculty Articles and Research

Optimism has been associated with reduced suicidal ideation, but there have been few studies in patients at high suicide risk. We analyzed data from three study populations (total N=319) with elevated risk of suicide: (1) patients with a recent acute cardiovascular event, (2) patients hospitalized for heart disease who had depression or an anxiety disorder, and (3) patients psychiatrically hospitalized for suicidal ideation or following a suicide attempt. For each study we analyzed the association between optimism (measured by the Life-Orientation Test-Revised) and suicidal ideation, and then completed an exploratory random effects meta-analysis of the findings to synthesize this data. …

Parasitic Diseases Of The Central Nervous System: Lessons For Clinicians And Policy Makers, Arturo Carpio, Matthew L. Romo, R.M.E. Parkhouse, Brooke Short, Tarun Dua

Publications and Research

Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, …

The Association Between Vitamin A Status Or Supplementation And Hiv/Aids, Mikaela Kathleen Curtis

Food Science and Nutrition

The human immunodeficiency virus (HIV) has infected millions of people since the start of the epidemic in the early 1980s. HIV is the etiologic agent of the acquired immunodeficiency syndrome (AIDS), which has taken millions of lives. It is extremely difficult for particular populations to receive medication to treat HIV infection and prevent the progression of HIV to AIDS. Multiple studies have examined the effect of vitamin A on HIV infection, due to its immune stimulating effects. It is unclear whether an association exists between vitamin A and different aspects of HIV. This review examined the effect of vitamin A …

Higher Risk For Incident Heart Failure And Cardiovascular Mortality Among Community-Dwelling Octogenarians Without Pneumococcal Vaccination, Momanna Ahmed, Kanan Patel, Gregg C. Fonarow, Charity J. Morgan, Javed Butler, Vera Bittner, Andrzej Kulczycki, Raya Kheirbek, Wilbert S. Aronow, Ross D. Fletcher, Cynthia J. Brown, Ali Ahmed

NYMC Faculty Publications

AIMS: Octogenarians have the highest incidence of heart failure (HF) that is not fully explained by traditional risk factors. We explored whether lack of pneumococcal vaccination is associated with higher risk of incident HF among octogenarians.

METHODS AND RESULTS: In the Cardiovascular Health Study (CHS), 5290 community-dwelling adults, ≥65 years of age, were free of baseline HF and had data on pneumococcal vaccination. Of these, 851 were octogenarians, of whom, 593 did not receive pneumococcal vaccination. Multivariable-adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for associations of lack of pneumococcal vaccination with incident HF and other outcomes during 13 …

Antiretroviral Drugs-Loaded Nanoparticles Fabricated By Dispersion Polymerization With Potential For Hiv/Aids Treatment, Winston Anderson

Department of Biology Faculty Publications

Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning …

Optimizing Electrocardiogram Interpretation And Catheterization Laboratory Activation In St-Segment Elevation Myocardial Infarct, Alexander E. Sullivan, Mortada Shams, Marco A. Mercader, Jacob Varghese, Abudureyimu Shajidan, Bassel Hassouna, Vimala V. Jayanthi

GW Research Days 2016 - 2020

Background: To achieve the 90-minute reperfusion goal in ST-segment elevation myocardial infarction (STEMI) care, providers must diagnose STEMIs from electrocardiograms (ECGs) obtained upon emergency room arrival and appropriately activate the catheterization lab. To enhance early STEMI care, we sought to improve medical student STEMI recognition and diagnostic accuracy with a teaching module we designed and developed.

Methods: Through a literature review, we identified evidenced-based criteria for classic STEMI patterns, STEMI-equivalents with non-classic STEMI patterns including hyperacute T-waves, STEMI with existing left bundle branch block (LBBB) and Wellens’ syndrome and non-ischemic STEMI-mimics such as known LBBB, pericarditis, ventricular aneurysm, …

Medical Help-Seeking For Sexual Concerns In Prostate Cancer Survivors, Melissa K. Hyde, Leah Zajdlewicz, Addie C. Wootten, Christian J. Nelson, Anthony Lowe, Jeff Dunn, Suzanne K. Chambers

Research outputs 2014 to 2021

Introduction: Although sexual dysfunction is common after prostate cancer, men's decisions to seek help for sexual concerns are not well understood.

Aim: Describe predictors of actual prior help-seeking and intended future medical help-seeking for sexual dysfunction in prostate cancer survivors.

Methods: A cross-sectional survey of 510 prostate cancer survivors assessed masculine beliefs, attitudes, support/approval from partner/peer networks (subjective norm), and perceived control as predictors of medical help-seeking for sexual concerns. A theory of planned behavior (TPB) perspective was used to examine actual prior and planned future behavior and contributing factors. Statistical analyses included multiple and logistic regressions.

Main Outcome Measures: …

Using A Tailored Health Information Technology- Driven Intervention To Improve Health Literacy And Medication Adherence In A Pakistani Population With Vascular Disease (Talking Rx) - Study Protocol For A Randomized Controlled Trial, Ayeesha Kamran Kamal, Abdul Muqeet, Kashfa Farhat, Wardah Khalid, Anum Jamil, Ambreen Gowani, Aliya Amin Muhammad, Fabiha Zaidi, Danyal Khan, Touseef Elahi, Shahrukh Sharif, Syedah Saira Bokhari, Nasir Rahman, Fateh Ali Tipoo Sultan, Saleem Sayani, Salim S. Virani

Section of Internal Medicine

Background: Vascular disease, manifesting as myocardial infarction and stroke, is a major cause of morbidity and mortality, especially in low- and middle-income countries. Current estimates are that only one in six patients have good adherence to medications and very few have sufficient health literacy. Our aim is to explore the effectiveness and acceptability of Prescription Interactive Voice Response (IVR) Talking Prescriptions (Talking Rx) and SMS reminders in increasing medication adherence and health literacy in Pakistani patients with vascular disease.
Methods: This is a randomized, controlled, single center trial. Adult participants, with access to a cell phone and a history of …

Pharmacokinetics And Bioequivalence Of A Liquid Formulation Of Hydroxyurea In Children With Sickle Cell Anemia., Jeremie H. Estepp, Chiara Melloni, Courtney D. Thornburg, Paweł Wiczling, Zora Rogers, Jennifer A. Rothman, Nancy S. Green, Robert Liem, Amanda M. Brandow, Shelley E. Crary, Thomas H. Howard, Maurine H. Morris, Andrew Lewandowski, Uttam Garg, William J. Jusko, Kathleen A. Neville, Best Pharmaceuticals For Children Act-Pediatric Trials Network Administrative Core Committee

Manuscripts, Articles, Book Chapters and Other Papers

Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability …

Techniques And Approaches To Genetic Analyses In Nephrological Disorders., Laurel K. Willig

Manuscripts, Articles, Book Chapters and Other Papers

Inherited renal disease is a leading cause of morbidity and mortality in pediatric nephrology. High throughput advancements in genomics have led to greater understanding of the biologic underpinnings of these diseases. However, the underlying genetic changes explain only part of the molecular biology that contributes to disease manifestation and progression. Other omics technologies will provide a more complete picture of these cellular processes. This review discusses these omics technologies in the context of pediatric renal disease.

Multi-Level Correlates Of Safer Conception Methods Awareness And Attitudes Among Ugandan Hiv Clients With Fertility Intentions., Glenn J. Wagner, Mahlet A. Woldetsadik, Jolly Beyeza-Kashesya, Kathy Goggin, Deborah Mindry, Sarah Finocchario-Kessler, Sarah Khanakwa, Rhoda K. Wanyenze

Manuscripts, Articles, Book Chapters and Other Papers

Many people living with HIV desire childbearing, but low cost safer conception methods (SCM) such as timed unprotected intercourse (TUI) and manual self-insemination (MSI) are rarely used. We examined awareness and attitudes towards SCM, and the correlates of these constructs among 400 HIV clients with fertility intentions in Uganda. Measures included awareness, self-efficacy, and motivation regarding SCM, as well as demographics, health management, partner and provider characteristics. Just over half knew that MSI (53%) and TUI (51%) reduced transmission risk during conception, and 15% knew of sperm washing and pre-exposure prophylaxis. In separate regression models for SCM awareness, motivation, and …

Chief Huntington’S Disease Drug Hunter: ‘Every Confidence First Treatments' In The Works, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Herpes Simplex Virus And Interferon Signaling Induce Novel Autophagic Clusters In Sensory Neurons, Sarah Katzenell, David A. Leib

Dartmouth Scholarship

Herpes simplex virus 1 (HSV-1) establishes lifelong infection in the neurons of trigeminal ganglia (TG), cycling between productive infection and latency. Neuronal antiviral responses are driven by type I interferon (IFN) and are crucial to controlling HSV-1 virulence. Autophagy also plays a role in this neuronal antiviral response, but the mechanism remains obscure. In this study, HSV-1 infection of murine TG neurons triggered unusual clusters of autophagosomes, predominantly in neurons lacking detectable HSV-1 antigen. Treatment of neurons with IFN-β induced a similar response, and cluster formation by infection or IFN treatment was dependent upon an intact IFN-signaling pathway. The autophagic …

Development Of A Spirometry T-Score In The General Population, Sei Won Lee, Hyun Kuk Kim, Seunghee Baek, Ji-Ye Jung, Young Sam Kim, Jae Seung Lee, Sang-Do Lee, David M. Mannino, Yeon-Mok Oh

Preventive Medicine and Environmental Health Faculty Publications

Background and objective: Spirometry values may be expressed as T-scores in standard deviation units relative to a reference in a young, normal population as an analogy to the T-score for bone mineral density. This study was performed to develop the spirometry T-score.

Methods: T-scores were calculated from lambda-mu-sigma-derived Z-scores using a young, normal age reference. Three outcomes of all-cause death, respiratory death, and COPD death were evaluated in 9,101 US subjects followed for 10 years; an outcome of COPD-related health care utilization (COPD utilization) was evaluated in 1,894 Korean subjects followed for 4 years.

Results: The …

Inferring Causal Molecular Networks: Empirical Assessment Through A Community-Based Effort, Steven M. Hill, Laura M. Heiser, Thomas Cokelaer, Michael Unger, Nicole K. Nesser, Daniel E. Carlin, Yang Zhang, Artem Sokolov, Evan O. Paull, Dong-Chul Kim

Computer Science Faculty Publications

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology …

Spatial Distribution And Cluster Analysis Of Retail Drug Shop Characteristics And Antimalarial Behaviors As Reported By Private Medicine Retailers In Western Kenya: Informing Future Interventions, Andria Rusk, Linda Highfield, J. Michael Wilkerson, Melissa Harrell, Andrew Obala, Benjamin Amick

Collected Faculty Scholarship

Background

Efforts to improve malaria case management in sub-Saharan Africa have shifted focus to private antimalarial retailers to increase access to appropriate treatment. Demands to decrease intervention cost while increasing efficacy requires interventions tailored to geographic regions with demonstrated need. Cluster analysis presents an opportunity to meet this demand, but has not been applied to the retail sector or antimalarial retailer behaviors. This research conducted cluster analysis on medicine retailer behaviors in Kenya, to improve malaria case management and inform future interventions.

Methods

Ninety-seven surveys were collected from medicine retailers working in the Webuye Health and Demographic Surveillance Site. Survey …

Drug Repurposing To Target Ebola Virus Replication And Virulence Using Structural Systems Pharmacology, Zheng Zhao, Che Martin, Raymond Fan, Philip E. Bourne, Lei Xie

Publications and Research

Background: The recent outbreak of Ebola has been cited as the largest in history. Despite this global health crisis, few drugs are available to efficiently treat Ebola infections. Drug repurposing provides a potentially efficient solution to accelerating the development of therapeutic approaches in response to Ebola outbreak. To identify such candidates, we use an integrated structural systems pharmacology pipeline which combines proteome-scale ligand binding site comparison, protein-ligand docking, and Molecular Dynamics (MD) simulation.

Results: One thousand seven hundred and sixty-six FDA-approved drugs and 259 experimental drugs were screened to identify those with the potential to inhibit the replication and virulence …

Molecular Evolution And Intraclade Recombination Of Enterovirus D68 During The 2014 Outbreak In The United States., Yi Tan, Ferdaus Hassan, Jennifer E. Schuster, Ari Simenauer, Rangaraj Selvarangan, Rebecca A. Halpin, Xudong Lin, Nadia Fedorova, Timothy B. Stockwell, Tommy Tsan-Yuk Lam, James D. Chappell, Tina V. Hartert, Edward C. Holmes, Suman R. Das

Manuscripts, Articles, Book Chapters and Other Papers

In August 2014, an outbreak of enterovirus D68 (EV-D68) occurred in North America, causing severe respiratory disease in children. Due to a lack of complete genome sequence data, there is only a limited understanding of the molecular evolution and epidemiology of EV-D68 during this outbreak, and it is uncertain whether the differing clinical manifestations of EV-D68 infection are associated with specific viral lineages. We developed a high-throughput complete genome sequencing pipeline for EV-D68 that produced a total of 59 complete genomes from respiratory samples with a 95% success rate, including 57 genomes from Kansas City, MO, collected during the 2014 …

Hydroxycarbamide Versus Chronic Transfusion For Maintenance Of Transcranial Doppler Flow Velocities In Children With Sickle Cell Anaemia-Tcd With Transfusions Changing To Hydroxyurea (Twitch): A Multicentre, Open-Label, Phase 3, Non-Inferiority Trial., Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Lori Luchtman-Jones, +Several Additional Authors

Pediatrics Faculty Publications

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.

METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible …

AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We …

Maternal Anxiety Associated With Newborn Hearing Screening, Stephen J. Tueller, Karl R. White

Journal of Early Hearing Detection and Intervention

The purpose of this study was to determine if newborn hearing screening increases maternal anxiety. Mothers whose infants were screened for hearing were asked how worried they were prior to hospital discharge and again six weeks later. They were also asked if they were more concerned about their baby’s hearing than they were about other aspects of the infant’s health and behavior.

Results showed that mothers worried as much or more about many other aspects of their infants’ health and behavior as about hearing. Mothers whose infants had a false positive screening result were initially more worried about hearing than …