Digital Commons Network^™

A Pilot Academic-Community Partnership To Advance The D.C. Healthy Schools Act, Nisha Narayanan, Jonathan Tatum, Margarita Ramos, Jessica Kim, Nisha Punatar, Michele L. Mietus-Snyder

GW Research Days 2014

No abstract provided.

Thiamine Pyrophosphokinase Deficiency Causes A Leigh Disease Like Phenotype In A Sibling Pair: Identification Through Whole Exome Sequencing And Management Strategies, Jamie L. Fraser, Adeline Vanderver, Sandra Yang, Taeun Chang, Laura Cramp, Gilbert Vezina, Uta Lichter-Konecki, Kristina Cusmano-Ozog, Patroula Smpokou, Kimberly A. Chapman, Dina Zand

Neurology Faculty Publications

We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of previously lost milestones. The diagnosis of TPK deficiency was difficult due to inconsistent biochemical and diagnostic parameters, rapidity of clinical demise and would not have been made in a timely manner without the use of whole exome sequencing. Molecular diagnosis allowed for attempt at dietary modification with cofactor supplementation …

Children's Hospital Association Consensus Statements For Comorbidities Of Childhood Obesity, Elizabeth Estrada, Ihuoma Eneli, Sarah Hampl, Michele L. Mietus-Snyder, Nazrat Mirza, Erinn Rhodes, Brooke Sweeney, Lydia Tinjaero-Deck, Susan J. Woolford, Stephen J. Pont

Pediatrics Faculty Publications

Background: Childhood obesity and overweight affect approximately 30% of US children. Many of these children have obesity-related comorbidities, such as hypertension, dyslipidemia, fatty liver disease, diabetes, polycystic ovary syndrome (PCOS), sleep apnea, psychosocial problems, and others. These children need routine screening and, in many cases, treatment for these conditions. However, because primary care pediatric providers (PCPs) often are underequipped to deal with these comorbidities, they frequently refer these patients to subspecialists. However, as a result of the US pediatric subspecialist shortage and considering that 12.5 million children are obese, access to care by subspecialists is limited. The aim of this …

Working Together For Global Health Goals: The United States Agency For International Development And Faith-Based Organizations, Clydette L. Powell

Pediatrics Faculty Publications

For many years, and before the term “FBO” was used for faith-based organizations, the United States Agency for International Development (USAID) has supported the work of FBOs in global health and development. The Agency has long recognized the impact of FBOs within that development space, because these organizations are often well positioned to reach the hard-to-reach and to go the last mile because of their strong ties to the community. Moreover, FBOs deliver a substantial percentage of the health services in some developing countries. Faith partners, whether Catholic, Protestant, Buddhist, Hindu, Muslim, or other, have an important role to play …

Proposed Guidelines For The Diagnosis And Management Of Methylmalonic And Propionic Acidemia., Matthias R Baumgartner, Friederike Hörster, Carlo Dionisi-Vici, Goknur Haliloglu, Daniela Karall, Kimberly A. Chapman, +19 Additional Authors

Pediatrics Faculty Publications

Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~ 1:100'000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA …

Aspirin Use And Knowledge In The Community: A Population- And Health Facility Based Survey For Measuring Local Health System Performance., Gregory A Roth, Catherine W. Gillespie, Ali A Mokdad, Danny D Shen, David W Fleming, Andy Stergachis, Christopher J L Murray, Ali H Mokdad

Pediatrics Faculty Publications

BACKGROUND: Little is known about the relationship between cardiovascular risk, disease and actual use of aspirin in the community.

METHODS: The Measuring Disparities in Chronic Conditions (MDCC) study is a community and health facility-based survey designed to track disparities in the delivery of health interventions for common chronic diseases. MDCC includes a survey instrument designed to collect detailed information about aspirin use. In King County, WA between 2011 and 2012, we surveyed 4633 white, African American, or Hispanic adults (45% home address-based sample, 55% health facility sample). We examined self-reported counseling on, frequency of use and risks of aspirin for …

A Systematic Review And Meta-Analysis Of Tobacco Use And Prostate Cancer Mortality And Incidence In Prospective Cohort Studies, F. Islami, D. M. Moreira, P. Boffetta, S. J. Freedland

Journal Articles

Context: An association between tobacco smoking and prostate cancer (PCa) incidence and mortality was suggested in an earlier meta-analysis of 24 prospective studies in which dose-response associations and risks per unit of tobacco use were not examined. Objective: We investigated the association between several measures of tobacco use and PCa mortality (primary outcome) and incidence (secondary outcome) including dose-response association. Evidence acquisition: Relevant articles from prospective studies were identified by searching the PubMed and Web of Science databases (through January 21, 2014) and reference lists of relevant articles. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using …

Cigarette Smoking Is Associated With An Increased Risk Of Biochemical Disease Recurrence, Metastasis, Castration-Resistant Prostate Cancer, And Mortality After Radical Prostatectomy: Results From The Search Database, D. M. Moreira, W. J. Aronson, M. K. Terris, C. J. Kane, C. L. Amling, M. R. Cooperberg, P. Boffetta, S. J. Freedland

Journal Articles

BACKGROUND: The current study was conducted to analyze the association between cigarette smoking and metastasis (the primary outcome) as well as time to biochemical disease recurrence (BCR), metastasis, castration-resistant prostate cancer (CRPC), and prostate cancer-specific and overall mortality (secondary outcomes) after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital cohort. METHODS: A retrospective analysis was performed of 1450 subjects for whom smoking status was available from preoperative notes. Analysis of baseline characteristics by smoking status was performed using the chi-square and rank sum tests. The association between smoking status and time to the event was analyzed …

Acute Mesenteric Ischemia: A Sequela Of Abdominal Aortography, S. Kedia, V. R. Bhatt, A. Koirala, S. Murukutla, J. Rijal, S. Pant, M. A. Wrzolek, A. Gottesman

Journal Articles

The use of abdominal angiography and transcatheter embolization has increased rapidly in the last few decades. Although improvement in angiographic techniques has made the procedure safe, ischemic colitis is a rare but potentially dreadful complication. We report a case of a 51-year-old woman who developed ischemic colitis following aortography, demonstrating that such angiographic studies may produce substantial morbidity.

Breast Cancer And Aging: Results Of The U13 Conference Breast Cancer Panel, M. F. Barginear, H. Muss, G. Kimmick, C. Owusu, E. Mrozek, A. Shahrokni, K. Ballman, A. Hurria

Journal Articles

Breast cancer is predominantly a disease of older women, yet there is a knowledge gap due to the persisting misalignment between the age distribution of women with breast cancer and the age distribution of participants in clinical trials. The purpose of this report is to state the U13 conference breast cancer panel's recommendations regarding therapeutic clinical trials that will fill gaps in knowledge regarding the care of older patients with breast cancer. The U13 conference was a collaboration between the Cancer and Aging Research Group and the National Institute on Aging and the National Cancer Institute (NCI). Clinical trials should …

Effects Of Pulmonary Rehabilitation On Fatigue Severity Scale In Patients With Lung Disease, A. Talwar, S. Sahni, S. John, S. Verma, J. Cardenas-Garcia, N. Kohn

Journal Articles

INTRODUCTION: Fatigue is a known symptom of advanced lung disease and impacts quality of life and psychological health. Many of these patients undergo pulmonary rehabilitation as part of their therapy. Understanding the effect of pulmonary rehabilitation on fatigue in these patients is important, as one may be able to design more focused rehabilitation programs. The aim of this study is to evaluate the effect of pulmonary rehabilitation on fatigue as measured by the Fatigue Severity Scale (FSS) in patients with advanced lung disease. MATERIAL AND METHODS: Patients were enrolled in a standardized 6 week pulmonary rehabilitation program. They were asked …

The Gut Microbiota Influences Blood-Brain Barrier Permeability In Mice, V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, B. T. Volpe, B. Diamond, S. Pettersson, +8 Additional Authors

Journal Articles

Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to …

Histological Healing Favors Lower Risk Of Colon Carcinoma In Extensive Ulcerative Colitis, B. I. Korelitz, K. Sultan, M. Kothari, L. Arapos, J. Schneider, G. Panagopoulos

Journal Articles

AIM: To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer (CC) or high grade dysplasia (HGD). METHODS: This is a single center (Lenox Hill Hospital) retrospective cohort and descriptive study of extensive ulcerative colitis (UC) for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis. Data analyzed included: duration of UC, date of diagnosis of (CC) or (HGD), number of surveillance colonoscopies, and biopsies showing histological inflammation and its …

Critical Periods Of Increased Fetal Vulnerability To A Maternal High Fat Diet, M. D. Plata, L. Williams, Y. Seki, K. Hartil, H. Kaur, C. L. Lin, A. Fiallo, A. S. Glenn, E. B. Katz, P. M. Vuguin, +2 Additional Authors

Journal Articles

Background: Fetal adaptations to high fat (HF) diet in utero (IU) that may predispose to Metabolic Syndrome (MetS) in adulthood include changes in fetal hepatic gene expression. Studies were performed to determine whether maternal exposure to HF diet at different stages during pregnancy had different effects on the fetus, including hepatic gene expression. Methods: Female wild type mice were fed either a HF or breeding chow (C) for 2 wks prior to mating. The experimental groups were composed of embryonic day (e) 18.5 fetuses obtained from WT female mice that were fed HF (HF, 35.5% fat) or breeding chow (C, …

In Utero Exposure To A Maternal High-Fat Diet Alters The Epigenetic Histone Code In A Murine Model, M. A. Suter, J. Ma, P. M. Vuguin, K. Hartil, A. Fiallo, R. A. Harris, M. J. Charron, K. M. Aagaard

Journal Articles

OBJECTIVE: Data from animal models show that in utero exposure to a maternal high-fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering the risk of adult disease. Because mice heterozygous for the Glut4 gene (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to an HFD in utero, we sought to analyze the genome-wide epigenetic changes that occur in the fetal liver in susceptible offspring. …

Bisphenol A Exposure Is Associated With Decreased Lung Function, A. J. Spanier, E. K. Fiorino, L. Trasande

Journal Articles

Objective To examine the associations of bisphenol A (BPA) exposure with lung function measures and exhaled nitric oxide (FeNO) in children. Study design We performed a cross-sectional analysis of a subsample of US children age 6-19 years who participated in the 2007-2010 National Health and Nutrition Examination Survey. We assessed univariate and multivariable associations of urinary BPA concentration with the predicted pulmonary function measures for age, sex, race/ethnicity and height (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], forced expiratory flow 25%-75%, and FEV1 divided by FVC) and with FeNO. Results Exposure and outcome data were available …

Maternal Magnesium Deficiency In Mice Leads To Maternal Metabolic Dysfunction And Altered Lipid Metabolism With Fetal Growth Restriction, M. Gupta, M. H. Solanki, P. K. Chatterjee, X. Y. Xue, A. Roman, N. Desai, B. Rochelson, C. N. Metz

Journal Articles

Inadequate magnesium (Mg) intake is a widespread problem, with over 50% of women of reproductive age consuming less than the Recommended Dietary Allowance (RDA). Because pregnancy increases the requirement for Mg and the beneficial effects of magnesium sulfate for preeclampsia/eclampsia and fetal neuroprotection are well described, we examined the outcomes of Mg deficiency during pregnancy. Briefly, pregnant Swiss Webster mice were fed either control or Mg-deficient diets starting on gestational day (GD) 6 through euthanasia on GD17. Mg-deficient dams had significantly reduced weight gain and higher plasma adipokines, in the absence of inflammation. Livers of Mg-deficient dams had significantly higher …

Diabetes Prevention Of The Hispanic Population: Health Lifestyle Management Education At Our Lady Of Guadelupe Clinic In Worthington, Minnesota., Laura J. Bade, Amber E. Dionne, Erin A. Manoles, Lisa R. Milbrant

All Electronic Theses and Dissertations

The purpose of this research study was to utilize educational tools on healthy lifestyles in order to promote Diabetes Mellitus Type II (DMII) prevention in the Hispanic population in Worthington, Minnesota. Hispanic adults are 1.7 times more likely to be diagnosed with Diabetes Mellitus (DM) by a physician than non-Hispanics. Since DMII is a preventable disease, education focused on nutrition and activity will help prevent diabetes and its associated comorbidities. An educational seminar was conducted at Our Lady of Guadalupe in Worthington, Minnesota. A pretest/posttest was administered to assess the knowledge gained with the utilization of the educational tool. Despite …

Risk Factors For Gi Adverse Events In A Phase Iii Randomized Trial Of Bevacizumab In First-Line Therapy Of Advanced Ovarian Cancer: A Gynecologic Oncology Group Study, R. A. Burger, M. F. Brady, M. A. Bookman, B. J. Monk, J. L. Walker, H. D. Homesley, J. Fowler, S. C. Rubin, N. Katsumata, S. X. Liang, +4 Additional Authors

Journal Articles

Purpose To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Patients and Methods Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade 2 perforation, fistula, necrosis, or hemorrhage. Results Of 1,873 patients enrolled, 1,759 (94%) …

25-Hydroxyvitamin D And Cardiovascular Disease In Patients With Systemic Lupus Erythematosus: Data From A Large International Inception Cohort, A. Lertratanakul, P. Wu, A. Dyer, M. Urowitz, D. Gladman, C. Aranow, J. Font, R. Van Vollenhoven, T. Stoll, R. Ramsey-Goldman, +20 Additional Authors

Journal Articles

Objective. An association between 25-hydroxyvitamin D (25[ OH] D; vitamin D) deficiency and increased cardiovascular (CV) risk factors and CV disease (CVD) has been shown in general population studies. Vitamin D deficiency has been noted in systemic lupus erythematosus (SLE), and CVD is a major cause of morbidity and mortality in SLE. The objectives of this study were to estimate the associations of 25(OH) D levels with CV risk factors and to determine whether low baseline 25(OH) D levels predict future CV events in patients participating in an international inception cohort. Methods. Data were collected on 890 participants, including demographics, …

The Treatment-Naive Microbiome In New-Onset Crohn's Disease, D. Gevers, S. Kugathasan, L. A. Denson, Y. Vazquez-Baeza, W. Van Treuren, B. Y. Ren, E. Schwager, D. Knights, J. Markowitz, R. J. Xavier, +22 Additional Authors

Journal Articles

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with …

Effectiveness Of Lurasidone In Schizophrenia Or Schizoaffective Patients Switched From Other Antipsychotics: A 6-Month, Open-Label, Extension Study, L. Citrome, P. J. Weiden, J. P. Mcevoy, C. U. Correll, J. Cucchiaro, J. Hsu, A. Loebel

Journal Articles

Objective. To evaluate the long-term safety and tolerability of lurasidone in schizophrenia and schizoaffective disorder patients switched to lurasidone. Method. Patients in this multicenter, 6-month open-label, flexible-dose, extension study had completed a core 6-week randomized trial in which clinically stable, but symptomatic, outpatients with schizophrenia or schizoaffective disorder were switched to lurasidone. Patients started the extension study on treatment with the same dose of lurasidone taken at study endpoint of the 6-week core study; following this, lurasidone was flexibly dosed (40-120 mg/day), if clinically indicated, starting on Day 7 of the extension study. The primary safety endpoints were the proportion …

Genetics Of Rheumatoid Arthritis Contributes To Biology And Drug Discovery, Y. Okada, D. Wu, G. Trynka, T. Raj, C. Terao, K. Ikari, Y. Kochi, K. Ohmura, P. K. Gregersen, R. M. Plenge, +85 Additional Authors

Journal Articles

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating approximately 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico …

Integration Of Sequence Data From A Consanguineous Family With Genetic Data From An Outbred Population Identifies Plb1 As A Candidate Rheumatoid Arthritis Risk Gene, Y. Okada, D. Diogo, J. D. Greenberg, F. Mouassess, W. A. L. Achkar, R. S. Fulton, J. C. Denny, N. Gupta, P. K. Gregersen, R. M. Plenge, +38 Additional Authors

Journal Articles

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G. C (p.G755R) mutation at the PLB1 gene on …

Celiac Disease: Advances In Diagnostic Testing?, Alicia A. Hanson

Physician Assistant Scholarly Project Posters

• Celiac disease (CD) is a gluten-sensitivity enteropathy that occurs in genetically susceptible individuals upon ingestion of gluten and resolves when gluten is withdrawn from one’s diet.

• Serological markers play a major role in the diagnosis of celiac disease, however a small intestinal biopsy is currently the gold standard in symptomatic individuals.

• The purpose of this study was to determine if serological testing alone is sufficient to confirm the diagnosis of CD and therefore eliminate the need for a biopsy.

• The review of literature explored studies that compared small intestinal biopsy with different serological testing in males …

Can Follow Up Phone Calls Decrease Complications Of Chemotherapy Toxicities In Adults?, Maire M. Blankenship

Doctor of Nursing Practice Technical Reports

Approximately 22% of all cancer patients in the United States receive chemotherapy. Older adults account for 60 % of new cancer diagnoses in the United States. The aging process is associated with comorbidities that potentially can increase toxicities associated with chemotherapy. These include coronary artery disease, hypertension, and diabetes. Monitoring for toxicities during treatment and intervening when needed allows patients to move forward in their treatment plan. Interruptions in the treatment plan have the potential to adversely affect treatment goals. The purpose of this study is to determine if patients receiving phone calls on predetermined days had fewer days of …

The Necessity Of Leisure And Physical Activity, Alison Clarke, Stephanie Goode

Case Studies from Age in Action

Educational Objectives

1. Explain the value and benefit of physical and leisure activity across the lifespan, regardless of physical limitations.

2. Identify barriers to participation in physical and leisure activity.

3. Discuss strategies to engage and maintain physical and recreational activity participation.

Metabolic Effects Of Acute Thiamine Depletion Are Reversed By Rapamycin In Breast And Leukemia Cells, Shuqian Liu, Sumitra Miriyala, Mignon A. Keaton, Craig T. Jordan, Christina Wiedl, Daret K. St. Clair, Jeffrey A. Moscow

Pediatrics Publications

Thiamine-dependent enzymes (TDEs) control metabolic pathways that are frequently altered in cancer and therefore present cancer-relevant targets. We have previously shown that the recombinant enzyme thiaminase cleaves and depletes intracellular thiamine, has growth inhibitory activity against leukemia and breast cancer cell lines, and that its growth inhibitory effects were reversed in leukemia cell lines by rapamycin. Now, we first show further evidence of thiaminase therapeutic potential by demonstrating its activity against breast and leukemia xenografts, and against a primary leukemia xenograft. We therefore further explored the metabolic effects of thiaminase in combination with rapamycin in leukemia and breast cell lines. …

Ceftriaxone Potentiates Warfarin Activity Greater Than Other Antibiotics In The Treatment Of Urinary Tract Infections, Lindsay M. Saum, Ryan P. Balmat

Scholarship and Professional Work – COPHS

Background: The cephalosporin class has been associated with an increased risk of bleeding among elderly patients receiving warfarin. Urinary tract infections (UTI) are the most prevalent infection in elderly patients.

Objective: To determine the extent of interaction between antibiotics used in the treatment of UTI, particularly specific cephalosporins and warfarin.

Methods: A retrospective chart review was conducted on chronic warfarin patients with a diagnosis of UTI treated with ceftriaxone, a first-generation cephalosporin, penicillin, or ciprofloxacin. The primary outcome was the comparison of the extent of international normalized ratio (INR) change from baseline between each antibiotic group.

Results: The ceftriaxone group …

Influence Of Diet And Obesity On Copd Development And Outcomes, Corrine K. Hanson, Erica P. Rutten, Emiel F.M. Wouters, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern. Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest. Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases. Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and …