Medicine and Health Sciences Commons^™

Patterns And Predictors Of Self-Medication In Northern Uganda., Moses Ocan, Freddie Bwanga, Godfrey S. Bbosa, Danstan Bagenda, Paul Waako, Jasper Ogwal-Okeng, Celestino Obua

Journal Articles: Epidemiology

Self-medication with antimicrobial agents is a common form of self-care among patients globally with the prevalence and nature differing from country to country. Here we assessed the prevalence and predictors of antimicrobial self-medication in post-conflict northern Uganda. A cross-sectional study was carried out using structured interviews on 892 adult (≥18 years) participants. Information on drug name, prescriber, source, cost, quantity of drug obtained, and drug use was collected. Households were randomly selected using multistage cluster sampling method. One respondent who reported having an illness within three months in each household was recruited. In each household, information was obtained from only …

How To Get The Most From Microarray Data: Advice From Reverse Genomics, Ivan P. Gorlov, Ji-Yeon Yang, Jinyoung Byun, Christopher Logothetis, Olga Y. Gorlova, Kim-Anh Do, Christopher Amos

Dartmouth Scholarship

Whole-genome profiling of gene expression is a powerful tool for identifying cancer-associated genes. Genes differentially expressed between normal and tumorous tissues are usually considered to be cancer associated. We recently demonstrated that the analysis of interindividual variation in gene expression can be useful for identifying cancer associated genes. The goal of this study was to identify the best microarray data–derived predictor of known cancer associated genes. We found that the traditional approach of identifying cancer genes—identifying differentially expressed genes—is not very efficient. The analysis of interindividual variation of gene expression in tumor samples identifies cancer-associated genes more effectively. The results …

Isoform- And Species-Specific Control Of Inositol 1,4,5-Trisphosphate (Ip3) Receptors By Reactive Oxygen Species., Száva Bánsághi, Tünde Golenár, Muniswamy Madesh, György Csordás, Satish P. Ramachandrarao, Kumar Sharma, David I Yule, Suresh K Joseph, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Reactive oxygen species (ROS) stimulate cytoplasmic [Ca(2+)] ([Ca(2+)]c) signaling, but the exact role of the IP3 receptors (IP3R) in this process remains unclear. IP3Rs serve as a potential target of ROS produced by both ER and mitochondrial enzymes, which might locally expose IP3Rs at the ER-mitochondrial associations. Also, IP3Rs contain multiple reactive thiols, common molecular targets of ROS. Therefore, we have examined the effect of superoxide anion (O2) on IP3R-mediated Ca(2+) signaling. In human HepG2, rat RBL-2H3, and chicken DT40 cells, we observed [Ca(2+)]c spikes and frequency-modulated oscillations evoked by a O2 donor, xanthine (X) + xanthine oxidase (XO), dose-dependently. …

Palatal Mucosa Derived Fibroblasts Present An Adaptive Behavior Regarding Cytokine Secretion When Grafted Onto The Gingival Margin, Fabíola Pontes Azevedo, Ana Carolina Morandini, Carla Renata Sipert, Thiago José Dionísio, Carlos Ferreira Santos, Carla Andreotti Damante, Maria Lúcia Rubo De Rezende, Adriana Campos Passanezi Sant'ana, Sebastião Luiz Aguiar Greghi

All Dugoni School of Dentistry Faculty Articles

BACKGROUND: Considering that grafted gingival tissue might have to be adapted to the receptor area and that fibroblasts have the ability to respond to bacterial stimuli through the release of various cytokines, this study investigated whether fibroblasts from the palatal mucosa behave differently when grafted onto the gingival margin regarding cytokine secretion.

METHODS: Biopsies from the palatal mucosa were collected at the time of free gingival graft surgery, and after four months re-collection was performed upon surgery for root coverage. Fibroblasts were isolated by the explant technique, cultured and stimulated with Porphyromonas gingivalis (Pg) and Escherichia coli (Ec) LPS for …

Interaction Between Allelic Variations In Vitamin D Receptor And Retinoid X Receptor Genes On Metabolic Traits, Karani S. Vimaleswaran, Alana Cavadino, Diane J. Berry, Massimo Mangino, Peter Andrews, Jason H. Moore

Dartmouth Scholarship

Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor, gamma (RXRG). Hence, we examined the potential interactions between the tagging polymorphisms in the VDR (22 tag SNPs) and RXRG (23 tag SNPs) genes on metabolic outcomes such as body mass index, waist circumference, waist-hip ratio (WHR), high- and low-density lipoprotein (LDL) cholesterols, serum triglycerides, systolic and diastolic blood pressures and glycated haemoglobin in the 1958 …

Integrated Assessment Of Predicted Mhc Binding And Cross-Conservation With Self Reveals Patterns Of Viral Camouflage, Lu He, Anne S. De Groot, Andres H. Gutierrez, William D. Martin, Lenny Moise, Chris Bailey-Kellogg

Dartmouth Scholarship

Immune recognition of foreign proteins by T cells hinges on the formation of a ternary complex sandwiching a constituent peptide of the protein between a major histocompatibility complex (MHC) molecule and a T cell receptor (TCR). Viruses have evolved means of "camouflaging" themselves, avoiding immune recognition by reducing the MHC and/or TCR binding of their constituent peptides. Computer-driven T cell epitope mapping tools have been used to evaluate the degree to which articular viruses have used this means of avoiding immune response, but most such analyses focus on MHC-facing ‘agretopes'. Here we set out a new means of evaluating the …

New Malignancies After Squamous Cell Carcinoma And Melanomas: A Population-Based Study From Norway, Trude E. Robsahm, Margaret R. Karagas, Judy R. Rees, Astri Syse

Dartmouth Scholarship

Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers.

Prevalence Of Small-For-Gestational Age And Its Mortality Risk Varies By Choice Of Birth-Weight-For-Gestation Reference Population, Joanne D. Katz, Lauren A. Wu, Luke C. Mullany, Christian L. Coles, Anne C.C. Lee, Naoko Kozuki, James M. Tielsch

Global Health Faculty Publications

Background

We use data from rural Nepal and South India to compare the prevalence of small-for-gestational-age (SGA) and neonatal mortality risk associated with SGA using different birth-weight-for-gestation reference populations.

Methods

We identified 46 reference populations in low-, middle-, and high-income countries, of which 26 met the inclusion criteria of being commonly cited and having numeric 10th percentile cut points published. Those reference populations were then applied to populations from two community-based studies to determine SGA prevalence and its relative risk of neonatal mortality.

Results

The prevalence of SGA ranged from 10.5% to 72.5% in Nepal, and 12.0% to 78.4% in …

Genes With A Large Intronic Burden Show Greater Evolutionary Conservation On The Protein Level, Olga Gorlova, Alexey Fedorov, Christopher Logothetis, Christopher Amos, Ivan Gorlov

Dartmouth Scholarship

Background: The existence of introns in eukaryotic genes is believed to provide an evolutionary advantage by increasing protein diversity through exon shuffling and alternative splicing. However, this eukaryotic feature is associated with the necessity of exclusion of intronic sequences, which requires considerable energy expenditure and can lead to splicing errors. The relationship between intronic burden and evolution is poorly understood. The goal of this study was to analyze the relationship between the intronic burden and the level of evolutionary conservation of the gene. Results: We found a positive correlation between the level of evolutionary conservation of a gene and its …

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …

Mitochondrial-Targeted Curcuminoids: A Strategy To Enhance Bioavailability And Anticancer Efficacy Of Curcumin, Cheruku Apoorva Reddy, Venkateswarlu Somepalli, Trimurtulu Golakoti, Anantha Koteswararao Kanugula, Santosh Karnewar, Karthikraj Rajendiran, Nagarjuna Vasagiri, Sripadi Prabhakar, Periannan Kuppusamy, Srigiridhar Kotamraju, Vijay Kumar Kutala

Dartmouth Scholarship

Although the anti-cancer effects of curcumin has been shown in various cancer cell types, in vitro, pre-clinical and clinical studies showed only a limited efficacy, even at high doses. This is presumably due to low bioavailability in both plasma and tissues, particularly due to poor intracellular accumulation. A variety of methods have been developed to achieve the selective targeting of drugs to cells and mitochondrion. We used a novel approach by conjugation of curcumin to lipophilic triphenylphosphonium (TPP) cation to facilitate delivery of curcumin to mitochondria. TPP is selectively taken up by mitochondria driven by the membrane potential by several …

Influence Of The X-Chromosome On Neuroanatomy: Evidence From Turner And Klinefelter Syndromes., David S Hong, Fumiko Hoeft, Matthew J Marzelli, Jean-Francois Lepage, David Roeltgen, Judith L. Ross, Allan L Reiss

Department of Psychiatry and Human Behavior Faculty Papers

Studies of sex effects on neurodevelopment have traditionally focused on animal models investigating hormonal influences on brain anatomy. However, more recent evidence suggests that sex chromosomes may also have direct upstream effects that act independently of hormones. Sex chromosome aneuploidies provide ideal models to examine this framework in humans, including Turner syndrome (TS), where females are missing one X-chromosome (45X), and Klinefelter syndrome (KS), where males have an additional X-chromosome (47XXY). As these disorders essentially represent copy number variants of the sex chromosomes, investigation of brain structure across these disorders allows us to determine whether sex chromosome gene dosage effects …

Investigating The Relation Between Striatal Volume And Iq., Penny A Macdonald, Hooman Ganjavi, D Louis Collins, Alan C Evans, Sherif Karama

Brain and Mind Institute Researchers' Publications

The volume of the input region of the basal ganglia, the striatum, is reduced with aging and in a number of conditions associated with cognitive impairment. The aim of the current study was to investigate the relation between the volume of striatum and general cognitive ability in a sample of 303 healthy children that were sampled to be representative of the population of the United States. Correlations between the WASI-IQ and the left striatum, composed of the caudate nucleus and putamen, were significant. When these data were analyzed separately for male and female children, positive correlations were significant for the …

Tachycardia Mediated Cardiomyopathy: Pathophysiology, Mechanisms, Clinical Features And Management., Shuchita Gupta, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Tachycardia mediated cardiomyopathy (TMC) is a reversible form of dilated cardiomyopathy that can occur with most supraventricular and ventricular arrhythmias. Despite the plethora of literature describing this entity in animal models, as well as humans, it remains poorly understood. Over the last decade, new etiologies of TMC, such as frequent premature ventricular complexes in normal hearts, have been identified. Recent advances in catheter-based ablation therapies, particularly for atrial fibrillation and ventricular arrhythmias, have added a new dimension to the treatment of this condition. This review describes the pathophysiology, proposed mechanisms, clinical features and management in various arrhythmic conditions.

High-Speed Optical Coherence Tomography As A Reliable Adjuvant Tool To Grade Ocular Anterior Chamber Inflammation., Ann O. Igbre, Mario C. Rico, Sunir Garg

Wills Eye Hospital Papers

PURPOSE: To evaluate the high-speed anterior segment optical coherence tomography (AS-OCT) grading of the AS inflammation in patients with ocular inflammation.

METHODS: A retrospective consecutive case series study. Patients with clinically visible AS inflammation in at least one eye underwent AS-OCT (Visante; Zeiss Meditec) with three to eight line scans per eye, performed by a trained masked examiner. The images were reviewed for hyperreflective spots, noise, and artifact, and these were correlated to clinical examination.

RESULTS: Seventy-eight eyes of 41 patients were imaged. Forty-seven eyes had anterior chamber cells on clinical examination, and 68 had hyperreflective spots visible on AS-OCT. …

Headstrong Intervention For Pediatric Migraine Headache: A Randomized Clinical Trial., Michael A. Rapoff, Mark Connelly, Jennifer Bickel, Scott W. Powers, Andrew D. Hershey, Janelle R. Allen, Cynthia W. Karlson, Catrina C. Litzenburg, John M. Belmont

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The purpose of this study was to evaluate the efficacy of a self-guided CD-ROM program ("Headstrong") containing cognitive-behavioral self-management strategies versus an educational CD-ROM program for treating headaches, headache-related disability, and quality of life.

METHODS: Participants were 35 children ages 7-12 years with migraine recruited from one university medical center and two children's hospital headache clinics. Participants were randomly assigned to complete the Headstrong or educational control CD-ROM program over a 4-week period. Data on headache frequency, duration, and severity, migraine-related disability, and quality of life (QOL) were obtained at baseline, post-intervention, and 3-months post-intervention.

RESULTS: At post-intervention, Headstrong …

Adiponectin Inhibits Tumor Necrosis Factor-Α-Induced Vascular Inflammatory Response Via Caveolin-Mediated Ceramidase Recruitment And Activation., Yajing Wang, Xiaoliang Wang, Wayne Bond Lau, Yuexing Yuan, David Booth, Jing-Jing Li, Rosario Scalia, Kyle Preston, Erhe Gao, Walter Koch, Xin-Liang Ma

Department of Medicine Faculty Papers

RATIONALE: Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered.

OBJECTIVE: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling.

METHODS AND RESULTS: Adiponectin significantly reduced tumor necrosis factor (TNF)α-induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P87% of adiponectin-induced nCDase …

Serum And Glucocorticoid-Inducible Kinase1 Increases Plasma Membrane Wt-Cftr In Human Airway Epithelial Cells By Inhibiting Its Endocytic Retrieval, Jennifer M. Bomberger, Bonita A. Coutermarsh, Roxanna L. Barnaby, J. Denry Sato, M. Christine Chapline, Bruce A. Stanton

Dartmouth Scholarship

Background: Chloride (Cl) secretion by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) located in the apical membrane of respiratory epithelial cells plays a critical role in maintenance of the airway surface liquid and mucociliary clearance of pathogens. Previously, we and others have shown that the serum and glucocorticoid-inducible kinase-1 (SGK1) increases wild type CFTR (wt-CFTR) mediated Cl transport in Xenopus oocytes by increasing the amount of wt-CFTR protein in the plasma membrane. However, the effect of SGK1 on the membrane abundance of wt-CFTR in airway epithelial cells has not been examined, and the mechanism whereby SGK1 increases membrane wt-CFTR has …

A Randomized Trial Of Bevacizumab For Newly Diagnosed Glioblastoma., Mark R Gilbert, James J Dignam, Terri S Armstrong, Jeffrey S Wefel, Deborah T Blumenthal, Michael A Vogelbaum, Howard Colman, Arnab Chakravarti, Stephanie Pugh, Minhee Won, Robert Jeraj, Paul D Brown, Kurt A Jaeckle, David Schiff, Volker W Stieber, David G Brachman, Maria Werner-Wasik, Ivo W Tremont-Lukats, Erik P Sulman, Kenneth D Aldape, Walter J Curran, Minesh P Mehta

Department of Radiation Oncology Faculty Papers

BACKGROUND: Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known.

METHODS: In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. …

Fundamentals Of Lung Auscultation, Abraham Bohadana, Gabriel Izbicki, Steve S. Kraman

Internal Medicine Faculty Publications

Chest auscultation has long been considered a useful part of the physical examination, going back to the time of Hippocrates. However, it did not become a widespread practice until the invention of the stethoscope by René Laënnec in 1816, which made the practice convenient and hygienic.1 During the second half of the 20th century, technological advances in ultrasonography, radiographic computed tomography (CT), and magnetic resonance imaging shifted interest from lung auscultation to imaging studies, which can detect lung disease with an accuracy never previously imagined. However, modern computer-assisted techniques have also allowed precise recording and analysis of lung sounds, prompting …

Anthropomorphic Breast Phantoms With Physiological Water, Lipid, And Hemoglobin Content For Near-Infrared Spectral Tomography, Kelly E. Michaelsen, Venkataramanan Krishnaswamy, Adele Shenoy, Emily Jordan, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

Breast mimicking tissue optical phantoms with sufficient structural integrity to be deployed as stand-alone imaging targets are developed and successfully constructed with biologically relevant concentrations of water, lipid, and blood. The results show excellent material homogeneity and reproducibility with inter- and intraphantom variability of 3.5 and 3.8%, respectively, for water and lipid concentrations ranging from 15 to 85%. The phantoms were long-lasting and exhibited water and lipid fractions that were consistent to within 5% of their original content when measured 2 weeks after creation. A breast-shaped three-compartment model of adipose, fibroglandular, and malignant tissues was created with water content ranging …

Irf8 Suppresses Pathological Cardiac Remodelling By Inhibiting Calcineurin Signalling., Ding-Sheng Jiang, Xiang Wei, Xiao-Fei Zhang, Yu Liu, Yan Zhang, Ke Chen, Lu Gao, Heng Zhou, Xue-Hai Zhu, Peter P. Liu, Wayne Bond Lau, Xin-Liang Ma, Yunzeng Zou, Xiao-Dong Zhang, Guo-Chang Fan, Hongliang Li

Department of Emergency Medicine Faculty Papers

Interferon regulatory factor 8 (IRF8) is known to affect the innate immune response, for example, by regulating the differentiation and function of immune cells. However, whether IRF8 can influence cardiac hypertrophy is unknown. Here we show that IRF8 levels are decreased in human dilated/hypertrophic cardiomyopathic hearts and in murine hypertrophic hearts. Mice overexpressing Irf8 specifically in the heart are resistant to aortic banding (AB)-induced cardiac hypertrophy, whereas mice lacking IRF8 either globally or specifically in cardiomyocytes develop an aggravated phenotype induced by pressure overload. Mechanistically, we show that IRF8 directly interacts with NFATc1 to prevent NFATc1 translocation and thus inhibits …

Influence Networks Based On Coexpression Improve Drug Target Discovery For The Development Of Novel Cancer Therapeutics, Nadia M. Penrod, Jason H. Moore

Dartmouth Scholarship

Background: Thedemandfornovelmolecularlytargeteddrugswillcontinuetoriseaswemoveforwardtowardthe goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. …

Safety With Ocrelizumab In Rheumatoid Arthritis: Results From The Ocrelizumab Phase Iii Program, Paul Emery, William Rigby, Paul P. Tak, Thomas Dörner, Ewa Olech, Carmen Martin, Laurie Millar, Helen Travers, Elena Fisheleva

Dartmouth Scholarship

Objective: The objective was to determine the safety of ocrelizumab (OCR) in patients with rheumatoid arthritis (RA).

Methods: This was an analysis of the double-blind, placebo-controlled periods and long-term follow-up of 4 OCR phase III trials in RA (SCRIPT, STAGE, FILM and FEATURE). Safety data per study and the results of a meta-analysis of serious infectious events (SIEs) are presented.

Results: Overall, 868 patients received placebo, 1064 patients OCR 200 mg×2 (or 400 mg×1) (OCR200), and 827 patients OCR 500 mg×2 (OCR500) plus background methotrexate (MTX) at baseline and 24 weeks. During the double-blind, placebo-controlled periods, the incidence of adverse …

The International Society Of Physical And Rehabilitation Medicine: The Way Forward - Ii., Marta Imamura, Christoph Gutenbrunner, Gerold Stucki, Jianan Li, Jorge Lains, Walter Frontera, John Olver, Levent Özçakar, Joel Delisa, Linamara Rizzo Battistella, John L. Melvin

Department of Rehabilitation Medicine Faculty Papers

This paper reports on recent changes and future plans concerning the International Society of Physical and Rehabilitation Medicine. Issues discussed are its structural organization, collaboration and recognition, liaison with the World Health Organization , work in strengthening science, and its future agenda.

A Review Of The Global Literature On Dental Therapists, David A. Nash, Jay W. Friedman, Kavita R. Mathu-Muju, Peter G. Robinson, Julie Satur, Susan Moffat, Rosemary Kardos, Edward C. M. Lo, Anthony H. H. Wong, Nasruddin Jaafar, Jos Van Den Heuvel, Prathip Phantumvanit, Eu Oy Chu, Rahul Naidu, Lesley Naidoo, Irving Mckenzie, Eshani Fernando

Oral Health Science Faculty Publications

OBJECTIVE: Access to adequate oral health care is deficient in many parts of the world. Many countries are now using dental therapists to increase access, particularly for children. To inform the discussion on dental therapists in the workforce, particularly in the United States, the W.K. Kellogg Foundation funded a review of the global literature to identify as many documents as possible related to the practice of dental therapists since the establishment of the School Dental Service in New Zealand in 1921.

METHODS: Consultants in each of the countries considered to have a substantive literature on dental therapists were …

Retina-Simulating Phantom For Optical Coherence Tomography., Jigesh Baxi, William Calhoun, Yasir Jamal Sepah, Daniel X. Hammer, Ilko Ilev, T. Joshua Pfefer, Quan Dong Nguyen, Anant Agrawal

Journal Articles: Ophthalmology

Optical coherence tomography (OCT) is a rapidly growing imaging modality, particularly in the field of ophthalmology. Accurate early diagnosis of diseases requires consistent and validated imaging performance. In contrast to more well-established medical imaging modalities, no standardized test methods currently exist for OCT quality assurance. We developed a retinal phantom which mimics the thickness and near-infrared optical properties of each anatomical retinal layer as well as the surface topography of the foveal pit. The fabrication process involves layer-by-layer spin coating of nanoparticle-embedded silicone films followed by laser micro-etching to modify the surface topography. The thickness of each layer and dimensions …

Expression Of Mir-15/107 Family Micrornas In Human Tissues And Cultured Rat Brain Cells, Wang-Xia Wang, Robert J. Danaher, Craig S. Miller, Joseph R. Berger, Vega G. Nubia, Bernard R. Wilfred, Janna H. Neltner, Christopher M. Norris, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs), sharing a 5' AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression …

A Novel In Vivo Model For Evaluating Functional Restoration Of A Tissue-Engineered Salivary Gland., Swati Pradhan-Bhatt, Daniel A Harrington, Randall L Duncan, Mary C Farach-Carson, Xinqiao Jia, Robert L Witt

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES/HYPOTHESIS: To create a novel model for development of a tissue-engineered salivary gland from human salivary gland cells that retains progenitor cell markers useful for treatment of radiation-induced xerostomia.

STUDY DESIGN: A three-dimensional (3D) hyaluronic acid (HA)-based hydrogel scaffold was used to encapsulate primary human salivary gland cells and to obtain organized acini-like spheroids. Hydrogels were implanted into rat models, and cell viability and receptor expression were evaluated.

METHODS: A parotid gland surgical resection model for xenografting was developed. Salivary cells loaded in HA hydrogels formed spheroids and in vitro were implanted in the three-fourths resected parotid bed of athymic …

Managing The Innovation Supply Chain To Maximize Personalized Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Personalized medicine epitomizes an evolving model of care tailored to the individual patient. This emerging paradigm harnesses radical technological advances to define each patient's molecular characteristics and decipher his or her unique pathophysiological processes. Translated into individualized algorithms, personalized medicine aims to predict, prevent, and cure disease without producing therapeutic adverse events. Although the transformative power of personalized medicine is generally recognized by physicians, patients, and payers, the complexity of translating discoveries into new modalities that transform health care is less appreciated. We often consider the flow of innovation and technology along a continuum of discovery, development, regulation, and application …