Digital Commons Network^™

Vitamin D And The Athlete: Risks, Recommendations, And Benefits, Dana Ogan, Kelly Pritchett

All Faculty Scholarship for the College of the Sciences

Vitamin D is well known for its role in calcium regulation and bone health, but emerging literature tells of vitamin D’s central role in other vital body processes, such as: signaling gene response, protein synthesis, hormone synthesis, immune response, plus, cell turnover and regeneration. The discovery of the vitamin D receptor within the muscle suggested a significant role for vitamin D in muscle tissue function. This discovery led researchers to question the impact that vitamin D deficiency could have on athletic performance and injury. With over 77% of the general population considered vitamin D insufficient, it’s likely that many athletes …

Dynamic Dual-Tracer Mri-Guided Fluorescence Tomography To Quantify Receptor Density In Vivo, Scott C. Davis, Kimberley S. Samkoe, Kenneth M. Tichauer, Kristian J. Sexton, Jason R. Gunn, Sophie J. Deharvengt, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model …

Peripheral T-Cell Lymphomas: A Review Of Current Approaches And Hopes For The Future., Alan P Skarbnik, Meher Burki, Barbara Pro

Kimmel Cancer Center Faculty Papers

Peripheral T-cell lymphomas (PTCL) are a diverse group of lymphoproliferative disorders, which share a common denominator of overall poor prognosis, with few exceptions. In this article, the authors review current standard of care approaches for the treatment of PTCLs, the role of stem-cell/bone marrow transplantation, and current developments in novel targeted therapies.

The Objectives, Design And Implementation Of The Intergrowth-21st Project, Villar J, Altman D. G, Purwar M, Noble J. A, Knight H. E, Ruyan P, Ismail L. Cheikh, Barros F. C, Lambert A, Papageorghiou A. T, Maria Carvalho, Jaffer Y. A, Bertino E, Gravett M. G, Bhutta Z. A, Kennedy S. H

Obstetrics and Gynaecology, East Africa

INTERGROWTH-21st is a multicentre, multiethnic, populationbased project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship …

Providing Family-Centered Care For Families And Patients With Autism Spectrum Disorders : A Guide For Healthcare Professionals, Kacie Wilson

Graduate Student Independent Studies

The purpose of this thesis is to provide healthcare professionals in the pediatric healthcare setting with the necessary tools to provide high quality family-centered care to children with ASD and to their families.

A Trip To The Epilepsy Monitoring Unit : Using Video Modeling To Prepare Children And Caregivers For Inpatient Eeg Monitoring, Peyton Katz

Graduate Student Independent Studies

The goal of this project was to outline the benefits of utilizing video modeling in the preparation of children and families within a child life department's preparation program.

Anr And Its Activation By Plch Activity In Pseudomonas Aeruginosa Host Colonization And Virulence, Angelyca A. Jackson, Maegan J. Gross, Emily F. Daniels, Thomas H. Hampton, John H. Hammond, Isabelle Vallet-Gely, Simon L. Dove, Bruce A. Stanton, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ΔplcHR mutant, known to be defective in virulence in animal models, was less able to colonize epithelial cell monolayers and was defective in biofilm formation on plastic when grown in lung surfactant. Microarray analyses found that strains defective in PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated the Anr regulon in an Anr-dependent manner under conditions where Anr activity was submaximal because of the presence of oxygen. Two PC catabolites, choline and glycine …

Withaferin A Effectively Targets Soluble Vimentin In The Glaucoma Filtration Surgical Model Of Fibrosis, Paola Bargagna-Mohan, Sunil P. Deokule, Kyle G. Thompson, John Wizeman, Cidambi Srinivasan, Sunil Vooturi, Uday B. Kompella, Royce Mohan

Ophthalmology and Visual Science Faculty Publications

Withaferin A (WFA) is a natural product that binds to soluble forms of the type III intermediate filament (IF) vimentin. Currently, it is unknown under what pathophysiological contexts vimentin is druggable, as cytoskeltal vimentin-IFs are abundantly expressed. To investigate druggability of vimentin, we exploited rabbit Tenon's capsule fibroblast (RbTCF) cell cultures and the rabbit glaucoma filtration surgical (GFS) model of fibrosis. WFA potently caused G₀/G₁ cell cycle inhibition (IC₅₀ 25 nM) in RbTCFs, downregulating ubiquitin E3 ligase skp2 and inducing p27(Kip1) expression. Transforming growth factor (TGF)-ß-induced myofibroblast transformation caused development of cell spheroids with numerous elongated invadopodia, which WFA blocked …

Flurbiprofen Benzyl Nitrate (Nbs-242) Inhibits The Growth Of A-431 Human Epidermoid Carcinoma Cells And Targets Β-Catenin, Niharika Nath, Xiaoping Liu, Lloydine Jacobs, Khosrow Kashfi

Publications and Research

Background: The Wnt/β-catenin/T cell factor (TCF) signaling pathway is important in the development of nonmelanoma skin cancers (NMSCs). Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemopreventive agents consisting of a traditional NSAID attached to an NO-releasing moiety through a chemical spacer. Previously we showed that an aromatic spacer enhanced the potency of a particular NO-NSAID compared to an aliphatic spacer.

Methods: We synthesized an NO-releasing NSAID with an aromatic spacer (flurbiprofen benzyl nitrate, NBS-242), and using the human skin cancer cell line A-431, we evaluated its effects on cell kinetics, Wnt/β-catenin, cyclin D1, and caspase-3.

Results: NBS-242 inhibited the growth of …

Perception, Expression And Management Of The Pain Of Childbirth, Mary H. Christenson

Senior Honors Theses

In order to be a competent nurse on an American labor and delivery unit it is important to have an understanding of the pain of childbirth. This includes a thorough understanding of pain as a sensation and its manifestation during the birthing experience. An understanding of pain is useless, however, unless standardized pain assessment practices are used. The most accurate pain assessment is associated with a general understanding of cultural trends in pain perception and expression. Along with culture, other factors also influence how a woman senses and copes with the pain of labor. Anxiety is one of these influential …

History And Hope: The International Humanitarian Reader, Kevin M. Cahill, M.D.

Institute of International Humanitarian Affairs

History and Hope: The International Humanitarian Reader provides a better understanding—both within and outside academia—of the multifaceted demands posed by humanitarian assistance programs. The Reader is a compilation of the most important chapters in the twelve-volume International Humanitarian Affairs book series published by Fordham University Press. Each selected chapter has been edited and updated. In addition, the series editor, Kevin M. Cahill, M.D., has written, among other chapters, an introductory essay explaining the academic evolution of the discipline of humanitarian assistance. It focuses on the “Fordham Experience”: its Institute of International Humanitarian Affairs (IIHA) has developed practical programs for training …

Medical Education Digest, Vol. 15 No. 3 (May/June 2013), Nova Southeastern University

Medical Education Digest

No abstract provided.

Characteristics Of Children With The Best And Poorest First- And Second-Year Growth During Rhgh Therapy: Data From 25 Years Of The Genentech National Cooperative Growth Study (Ncgs), Paul B. Kaplowitz, Dorothy I. Shulman, James W. Frane, Joan Jacobs, Barbara Lippe

Pediatrics Faculty Publications

Background

Models assessing characteristics contributing to response to recombinant human growth hormone (rhGH) response rarely address growth extremes in both years 1 and 2 or examine how children track from year to year. Using National Cooperative Growth Study (NCGS) data, we determined characteristics contributing to responsiveness to rhGH and the pattern of change from years 1 to 2.

Patients and methods

Height velocity standard deviation score (HV SDS) for 2 years for prepubertal children with idiopathic GH deficiency (IGHD) (n = 1899) and idiopathic short stature (ISS) (n = 1186) treated with similar doses for two years were computed. Group …

Molecular Mechanisms Underlying Rb Protein Function, Frederick A. Dick, Seth M. Rubin

Paediatrics Publications

Inactivation of the RB protein is one of the most fundamental events in cancer. Coming to a molecular understanding of its function in normal cells and how it impedes cancer development has been challenging. Historically, the ability of RB to regulate the cell cycle placed it in a central role in proliferative control, and research focused on RB regulation of the E2F family of transcription factors. Remarkably, several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis. These advances and new structural studies are combining to define …

Polypharmacy In Elderly: A Cautious Trail To Tread, Saniya Raghib Sabzwari, Waris Qidwai, Seema Bhanji

Department of Family Medicine

Polypharmacy has now increasingly come into focus as the recipient of healthcare in old age worldwide. In elderly it is associated with frequent adverse drug reactions (ADRs) and drug-drug interactions resulting in significant morbidity. Geriatrics is still an emerging specialty in South Asia, especially in Pakistan, where multiple reasons for polypharmacy exist. An extensive literature review of articles using key words like \'polypharmacy,\' \'elderly\' was conducted. The recently updated Beers Criteria of classification of inappropriate drugs in the elderly was reviewed in detail. Articles of relevance to polypharmacy and evaluation of guidelines for appropriate interventions to minimise inappropriate drug prescribing …

Neuropathogenic Escherichia Coli K1 Does Not Exhibit Proteolytic Activities To Exert Its Pathogenicity, Junaid Iqbal, Mehak Rajan, Ruqaiyyah Siddiqu, Naveed Ahmed Khan

Department of Biological & Biomedical Sciences

Background: Proteases are well-known virulence factors that promote survival, pathogenesis and immune evasion of many pathogens. Several lines of evidence suggest that the blood-brain barrier permeability is a prerequisite in microbial invasion of the central nervous system. Because proteases are frequently associated with vascular permeability by targeting junctional proteins, here it is hypothesized that neuropathogenic Escherichia coli K1 exhibit proteolytic activities to exert its pathogenicity.
Methods: Zymographic assays were performed using collagen and gelatin as substrates. The lysates of whole E. coli K1 strain E44, or E. coli K-12 strain HB101 were tested for proteolytic activities. The conditioned media were …

Antibody Quality And Protection From Lethal Ebola Virus Challenge In Nonhuman Primates Immunized With Rabies Virus Based Bivalent Vaccine., Joseph E Blaney, Andrea Marzi, Mallory Willet, Amy B Papaneri, Christoph Wirblich, Friederike Feldmann, Michael Holbrook, Peter Jahrling, Heinz Feldmann, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced …

Healthcare Delivery System Improvements: A Way Forward To Improve Health In Developing Countries And Pakistan, Waris Qidwai

Department of Family Medicine

No abstract provided.

Cinacalcet As Adjunctive Therapy For Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets., Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Secondary hyperparathyroidism from inadequate calcium absorption in the gut, is the underlying pathophysiology for rachitic changes in hereditary vitamin D-resistant rickets (HVDRR). We describe a novel use of Cinacalcet to treat a child with HVDRR in whom conventional modes of therapy had to be discontinued. Cinacalcet therapy with high-dose oral calcium effectively normalized the metabolic abnormalities and bone condition. The relative ease of administration of the calcimimetic as a once- or twice-daily oral preparation, compared with traditional intravenous calcium administration, should encourage its move to the frontline of treatment of the disorder.

B-Type Natriuretic Peptide Versus Amino Terminal Pro-B Type Natriuretic Peptide: Selecting The Optimal Heart Failure Marker In Patients With Impaired Kidney Function, Lena Jafri, Waqar Kashif, Javed Tai, Imran Siddiqui, Iqbal Azam, Hira Shahzad, Farooq Ghani

Department of Pathology and Laboratory Medicine

Background: The effect of impaired kidney function on B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) is vague. This study was performed to examine the effect of kidney dysfunction on the afore-mentioned markers and determine appropriate cutoffs for systolic heart failure (SHF).

Methods: In this cross sectional study adults with estimated glomerular filtration rate (eGFR)/min for ≥3 months were identified in consulting clinics from June 2009 to March 2010. SHF was defined as documented by a cardiologist with ejection fraction of < 40% and assessed by New York Heart Association classification (NYHA). Plasma was assayed for creatinine (Cr), BNP and NT-proBNP.

Results: A total of 190 subjects were enrolled in the study, 95 with and 95 without SHF. The mean …

The Impact Of Family History On Medullary Thyroid Cancer In Men2a Patients, Nicole D. Mohrbacher

Dissertations and Theses (Open Access)

The American Thyroid Association recently classified all MEN2A-associated codons into increasing risk levels A-C and stated that some patients may delay prophylactic thyroidectomy if certain criteria are met. One criterion is a less aggressive family history of MTC but whether families with the same mutated codon have variable MTC aggressiveness is not well described. We developed several novel measures of MTC aggressiveness and compared families with the same mutated codon to determine if there is significant inter-familial variability. Pedigrees of families with MEN2A were reviewed for codon mutated and proportion of RET mutation carriers with MTC. Individuals with MTC were …

A Public Health Response Against Strongyloides Stercoralis: Time To Look At Soil-Transmitted Helminthiasis In Full., Alejandro J Krolewiecki, Patrick Lammie, Julie Jacobson, Albis-Francesco Gabrielli, Bruno Levecke, Eugenia Socias, Luis M Arias, Nicanor Sosa, David Abraham, Ruben Cimino, Adriana Echazú, Favio Crudo, Jozef Vercruysse, Marco Albonico

Department of Microbiology and Immunology Faculty Papers

Strongyloides stercoralis infections have a worldwide distribution with a global burden in terms of prevalence and morbidity that is largely ignored. A public health response against soil-transmitted helminth (STH) infections should broaden the strategy to include S. stercoralis and overcome the epidemiological, diagnostic, and therapeutic challenges that this parasite poses in comparison to Ascaris lumbricoides, Trichuris trichiura, and hookworms. The relatively poor sensitivity of single stool evaluations, which is further lowered when quantitative techniques aimed at detecting eggs are used, also complicates morbidity evaluations and adequate drug efficacy measurements, since S. stercoralis is eliminated in stools in a larval stage. …

Novel Therapeutic Targets Identified By High-Throughput Technologies For Triple-Negative Breast Cancer, Christine Shiang

Dissertations and Theses (Open Access)

Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to …

Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao

Dissertations and Theses (Open Access)

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with ^99mTc and ⁶⁸Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both ^99mTc-N4amG and ^99mTc-GP were stable up to 6 hours, whereas ⁶⁸Ga-GP was stable up to 2 hours. Cell culture studies …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Alpcs(2a)-Mediated Photochemical Internalization Of Bleomycin And Concurrent Hyperthermia Of Multicellular Tumor Spheroids, Aaron Andersen

UNLV Theses, Dissertations, Professional Papers, and Capstones

Treatments for glioblastoma multiforme and invasive ductal carcinoma involve surgical resection and adjuvant or concurrent targeted therapies. The goal of the secondary treatment is to reduce the cancer cells in the resection margin and other areas of suspected involvement. Photochemical internalization is a targeted therapy using light to activate photosensitizers embedded in cellular structures to improve the delivery of macromolecules within the cell.

In a previous study, optimized treatment parameters including radiant exposure, and irradiance, concentration of AlPcS(2a), temperature, and the concentration of bleomycin were determined for human ACBT glioma multicell spheroids. The current study investigates the effectiveness of the …

Listeria Monocytogenes Cholecystitis: A Possible New Syndrome., Jackrapong Bruminhent, Timothy K Lynch, Jonathan Gefen, Jerome Santoro

Division of Internal Medicine Faculty Papers & Presentations

: The U.S. Food and Drug Administration recently added potentially fatal Listeria monocytogenes infection to the list of opportunistic infections that can occur in patients who receive tumor necrosis factor inhibitor therapy. In this study, the first reported case of L monocytogenes cholecystitis associated with etanercept use is described. It also appears that tumor necrosis factor inhibitor therapy likely increases the risk for Listeria cholecystitis. Clinicians need to be aware of this association when selecting antimicrobial therapy for these patients.

The Karabus Affair Speaks To Larger Issues For American Academic And Medical Centers., Leonard A Zwelling, Md, Mba, Razelle Kurzrock, Md, Philip R Cohen, Md, Bernard Levin, Md, Ch, Lawrence Parish, Md

Department of Dermatology and Cutaneous Biology Faculty Papers

Finally, on March 12, 2013, a major American newspaper, The Wall Street Journal, reported on the plight of Dr. Cyril Karabus (1,2). Dr. Karabus is the 78 year old pediatric oncologist from Claremont, Capetown, South Africa who is well known as the retired head of the Oncology and Hematology Unit of the Red Cross Children’s Hospital, University of Cape Town, as well as for his devoted service to poor children in the apartheid era. In 2002, he cared for a three-year old Yemeni girl with acute myelogenous leukemia during a locum tenens in the United Arab Emirates (UAE).

Qcm Aptasensor For Rapid And Specific Detection Of Avian Influenza Virus, Luke Brockman

Graduate Theses and Dissertations

There has been a need for rapid detection of avian influenza virus (AIV) H5N1 due to it being a potential pandemic threat. Most of the current methods, including culture isolation and PCR, are very sensitive and specific but require specialized laboratories and trained personnel in order to complete the tests and are time-consuming. The goal of this study was to design a biosensor that would be able to rapidly detect AIV H5N1 using aptamers as biosensing material and a quartz crystal microbalance (QCM) for transducing method. Specific DNA aptamers against AIV H5N1 were immobilized, through biotin and streptavidin conjugation, onto …

Physical Activity And Exercise During Adolescence And Young Adulthood Can Act As Preventative Measures Against The Development Of Osteoporosis In Elderly People, Christine C. Center

Honors College Theses

Osteoporosis, “the silent killer,” is responsible for 8.9 million annual fractures. Although not bound to these factors, osteoporosis typically targets females that are post-menopausal and have a family history of the disease. Osteoporosis is caused by a decrease in bone mass density. Physical activity and exercise and often spoken about when the topic of osteoporosis is discussed because of the impact they have on maintaining bone mass density in an effort to delay osteoporosis. This paper first provides an overview of osteoporosis, explanation of methods of diagnosing osteoporosis, risk factors, complications and treatment for osteoporosis. Topics covered include, bone mass …