Diseases Commons^™

The Scripps Research Institute Summer Undergraduate Research Fellowship, Ezana Assefa

Trick to the Treat of Internships and Research

This program is a 10-week internship designed for undergraduates interested in the scientific field to engage in current research. Students have the option of requesting to work under three mentors, one of which they will be paired. Students will work in the lab with the principal investigator and other members of the lab. Along with working in the lab, students in the program will also attend bi-weekly talks/lectures from researchers, grad students, and professionals at TSRI as well as participating in two presentations and a final poster or oral presentation.

A Proteogenomic Approach To Understanding Myc Function In Metastatic Medulloblastoma Tumors., Jerome A Staal, Yanxin Pei, Brian R. Rood

Pediatrics Faculty Publications

Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite …

Ionis Phase I Huntington’S Disease Trial At Halfway Mark: 'No Surprises So Far' Means Good News, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

A Multistep Approach To Single Nucleotide Polymorphism–Set Analysis: An Evaluation Of Power And Type I Error Of Gene-Based Tests Of Association After Pathway-Based Association Tests, Alessandra Valcarcel, Kelsey Griinde, Kaitlyn Cook, Alden Green, Nathan L. Tintle

Faculty Work Comprehensive List

The aggregation of functionally associated variants given a priori biological information can aid in the discovery of rare variants associated with complex diseases. Many methods exist that aggregate rare variants into a set and compute a single p value summarizing association between the set of rare variants and a phenotype of interest. These methods are often called gene-based, rare variant tests of association because the variants in the set are often all contained within the same gene. A reasonable extension of these approaches involves aggregating variants across an even larger set of variants (eg, all variants contained in genes within …

Evolving Healthy Populations, Nina H. Fefferman

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Influence Of Preventive Measures To Eradicate The Spread Of The Zika Arbovirus, Pradyuta Padmanabhan, Padmanabhan Seshaiyer

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Impact Of Devil Facial Tumor Disease On The Tasmanian Devil Age Structure, Christopher Bruno, Vashni Vasquez

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Kinetics Of Type 1 Interferons During Influenza Virus Infection, Margaret A. Myers

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Optimal Control Of Vaccination Rate In An Epidemiological Model Of Clostridium Difficile Transmission, Brittany Stephenson

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Bill Of Rights: What Does It Say?, The U.S. National Archives And Records Administration

Pandemic Response and Religion in the USA: Law and Public Policy

No abstract provided.

Noncanonical Sqstm1/P62-Nrf2 Pathway Activation Mediates Proteasome Inhibitor Resistance In Multiple Myeloma Cells Via Redox, Metabolic And Translational Reprogramming., Irene Riz, Teresa S Hawley, Jeffrey W Marsal, Robert G Hawley

Anatomy and Regenerative Biology Faculty Publications

Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its positive regulator, the autophagy receptor sequestosome 1 (SQSTM1)/p62. The eukaryotic translation initiation factor gene EIF4E3 was among the Nrf2 target genes upregulated in LP-1/Cfz cells, suggesting existence …

Testing Modeling Assumptions In The West Africa Ebola Outbreak, Matthew C. Ingram, Keith Burghardt, Christopher Verzijl, Junming Huang, Binyang Song, Marie-Pierre Hasne

Political Science Faculty Scholarship

The Ebola virus in West Africa has infected almost 30,000 and killed over 11,000 people. Recent models of Ebola Virus Disease (EVD) have often made assumptions about how the disease spreads, such as uniform transmissibility and homogeneous mixing within a population. In this paper, we test whether these assumptions are necessarily correct, and offer simple solutions that may improve disease model accuracy. First, we use data and models of West African migration to show that EVD does not homogeneously mix, but spreads in a predictable manner. Next, we estimate the initial growth rate of EVD within country administrative divisions and …

Reducing Disparities By Way Of A Cancer Disparities Research Training Program, Lee S. Caplan, Tabia H. Akintobi, Tandeca K. Gordon, Tiffany Zellner, Selina A. Smith, Daniel S. Blumenthal

Journal of Health Disparities Research and Practice

Background: For minority populations, there is a continuing disparity in the burden of death and illness from cancer. Research to address this disparity should be conducted by investigators who can best understand and address the needs of culturally diverse communities. However, minorities are under-represented in health-related research. The goal of this project was to develop and evaluate an approach to motivating and preparing master’s degree students for careers dedicated to cancer disparities research.

Method: A Cancer Disparities Research Training Program (CDRTP) was initiated in 2010. The program consists of coursework, practicum experiences, and research opportunities. Assessment of the curriculum is …

Acceptability And Feasibility Of Web-Based Diabetes Instruction For Latinos With Limited Education And Computer Experience, Sharon A. Fitzgerald, Victor E. Martinez-Zavala, Kenia Yazmin Reyna Blanco, A Paula Cupertino, Mugur V. Geana, Edward F. Ellerbeck

Journal of Health Disparities Research and Practice

Introduction: The internet offers an important avenue for developing diabetes self-management skills, but many Latinos have limited experience with computer-based instruction.

Objective: To evaluate the feasibility and acceptability of delivering a web-based diabetes education program in a computer classroom for Spanish-speaking Latinos.

Methods: Spanish-speaking Latinos (n=26) attended two classroom sessions to learn computer skills while navigating a web-based diabetes education platform. Diabetes knowledge was assessed before and after the intervention; structured interviews were completed to assess program acceptability.

Results: Half of participants (50%) had not previously used a computer. Post-intervention, diabetes knowledge improved significantly (p=.001). The majority of participants (86%) …

Feasibility Of A Community-Based Sickle Cell Trait Testing And Counseling Program, Ashley Housten, Regina Abel, Terianne Lindsey, Allison King

Journal of Health Disparities Research and Practice

Background: Sickle cell trait (SCT) screening is required at birth in the United States; however, adults rarely know their SCT status prior to having children.

Purpose: Assess feasibility of a community-based SCT education and testing intervention.

Methods: Participants were recruited from eight community sites to complete an educational program and offered a hemoglobin analysis. A genetic counselor met individually with participants to discuss lab results.

Results: Between July 14, 2010 and May 31, 2012, 637 participants completed the educational program. Five hundred seventy (89.5%) provided a blood sample, and 61 (10.9%) had SCT or other hemoglobinopathies. The genetic counselor met …

Family Based Treatment For Adults With Anorexia Nervosa Using Insights From Neurobiology, The Center For Balanced Living

Learning Showcase 2016: A Celebration of Discovery, Transformation and Success

Anorexia Nervosa (AN) is a biologically-based brain disorder, which has the highest death rate of all mental illnesses. No effective treatments exist for adults with severe and enduring AN (5-7+ years). Brain imaging studies at University of California San Diego on AN temperament, cognition and eating show common traits related to neural function. The temperaments are characterized by increased trait anxiety and state anxiety related to food and eating, high incidence of co-morbid anxiety disorders, high punishment sensitivity and low reward reactivity, elevated intolerance of uncertainty and exaggerated harm avoidance (HA). HA is a multifaceted temperament trait that contains elements …

Electro-Chemotactic Fields Induce Cooperative Movement Of Cns Cells, Shawn Mishra, Stephen Redenti, Maribel Vazquez

Publications and Research

Vision loss in adults with Age Related Macular Degeneration (AMD) is attributed to damage of retinal photoreceptor cells that initiate vision by absorbing light. Mouse models have suggested that transplantation of precursor cells may be a novel approach to restore vision. This project uses a combination of electrotactic and chemotactic stimuli to promote and guide CNS cell migration within a microdevice model.

Temporal Trends In Care And Outcomes Of Patients Receiving Fibrinolytic Therapy Compared To Primary Percutaneous Coronary Intervention: Insights From The Get With The Guidelines Coronary Artery Disease (Gwtg-Cad) Registry, Ravi S. Hira, Deepak L. Bhatt, Gregg C. Fonarow, Paul A. Heidenreich, Christine Ju, Salim S. Virani, Biykem Bozkurt, Laura A. Petersen, Adrian F. Hernandez, Lee H. Schwamm

Office of the Provost

Background: Timely reperfusion after ST-elevation myocardial infarction (STEMI) improves survival. Guidelines recommend primary percutaneous coronary intervention (PPCI) within 90 minutes of arrival at a PCI-capable hospital. The alternative is fibrinolysis within 30 minutes for those in those for whom timely transfer to a PCI-capable hospital is not feasible.
Methods and Results: We identified STEMI patients receiving reperfusion therapy at 229 hospitals participating in the Get With the Guidelines-Coronary Artery Disease (GWTG-CAD) database (January 1, 2003 through December 31, 2008). Temporal trends in the use of fibrinolysis and PPCI, its timeliness, and in-hospital mortality outcomes were assessed. We also assessed predictors …

Sulfatase 2 Facilitates Lymphangiogenesis In Breast Cancer By Regulating Vegf-D., Chenfang Zhu, Xiaoliang Qi, Xin Zhou, Xin Nie, Yan Gu

Surgery Faculty Publications

In our previous studies, sulfatase 2 (Sulf2) was found to upregulate vascular endothelial growth factor-D (VEGF-D) expression in breast cancer. As VEGF-D plays an important role in lymphangiogenesis, we hypothesized that Sulf2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. To evaluate the functions of Sulf2 on lymphangiogenesis in breast cancer, proliferation, apoptosis, cell cycle, cell mobility and tube-formation of lymphatic endothelial cells (LECs) were measured in vitro. Lymphangiogenesis in nude mouse ears and breast cancer xenografts were examined in vivo. Furthermore, the expression levels of related signaling pathway genes were screened and verified in LECs. We found that Sulf2 …

Defining And Targeting Health Disparities In Chronic Obstructive Pulmonary Disease, Roy A. Pleasants, Isaretta L. Riley, David M. Mannino

Preventive Medicine and Environmental Health Faculty Publications

The global burden of chronic obstructive pulmonary disease (COPD) continues to grow in part due to better outcomes in other major diseases and in part because a substantial portion of the worldwide population continues to be exposed to inhalant toxins. However, a disproportionate burden of COPD occurs in people of low socioeconomic status (SES) due to differences in health behaviors, sociopolitical factors, and social and structural environmental exposures. Tobacco use, occupations with exposure to inhalant toxins, and indoor biomass fuel (BF) exposure are more common in low SES populations. Not only does SES affect the risk of developing COPD and …

Rationale And Design Of The Children's Oncology Group (Cog) Study Alte1621: A Randomized, Placebo-Controlled Trial To Determine If Low-Dose Carvedilol Can Prevent Anthracycline-Related Left Ventricular Remodeling In Childhood Cancer Survivors At High Risk For Developing Heart Failure., Saro H. Armenian, Melissa M. Hudson, Ming Hui Chen, Steven D. Colan, Lanie Lindenfeld, George Mills, Aida Siyahian, Sarah Gelehrter, Ha Dang, Wendy Hein, Daniel M M. Green, Leslie L. Robison, F Lennie Wong, Pamela S. Douglas, Smita Bhatia

Manuscripts, Articles, Book Chapters and Other Papers

Background: Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy …

Tgf-Β Signaling: New Insights Into Aortic Aneurysms, Sean E. Thatcher

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Kcnq2 Encephalopathy, John Millichap, Kristen Park, Tammy N. Tsuchida, Bruria Ben-Zeev, Lionel Carmant, On Behalf Of The Rikee Consortium

Neurology Faculty Publications

Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments.

Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients.

Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures …

Hiv-1 Integrates Widely Throughout The Genome Of The Human Blood Fluke Schistosoma Mansoni., Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H. Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I. Bukrinsky, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein. The appearance of strong stop and positive strand cDNAs indicated that virions fused to schistosome cells, the nucleocapsid internalized and the …

The Nih-Niaid Schistosomiasis Resource Center At The Biomedical Research Institute: Molecular Redux., James J Cody, Wannaporn Ittiprasert, André N Miller, Lucie Henein, Margaret M Mentink-Kane, Michael H. Hsieh

Urology Faculty Publications

Schistosomiasis remains a health burden in many parts of the world. The complex life cycle of Schistosoma parasites and the economic and societal conditions present in endemic areas make the prospect of eradication unlikely in the foreseeable future. Continued and vigorous research efforts must therefore be directed at this disease, particularly since only a single World Health Organization (WHO)-approved drug is available for treatment. The National Institutes of Health (NIH)-National Institute of Allergy and Infectious Diseases (NIAID) Schistosomiasis Resource Center (SRC) at the Biomedical Research Institute provides investigators with the critical raw materials needed to carry out this important research. …

Developing Nations And Disadvantaged Populations: How The 2009 H1n1 Influenza Pandemic Exacerbated Disparities And Inequities, Rebecca Lebeaux

Independent Study Project (ISP) Collection

The 2009 H1N1 influenza pandemic, although not as deadly or long lasting as initially projected, demonstrated that the world was and is ill prepared to handle a mass pandemic. As the first pandemic of the twenty-first century, the pandemic revealed global health insecurities and asymmetrical disease burdens for disadvantaged individuals and countries. This paper will analyze why both developing countries and disadvantaged individuals suffered disproportionately from the pandemic. Using the framework of structural violence, this paper will investigate how socioeconomic and political disparities encountered before and during the pandemic caused differential health, societal, political, and economic outcomes. These preexisting disparities …

Continuous Care In Complex Contexts: Access To Health Services For Noncommunicable Diseases Among Syrian Refugee Women In Jordanian Host Communities, Jennifer Ostrowski

Independent Study Project (ISP) Collection

This study examines how, when and where Syrian refugee women living in a host community in central Jordan access health services related to noncommunicable diseases. Noncommunicable diseases are the leading cause of death and disability worldwide, but can be effectively managed through timely treatment. Examining access to care for these diseases in the context of humanitarian emergencies, such as war and displacement, is particularly important because they require continuous care, which may be interrupted during emergencies, and because they can cause acute complications, which may be exacerbated by emergencies (WHO, 2016).

Previous studies indicate a high burden of NCDs among …

Hdqlife: Development And Assessment Of Health-Related Quality Of Life In Huntington Disease (Hd), N E Carlozzi, S G Schilling, J-S Lai, J S Paulsen, E A Hahn, J S Perlmutter, C A Ross, N R Downing, A L Kratz, M K Mccormack, M A Nance, K A Quaid, J C Stout, R C Gershon, R E Ready, J A Miner, S K Barton, S L Perlman, S M Rao, S Frank, I Shoulson, H Marin, M D Geschwind, P Dayalu, S M Goodnight, D Cella

Rowan-Virtua School of Osteopathic Medicine Departmental Research

PURPOSE: Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS …

Multi-Sector Analysis Of The Progress And Challenges Of Soil-Transmitted Helminth Eradication In Rural Udaipur, Jessica Ellis

Independent Study Project (ISP) Collection

India is home to 240 million children currently at risk of Soil-Transmitted Helminthiasis, which is spread via unclean water, soil, and food, and causes acute pain and malnutrition. While acknowledging the research debates over WASH and mass drug administration, this study seeks to identify the systemic multidisciplinary issues affecting STH elimination efforts in rural Udaipur. Twenty-three interviews were conducted in villages, government departments, NGOs, and medical sectors to identify the challenges within each approach to deworming, and their experiences with multi-sectoral collaboration. The most recurring issues across disciplines were need for invested local leadership, increase in health literacy of adults, …

Epigenetics Of Lipid Phenotypes, Sergi Sayols-Baixeras, Marguerite R. Irvin, Donna K. Arnett, Roberto Elosua, Stella W. Aslibekyan

Epidemiology and Environmental Health Faculty Publications

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay …