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Pomalidomide Reverses Gamma-Globin Silencing Through The Transcriptional Reprogramming Of Adult Hematopoietic Progenitors, B. M. Dulmovits, A. O. Appiah-Kubi, J. Papoin, M. He, Y. Al-Abed, S. Didier, M. Gould, S. Husain-Krautter, S. A. Singh, A. Vlachos, S. L. Allen, J. M. Lipton, J. M. Liu, L. Blanc, +7 Additional Authors

Journal Articles

Current therapeutic strategies for sickle cell anemia are aimed at reactivating fetal hemoglobin. Pomalidomide, a third-generation immunomodulatory drug, was proposed to induce fetal hemoglobin production by an unknown mechanism. Here, we report that pomalidomide induced a fetal-like erythroid differentiation program, leading to a reversion of gamma-globin silencing in adult human erythroblasts. Pomalidomide acted early by transiently delaying erythropoiesis at the BFU-E/CFU-E transition, but without affecting terminal differentiation. Further, the transcription networks involved in gamma-globin repression were selectively and differentially affected by pomalidomide including BCL11A, SOX6, IKZF1, KLF1, and LSD1. IKAROS (IKZF1), a known target of pomalidomide, was degraded by the …

High-Density Lipoprotein (Hdl) Counter-Regulates Serum Amyloid A (Saa)-Induced Spla(2)-Iie And Spla(2)-V Expression In Macrophages, S. Zhu, Y. Wang, W. Chen, W. Li, A. Wang, J. Li, H. Yang, K. J. Tracey, J. D'Angelo, H. Wang, +2 Additional Authors

Journal Articles

No abstract provided.

Cancer Beliefs And Cancer Screening Behaviors Among Low Income Chinese Immigrants – Implications For Culturally Relevant Interventions, Kam Man Kenny Kwong

Graduate School of Social Work Publications and Research

Objective: To effectively plan and provide culturally appropriate cancer education and screening services for low income Chinese immigrants, accurate disaggregated data are very much needed in understanding their cultural beliefs, attitudes, and practices toward cancer screening and education. This study explored the views of medically underserved Chinese immigrants in the United States and assessed their beliefs and attitudes toward the cause and prevention of breast, cervical, and prostate cancer, and their cancers screening behaviors.

Methods: Guided by both the Explanatory Model Interview Catalogue and the Health Belief Model, an exploratory research methodology was used. Narrative data from in-depth interviews and …

Increased Hepcidin In Transferrin-Treated Thalassemic Mice Correlates With Increased Liver Bmp2 Expression And Decreased Hepatocyte Erk Activation, H. Chen, T. Choesang, H. Li, S. Sun, P. Pham, W. Bao, M. Feola, M. Westerman, L. Blanc, Y. Z. Ginzburg, +4 Additional Authors

Journal Articles

Iron overload results in significant morbidity and mortality in beta-thalassemic patients. Insufficient hepcidin is implicated in parenchymal iron overload in beta-thalassemia and approaches to increase hepcidin have therapeutic potential. We have previously shown that exogenous apo-transferrin markedly ameliorates ineffective erythropoiesis and increases hepcidin expression in Hbb(th1/th1) (thalassemic) mice. We utilize in vivo and in vitro systems to investigate effects of exogenous apo-transferrin on Smad and ERK1/2 signaling, pathways that participate in hepcidin regulation. Our results demonstrate that apo-transferrin increases hepcidin expression in vivo despite decreased circulating and parenchymal iron concentrations and unchanged liver Bmp6 mRNA expression in thalassemic mice. Hepatocytes …

Effect Of The Normalized Prescription Isodose Line On The Magnitude Of Monte Carlo Vs. Pencil Beam Target Dose Differences For Lung Stereotactic Body Radiotherapy, D. Zheng, Q. Zhang, X. Liang, X. Zhu, V. Verma, S. Wang, S. Zhou

Journal Articles

© This work is licensed under a Creative Commons Attribution 3.0 Unported License. In lung stereotactic body radiotherapy (SBRT) cases, the pencil beam (PB) dose calculation algorithm is known to overestimate target dose as compared to the more accurate Monte Carlo (MC) algorithm. We investigated whether changing the normalized prescription isodose line affected the magnitude of MC vs. PB target dose differences. Forty-eight patient plans and twenty virtual-tumor phantom plans were studied. For patient plans, four alternative plans prescribed to 60%, 70%, 80%, and 90% isodose lines were each created for 12 patients who previously received lung SBRT treatments. Using …

Cytoplasmic, Full Length And Novel Cleaved Variant, Tblr1 Reduces Apoptosis In Prostate Cancer Under Androgen Deprivation, G. Daniels, X. Zhang, X. Zhong, L. Santiago, L. H. Wang, X. Wu, J. Y. Zhang, F. Liang, X. Li, P. Lee, +6 Additional Authors

Journal Articles

No abstract provided.

Rapamycin Attenuates Cardiac Fibrosis In Experimental Uremic Cardiomyopathy By Reducing Marinobufagenin Levels And Inhibiting Downstream Pro-Fibrotic Signaling, Steven T. Haller Phd, Yanling Yan Phd, Christopher A. Drummond Phd, Joe Xie Md, Jiang Tian Phd, David J. Kennedy Phd, Victoria Y. Shilova Phd, Zijian Xie Phd, Jiang Liu Phd, Christopher J. Cooper Md, Deepak Malhotra Md, Phd, Joseph I. Shapiro Md, Olga V. Fedorova Phd, Alexei Y. Bagrov Md, Phd

Pharmaceutical Science and Research

Background: Experimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K‐ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K‐ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway.

Methods and Results: Biosynthesis of MBG by cultured human JEG‐3 cells is initiated by CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 …

Differential Rna Expression Profile Of Skeletal Muscle Induced By Experimental Autoimmune Myasthenia Gravis In Rats, Henry J. Kaminski, Keiichi Himuro, Jumana Alshaikh, Bendi Gong, Georgiama Cheng, Linda L. Kusner

Neurology Faculty Publications

The differential susceptibility of skeletal muscle by myasthenia gravis (MG) is not well understood. We utilized RNA expression profiling of extraocular muscle (EOM), diaphragm (DIA), and extensor digitorum (EDL) of rats with experimental autoimmune MG (EAMG) to evaluate the hypothesis that muscles respond differentially to injury produced by EAMG. EAMG was induced in female Lewis rats by immunization with acetylcholine receptor purified from the electric organ of the Torpedo. Six weeks later after rats had developed weakness and serum antibodies directed against the AChR, animals underwent euthanasia and RNA profiling performed on DIA, EDL, and EOM. Profiling results were validated …

Protective Role Of Dietary Curcumin In The Prevention Of The Oxidative Stress Induced By Chronic Alcohol With Respect To Hepatic Injury And Antiatherogenic Markers, Ravi Varatharajalu, Mamatha Garige, Leslie C Leckey, Karina Reyes-Gordillo, Ruchi Shah, M. Raj Lakshman

Biochemistry and Molecular Medicine Faculty Publications

No abstract provided.

Attitudes And Factors Affecting Acceptability Of Self-Administered Cervicovaginal Sampling For Human Papillomavirus (Hpv) Genotyping As An Alternative To Pap Testing Among Multiethnic Malaysian Women., Mahirah Ma'som, Nirmala Bhoo-Pathy, Nazrila Hairizan Nasir, Jerome Bellinson, Shridevi Subramaniam, Yuntong Ma, Siew-Hwei Yap, Pik-Pin Goh, Patti Gravitt, Yin Ling Woo

Global Health Faculty Publications

OBJECTIVE: The objective of this study was to determine the attitudes and acceptability of self-administered cervicovaginal sampling compared with conventional physician-acquired Papanicolaou (Pap) smear among multiethnic Malaysian women.

METHOD: A cross-sectional study was carried out via interviewer-administered surveys from August 2013 through August 2015 at five government-run, urban health clinics in the state of Selangor. Subjects were participants from an ongoing community-based human papillomavirus (HPV) prevalence study who answered a standard questionnaire before and after self-sampling. The cervicovaginal self-sampling for HPV genotyping was performed using a simple brush ('Just for Me'; Preventive Oncology International, Hong Kong). Detailed data on sociodemographics, …

Com Outlook Winter 2016, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Gallic Acid, A Phenolic Compound, Exerts Anti-Angiogenic Effects Via The Pten/Akt/Hif-1Α/Vegf Signaling Pathway In Ovarian Cancer Cells, Zhiping He, Allen Y. Chen, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Gallic acid (GA), a polyphenol, is widely found in numerous fruits and vegetables, particularly in hickory nuts. In the present study, we found that gallic acid, a natural phenolic compound isolated from fruits and vegetables, had a more potent growth inhibitory effect on two ovarian cancer cell lines, OVCAR-3 and A2780/CP70, than the effect on a normal ovarian cell line, IOSE-364. These results demonstrated that GA selectively inhibits the growth of cancer cells. Gene expression was examined by ELISA and western blot analysis, and gene pathways were examined by luciferase assay. It was found that GA inhibited VEGF secretion and …

Children's Mercy Hospital Annual Report 2015, Children's Mercy Hospital

Children's Mercy Annual Reports

Annual report for The Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

Metataxonomic And Metagenomic Approaches Vs. Culture-Based Techniques For Clinical Pathology., Sarah K. Hilton, Eduardo Castro-Nallar, Marcos Pérez-Losada, Ian Toma, Timothy A. Mccaffrey, Eric P. Hoffman, Marc O. Siegel, Gary L. Simon, W. Evan Johnson, Keith Crandall

Genomics and Precision Medicine Faculty Publications

Diagnoses that are both timely and accurate are critically important for patients with life-threatening or drug resistant infections. Technological improvements in High-Throughput Sequencing (HTS) have led to its use in pathogen detection and its application in clinical diagnoses of infectious diseases. The present study compares two HTS methods, 16S rRNA marker gene sequencing (metataxonomics) and whole metagenomic shotgun sequencing (metagenomics), in their respective abilities to match the same diagnosis as traditional culture methods (culture inference) for patients with ventilator associated pneumonia (VAP). The metagenomic analysis was able to produce the same diagnosis as culture methods at the species-level for five …

Biosimilars: Potential Implications For Clinicians, Misty G. Eleryan, Sophia Akhiyat, Monica Rengifo-Pardo, Alison Ehrlich

Dermatology Faculty Publications

With the expiration of patent protection for several biologics looming, the production of highly similar therapeutic agents has begun to emerge on the pharmaceutical market. These alternative drugs are referred to as biosimilars. Many anticipate that the introduction of these agents will result in a reduction in health care costs, which may create a more affordable biopharmaceutical market and also improve patient access. In contrast to generics, which are exact copies of their original products, biosimilars are not identical to their reference products. Due to concern about the safety and efficacy of biosimilars, separate regulatory approval pathways have been developed …

Supersilac Quantitative Proteome Profiling Of Murine Middle Ear Epithelial Cell Remodeling With Nthi, Stephanie Val, Katelyn Burgett, Kristy J. Brown, Diego A. Preciado

Pediatrics Faculty Publications

Background

Chronic Otitis Media with effusion (COME) develops after sustained inflammation and is characterized by secretory middle ear epithelial metaplasia and effusion, most frequently mucoid. Non-typeable Haemophilus influenzae (NTHi), the most common acute Otitis Media (OM) pathogen, is postulated to promote middle ear epithelial remodeling in the progression of OM from acute to chronic. The goals of this study were to examine histopathological and quantitative proteomic epithelial effects of NTHi challenge in a murine middle ear epithelial cell line.

Methods

NTHi lysates were generated and used to stimulate murine epithelial cells (mMEEC) cultured at air-liquid interface over 48 hours– …

Sexual Minority (Lgbtq) Youth And Role Of Health Care Provider, Mandakini Sadhir, Stephanie J. Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Adolescence is a time period of physical, psychological and cognitive changes. It is an important phase for an individual to discover who they really are (self-identity), how they are perceived (social identity) and how they fit into the environment they live in.¹ One of the major tasks of adolescence is sexual maturation and sexual and /or gender identity development.² Adolescents who are developing as gay, lesbian, bisexual or transgender face a tremendous challenge of establishing their identity which is often complex.³ They cope with the feelings of being different and are in constant dilemmas about revealing their …

Screening Of Exosomal Micrornas From Colorectal Cancer Cells, Cillian Clancy, Sonja Khan, Claire L. Glynn, Emma Holian, Peter Dockery, Pierce Lalor, James A.L. Brown, Myles Joyce, Michael J. Kerin, Roisin M. Dwyer

Forensic Science Publications

BACKGROUND: Cells release extracellular membrane vesicles including microvesicles known as exosomes. Exosomes contain microRNAs (miRNAs) however the full range within colorectal cancer cell secreted exosomes is unknown. OBJECTIVE: To identify the full range of exosome encapsulated miRNAs secreted from 2 colorectal cancer cell lines and to investigate engineering of exosomes over-expressing miRNAs. METHODS: Exosomes were isolated from HCT-116 and HT-29 cell lines. RNA was extracted from exosomes and microRNA array performed. Cells were engineered to express miR-379 (HCT-116-379) or a non-targeting control (HCT-116-NTC) and functional effects were determined. Exosomes secreted by engineered cells were transferred to recipient cells and the …

The Diagnostic Accuracy Of Determine™ Tb Lam Antigen In Detection Of Extra Pulmonary Tuberculosis (Eptb), Fatimah Osman Juma

Master of Medicine in Internal Medicine

Background: TB remains a key global health challenge; particularly Extra pulmonary Tuberculosis (EPTB) and is also a major cause of morbidity and mortality in sub-Saharan Africa. The increasing incidence of EPTB compounded by difficulties in making a timely diagnosis portends to poor prognosis and increased mortality. Delays in diagnosis and misdiagnosis of EPTB in suspected patients account for mortality as well. Challenges in diagnosis of EPTB are mainly due to disease related factors, the paucibacillary nature of disease and challenges with sample collection and processing. Reference standard test such as TB culture, geneXpert and histology which are used in the …

Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).

METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed …

Effect Of Provision Of An Integrated Neonatal Survival Kit And Early Cognitive Stimulation Package By Community Health Workers On Developmental Outcomes Of Infants In Kwale County, Kenya: Study Protocol For A Cluster Randomized Trial, Lisa G. Pell, Diego G. Bassani, Lucy Nyaga, Isaac Njagi, Catherine Wanjiku, Thulasi Thiruchselvam, William Macharia, Ripudaman S. Minhas, Patricia Kitsao-Wekulo, Amyn Lakhani, Zulfiqar Ahmed Bhutta, Robert Armstrong, Shaun K. Morris

Paediatrics and Child Health, East Africa

Background: Each year, more than 200 million children under the age of 5 years, almost all in low- and middle-income countries (LMICs), fail to achieve their developmental potential. Risk factors for compromised development often coexist and include inadequate cognitive stimulation, poverty, nutritional deficiencies, infection and complications of being born low birthweight and/or premature. Moreover, many of these risk factors are closely associated with newborn morbidity and mortality. As compromised development has significant implications on human capital, inexpensive and scalable interventions are urgently needed to promote neurodevelopment and reduce risk factors for impaired development.

Method/Design: This cluster randomized trial aims at …

Self-Reported Practices Among Traditional Birth Attendants Surveyed In Western Kenya: A Descriptive Study, Sherri Bucher, Olive Konana, Edward Liechty, Ana Garces, Peter Gisore, Irene Marete, Constance Tenge, Evelyn Shipala, Linda Wright, Fabian Esamai

Paediatrics and Child Health, East Africa

Background: The high rate of home deliveries conducted by unskilled birth attendants in resource-limited settings is an important global health issue because it is believed to be a significant contributing factor to maternal and newborn mortality. Given the large number of deliveries that are managed by unskilled or traditional birth attendants outside of health facilities, and the fact that there is on-going discussion regarding the role of traditional birth attendants in the maternal newborn health (MNH) service continuum, we sought to ascertain the practices of traditional birth attendants in our catchment area. The findings of this descriptive study might help …

Pharmacogenomic Management Of Familial Hypercholesterolemia: An Integrative Review Of The Literature, Brian V. Skibo

Honors Undergraduate Theses

The purpose of this thesis is to examine familial hypercholesterolemia (FH) and emerging pharmacogenomics therapies that propose to lower serum low density lipid (LDL) levels. The search of various data bases resulted in nine research articles being selected for review. Syntheses of the articles suggest emerging phamacogenomic drug therapy can improve treatment outcomes for individuals with a diagnosis of FH. The Human Genome Project (HGP) has had far reaching applications for genomic technologies and pharmacagenomic interventions, tailored to human conditions associated with select genomic traits. Synthesis of nine research articles demonstrate that little is known on the topic and reveals …

Hiv/Aids Care And Prevention Infrastructure In The U.S. Deep South, Susan S. Reif, Kristen Sullivan, Elena Wilson, Miriam Berger, Carolyn Mcallaster

Faculty Scholarship

No abstract provided.

Nutrition Resources For Football Players In Division I Institutions: The Athletic Trainer's Perspective And Role, Giovanna Marie Giannini

Honors Undergraduate Theses

Background: The importance of nutrition on athletic performance is evident. Athletic trainers (ATs), nutritionists/RDs, strength and conditioning specialists (SCSs), and other athletic department personnel may be available to student-athletes and can be solicited for nutrition advice. Multiple studies have found that although some universities have a sports nutritionist on staff, student-athletes approached an AT most often for nutrition advice rather than an SCS, nutritionist or other person. ATs have the necessary education to provide proper nutrition information to student-athletes; however, it is not the primary role of an AT.

Objective: The purpose of this study was to examine the quantity, …

Nf45 And Nf90 Bind Hiv-1 Rna And Modulate Hiv Gene Expression, Yan Li, Michael Belshan

Nebraska Center for Virology: Faculty Publications

A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1) replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 …

Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5- fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. …

The Impact And Successes Of A Paediatric Endocrinology Fellowship Program In Africa, Gordon Otieno Odundo, Thomas Ngwiri, Olivia Otuoma, Paul Laigong, Renson Mukhwana, Mary Limbe, Nadia Musimbi Chanzu

Paediatrics and Child Health, East Africa

Background: The prevalence and distribution of endocrine disorders in children in Africa are not well known because most cases are often undiagnosed or diagnosed too late. The awareness of this led to the launch of the Paediatric Endocrinology Training Center for Africa (PETCA) designed to improve quality and access to health care by training paediatricians from Africa in paediatric endocrinology.

Methods: The fellowship is undertaken over an 18-month period: six months of clinical and theoretical training in Kenya, nine months of project research at the fellow’s home country, and three months of consolidation in Kenya. Upon completion, certified paediatricians are …

Application Of Pre-Participation Cardiovascular Screening Guidelines To Novice Older Runners And Endurance Athletes, Justin R. Abbatemarco, Courtney Bennett, Adrian J. Bell, Laura Dunne, Martin E. Matsumura

Neurology Faculty Publications

Objectives: Despite robust growth in participation in marathons and endurance sports among older individuals, guidance regarding pre-participation cardiovascular evaluation of these athletes is lacking. The objective of this study was to assess the utility of currently available pre-participation cardiovascular evaluation guidelines as applied to a cohort of older novice endurance athletes.

Methods: We applied data from 1457 novice runners and endurance athletes aged 35 years and older to two pre-participation screening tools, the American Heart Association/American College of Sports Medicine Pre-Participation Questionnaire and the 2001 Working Group recommendations for pre-participation screening of masters athletes (2001 Masters).

Results: Application of the …

Oncolog, Volume 61, Number 01, January 2016, Sarah Bronson, Bryan Tutt, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Proactive Management of Li-Fraumeni Syndrome Benefits Patients: Li-Fraumeni syndromes a hereditary disorder that confers an extremely high likelihood of developing cancer on affected individuals.
• Clinical Trial Tests High-Dose Radiation Therapy for Limited Stage Small Cell Lung Cancer: Small cell lung cancer carries a poor prognosis, even for patients without metastatic disease. But a phase III trial of high-dose daily or accelerated twice-daily thoracic radiation therapy for limited stage small cell kung cancer may lead to longer survival.
• Reducing Complications and Hospital Readmissions after Liver Surgery: Hepatectomy carries a risk of complications that can lead to hospital readmission and even death. …