Digital Commons Network^™

Reliability Of Pressure Ulcer Rates: How Precisely Can We Differentiate Among Hospital Units, And Does The Standard Signal-Noise Reliability Measure Reflect This Precision?, Vincent S. Staggs, Emily Cramer

Manuscripts, Articles, Book Chapters and Other Papers

Hospital performance reports often include rankings of unit pressure ulcer rates. Differentiating among units on the basis of quality requires reliable measurement. Our objectives were to describe and apply methods for assessing reliability of hospital-acquired pressure ulcer rates and evaluate a standard signal-noise reliability measure as an indicator of precision of differentiation among units. Quarterly pressure ulcer data from 8,199 critical care, step-down, medical, surgical, and medical-surgical nursing units from 1,299 US hospitals were analyzed. Using beta-binomial models, we estimated between-unit variability (signal) and within-unit variability (noise) in annual unit pressure ulcer rates. Signal-noise reliability was computed as the ratio …

The Occurrence Of Hyponatremia And Its Importance As A Prognostic Factor In A Cross-Section Of Cancer Patients, Jorge J. Castillo, Ilya G. Glezerman, Susan H. Boklage, Joseph Chiodo, Beni A. Tidwell, Lois E. Lamerato, Kathy L. Schulman

Public Health Sciences Articles

BACKGROUND: Hyponatremia is prognostic of higher mortality in some cancers but has not been well studied in others. We used a longitudinal design to determine the incidence and prognostic importance of euvolemic and hypervolemic hyponatremia in patients following diagnosis with lymphoma, breast (BC), colorectal (CRC), small cell lung (SCLC), or non-small cell lung cancer (NSCLC).

METHODS: Medical record and tumor registry data from two large integrated delivery networks were combined for patients diagnosed with lymphoma, BC, CRC, or lung cancers (2002-2010) who had ≥1 administration of radiation/chemotherapy within 6 months of diagnosis and no evidence of hypovolemic hyponatremia. Hyponatremia incidence …

Definitions For Sepsis And Septic Shock, Sean R. Townsend, Emanuel Rivers, Lemeneh Tefera

Emergency Medicine Articles

No abstract provided.

Magic Study: Aims, Design And Methods Using Systemchange™ To Improve Immunosuppressive Medication Adherence In Adult Kidney Transplant Recipients., Cynthia L. Russell, Shirley Moore, Donna Hathaway, An-Lin Cheng, Guoqing Chen, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Among adult kidney transplant recipients, non-adherence to immunosuppressive medications is the leading predictor of poor outcomes, including rejection, kidney loss, and death. An alarming one-third of kidney transplant patients experience medication non-adherence even though the problem is preventable. Existing adherence interventions have proven marginally effective for those with acute and chronic illnesses and ineffective for adult kidney transplant recipients. Our purpose is to describe the design and methods of the MAGIC (Medication Adherence Given Individual SystemCHANGE™) trial

METHODS/DESIGN: We report the design of a randomized controlled trial with an attention-control group to test an innovative 6-month SystemCHANGE™ intervention designed …

Intrinsic Disorder In Transmembrane Proteins: Roles In Signaling And Topology Prediction, Jérôme Bürgi, Bin Xue, Vladimir N Uversky, F Gisou Van Der Goot

Molecular Biosciences Faculty Publications

Intrinsically disordered regions (IDRs) are peculiar stretches of amino acids that lack stable conformations in solution. Intrinsic Disorder containing Proteins (IDP) are defined by the presence of at least one large IDR and have been linked to multiple cellular processes including cell signaling, DNA binding and cancer. Here we used computational analyses and publicly available databases to deepen insight into the prevalence and function of IDRs specifically in transmembrane proteins, which are somewhat neglected in most studies. We found that 50% of transmembrane proteins have at least one IDR of 30 amino acids or more. Interestingly, these domains preferentially localize …

Iron Therapy Challenges For The Treatment Of Nondialysis Ckd Patients, Francesco Locatelli, Sandro Mazzaferro, Jerry Yee

Nephrology Articles

The clinical consequences of untreated, severe anemia in patients with nondialysis CKD can be significant, but disparities exist in the anemia treatment guidelines and position papers issued from working groups and associations across the world. These differ in hemoglobin target and iron levels and their emphasis on various iron markers and other clinical outcomes. Not surprisingly, disparities are observed in anemia treatment strategies among patients with nondialysis CKD across different areas of the world. Over the past decade, the prescription and dosage of both iron therapies and erythropoiesis-stimulating agents have shifted, with notable regional differences observed. Moreover, there is ongoing …

Renin-Angiotensin System Gene Expression And Neurodegenerative Diseases., Benjamin Goldstein, Robert Charles Speth, Malav Suchin Trivedi

Faculty Articles

HYPOTHESIS: Single nucleotide polymorphisms and altered gene expression of components of the renin-angiotensin system (RAS) are associated with neurodegenerative diseases.

INTRODUCTION: Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease.

MATERIALS AND METHODS: A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis.

RESULTS: No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with …

Improving Transitions In Ckd: Failure Mode, Jerry Yee

Nephrology Articles

No abstract provided.

Adverse Drug Effects And Preoperative Medication Factors Related To Perioperative Low-Dose Ketamine Infusions., Eric S. Schwenk, Stephen F. Goldberg, Ronak D. Patel, Jon Zhou, Douglas R. Adams, Jaime L. Baratta, Eugene R. Viscusi, Richard H. Epstein

Department of Anesthesiology Faculty Papers

High-dose opioid administration is associated with significant adverse events. Evidence suggests that low-dose ketamine infusions improve perioperative analgesia over conventional opioid management, but usage is highly variable. Ketamine's adverse drug effects (ADEs) are well known, but their prevalence during low-dose infusions in a clinical setting and how often they lead to infusion discontinuation are unknown. The purposes of this study were 3-fold: (1) to identify patient factors associated with initiation of ketamine infusions during spine surgery, (2) to identify specific spine procedures in which ketamine has been used most frequently, and (3) to identify ADEs associated with postoperative ketamine infusions …

Placing Evidence-Based Interventions At The Fingertips Of School Social Workers, Jose Castillo, Tommi Rivers, Catherine Randall, Ken Gaughan, Tiina Ojanen, Oliver Tom Massey, Donna L. Burton

Psychology Faculty Publications

Through a university-community collaborative partnership, the perceived needs of evidence-based practices (EBPs) among school social workers (SSWs) in a large school district in central Florida was assessed. A survey (response rate = 83.6%) found that although 70% of SSWs claim to use EBPs in their everyday practice, 40% do not know where to find them, which may partially explain why 78% of respondents claim to spend 1 to 4 h every week looking for adequate EBPs. From this needs assessment, the translational model was used to address these perceived needs. A systematic review of the literature found 40 tier 2 …

Early Goal-Directed Therapy In Severe Sepsis And Septic Shock: Insights And Comparisons To Process, Promise, And Arise., H B. Nguyen, Anja K. Jaehne, Namita Jayaprakash, Matthew W. Semler, Sara Hegab, Angel C. Yataco, Geneva Tatem, Dhafer Salem, Steven Moore, Kamran Boka, Jasreen Gill, Jayna Gardner-Gray, Jacqueline Pflaum, Juan P. Domecq, Gina Hurst, Justin B. Belsky, Raymond Fowkes, Ronald B. Elkin, Steven Q. Simpson, Jay L. Falk, Daniel J. Singer, Emanuel Rivers

Emergency Medicine Articles

Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was …

Impact Of Dietary Resistant Starch Type 4 On Human Gut Microbiota And Immunometabolic Functions, Bijaya Upadhyaya, Lacey Mccormack, Ali Reza Fardin-Kia, Robert M. Juenemann, Sailendra Nichenametla, Jeffrey A. Clapper, Bonny Specker, Moul Dey

Health and Nutritional Sciences Faculty Publications

Dietary modulation of the gut microbiota impacts human health. Here we investigated the hitherto unknown effects of resistant starch type 4 (RS4) enriched diet on gut microbiota composition and short-chain fatty acid (SCFA) concentrations in parallel with host immunometabolic functions in twenty individuals with signs of metabolic syndrome (MetS). Cholesterols, fasting glucose, glycosylated haemoglobin, and proinflammatory markers in the blood as well as waist circumference and % body fat were lower post intervention in the RS4 group compared with the control group. 16S-rRNA gene sequencing revealed a differential abundance of 71 bacterial operational taxonomic units, including the enrichment of three …

Characterization Of The Microbiome Of Nipple Aspirate Fluid Of Breast Cancer Survivors., Alfred A Chan, Mina Bashir, Magali N Rivas, Karen Duvall, Peter A Sieling, Thomas R Pieber, Parag A Vaishampayan, Susan M Love, Delphine J Lee

Articles, Abstracts, and Reports

The microbiome impacts human health and disease. Until recently, human breast tissue and milk were presumed to be sterile. Here, we investigated the presence of microbes in the nipple aspirate fluid (NAF) and their potential association with breast cancer. We compared the NAF microbiome between women with a history of breast cancer (BC) and healthy control women (HC) using 16S rRNA gene amplicon sequencing. The NAF microbiome from BC and HC showed significant differences in community composition. Two Operational Taxonomic Units (OTUs) showed differences in relative abundances between NAF collected from BC and HC. In NAF collected from BC, there …

Staphylococcus Aureus Coordinates Leukocidin Expression And Pathogenesis By Sensing Metabolic Fluxes Via Rpirc, Divya Balasubramanian, Elizabeth A Ohneck, Jessica Chapman, Andy Weiss, Min Kyung Kim, Tamara Reyes-Robles, Judy Zhong, Lindsey N. Shaw, Desmond S. Lun, Beatrix Ueberheide, Bo Shopsin, Victor J Torres

Molecular Biosciences Faculty Publications

Staphylococcus aureus is a formidable human pathogen that uses secreted cytolytic factors to injure immune cells and promote infection of its host. Of these proteins, the bicomponent family of pore-forming leukocidins play critical roles in S. aureus pathogenesis. The regulatory mechanisms governing the expression of these toxins are incompletely defined. In this work, we performed a screen to identify transcriptional regulators involved in leukocidin expression in S. aureus strain USA300. We discovered that a metabolic sensor-regulator, RpiRc, is a potent and selective repressor of two leukocidins, LukED and LukSF-PV. Whole-genome transcriptomics, S. aureus exoprotein proteomics, and metabolomic analyses revealed that …

A Randomized, Double-Blind, Placebo-Controlled Phase Ii Trial Investigating The Safety And Immunogenicity Of Modified Vaccinia Ankara Smallpox Vaccine (Mva-Bn®) In 56-80-Year-Old Subjects, Richard N. Greenberg, Christine M. Hay, Jack T. Stapleton, Thomas C. Marbury, Eva Wagner, Eva Kreitmeir, Siegfried Röesch, Alfred Von Krempelhuber, Philip Young, Richard Nichols, Thomas P. Meyer, Darja Schmidt, Josef Weigl, Garth Virgin, Nathaly Arndtz-Wiedemann, Paul Chaplin

Internal Medicine Faculty Publications

Background Modified Vaccinia Ankara MVA-BN^® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN^® (MVA) was assessed in a 56–80 years old population.

Methods MVA with a virus titer of 1 x 10⁸ TCID₅₀/dose was administered via subcutaneous injection to 56–80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated …

The Brain Imaging Data Structure, A Format For Organizing And Describing Outputs Of Neuroimaging Experiments, Krzysztof Gorgolewski, Tibor Auer, Vince Calhoun, R Cameron Craddock, Samir Das, Eugene Duff, Guillaume Flandin, Tristan Glatard, Yaroslav Halchenko

Dartmouth Scholarship

The development of magnetic resonance imaging (MRI) techniques has defined modern neuroimaging. Since its inception, tens of thousands of studies using techniques such as functional MRI and diffusion weighted imaging have allowed for the non-invasive study of the brain. Despite the fact that MRI is routinely used to obtain data for neuroscience research, there has been no widely adopted standard for organizing and describing the data collected in an imaging experiment. This renders sharing and reusing data (within or between labs) difficult if not impossible and unnecessarily complicates the application of automatic pipelines and quality assurance protocols. To solve this …

De Novo Deciphering Three-Dimensional Chromatin Interaction And Topological Domains By Wavelet Transformation Of Epigenetic Profiles., Yong Chen, Yunfei Wang, Zhenyu Xuan, Min Chen, Michael Q Zhang

College of Science & Mathematics Departmental Research

Defining chromatin interaction frequencies and topological domains is a great challenge for the annotations of genome structures. Although the chromosome conformation capture (3C) and its derivative methods have been developed for exploring the global interactome, they are limited by high experimental complexity and costs. Here we describe a novel computational method, called CITD, for de novo prediction of the chromatin interaction map by integrating histone modification data. We used the public epigenomic data from human fibroblast IMR90 cell and embryonic stem cell (H1) to develop and test CITD, which can not only successfully reconstruct the chromatin interaction frequencies discovered by …

Asfotase Alfa Therapy For Children With Hypophosphatasia, Michael P. Whyte, Katherine L. Madson, Dawn Phillips, Amy L. Reeves, William H. Mcalister, Amy Yakimoski, Karen E. Mack, Kim Hamilton, Kori Kagan, Kenji P. Fujita, David D. Thompson, Scott Moseley, Tatjana Odrljin, Cheryl Rockman-Greenberg

Open Access Publications

No abstract provided.

Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S Mhashilkar, Sai L Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R Palli, H. Lee Woodcock Iii, Thomas R Unnasch

Chemistry Faculty Publications

BACKGROUND: A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

METHODOLOGY/ PRINCIPAL FINDINGS: Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. …

Smartphone Apps: A Patient's New Best Friend?, Tejas Desai, Jerry Yee, Sandeep Soman

Nephrology Articles

No abstract provided.

American Academy Of Neurology Guidelines And The Neurologic Determination Of Death-Reply, David M. Greer, Panayiotis N. Varelas, Eelco Fm Wijdicks

Neurology Articles

No abstract provided.

Improved Student Learning Through A Faculty Learning Community: How Faculty Collaboration Transformed A Large-Enrollment Course From Lecture To Student Centered, Emily R. Elliott, Robert D. Reason, Clark R. Coffman, Eric J. Gangloff, Jeffrey R Raker, Jo Anne Powell-Coffman, Craig A. Ogilvie

Chemistry Faculty Publications

Undergraduate introductory biology courses are changing based on our growing understanding of how students learn and rapid scientific advancement in the biological sciences. At Iowa State University, faculty instructors are transforming a second-semester large-enrollment introductory biology course to include active learning within the lecture setting. To support this change, we set up a faculty learning community (FLC) in which instructors develop new pedagogies, adapt active-learning strategies to large courses, discuss challenges and progress, critique and revise classroom interventions, and share materials. We present data on how the collaborative work of the FLC led to increased implementation of active-learning strategies and …

Fresh Autologous Pericardium To Reconstruct The Pulmonary Valve At The Annulus When Tetralogy Of Fallot Requires A Transannular Patch At Midterm, Shantanu Pande, Jugal K Sharma, C R Siddartha, Anubhav Bansal, Surendra K Agarwal, Prabhat Tewari, Aditya Kapoor

The Texas Heart Institute Journal

Tetralogy of Fallot often requires reconstruction of the right ventricular outflow tract with a transannular patch (TAP), but this renders the pulmonary valve incompetent and eventually leads to right ventricular dysfunction.

We retrospectively evaluated the efficacy of a reconstructed pulmonary valve and annulus in 70 patients who underwent, from December 2006 through December 2010, complete correction of tetralogy of Fallot. We divided the 70 patients into 2 groups in accordance with whether they required (n=50) or did not require (n=20) a TAP. We used autologous untreated pericardium to fashion the TAP and to create both an annulus of the correct …

Emergency Coronary Artery Bypass Grafting: Indications And Outcomes From 2003 Through 2013, Erin M Schumer, John H Chaney, Jaimin R Trivedi, Paul L Linsky, Matthew L Williams, Mark S Slaughter

The Texas Heart Institute Journal

Emergency coronary artery bypass grafting (CABG) is associated with increased in-hospital mortality rates and adverse events. This study retrospectively evaluated indications and outcomes in patients who underwent emergency CABG.

The Society of Thoracic Surgeons database for a single center (Jewish Hospital) was queried to identify patients undergoing isolated CABG. Univariate analysis was performed.

From January 2003 through December 2013, 5,940 patients underwent CABG; 212 presented with emergency status. A high proportion of female patients (28.2%) underwent emergency surgery. Emergency CABG patients experienced high rates of intra-aortic balloon pump support, bleeding, dialysis, in-hospital death, and prolonged length of stay. The proportion …

Two Cases Of Transcatheter Closure Of Central Aortopulmonary Shunts: One With An Amplatzer Duct Occluder Ii And One With An Amplatzer Vascular Plug I, Ahmet Celebi, Ilker Kemal Yucel, Sevket Balli, Mehmet Kucuk

The Texas Heart Institute Journal

When total correction is not possible in infants who have a cyanotic congenital heart disease, creation of a palliative aortopulmonary shunt is essential. A central aortopulmonary shunt is preferable, because of its technical and hemodynamic advantages. Overcirculation, thrombosis, and stenosis of the shunt are the main postoperative sequelae that necessitate urgent reintervention. Percutaneous transcatheter closure of aortopulmonary shunts can eliminate the need for reoperation and substantially decrease postoperative morbidity and mortality rates. We report our successful transcatheter closures of central aortopulmonary shunts in a 3-month-old infant and a 15-year-old girl, with use of an Amplatzer Duct Occluder II and an …

The Hiv-1 Tat Protein Is Monomethylated At Lysine 71 By The Lysine Methyltransferase Kmt7, Ibraheem Ali, Holly Ramage, Daniela Boehm, Lynnette M. A. Dirk, Naoki Sakane, Kazuki Hanada, Sara Pagans, Katrin Kaehlcke, Katherine Aull, Leor Weinberger, Raymond Trievel, Martina Schnoelzer, Masafumi Kamada, Robert L. Houtz, Melanie Ott

Horticulture Faculty Publications

The HIV-1 transactivator protein Tat is a critical regulator of HIV transcription primarily enabling efficient elongation of viral transcripts. Its interactions with RNA and various host factors are regulated by ordered, transient post-translational modifications. Here, we report a novel Tat modification, monomethylation at lysine 71 (K71). We found that Lys-71 monomethylation (K71me) is catalyzed by KMT7, a methyltransferase that also targets lysine 51 (K51) in Tat. Using mass spectrometry, in vitro enzymology, and modification-specific antibodies, we found that KMT7 monomethylates both Lys-71 and Lys-51 in Tat. K71me is important for full Tat transactivation, as KMT7 knockdown impaired the transcriptional activity …

Quantitative Mass Spectrometry Reveals Changes In Histone H2b Variants As Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation, Matthew Rea, Tingting Jiang, Rebekah Eleazer, Meredith Eckstein, Alan G. Marshall, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Exposure to inorganic arsenic, a ubiquitous environmental toxic metalloid, leads to carcinogenesis. However, the mechanism is unknown. Several studies have shown that inorganic arsenic exposure alters specific gene expression patterns, possibly through alterations in chromatin structure. While most studies on understanding the mechanism of chromatin-mediated gene regulation have focused on histone post-translational modifications, the role of histone variants remains largely unknown. Incorporation of histone variants alters the functional properties of chromatin. To understand the global dynamics of chromatin structure and function in arsenic-mediated carcinogenesis, analysis of the histone variants incorporated into the nucleosome and their covalent modifications is required. Here …

Franklin Delano Roosevelt: The Diagnosis Of Poliomyelitis Revisited., John F. Ditunno, Jr, Bruce E. Becker, Gerald J. Herbison

Department of Rehabilitation Medicine Faculty Papers

Revisiting the ailments of famous historical persons in light of contemporary medical understanding has become a common academic hobby. Public discussion of Franklin Delano Roosevelt's (FDR) diagnosis of poliomyelitis after his sudden onset of paralysis in 1921 has received just such a revisitation. Recently, this 2003 historical analysis has been referenced widely on the Internet and in biographies, raising speculation that his actual diagnosis should have been Guillain-Barré Syndrome, a noncontagious disease of the peripheral nervous system rather than poliomyelitis. The authors of that 2003 analysis used a statistical analysis of his case by selectively choosing some of his reported …

Intensive Care Unit Renal Replacement Therapy: Less Is More (Or Better), Jerry Yee

Nephrology Articles

No abstract provided.

Continuous Renal Replacement Therapy For The Management Of Acid-Base And Electrolyte Imbalances In Acute Kidney Injury, Lenar Yessayan, Jerry Yee, Stan Frinak, Balazs Szamosfalvi

Nephrology Articles

Continuous renal replacement therapy (CRRT) is used to manage electrolyte and acid-base imbalances in critically ill patients with acute kidney injury. Although a standard solution and prescription is acceptable in most clinical circumstances, specific disorders may require a tailored approach such as adjusting fluid composition, regulating CRRT dose, and using separate intravenous infusions to mitigate and correct these disturbances. Errors in fluid prescription, compounding, or delivery can be rapidly fatal. This article provides an overview of the principles of acid-base and electrolyte management using CRRT.