Other Medical Specialties Commons^™

Trna-Derived Short Non-Coding Rna As Interacting Partners Of Argonaute Proteins., Megumi Shigematsu, Yohei Kirino, Phd

Computational Medicine Center Faculty Papers

The advent of next-generation sequencing technologies has not only accelerated findings on various novel non-coding RNA (ncRNA) species but also led to the revision of the biological significance and versatility of fundamental RNA species with canonical function, such as transfer RNAs (tRNAs). Although tRNAs are best known as adapter components of translational machinery, recent studies suggest that tRNAs are not always end products but can further serve as a source for short ncRNAs. In many organisms, various tRNA-derived ncRNA species are produced from mature tRNAs or their precursor transcripts as functional molecules involved in various biological processes beyond translation. In …

Pleiotropic Effects Of Bitter Taste Receptors On [Ca2+]I Mobilization, Hyperpolarization, And Relaxation Of Human Airway Smooth Muscle Cells., Blanca Camoretti-Mercado, Susan H Pauer, Hwan Mee Yong, Dan'elle C Smith, Deepak A. Deshpande, Phd, Steven S An, Stephen B Liggett

Center for Translational Medicine Faculty Papers

Asthma is characterized by airway inflammation and airflow obstruction from human airway smooth muscle (HASM) constriction due to increased local bronchoconstrictive substances. We have recently found bitter taste receptors (TAS2Rs) on HASM, which increase [Ca2+]i and relax the muscle. We report here that some, but not all, TAS2R agonists decrease [Ca2+]i and relax HASM contracted by G-protein coupled receptors (GPCRs) that stimulate [Ca2+]i. This suggests both a second pathway by which TAS2Rs relax, and, a heterogeneity of the response phenotype. We utilized eight TAS2R agonists and five procontractile GPCR agonists in cultured HASM cells. We find that heterogeneity in the …

Flattening Filter-Free Accelerators: A Report From The Aapm Therapy Emerging Technology Assessment Work Group., Ying Xiao, Stephen F Kry, Richard Popple, Ellen Yorke, Niko Papanikolaou, Sotirios Stathakis, Ping Xia, Saiful Huq, John Bayouth, James Galvin Phd, Fang-Fang Yin

Department of Medicine Faculty Papers

This report describes the current state of flattening filter-free (FFF) radiotherapy beams implemented on conventional linear accelerators, and is aimed primarily at practicing medical physicists. The Therapy Emerging Technology Assessment Work Group of the American Association of Physicists in Medicine (AAPM) formed a writing group to assess FFF technology. The published literature on FFF technology was reviewed, along with technical specifications provided by vendors. Based on this information, supplemented by the clinical experience of the group members, consensus guidelines and recommendations for implementation of FFF technology were developed. Areas in need of further investigation were identified. Removing the flattening filter …

Successful Isolation Of Viable Adipose-Derived Stem Cells From Human Adipose Tissue Subject To Long-Term Cryopreservation: Positive Implications For Adult Stem Cell-Based Therapeutics In Patients Of Advanced Age., Sean Devitt, Md, Cynthia M Carter, Raia Dierov, Scott Weiss, Robert P Gersch, Ivona Percec

Jefferson Hospital Staff Papers and Presentations

We examined cell isolation, viability, and growth in adipose-derived stem cells harvested from whole adipose tissue subject to different cryopreservation lengths (2-1159 days) from patients of varying ages (26-62 years). Subcutaneous abdominal adipose tissue was excised during abdominoplasties and was cryopreserved. The viability and number of adipose-derived stem cells isolated were measured after initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with respect to cryopreservation duration and patient age. Significantly more viable cells were initially isolated from tissue cryopreserved2 years, irrespective of patient age. However, this difference did not persist with continued growth and …

Evaluation Of The American-English Quality Of Life In Short Stature Youth (Qolissy) Questionnaire In The United States., Monika Bullinger, Rachel Sommer, Andreas Pleil, Nelly Mauras, Judith L. Ross, Ron Newfield, Lawrence Silverman, Anja Rohenkohl, Janet Fox, Julia Quitmann

Department of Medical Genetics Faculty Papers

BACKGROUND: The European Quality of Life in Short Stature Youth (QoLISSY) is a novel condition-specific instrument developed to assess health related quality of life (HrQoL) in children/adolescents with short stature from patient and parent perspectives. Study objective was to linguistically validate and psychometrically test the American-English version of the QoLISSY instrument.

METHODS: Upon conversion of the British-English version to American-English, content validity and acceptance of the questionnaire were examined through focus group discussions with cognitive debriefing in 28 children/adolescents with growth hormone deficiency (GHD) or idiopathic short stature (ISS) and their parents. In the subsequent field test with 51 families …

Implementation Of Antimicrobial Stewardship Policies In U.S. Hospitals: Findings From A National Survey., Monika Pogorzelska-Maziarz, Carolyn T A Herzig, Elaine L Larson, E Yoko Furuya, Eli N Perencevich, Patricia W Stone

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To describe the use of antimicrobial stewardship policies and to investigate factors associated with implementation in a national sample of acute care hospitals.

DESIGN: Cross-sectional survey.

PARTICIPANTS: Infection Control Directors from acute care hospitals participating in the National Healthcare Safety Network (NHSN).

METHODS: An online survey was conducted in the Fall of 2011. A subset of hospitals also provided access to their 2011 NHSN annual survey data.

RESULTS: Responses were received from 1,015 hospitals (30% response rate). The majority of hospitals (64%) reported the presence of a policy; use of antibiograms and antimicrobial restriction policies were most frequently utilized …

State Law Mandates For Reporting Of Healthcare-Associated Clostridium Difficile Infections In Hospitals., Julie Reagan, Carolyn T A Herzig, Monika Pogorzelska-Maziarz, Andrew W Dick, Patricia W Stone, Jd Divya Srinath

Department of Nursing papers and presentations

US state and territorial laws were reviewed to identify Clostridium difficile infection reporting mandates. Twenty states require reporting either under state law or by incorporating federal Centers for Medicare & Medicaid Services' reporting requirements. Although state law mandates are more common, the incorporation of federal reporting requirements has been increasing.

Population Health: Where's The Beef?, David B. Nash

College of Population Health Faculty Papers

No abstract provided.

What Is Translational Bioinformatics?, Eric R. Londin, Carol I. Barash

Computational Medicine Center Faculty Papers

No abstract provided.

Kallikrein Family Proteases Klk6 And Klk7 Are Potential Early Detection And Diagnostic Biomarkers For Serous And Papillary Serous Ovarian Cancer Subtypes., Ayala Tamir, Ushma Jag, Sreeja Sarojini, Craig Schindewolf, Takemi Tanaka, Rajendra Gharbaran, Hiren Patel, Anil Sood, Wei Hu, Ruzeen Patwa, Patrick Blake, Polina Chirina, Jin Oh Jeong, Heejin Lim, Andre Goy, Andrew Pecora, K Stephen Suh

Department of Medicine Faculty Papers

BACKGROUND: Early detection of ovarian cancer remains a challenge due to widespread metastases and a lack of biomarkers for early-stage disease. This study was conducted to identify relevant biomarkers for both laparoscopic and serum diagnostics in ovarian cancer.

METHODS: Bioinformatics analysis and expression screening in ovarian cancer cell lines were employed. Selected biomarkers were further validated in bio-specimens of diverse cancer types and ovarian cancer subtypes. For non-invasive detection, biomarker proteins were evaluated in serum samples from ovarian cancer patients.

RESULTS: Two kallikrein (KLK) serine protease family members (KLK6 and KLK7) were found to be significantly overexpressed relative to normal …

The New Oral Anticoagulants For The Treatment Of Venous Thromboembolism: A New Paradigm Shift In Antithrombotic Therapy., Taki Galanis, Gina Keiffer, Geno J Merli

Department of Medicine Faculty Papers

BACKGROUND: Several novel oral anticoagulants have been studied for the prevention and treatment of venous thromboembolism (VTE) in different patient populations. Clinicians will increasingly encounter scenarios in which they must choose among these and conventional anticoagulants for the treatment of this potentially fatal condition.

OBJECTIVE: To review the results of Phase III clinical trials that investigated the novel oral anticoagulants for the treatment of deep vein thrombosis and pulmonary embolism. Potential advantages and disadvantages of these anticoagulant agents with respect to each other and conventional therapy will also be explored through a case-based approach.

METHODS: A literature search in PubMed …

The Emerging Roles Of Gprc5a In Diseases., Honglei Zhou, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

The 'Retinoic Acid-Inducible G-protein-coupled receptors' or RAIG are a group comprising the four orphan receptors GPRC5A, GPRC5B, GPRC5C and GPRC5D. As the name implies, their expression is induced by retinoic acid but beyond that very little is known about their function. In recent years, one member, GPRC5A, has been receiving increasing attention as it was shown to play important roles in human cancers. As a matter of fact, dysregulation of GPRC5A has been associated with several cancers including lung cancer, breast cancer, colorectal cancer, and pancreatic cancer. Here we review the current state of knowledge about the heterogeneity and evolution …

Isomir Expression Profiles In Human Lymphoblastoid Cell Lines Exhibit Population And Gender Dependencies., Phillipe Loher, Eric R Londin, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

For many years it was believed that each mature microRNA (miRNA) existed as a single entity with fixed endpoints and a 'static' and unchangeable primary sequence. However, recent evidence suggests that mature miRNAs are more 'dynamic' and that each miRNA precursor arm gives rise to multiple isoforms, the isomiRs. Here we report on our identification of numerous and abundant isomiRs in the lymphoblastoid cell lines (LCLs) of 452 men and women from five different population groups. Unexpectedly, we find that these isomiRs exhibit an expression profile that is population-dependent and gender-dependent. This is important as it indicates that the LCLs …

Plasma Adiponectin, Clinical Factors, And Patient Outcomes During The Acute Respiratory Distress Syndrome., Allan J Walkey, Serkalem Demissie, Dilip Shah, Freddy Romero, Leah Puklin, Ross S Summer

Center for Translational Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS).

METHODS: We performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.

RESULTS: Plasma APN concentrations were measured in 816 (81.6%) trial participants at baseline and in 568 (56.8%) subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, …

Emerging Multidrug Resistance Of Methicillin-Resistant Staphylococcus Aureus In Hand Infections., Rick Tosti, Brian T Samuelsen, Samantha Bender, John R Fowler, John Gaughan, Alyssa A Schaffer, Asif M Ilyas

Rothman Institute Papers

BACKGROUND: Methicillin-resistant Staphylococcus aureus has been the most commonly identified pathogen in hand infections at urban centers, but the evolving antibiotic sensitivity profiles of methicillin-resistant Staphylococcus aureus are not known. The purposes of this study are to determine if multidrug resistance in methicillin-resistant Staphylococcus aureus is emerging and to provide current recommendations for empiric antibiotic selection for hand infections in endemic regions.

METHODS: An eight-year longitudinal, retrospective chart review was performed on all culture-positive hand infections encountered by an urban hospital from 2005 to 2012. The proportions of all major organisms were calculated for each year. Methicillin-resistant Staphylococcus aureus infections …

Glutathione: A Possible Link To Autophagy In Systemic Lupus Erythematosus, Dilip Shah, Swapan K. Nath

Center for Translational Medicine Faculty Papers

No abstract provided.

Nuclear And Mitochondrial Trna-Lookalikes In The Human Genome., Aristeidis G Telonis, Phillipe Loher, Yohei Kirino, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

We are interested in identifying and characterizing loci of the human genome that harbor sequences resembling known mitochondrial and nuclear tRNAs. To this end, we used the known nuclear and mitochondrial tRNA genes (the "tRNA-Reference" set) to search for "tRNA-lookalikes" and found many such loci at different levels of sequence conservation. We find that the large majority of these tRNA-lookalikes resemble mitochondrial tRNAs and exhibit a skewed over-representation in favor of some mitochondrial anticodons. Our analysis shows that the tRNA-lookalikes have infiltrated specific chromosomes and are preferentially located in close proximity to known nuclear tRNAs (z-score ≤ -2.54, P-value ≤ …

Mir-103a-3p Targets The 5' Utr Of Gprc5a In Pancreatic Cells., Honglei Zhou, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

MicroRNAs (miRNAs) are short noncoding RNAs that regulate the expression of their targets in a sequence-dependent manner. For protein-coding transcripts, miRNAs regulate expression levels through binding sites in either the 3' untranslated region (3' UTR) or the amino acid coding sequence (CDS) of the targeted messenger RNA (mRNA). Currently, for the 5' untranslated region (5' UTR) of mRNAs, very few naturally occurring examples exist whereby the targeting miRNA down-regulates the expression of the corresponding mRNA in a seed-dependent manner. Here we describe and characterize two miR-103a-3p target sites in the 5' UTR of GPRC5A, a gene that acts as a …

Understanding Patient Options, Utilization Patterns, And Burdens Associated With Breast Cancer Screening., Susan C Harvey, Ashok Vegesna, Sharon Mass, Janice L. Clarke, Alexandria Skoufalos

College of Population Health Faculty Papers

Abstract Despite ongoing awareness, educational campaigns, and advances in technology, breast cancer screening remains a complex topic for women and for the health care system. Lack of consensus among organizations developing screening guidelines has caused confusion for patients and providers. The psychosocial factors related to breast cancer screening are not well understood. The prevailing algorithm for screening results in significant rates of patient recall for further diagnostic imaging or procedures, the majority of which rule out breast cancer rather than confirming it. For women, the consequences of the status quo range from unnecessary stress to additional out-of-pocket expenses to indirect …

Adrenergic Signaling Regulates Mitochondrial Ca2+ Uptake Through Pyk2-Dependent Tyrosine Phosphorylation Of The Mitochondrial Ca2+ Uniporter., Jin O-Uchi, Bong Sook Jhun, Shangcheng Xu, Stephen Hurst, Anna Raffaello, Xiaoyun Liu, Bing Yi, Huiliang Zhang, Polina Gross, Jyotsna Mishra, Alina Ainbinder, Sarah Kettlewell, Godfrey L Smith, Robert T Dirksen, Wang Wang, Rosario Rizzuto, Shey-Shing Sheu

Department of Medicine Faculty Papers

AIMS: Mitochondrial Ca2+ homeostasis is crucial for balancing cell survival and death. The recent discovery of the molecular identity of the mitochondrial Ca2+ uniporter pore (MCU) opens new possibilities for applying genetic approaches to study mitochondrial Ca2+ regulation in various cell types, including cardiac myocytes. Basal tyrosine phosphorylation of MCU was reported from mass spectroscopy of human and mouse tissues, but the signaling pathways that regulate mitochondrial Ca2+ entry through posttranslational modifications of MCU are completely unknown. Therefore, we investigated α1-adrenergic-mediated signal transduction of MCU posttranslational modification and function in cardiac cells.

RESULTS: α1-adrenoceptor (α1-AR) signaling translocated activated proline-rich tyrosine …

Mitochondrial Ion Channels/Transporters As Sensors And Regulators Of Cellular Redox Signaling., Jin O-Uchi, Shin-Young Ryu, Bong Sook Jhun, Stephen Hurst, Shey-Shing Sheu

Department of Medicine Faculty Papers

SIGNIFICANCE: Mitochondrial ion channels/transporters and the electron transport chain (ETC) serve as key sensors and regulators for cellular redox signaling, the production of reactive oxygen species (ROS) and nitrogen species (RNS) in mitochondria, and balancing cell survival and death. Although the functional and pharmacological characteristics of mitochondrial ion transport mechanisms have been extensively studied for several decades, the majority of the molecular identities that are responsible for these channels/transporters have remained a mystery until very recently.

RECENT ADVANCES: Recent breakthrough studies uncovered the molecular identities of the diverse array of major mitochondrial ion channels/transporters, including the mitochondrial Ca2+ uniporter pore, …

Breach Of Tolerance: Primary Biliary Cirrhosis., Lifeng Wang, Fu-Sheng Wang, Christopher Chang, M Eric Gershwin

Department of Medical Genetics Faculty Papers

In primary biliary cirrhosis (PBC), the breach of tolerance that leads to active disease involves a disruption in several layers of control, including central tolerance, peripheral anergy, a "liver tolerance effect," and the action of T regulatory cells and their related cytokines. Each of these control mechanisms plays a role in preventing an immune response against self, but all of them act in concert to generate effective protection against autoimmunity without compromising the ability of the host immune system to mount an effective response to pathogens. At the same time, genetic susceptibility, environmental factors, including infection agents and xenobiotics, play …

Multisite Phosphorylation Of The Sum1 Transcriptional Repressor By S-Phase Kinases Controls Exit From Meiotic Prophase In Yeast., Daniel Corbi, Sham Sunder, Michael Weinreich, Aikaterini Skokotas, Erica S Johnson, Edward Winter

Department of Biochemistry and Molecular Biology Faculty Papers

Activation of the meiotic transcription factor Ndt80 is a key regulatory transition in the life cycle of Saccharomyces cerevisiae because it triggers exit from pachytene and entry into meiosis. The NDT80 promoter is held inactive by a complex containing the DNA-binding protein Sum1 and the histone deacetylase Hst1. Meiosis-specific phosphorylation of Sum1 by the protein kinases Cdk1, Ime2, and Cdc7 is required for NDT80 expression. Here, we show that the S-phase-promoting cyclin Clb5 activates Cdk1 to phosphorylate most, and perhaps all, of the 11 minimal cyclin-dependent kinase (CDK) phospho-consensus sites (S/T-P) in Sum1. Nine of these sites can individually promote …

Overexpression Of The Astrocyte Glutamate Transporter Glt1 Exacerbates Phrenic Motor Neuron Degeneration, Diaphragm Compromise, And Forelimb Motor Dysfunction Following Cervical Contusion Spinal Cord Injury., Ke Li, Charles Nicaise, Daniel Sannie, Tamara J Hala, Elham Javed, Jessica L Parker, Rajarshi Putatunda, Kathleen A Regan, Valérie Suain, Jean-Pierre Brion, Fred Rhoderick, Megan C Wright, David J Poulsen, Angelo C Lepore

Farber Institute for Neuroscience Faculty Papers

A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, …

The P53-Induced Factor Ei24 Inhibits Nuclear Import Through An Importin Β-Binding-Like Domain., Kim G Lieu, Eun-Hee Shim, Jinling Wang, Ravi K Lokareddy, Tao Tao, Gino Cingolani, Gerard P Zambetti, David A Jans

Department of Biochemistry and Molecular Biology Faculty Papers

The etoposide-induced protein Ei24 was initially identified as a p53-responsive, proapoptotic factor, but no clear function has been described. Here, we use a nonbiased proteomics approach to identify members of the importin (IMP) family of nuclear transporters as interactors of Ei24 and characterize an IMPβ-binding-like (IBBL) domain within Ei24. We show that Ei24 can bind specifically to IMPβ1 and IMPα2, but not other IMPs, and use a mutated IMPβ1 derivative to show that Ei24 binds to the same site on IMPβ1 as the IMPα IBB. Ectopic expression of Ei24 reduced the extent of IMPβ1- or IMPα/β1-dependent nuclear protein import specifically, …

Prospective Unmasked Randomized Evaluation Of The Istent Inject (®) Versus Two Ocular Hypotensive Agents In Patients With Primary Open-Angle Glaucoma., Antonio M Fea, Jose I Belda, Marek Rękas, Anselm Jünemann, Lydia Chang, Luis Pablo, Lilit Voskanyan, L Jay Katz

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to compare outcomes of subjects with open-angle glaucoma (OAG) not controlled on one medication who underwent either implantation of two iStent inject (®) trabecular micro-bypass devices or received medical therapy consisting of a fixed combination of latanoprost/timolol.

PATIENTS AND METHODS: Of 192 subjects who qualified for the study and were enrolled, 94 were randomized to surgery with implantation of two iStent inject(®) devices in the treated eye and 98 to receive medical therapy.

RESULTS: At the month 12 visit, 94.7% of eyes (89/94) in the stent group reported an unmedicated intraocular pressure (IOP) …

Permeation Redux: Thermodynamics And Kinetics Of Ion Movement Through Potassium Channels., Richard Horn, Benoît Roux, Johan Aqvist

Department of Molecular Physiology and Biophysics Faculty Papers

The fundamental biophysics underlying the selective movement of ions through ion channels was launched by George Eisenman in the 1960s, using glass electrodes. This minireview examines the insights from these early studies and the explosive progress made since then.

Detection Of Vascular Endothelial Growth Factor In Colon Cancer Xenografts Using Bevacizumab Based Near Infrared Fluorophore Conjugate., Bishnuhari Paudyal, Pramila Paudyal, Dilip Shah, Hideyuki Tominaga, Yoshito Tsushima, Keigo Endo

Department of Radiology Faculty Papers

BACKGROUND: The aim of this study was to develop the near infrared fluorescence (NIRF)-based imaging agent for the visualization of vascular endothelial growth factor (VEGF) in colon cancer. AlexaFluor 750 conjugating with bevacizumab, and injected intravenously into nude mice bearing VEGF over-expressing HT29 human colorectal cancer. Optical imaging was performed at 15 min, 24 h and 48 h post injection. Immunofluorescences staining of the tumor sections were performed. HT29 colorectal cancer xenografts were clearly visualized with bevacizumab-AlexaFluor 750.

RESULTS: Ex vivo analysis showed 2.1 ± 0.4%, 37.6 ± 6.3% and 38.5 ± 6.2% injected dose/g accumulated in the tumors at …

The Human Platelet: Strong Transcriptome Correlations Among Individuals Associate Weakly With The Platelet Proteome., Eric R Londin, Eleftheria Hatzimichael, Phillipe Loher, Leonard Edelstein, Chad Shaw, Kathleen Delgrosso, Paolo Fortina, Paul Bray, Steven E. Mckenzie, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

BACKGROUND: For the anucleate platelet it has been unclear how well platelet transcriptomes correlate among different donors or across different RNA profiling platforms, and what the transcriptomes' relationship is with the platelet proteome. We profiled the platelet transcriptome of 10 healthy young males (5 white and 5 black) with no notable clinical history using RNA sequencing and by Affymetrix microarray.

RESULTS: We found that the abundance of platelet mRNA transcripts was highly correlated across the 10 individuals, independently of race and of the employed technology. Our RNA-seq data showed that these high inter-individual correlations extend beyond mRNAs to several categories …

Characteristics Of Acute Care Utilization Of A Delaware Adult Sickle Cell Disease Patient Population., Nina Anderson, Jennifer L. Bellot, Oluseyi Senu-Oke, Samir K. Ballas

Department of Nursing papers and presentations

Sickle cell disease (SCD) is an inherited blood disorder that is chronic in nature and manifests itself through many facets of the patient's life. Comprehensive specialty centers have the potential to reduce health care costs and improve the quality of care for patients who have chronic medical conditions such as heart failure and SCD. The purpose of this practice inquiry was to analyze de-identified data for acute care episodes involving SCD in order to create a detailed picture of acute care utilization for adult patients in Delaware with SCD from 2007 to 2009. Gaining a better understanding of acute care …