Digital Commons Network^™

Variability In Splanchnic Tissue Oxygenation During Preterm Red Blood Cell Transfusion Given For Symptomatic Anaemia May Reveal A Potential Mechanism Of Transfusion-Related Acute Gut Injury, Sean M. Bailey, Karen D. Hendricks-Muñoz, Pradeep V. Mally

Pediatrics Publications

Background

There is increasing evidence indicating an association between red blood cell (RBC) transfusions and necrotising enterocolitis (NEC) in preterm infants, especially late-onset NEC. This phenomenon is referred to as transfusion-related acute gut injury (TRAGI). One theory as to a pathophysiological mechanism is that transfusion may result in an ischemia-reperfusion injury to intestinal tissue. We tested the hypothesis that there is significantly greater variability during transfusion in splanchnic tissue oxygen saturation (SrSO2) than in cerebral tissue oxygen saturation (CrSO2).

Materials and methods

This was a prospective, observational study using near-infrared spectroscopy to monitor SrSO2 and CrSO2in preterm neonates undergoing RBC …

Current Usage Of Animal Assisted Therapy In Nursing Homes In Ramsey County, Minnesota, Lauren K. Duerst, Natalie E. Nikonovich, Ashley M. Young

All Electronic Theses and Dissertations

The main purpose of this study was to determine the use of animal assisted therapy (AAT) for residents living in nursing home facilities in Ramsey County, Minnesota. Furthermore we compiled the thoughts and opinions of each facility director regarding the usage and perceived barriers that accompany the implementation of AAT programs.

Chemically Self-Assembled Antibody Nanorings: A Novel Approach To Bispecific Design For Cancer Therapeutics, Kari A. Gabrielse

All Electronic Theses and Dissertations

Targeted antibody therapeutics are currently being developed for treatment of a wide variety of cancers. By extending the scope of targeted antibody therapeutics into a bispecific design, it has been shown that simultaneous targeting of the CD3 T cell receptor and cancer cell receptors is possible. While great success has been achieved with the use of bispecific agents, many of these agents are genetically fused antibody fragments that can only target one type of cancerous receptor. Here we describe a simple and straightforward method of spontaneously assembling bispecific antibody therapeutics. Using fusion proteins consisting of two dihydrofolate reductase proteins and …

Prevalence Of Non-Conventional And Folk Medicine Usage Among Hmong In St. Paul, Minnesota, Matthew T. Vang

All Electronic Theses and Dissertations

Hmong Americans have been identified to utilize various modes of medicine including: folk/herbal remedies, spiritual/shamanistic rituals, and adapted treatments from countries like Thailand or Laos. However, there is a lack of studies that measured the prevalence of these medications among the Hmong community in Saint Paul, Minnesota. A questionnaire was distributed at a Saint Paul, Minnesota Hmong market to explore the prevalence of Hmong medicine usage. Demographical information was also collected to help determine any relationships that might exist between certain socio-cultural factors and Hmong medicine usage. The study had a total of 54 participants. Of the 54 participants, twenty-eight …

Inhibitory Behavioral Control: A Stochastic Dynamic Causal Modeling Study Comparing Cocaine Dependent Subjects And Controls, Liangsuo Ma, Joel L. Steinberg, Kathryn A. Cunningham, Scott D. Lane, James M. Bjork, Harshini Neelakantan, Amanda E. Price, Ponnada A. Narayana, Thomas R. Kosten, Antoine Bechara, F. Gerard Moeller

Radiology Publications

Cocaine dependence is associated with increased impulsivity in humans. Both cocaine dependence and impulsive behavior are under the regulatory control of cortico-striatal networks. One behavioral laboratory measure of impulsivity is response inhibition (ability to withhold a prepotent response) in which altered patterns of regional brain activation during executive tasks in service of normal performance are frequently found in cocaine dependent (CD) subjects studied with functional magnetic resonance imaging (fMRI). However, little is known about aberrations in specific directional neuronal connectivity in CD subjects. The present study employed fMRI-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity associated …

The Piriform, Perirhinal, And Entorhinal Cortex In Seizure Generation, Marta S. Vismer, Patrick A. Forcelli, Mark D. Skopin, Karen Gale, Mohamad Z. Koubeissi

Neurology Faculty Publications

Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of the limbic and cortical regions of the mammalian brain provide the substrate for the hypersynchrony and hyperexcitability associated with epilepsy and seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition …

The Piriform, Perirhinal, And Entorhinal Cortex In Seizure Generation., Marta S Vismer, Patrick A Forcelli, Mark D Skopin, Karen Gale, Mohamad Z. Koubeissi

Neurology Faculty Publications

Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of mammalian limbic and neocortical brain regions provide the substrate for the hypersynchrony and hyperexcitability associated with seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition of these cortical regions are …

Metabolic Resting-State Brain Networks In Health And Disease, P. G. Spetsieris, J. H. Ko, C. C. Tang, A. Nazem, W. Sako, S. Peng, Y. Ma, V. Dhawan, D. Eidelberg

Journal Articles

The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood …

Implications Of Epigenetic Variability Within A Cell Population For "Cell Type" Classification, I. Tabansky, J. N.H. Stern, D. W. Pfaff

Journal Articles

Here, we propose a new approach to defining nerve "cell types" in reaction to recent advances in single cell analysis. Among cells previously thought to be equivalent, considerable differences in global gene expression and biased tendencies among differing developmental fates have been demonstrated within multiple lineages. The model of classifying cells into distinct types thus has to be revised to account for this intrinsic variability. A "cell type" could be a group of cells that possess similar, but not necessarily identical properties, variable within a spectrum of epigenetic adjustments that permit its developmental path toward a specific function to be …

Parkinson's Disease-Related Spatial Covariance Pattern Identified With Resting-State Functional Mri, T. Wu, Y. Ma, Z. Zheng, S. Peng, X. Wu, D. Eidelberg, P. Chan

Journal Articles

In this study, we sought to identify a disease-related spatial covariance pattern of spontaneous neural activity in Parkinson's disease using resting-state functional magnetic resonance imaging (MRI). Time-series data were acquired in 58 patients with early to moderate stage Parkinson's disease and 54 healthy controls, and analyzed by Scaled Subprofile Model Principal Component Analysis toolbox. A split-sample analysis was also performed in a derivation sample of 28 patients and 28 control subjects and validated in a prospective testing sample of 30 patients and 26 control subjects. The topographic pattern of neural activity in Parkinson's disease was characterized by decreased activity in …

First-In-Human, Phase 1, Randomized, Dose-Escalation Trial With Recombinant Anti-Il-20 Monoclonal Antibody In Patients With Psoriasis, A. B. Gottlieb, J. G. Krueger, M. Sandberg Lundblad, M. Gothberg, B. E. Skolnick

Journal Articles

BACKGROUND: The current trial was a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the recombinant monoclonal anti-interleukin-20 (IL-20) antibody, NNC0109-0012, which targets the inflammatory cytokine IL-20. METHODS: In total, 48 patients aged 18 to 75 years with moderate to severe stable chronic plaque psoriasis with affected body surface area >/=15% and physician global assessment score >/=3 were enrolled in this randomized, double-blind, multicenter, placebo-controlled, phase 1 dose-escalation trial. Patients were randomized within each single dose cohort (0.01, 0.05, 0.2, 0.6, 1.5, or 3.0 mg/kg) or multiple dose cohort (0.05, 0.2, 0.5, 1.0, or 2.0 …

Microvolt T-Wave Alternans In Patients Undergoing Elective Coronary Artery Bypass Grafting: A Pilot Study, G. Khoueiry, M. Abdallah, M. Shariff, M. Kowalski, J. Lafferty

Journal Articles

INTRODUCTION: We designed a prospective observational study targeting a selective population of patients undergoing elective coronary artery bypass grafting with normal systolic function. In this study we looked at the prevalence of pre-operative microvolt T-wave alternans and if it predicts atrial fibrillation after surgery. METHODS: The inclusion criteria included all patients referred to the cardiothoracic outpatient clinic for elective bypass, who can perform aerobic exercise, with a recent exercise stress test exercising at least to 85% of the maximal predicted heart rate (220 - age) and with non-limiting chest pain at maximal exercise. Twenty patients met the inclusion/exclusion criteria between …

Left Ventricular Metastasis From A Primary Pancreatobiliary Tumor, A. N. Makaryus, L. Boxt

Journal Articles

Metastatic disease to the heart is not uncommon. We describe a case of a man in his 60s with an unusual metastasis to the heart and detail its intracardiac location by means of cardiac computerized tomography (CCT) and transthoracic echocardiography. To our knowledge, this is the first report of a pancreatobiliary tumor metastasizing exclusively to the left ventricle (LV) of the heart.

A Common Polymorphism In Scn2a Predicts General Cognitive Ability Through Effects On Pfc Physiology, M. A. Scult, J. W. Trampush, F. Zheng, E. D. Conley, T. Lencz, A. K. Malhotra, D. Dickinson, D. R. Weinberger, A. R. Hariri

Journal Articles

Here we provide novel convergent evidence across three independent cohorts of healthy adults (n = 531), demonstrating that a common polymorphism in the gene encoding the alpha2 subunit of neuronal voltage-gated type II sodium channels (SCN2A) predicts human general cognitive ability or "g." Using meta-analysis, we demonstrate that the minor T allele of a common polymorphism (rs10174400) in SCN2A is associated with significantly higher "g" independent of gender and age. We further demonstrate using resting-state fMRI data from our discovery cohort (n = 236) that this genetic advantage may be mediated by increased capacity for information processing between the dorsolateral …

Reciprocal Interaction Of Wnt And Rxr-Alpha Pathways In Hepatocyte Development And Hepatocellular Carcinoma, J. Li, M. Chanrion, E. Sawey, T. Wang, E. Chow, A. Tward, Y. Su, W. Xue, R. Lucito, L. Zender, +3 Additional Authors

Journal Articles

Genomic analysis of human hepatocellular carcinoma (HCC) is potentially confounded by the differentiation state of the hepatic cell-of-origin. Here we integrated genomic analysis of mouse HCC (with defined cell-of-origin) along with normal development. We found a major shift in expression of Wnt and RXR-alpha pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-alpha gene signature categorized HCCs into two subtypes (high Wnt, low RXR-alpha and low Wnt, high RXR-alpha), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-alpha levels in hepatocytes increased Wnt …

A Massive Overdose Of Dalfampridine, L. J. Fil, P. Sud, S. Sattler

Journal Articles

Multiple sclerosis (MS) is an immune mediated inflammatory disease that attacks myelinated axons in the central nervous system. Dalfampridine (4-aminopyridine) was approved by the Food and Drug Administration in January 2010 for treatment of MS. Our patient was a 34-year-old male with a history of MS, who was brought to the emergency department after being found unresponsive. His current medications were valacyclovir, temazepam, dalfampridine (4-AP) and a tysabri intravenous (IV) infusion. Fifteen minutes after arrival the patient seized. The seizures were refractory to benzodiazepines, barbiturates and phenytoin. The 4-AP level was 530ng/mL (25ng/mL and 49ng/mL). The patient stopped seizing on …

Managing The Inherent Patient Safety Risks Of Electronic Health Records, G.S. Rudolph

Journal Articles

No abstract provided.

Hspb1 As A Novel Regulator Of Ferroptotic Cancer Cell Death, X. Sun, Z. Ou, M. Xie, R. Kang, Y. Fan, X. Niu, H. Wang, L. Cao, D. Tang

Journal Articles

Ferroptosis is an iron-dependent form of non-apoptotic cell death, but its molecular mechanism remains largely unknown. Here, we demonstrate that heat shock protein beta-1 (HSPB1) is a negative regulator of ferroptotic cancer cell death. Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in cancer cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis. Protein kinase C-mediated HSPB1 phosphorylation confers protection against ferroptosis by reducing iron-mediated production of lipid reactive oxygen species. Moreover, inhibition of the HSF1-HSPB1 pathway and HSPB1 phosphorylation increases the anticancer activity …

The Role Of Factor Xa Inhibitors In Venous Thromboembolism Treatment, K. P. Cabral, J. E. Ansell

Journal Articles

Three factor Xa inhibitors have been studied in the treatment of venous thromboembolism, both for acute therapy and as extended therapy to prevent recurrent events. Rivaroxaban, apixaban, and edoxaban have all proven to be effective in Phase III clinical trials for this indication when compared to current standard of therapy with similar or less bleeding. Nevertheless, the agents all offer different pharmacological profiles, which have an impact on patient selection and potential advantages in clinical practice.

Reducing The Risk For Waterborne Nosocomial Neonatal Legionellosis, J. S. Cervia

Journal Articles

No abstract provided.

Full-Length Soluble Urokinase Plasminogen Activator Receptor Down-Modulates Nephrin Expression In Podocytes, M. Alfano, P. Cinque, G. Giusti, S. Proietti, M. Nebuloni, S. Danese, S. D'Alessio, M. Genua, P. C. Singhal, J. Mikulak, +5 Additional Authors

Journal Articles

Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms' tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of alpha v beta 3 integrin RGDfv blocked suPAR-induced suppression of …

Hypersensitivity To Intravenous Iron: Classification, Terminology, Mechanisms And Management, J. Szebeni, S. Fishbane, M. Hedenus, S. Howaldt, F. Locatelli, S. Patni, D. Rampton, G. Weiss, J. Folkersen

Journal Articles

Intravenous (IV) iron therapy is widely used in iron deficiency anemias when oral iron is not tolerated or ineffective. Administration of IV iron is considered a safe procedure, but severe hypersensitivity reactions (HSRs) can occur at a very low frequency. Recently, new guidelines have been published by the European Medicines Agency (EMA) with the intention of making IV-iron therapy safer; however, the current protocols are still non-specific, non-evidence-based empiric measures which neglect the fact that the majority of IV-iron reactions are not Ig-E-mediated anaphylactic reactions. The field would benefit from new specific and effective methods for the prevention and treatment …

Apolipoprotein L1 (Apol1) Variants (Vs) A Possible Link Between Heroin-Associated Nephropathy (Han) And Hiv-Associated Nephropathy (Hivan), X. Lan, T. K. Rao, P. N. Chander, K. Skorecki, P. C. Singhal

Journal Articles

In 1970s, Heroin-associated Nephropathy (HAN), one form of focal and segmental glomerulosclerosis (FSGS), was a predominant cause of End-stage Kidney Disease (ESKD) in African-Americans (AAs). In 1980s, with the surge of Acquired Immune Deficiency Syndrome (AIDS) in AAs, HAN more or less disappeared, and the incidence of Human Immunodeficiency Virus associated Nephropathy (HIVAN) markedly increased. Recent studies in AAs have identified APOL1 variants (Vs) as a major risk factor for the development and progression of non-diabetic kidney diseases including idiopathic FSGS and hypertension-attributed nephrosclerosis. These observations have also offered partial insights into the mechanisms of development, and higher rate of …

Cardiorenal Syndrome And The Role Of The Bone-Mineral Axis And Anemia, D. M. Charytan, S. Fishbane, J. Malyszko, P. A. Mccullough, D. Goldsmith

Journal Articles

The association between chronic kidney disease (CKD) and cardiovascular disease (CVD) is well established, and there is mounting evidence of interorgan cross talk that may accelerate pathologic processes and the progression of organ dysfunction in both systems. This process, termed cardiorenal syndrome (CRS) by the Acute Dialysis Quality Initiative, is considered a major health problem: patients with CKD and CVD are at much higher risk of mortality than patients with either condition alone. To date, the majority of CRS research has focused on neurohormonal mechanisms and hemodynamic alterations. However, mounting evidence suggests that abnormalities in the normal pathophysiology of the …

First Human Treatment With Investigational Rhgus Enzyme Replacement Therapy In An Advanced Stage Mps Vii Patient, J. E. Fox, L. Volpe, J. Bullaro, E. D. Kakkis, W. S. Sly

Journal Articles

Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme beta-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy …

Abnormal Erythroid Maturation Leads To Microcytic Anemia In The Tsap6/Steap3 Null Mouse Model, L. Blanc, J. Papoin, G. Debnath, M. Vidal, R. Amson, A. Telerman, X. L. An, N. Mohandas

Journal Articles

Genetic ablation of the ferrireductase STEAP3, also known as TSAP6, leads to severe microcytic and hypochromic red cells with moderate anemia in the mouse. However, the mechanism leading to anemia is poorly understood. Previous results indicate that TSAP6/Steap3 is a regulator of exosome secretion. Using TSAP6/Steap3 knockout mice, we first undertook a comprehensive hematologic characterization of the red cell compartment, and confirmed a dramatic decrease in the volume and hemoglobin content of these erythrocytes. We observed marked anisocytosis as well as the presence of fragmenting erythrocytes. Consistent with these observations, we found by ektacytometry decreased membrane mechanical stability of knockout …

Association Of Prenatal Perchlorate, Thiocyanate, And Nitrate Exposure With Neonatal Size And Gestational Age, K. A. Evans, D. Q. Rich, B. Weinberger, A. M. Vetrano, L. Valentin-Blasini, P. O. Strickland, B. C. Blount

Journal Articles

BACKGROUND: Perchlorate and similar anions compete with iodine for uptake into the thyroid by the sodium iodide symporter (NIS). This may restrict fetal growth via impaired thyroid hormone production. METHODS: We collected urine samples from 107 pregnant women and used linear regression to estimate differences in newborn size and gestational age associated with increases in perchlorate, thiocyanate, nitrate, and perchlorate equivalence concentrations (PEC; measure of total NIS inhibitor exposure). RESULTS: NIS inhibitor concentrations were not associated with newborn weight, length, or gestational age. Each 2.62ng/mug creatinine increase in perchlorate was associated with smaller head circumference (0.32cm; 95% CI: -0.66, 0.01), …

Congenital Adrenal Hyperplasia, P. W. Speiser

Journal Articles

Congenital adrenal hyperplasia associated with deficiency of steroid 21-hydroxylase is the most common inborn error in adrenal function and the most common cause of adrenal insufficiency in the pediatric age group. As patients now survive into adulthood, adult health-care providers must also be familiar with this condition. Over the past several years, F1000 has published numerous commentaries updating research and practical guidelines for this condition. The purposes of this review are to summarize basic information defining congenital adrenal hyperplasia and to highlight current knowledge and controversies in management.

[In Time: Human Milk Is The Feeding Strategy To Prevent Necrotizing Enterocolitis], R. J. Schanler

Journal Articles

No abstract provided.

Inherited Disorders Of Bilirubin Clearance, N. Memon, B. I. Weinberger, T. Hegyi, L. M. Aleksunes

Journal Articles

Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy.Pediatric Research (2015); doi:10.1038/pr.2015.247.