Medicine and Health Sciences Commons^™

Extracellular Traps Are Associated With Human And Mouse Neutrophil And Macrophage Mediated Killing Of Larval Strongyloides Stercoralis., Sandra Bonne-Annee, Laura A. Kerepesi, Jessica A. Hess, Jordan Wesolowski, Fabienne Paumet, James B. Lok, Thomas J. Nolan, David Abraham

Department of Microbiology and Immunology Faculty Papers

Neutrophils are multifaceted cells that are often the immune system's first line of defense. Human and murine cells release extracellular DNA traps (ETs) in response to several pathogens and diseases. Neutrophil extracellular trap (NET) formation is crucial to trapping and killing extracellular pathogens. Aside from neutrophils, macrophages and eosinophils also release ETs. We hypothesized that ETs serve as a mechanism of ensnaring the large and highly motile helminth parasite Strongyloides stercoralis thereby providing a static target for the immune response. We demonstrated that S. stercoralis larvae trigger the release of ETs by human neutrophils and macrophages. Analysis of NETs revealed …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

Self-Rated Health Predicts Healthcare Utilization In Heart Failure, Alanna M. Chamberlain, Sheila M. Manemann, Shannon M. Dunlay, John A. Spertus, Debra K. Moser, Cecilia Berardi, Robert L. Kane, Susan A. Weston, Margaret M. Redfield, Véronique L. Roger

Nursing Faculty Publications

BACKGROUND: Heart failure (HF) patients experience impaired functional status, diminished quality of life, high utilization of healthcare resources, and poor survival. Yet, the identification of patient-centered factors that influence prognosis is lacking.

METHODS AND RESULTS: We determined the association of 2 measures of self-rated health with healthcare utilization and skilled nursing facility (SNF) admission in a community cohort of 417 HF patients prospectively enrolled between October 2007 and December 2010 from Olmsted County, MN. Patients completed a 12-item Short Form Health Survey (SF-12). Low self-reported physical functioning was defined as a score ≤ 25 on the SF-12 physical component. The …

Human Judgment And Health Care Policy., Benjamin Djulbegovic, Jason Beckstead, David B. Nash

College of Population Health Faculty Papers

No abstract provided.

Functional Health Status In Children And Adolescents After Fontan: Comparison Of Generic And Disease-Specific Assessments., Brian W. Mccrindle, Victor Zak, Victoria L. Pemberton, Linda M. Lambert, Victoria L. Vetter, Wyman W. Lai, Karen Uzark, Renee Margossian, Andrew M. Atz, Amanda Cook, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: The aim of this study was to compare associations between generic versus disease-specific functional health status assessments and patient and clinical characteristics for patients with severe congenital heart disease.

METHODS: This was a cross-sectional observational study involving 325 single ventricle patients, aged 10-18 years, after Fontan procedure. Enrolled patients underwent a medical history review, laboratory testing, and assessment of the functional health status by completion of the generic Child Report Child Health Questionnaire and the disease-specific Congenital Heart Adolescent and Teenage questionnaire. Correlated conceptually equivalent domains from both questionnaires were identified and their associations with patient and clinical variables …

Understanding The Power Of Perinatal Events And Metabolic Status In Childhood., Bonita Falkner, Julie Ingelfinger

Department of Medicine Faculty Papers

No abstract provided.

Sex-Specific Biatrial Volumetric Measurements Obtained With Use Of Multidetector Computed Tomography In Subjects With And Without Coronary Artery Disease, Matthew J Budoff, Sandeep R Pagali, Yasmin S Hamirani, Andy Chen, Gordon Cheu, Yanlin Gao, Dong Li, Songshou Mao

The Texas Heart Institute Journal

Atrial volumetric measurement has proven clinical implications. Advances in cardiac imaging, notably the precision enabled by multidetector computed tomography (MDCT), herald the need for new criteria of what constitutes normal volumetric measurements. With use of 64-slice MDCT, we compared the atrial volumes in healthy individuals with those in individuals with coronary artery disease.

By means of manual segmentation, we measured biatrial volume in 686 participants who underwent retrospective electrocardiographic-gated MDCT angiographic evaluation. The study population included a control group of 203 persons with no cardiac abnormalities, and a study group of 483 patients with obstructive coronary artery disease. All variables …

Spontaneous Coronary Artery Dissection (Scad): New Insights Into This Not-So-Rare Condition, Sharonne N Hayes

The Texas Heart Institute Journal

No abstract provided.

Natural Progression Of Low-Gradient Severe Aortic Stenosis With Preserved Ejection Fraction, Antony Leslie Innasimuthu, Sanjay Kumar, Jason Lazar, William E Katz

The Texas Heart Institute Journal

Because the natural progression of low-gradient aortic stenosis (LGAS) has not been well defined, we performed a retrospective study of 116 consecutive patients with aortic stenosis who had undergone follow-up echocardiography at a median interval of 698 days (range, 371–1,020 d). All patients had preserved left ventricular ejection fraction (>0.50) during and after follow-up.

At baseline, patients were classified by aortic valve area (AVA) as having mild stenosis (≥1.5 cm2), moderate stenosis (≥1 to <1.5 cm2), or severe stenosis (<1 cm2). Severe aortic stenosis was further classified by mean gradient (LGAS, mean <40 mmHg; high-gradient aortic stenosis [HGAS], mean ≥40 mmHg). We compared baseline and follow-up values among 4 groups: patients with mild stenosis, moderate stenosis, LGAS, and HGAS.

At baseline, 30 patients had mild stenosis, 54 had moderate stenosis, 24 had LGAS, and 8 had HGAS. Compared with the moderate group, the LGAS …

Outpatient Management Of Heart Failure In The United States, 2006-2008, Kailash Mosalpuria, Sunil K Agarwal, Sirin Yaemsiri, Bredy Pierre-Louis, Samir Saba, Rene Alvarez, Stuart D Russell

The Texas Heart Institute Journal

Better outpatient management of heart failure might improve outcomes and reduce the number of rehospitalizations. This study describes recent outpatient heart-failure management in the United States.

We analyzed data from the National Ambulatory Medical Care Survey of 2006–2008, a multistage random sampling of non-Federal physician offices and hospital outpatient departments.

Annually, 1.7% of all outpatient visits were for heart failure (51% females and 77% non-Hispanic whites; mean age, 73 ± 0.5 yr). Typical comorbidities were hypertension (62%), hyperlipidemia (36%), diabetes mellitus (35%), and ischemic heart disease (29%). Body weight and blood pressure were recorded in about 80% of visits, and …

Exertional Dyspnea As A Symptom Of Infrarenal Aortic Occlusive Disease, Stacey L Schott, Fernanda Porto Carreiro, James R Harkness, Mahmoud B Malas, Stephen M Sozio, Sammy Zakaria

The Texas Heart Institute Journal

Advanced atherosclerosis of the aorta can cause severe ischemia in the kidneys, refractory hypertension, and claudication. However, no previous reports have clearly associated infrarenal aortic stenosis with shortness of breath. A 77-year-old woman with hypertension and hyperlipidemia presented with exertional dyspnea. Despite extensive testing and observation, no apparent cause for this patient's dyspnea was found. Images revealed severe infrarenal aortic stenosis. After the patient underwent stenting of the aortic occlusion, she had immediate symptomatic improvement and complete resolution of her dyspnea within one month. Twelve months after vascular intervention, the patient remained asymptomatic. In view of the distinct and lasting …

Integrating Addiction Treatment Into Primary Care Using Mobile Health Technology: Protocol For An Implementation Research Study, Andrew R. Quanbeck, David H. Gustafson, Lisa A. Marsch, Fiona Mctavish

Dartmouth Scholarship

Healthcare reform in the United States is encouraging Federally Qualified Health Centers and other primary-care practices to integrate treatment for addiction and other behavioral health conditions into their practices. The potential of mobile health technologies to manage addiction and comorbidities such as HIV in these settings is substantial but largely untested. This paper describes a protocol to evaluate the implementation of an E-Health integrated communication technology delivered via mobile phones, called Seva, into primary-care settings. Seva is an evidence-based system of addiction treatment and recovery support for patients and real-time caseload monitoring for clinicians.

Manage At Work: A Randomized, Controlled Trial Of A Self-Management Group Intervention To Overcome Workplace Challenges Associated With Chronic Physical Health Conditions, William S. Shaw, Elyssa Besen, Glenn Pransky, Cécile R. L. Boot, Michael K. Nicholas, Robert K. Mclellan, Torill H. Tveito

Dartmouth Scholarship

Background: The percentage of older and chronically ill workers is increasing rapidly in the US and in many other countries, but few interventions are available to help employees overcome the workplace challenges of chronic pain and other physical health conditions. While most workers are eligible for job accommodation and disability compensation benefits, other workplace strategies might improve individual-level coping and problem solving to prevent work disability. In this study, we hypothesize that an employer-sponsored group intervention program employing self-management principles may improve worker engagement and reduce functional limitation associated with chronic disorders.

Methods: In a randomized controlled trial (RCT), workers …

Conflict Translates Environmental And Social Risk Into Business Costs, Daniel M. Franks, Rachel Davis, Anthony J. Bebbington, Saleem H. Ali, Deanna Kemp, Martin Scurrah

Faculty Publications

Sustainability science has grown as a field of inquiry, but has said little about the role of large-scale private sector actors in socio-ecological systems change. However, the shaping of global trends and transitions depends greatly on the private sector and its development impact. Market-based and command-and-control policy instruments have, along with corporate citizenship, been the predominant means for bringing sustainable development priorities into private sector decision-making. This research identifies conflict as a further means through which environmental and social risks are translated into business costs and decision making. Through in-depth interviews with finance, legal, and sustainability professionals in the extractive …

A Global Compendium Of Human Dengue Virus Occurrence, Jane P. Messina, Oliver J Brady, David M. Pigott, John S. Brownstein, Anne Hoen, Simon Hay

Dartmouth Scholarship

A global geographic database of human dengue virus occurrence was produced to generate a global risk map and associated burden estimates1. Herein we present the database, which comprises occurrence data linked to point or polygon locations, derived from peer-reviewed literature and case reports as well as informal online sources. Entries date from 1960 to 2012. We describe all data collection processes in full, as well as geo-positioning, database management and quality-control procedures. This is the most comprehensive database of confirmed human dengue infection to-date, consisting of 8,309 geo-positioned occurrences in total.

Interventions To Improve Delivery Of Isoniazid Preventive Therapy: An Overview Of Systematic Reviews, Lisa V. Adams, Elizabeth A. Talbot, Karen Odato, Heather Blunt, Karen R. Steingart

Dartmouth Scholarship

Background:

Uptake of isoniazid preventive therapy (IPT) to prevent tuberculosis has been poor, particularly in the highest risk populations. Interventions to improve IPT delivery could promote implementation. The large number of existing systematic reviews on treatment adherence has made drawing conclusions a challenge. To provide decision makers with the evidence they need, we performed an overview of systematic reviews to compare different organizational interventions to improve IPT delivery as measured by treatment completion among those at highest risk for the development of TB disease, namely child contacts or HIV-infected individuals.

Methods:

We searched the Cochrane Database of Systematic Reviews, the …

Health System Characteristics And Rates Of Readmission After Acute Myocardial Infarction In The United States, Jeremiah R. Brown, Chiang-Hua Chang, Weiping Zhou, Todd A. Mackenzie, David J. Malenka, David C. Goodman

Dartmouth Scholarship

Background:

Interventions to reduce early readmissions have focused on patient characteristics and the importance of early follow‐up; however, less is known about the characteristics of health systems, including quality, capacity, and intensity, and their influence on readmission rates in the United States. Therefore, we examined the association of hospital patterns of medical care with rates of 30‐day readmission.

Methods and Results:

Medicare beneficiaries hospitalized for an AMI (n=188 611) between 2008 and 2009 in 1088 hospitals in the United States were included in our cohort. We tested the association between hospital patterns of medical care quality (discharge planning care quality), …

Airway Obstruction In Congenital Central Hypoventilation Syndrome, Alexandra K Reverdin, Ricardo Mosquera, Giuseppe N Colasurdo, Cindy K Jon, Roya M Clements

Faculty, Staff and Student Publications

Congenital central hypoventilation syndrome (CCHS) is the failure of the autonomic system to control adequate ventilation while asleep with preserved ventilatory response while awake. We report a case of a patient with CCHS who presented with intrathoracic and extrathoracic airway obstruction after tracheostomy tube decannulation and phrenic nerve pacer placement. Nocturnal polysomnography (NPSG) revealed hypoxia, hypercapnia and obstructive sleep apnoea, which required bilevel positive airway pressure titration. Airway endoscopy demonstrated tracheomalacia and paretic true vocal cords in the paramedian position during diaphragmatic pacing. Laryngeal electromyography demonstrated muscular electrical impulses that correlated with diaphragmatic pacer settings. Thus, we surmise that the …

Ultraviolet Radiation, Aging And The Skin: Prevention Of Damage By Topical Camp Manipulation, Alexandra Amaro-Ortiz, Betty Yan, John A. D’Orazio

Markey Cancer Center Faculty Publications

Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. …

Importance Of Cbct Setup Verification For Optical-Guided Frameless Radiosurgery., Lei Fu, Harold Perera, Xiao Ying, Yan Yu

Department of Medical Genetics Faculty Papers

The purpose of this study is to quantify the discrepancy between optical guidance platform (OGP) frameless localization system (Varian) and Trilogy on-board imaging (OBI) system (Varian) for setting up phantom and stereotactic radiosurgery (SRS) patient; and to determine whether cone-beam CT (CBCT) is necessary for OGP patient setup, and compare CBCT and orthogonal kV-kV in term of their verification capability. Three different phantoms were used in the study: a custom-made phantom, a Penta-Guide phantom, and a RANDO phantom. Five patients using both OGP and CBCT setup and 14 patients using CBCT setup alone were analyzed. One patient who had big …

Targeting Lactate Dehydrogenase-A Inhibits Tumorigenesis And Tumor Progression In Mouse Models Of Lung Cancer And Impacts Tumor-Initiating Cells, Han Xie, Jun-Ichi Hanai, Jian-Guo Ren, Lev Kats, Kerri Burgess, Parul Bhargava, Sabina Signoretti, Julia Billiard, Kevin J. Duffy, Aaron Grant, Xiaoen Wang, Pawel Lorkiewicz, Sabrina Schatzman, Michael Bousamra, Andrew N. Lane, Richard M. Higashi, Teresa W-M Fan, Pier Paolo Pandolfi, Vikas P. Sukhatme, Pankaj Seth

Toxicology and Cancer Biology Faculty Publications

The lactate dehydrogenase-A (LDH-A) enzyme catalyzes the interconversion of pyruvate and lactate, is upregulated in human cancers, and is associated with aggressive tumor outcomes. Here we use an inducible murine model and demonstrate that inactivation of LDH-A in mouse models of NSCLC driven by oncogenic K-RAS or EGFR leads to decreased tumorigenesis and disease regression in established tumors. We also show that abrogation of LDH-A results in reprogramming of pyruvate metabolism, with decreased lactic fermentation in vitro, in vivo, and ex vivo. This was accompanied by reactivation of mitochondrial function in vitro, but not in vivo …

Volume Of Carotid Artery Ulceration As A Predictor Of Cardiovascular Events, Mariya Kuk, Thapat Wannarong, Vadim Beletsky, Grace Parraga, Aaron Fenster, J David Spence

Medical Biophysics Publications

BACKGROUND AND PURPOSE: Previous studies have shown the presence of ulceration in atherosclerotic plaque either by categorizing the plaque as complex (irregular morphology with ulcers) or smooth or by quantifying the number of ulcers observed in a specific region of interest. The aim of this study was to quantify carotid total ulcer volume by 3-dimensional ultrasound to investigate the relationship of total ulcer volume to vascular events (strokes, transient ischemic attack, myocardial infarction, revascularization, or death because of cardiovascular reasons).

METHODS: In total, 349 at-risk subjects provided written informed consent to carotid 3-dimensional ultrasound and were analyzed for ulcerations. Ulcer …

Genomics Into Healthcare: The 5th Pan Arab Human Genetics Conference And 2013 Golden Helix Symposium., Paolo Fortina, Najib Al Khaja, Mahmoud Taleb Al Ali, Abdul Rezzak Hamzeh, Pratibha Nair, Federico Innocenti, George P. Patrinos, Larry J. Kricka

Department of Cancer Biology Faculty Papers

The joint 5th Pan Arab Human Genetics conference and 2013 Golden Helix Symposium, "Genomics into Healthcare" was coorganized by the Center for Arab Genomic Studies (http://www.cags.org.ae) in collaboration with the Golden Helix Foundation (http://www.goldenhelix.org) in Dubai, United Arab Emirates from 17 to 19 November, 2013. The meeting was attended by over 900 participants, doctors and biomedical students from over 50 countries and was organized into a series of nine themed sessions that covered cancer genomics and epigenetics, genomic and epigenetic studies, genomics of blood and metabolic disorders, cytogenetic diagnosis and molecular profiling, next-generation sequencing, consanguinity and hereditary diseases, clinical genomics, …

Clinically Relevant Interactions Between Newer Antidepressants And Second-Generation Antipsychotics, Edoardo Spina, Jose De Leon

Psychiatry Faculty Publications

INTRODUCTION: Combinations of newer antidepressants and second-generation antipsychotics (SGAs) are frequently used by clinicians. Pharmacokinetic drug interaction (PK DI) and poorly understood pharmacodynamic (PD) drug interaction (PD DI) can occur between them.

AREAS COVERED: This paper comprehensively reviews PD DI and PK DI studies.

EXPERT OPINION: More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to …

University Students And The Risk Of Hiv And Other Sexually Transmitted Infections In Uganda: The Crane Survey., George W. Rutherford, Andrew Anglemyer, Danstan Bagenda, Michael Muyonga, Christina P. Lindan, Joseph L. Barker, Lisa Johnston, Wolfgang Hladik

Journal Articles: Epidemiology

Adolescents and young adults are at high risk of human immunodeficiency virus (HIV) infection in sub-Saharan Africa. Previous reports have found that university students in Africa comprise a sexually active population, although the prevalence of HIV or sexually transmitted infections (STI) has not been measured. We conducted a cross-sectional survey of students from five large universities in Kampala, Uganda, using respondent-driven sampling. We asked students to complete behavioral questionnaires and provide biological samples to test for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, and bacterial vaginosis. We enrolled 649 students and obtained interpretable data from 640. Around 50% …

Prostate Cancer: Alcohol, Cancer And 5Α-Reductase Inhibitors-Is There A Link?, Leonard G Gomella

Department of Urology Faculty Papers

Two major trials have been performed to determine the effect of 5α-reductase inhibitors on subsequent diagnoses of prostate cancer. Both trials showed that high alcohol intake significantly increased prostate cancer risk among men allocated to the treatment arms. The recommendation that patients eliminate alcohol when taking 5α-reductase inhibitors seems appropriate.

Lean Body Mass May Explain Apparent Racial Differences In Carotid Intima-Media Thickness In Obese Children., Shahryar M. Chowdhury, Melissa H. Henshaw, Brad Friedman, J Philip Saul, Girish S. Shirali, Janet Carter, Bryana M. Levitan, Tom Hulsey

Manuscripts, Articles, Book Chapters and Other Papers

Background: Racial differences in carotid intima-media thickness (cIMT) have been suggested to be associated with the disproportionally high prevalence of cardiovascular disease in black adults. The objective of this study was to evaluate the effects of cardiovascular risk factors on the racial differences seen in cIMT in obese children.

Methods: Obese subjects aged 4 to 21 years were recruited prospectively. Height, weight, blood pressure, fasting insulin, glucose, lipid panel, high-sensitivity C-reactive protein, and body composition by dual-energy x-ray absorptiometry were obtained. B-mode carotid imaging was analyzed by a single blinded physician.

Results: A total of 120 subjects (46 white, 74 …

A Refresher On Tourette Syndrome., James R. Batterson, Shayla Sullivant, Jean-Baptist Lepichon, Christy Kleinsorge, Sandy Price, Stephanie Andrews

Manuscripts, Articles, Book Chapters and Other Papers

Tourette Syndrome (TS) is recognized as a more common neurodevelopmental disorder than once thought. In this article we present an update on TS including the DSM-5 revised criteria, new findings in the genetics of TS, treatment advances such as new medications for tics and the use of new tools including Cognitive Behavioral Intervention for Tics (CBIT). We also explore supportive services for the ongoing care of patients using nursing education and family therapy.

Pharmacologic Suppression Of Jak1/2 By Jak1/2 Inhibitor Azd1480 Potently Inhibits Il-6-Induced Experimental Prostate Cancer Metastases Formation., Lei Gu, Pooja Talati, Paraskevi Vogiatzi, Ana L Romero-Weaver, Junaid Abdulghani, Zhiyong Liao, Benjamin E. Leiby, David T. Hoang, Tuomas Mirtti, Kalle Alanen, Michael Zinda, Dennis Huszar, Marja T. Nevalainen

Department of Medical Oncology Faculty Papers

Metastatic prostate cancer is lethal and lacks effective strategies for prevention or treatment, requiring novel therapeutic approaches. Interleukin-6 (IL-6) is a cytokine that has been linked with prostate cancer pathogenesis by multiple studies. However, the direct functional roles of IL-6 in prostate cancer growth and progression have been unclear. In the present study, we show that IL-6 is produced in distant metastases of clinical prostate cancers. IL-6-activated signaling pathways in prostate cancer cells induced a robust 7-fold increase in metastases formation in nude mice. We further show that IL-6 promoted migratory prostate cancer cell phenotype, including increased prostate cancer cell …

Thermal Dosimetry Characteristics Of Deep Regional Heating Of Non-Muscle Invasive Bladder Cancer., Titania Juang, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Yu Yuan, Shiva K Das, Mark W Dewhirst, Brant A Inman, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: The aim of this paper is to report thermal dosimetry characteristics of external deep regional pelvic hyperthermia combined with intravesical mitomycin C (MMC) for treating bladder cancer following transurethral resection of bladder tumour, and to use thermal data to evaluate reliability of delivering the prescribed hyperthermia dose to bladder tissue.

MATERIALS AND METHODS: A total of 14 patients were treated with MMC and deep regional hyperthermia (BSD-2000, Sigma Ellipse or Sigma 60). The hyperthermia objective was 42° ± 2 °C to bladder tissue for ≥40 min per treatment. Temperatures were monitored with thermistor probes and recorded values were used …