Medicine and Health Sciences Commons^™

Isomirmap-Fast, Deterministic, And Exhaustive Mining Of Isomirs From Short Rna-Seq Datasets., Phillipe Loher, Nestoras Karathanasis, Eric R Londin, Paul Bray, Venetia Pliatsika, Aristeidis G. Telonis, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

MOTIVATION: MicroRNA (miRNA) precursor arms give rise to multiple isoforms simultaneously called "isomiRs." IsomiRs from the same arm typically differ by a few nucleotides at either their 5´ or 3´ termini, or both. In humans, the identities and abundances of isomiRs depend on a person's sex, population of origin, race/ethnicity, and on tissue type, tissue state, and disease type/subtype. Moreover, nearly half of the time the most abundant isomiR differs from the miRNA sequence found in public databases. Accurate mining of isomiRs from deep sequencing data is thus important.

RESULTS: We developed isoMiRmap, a fast, standalone, user-friendly mining tool that …

Utilization Of Hiv-1 Envelope V3 To Identify X4- And R5-Specific Tat And Ltr Sequence Signatures., Gregory C Antell, Will Dampier, Benjamas Aiamkitsumrit, Michael R Nonnemacher, Jeffrey M Jacobson, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Gregory Schwartz, Uri Hershberg, Fred C Krebs, Brian Wigdahl

Department of Medicine Faculty Papers

BACKGROUND: HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference during entry, and machine learning predictive algorithms have been developed to characterize sequences as CCR5-utilizing (R5) or CXCR4-utilizing (X4). It was hypothesized that while the V3 loop is predominantly responsible for determining co-receptor binding, additional components of the HIV-1 genome may contribute to overall viral tropism and display sequence signatures …

Reduction Of Ctrp9, A Novel Anti-Platelet Adipokine, Contributes To Abnormal Platelet Activity In Diabetic Animals., Wenqing Wang, Wayne Bond Lau, Yajing Wang, Xin-Liang Ma, Rong Li

Department of Medicine Faculty Papers

Platelet hyper-reactivity is a crucial cause of accelerated atherosclerosis increasing risk of thrombotic vascular events in diabetic patients. The mechanisms leading to abnormal platelet activity during diabetes are complex and not fully defined. The current study attempted to clarify the role of CTRP9, a novel adiponectin paralog, in enhanced platelet activity and determined whether CTRP9 may inhibit platelet activity. Adult male C57BL/6 J mice were randomized to receive high-fat diet (HFD) or normal diet (ND). 8 weeks after HFD, animals were sacrificed, and both plasma CTRP9 and platelet aggregation were determined. HFD-fed animals increased weight gain significantly, and became hyperglycemic …

Neurovascular Disorders: Novel Perspectives On Pathogenesis, Diagnosis, And Treatment., David Hasan, Nohra Chalouhi, Md, Aaron S Dumont, Robert M Starke, Pascal Jabbour Md

Department of Neurosurgery Faculty Papers

No abstract provided.

Chimeric Cells Of Maternal Origin Do Not Appear To Be Pathogenic In The Juvenile Idiopathic Inflammatory Myopathies Or Muscular Dystrophy., Carol M Artlett, Sihem Sassi-Gaha, Ronald C Ramos, Frederick W Miller, Lisa G Rider

Department of Medicine Faculty Papers

INTRODUCTION: Microchimeric cells have been studied for over a decade, with conflicting reports on their presence and role in autoimmune and other inflammatory diseases. To determine whether microchimeric cells were pathogenic or mediating tissue repair in inflammatory myopathies, we phenotyped and quantified microchimeric cells in juvenile idiopathic inflammatory myopathies (JIIM), muscular dystrophy (MD), and noninflammatory control muscle tissues.

METHOD: Fluorescence immunophenotyping for infiltrating cells with sequential fluorescence in situ hybridization was performed on muscle biopsies from ten patients with JIIM, nine with MD and ten controls.

RESULTS: Microchimeric cells were significantly increased in MD muscle (0.079 ± 0.024 microchimeric cells/mm(2) …

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 …

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.

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 …

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

College of Population Health 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 …

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 Faculty 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 ≤ …

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 …

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 …

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, …

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.

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 …

Isprm Discussion Paper: Proposing A Conceptual Description Of Health-Related Rehabilitation Services., Thorsten Meyer, Christoph Gutenbrunner, Carlotte Kiekens, Dimitrios Skempes, John L Melvin, Kuno Schedler, Marta Imamura, Gerold Stucki

Department of Rehabilitation Medicine Faculty Papers

There is a need for a comprehensive classification system of health-related rehabilitation services. For conceptual clarity our aim is to provide a health-related conceptual description of the term "rehabilitation service". First, we introduce a common understanding of the term "rehabilitation", based on the current definition in the World Health Organization's World Report on Disability, and a conceptual description of rehabilitation agreed upon by international Physical and Rehabilitation Medicine organizations. From a health perspective, rehabilitation can be regarded as a general health strategy with the aim of enabling persons with health conditions experiencing or likely to experience disability to achieve and …

Perspectives Of Older Adults On Co-Management Of Low Back Pain By Doctors Of Chiropractic And Family Medicine Physicians: A Focus Group Study., Kevin J Lyons, Stacie A Salsbury, Maria A Hondras, Mark E Jones, Andrew A Andresen, Christine M Goertz

Department of Medical Genetics Faculty Papers

BACKGROUND: While older adults may seek care for low back pain (LBP) from both medical doctors (MDs) and doctors of chiropractic (DCs), co-management between these providers is uncommon. The purposes of this study were to describe the preferences of older adults for LBP co-management by MDs and DCs and to identify their concerns for receiving care under such a treatment model.

METHODS: We conducted 10 focus groups with 48 older adults who received LBP care in the past year. Interviews explored participants' care seeking experiences, co-management preferences, and perceived challenges to successful implementation of a MD-DC co-management model. We analyzed …

Insulin Promotes Glucose Consumption Via Regulation Of Mir-99a/Mtor/Pkm2 Pathway., Wei Li, Jing Wang, Qiu-Dan Chen, Xu Qian, Qi Li, Yu Yin, Zhu-Mei Shi, Lin Wang, Jie Lin, Ling-Zhi Liu, Bing-Hua Jiang

Kimmel Cancer Center Faculty Papers

Insulin is known to regulate multiple cellular functions and is used for the treatment of diabetes. MicroRNAs have been demonstrated to be involved in many human diseases, including Type 2 diabetes. In this study, we showed that insulin decreased miR-99a expression levels, but induced glucose consumption and lactate production, and increased the expression of mTOR, HIF-1α and PKM2 in HepG2 and HL7702 cells. Forced expression of miR-99a or rapamycin treatment blocked insulin-induced PKM2 and HIF-1α expression, and glucose consumption and lactate production. Meanwhile, knockdown of HIF-1α inhibited PKM2 expression and insulin-induced glucose consumption. Taken together, these findings will reveal the …

Glucose Stimulation Induces Dynamic Change Of Mitochondrial Morphology To Promote Insulin Secretion In The Insulinoma Cell Line Ins-1e., Bong Sook Jhun, Hakjoo Lee, Zheng-Gen Jin, Yisang Yoon

Center for Translational Medicine Faculty Papers

Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change …

Life History Theory And Social Psychology., Donald F Sacco, Karol Osipowicz

Department of Neurology Faculty Papers

No abstract provided.

Biosynthetic Pathways And The Role Of The Mas Receptor In The Effects Of Angiotensin-(1-7) In Smooth Muscles., Marcio Augusto Fressatto De Godoy, Larissa Pernomian, Ana Maria De Oliveira, Satish Rattan

Department of Medicine Faculty Papers

Ang-(1-7) is produced via degradation of Ang II by the human angiotensin converting enzyme, also known as ACE2. In the cardiovascular system, Ang-(1-7) has been shown to produce effects that are opposite to those of Ang II. These include smooth muscle relaxation and cardioprotection. While the roles of Ang-(1-7) in other systems are currently topic of intense research, functional data suggest a relaxation action in gastrointestinal smooth muscles in a way that corroborates the results obtained from vascular tissues. However, more studies are necessary to determine a relevant role for Ang-(1-7) in the gastrointestinal system. The Ang-(1-7) actions are mediated …

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Mitochondria Take Center Stage., Shey-Shing Sheu, Robert T Dirksen, Edward N Pugh

Center for Translational Medicine Faculty Papers

No abstract provided.

Loss Of Αt-Catenin Alters The Hybrid Adhering Junctions In The Heart And Leads To Dilated Cardiomyopathy And Ventricular Arrhythmia Following Acute Ischemia., Jifen Li, Steven Goossens, Jolanda Van Hengel, Erhe Gao, Lan Cheng, Koen Tyberghein, Xiying Shang, Riet De Rycke, Frans Van Roy, Glenn L Radice

Center for Translational Medicine Faculty Papers

It is generally accepted that the intercalated disc (ICD) required for mechano-electrical coupling in the heart consists of three distinct junctional complexes: adherens junctions, desmosomes and gap junctions. However, recent morphological and molecular data indicate a mixing of adherens junctional and desmosomal components, resulting in a 'hybrid adhering junction' or 'area composita'. The α-catenin family member αT-catenin, part of the N-cadherin-catenin adhesion complex in the heart, is the only α-catenin that interacts with the desmosomal protein plakophilin-2 (PKP2). Thus, it has been postulated that αT-catenin might serve as a molecular integrator of the two adhesion complexes in the area composita. …

The Diagnosis Of Adrenal Insufficiency In The Critically Ill Patient: Does It Really Matter?, Paul E. Marik

Division of Pulmonary and Critical Care Medicine Faculty Papers

No abstract provided.