Digital Commons Network^™

A 129-Kb Deletion On Chromosome 12 Confers Substantial Protection Against Rheumatoid Arthritis, Implicating The Gene Slc2a3, C. D. Veal, K. E. Reekie, J. C. Lorentzen, P. K. Gregersen, L. Padyukov, A. J. Brookes

Journal Articles

We describe a copy-number variant (CNV) for which deletion alleles confer a protective affect against rheumatoid arthritis (RA). This CNV reflects net unit deletions and expansions to a normal two-unit tandem duplication located on human chr12p13.31, a region with conserved synteny to the rat RA susceptibility quantitative trait loci Oia2. Genotyping, using the paralogue ratio test and SNP intensity data, in Swedish samples (2,403 cases, 1,269 controls) showed that the frequency of deletion variants is significantly lower in cases (P=0.0012, OR=0.442 [95%CI 0.258-0.755]). Reduced frequencies of deletion variants were also seen in replication materials comprising 9,201 UK samples (1,846 cases, …

Expression And Prognostic Impact Of Lncrnas In Acute Myeloid Leukemia, R. Garzon, S. Volinia, D. Papaioannou, D. Nicolet, J. Kohlschmidt, P. S. Yan, K. Mrozek, D. Bucci, J. E. Kolitz, C. D. Bloomfield, +15 Additional Authors

Journal Articles

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged >/=60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive …

Hypersensitivity Reactions To Intravenous Iron: Guidance For Risk Minimization And Management, D. Rampton, J. Folkersen, S. Fishbane, M. Hedenus, S. Howaldt, F. Locatelli, S. Patni, J. Szebeni, G. Weiss

Journal Articles

Intravenous iron is widely used for the treatment of iron deficiency anemia when oral iron is inappropriate, ineffective or poorly tolerated. Acute hypersensitivity reactions during iron infusions are very rare but can be life-threatening. This paper reviews their frequency, pathogenesis and risk factors, and provides recommendations about their management and prevention. Complement activation-related pseudo-allergy triggered by iron nanoparticles is probably a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple …

Immunochip Identifies Novel, And Replicates Known, Genetic Risk Loci For Rheumatoid Arthritis In Black South Africans, N. Govind, A. Choudhury, B. Hodkinson, C. Ickinger, J. Frost, A. Lee, P. K. Gregersen, R. J. Reynolds, S. L. Bridges, M. Tikly, +2 Additional Authors

Journal Articles

The aim of this study was to identify genetic variants associated with rheumatoid arthritis (RA) risk in black South Africans. Black South African RA patients (n = 263) were compared with healthy controls (n = 374). Genotyping was performed using the Immunochip, and four-digit high-resolution human leukocyte antigen (HLA) typing was performed by DNA sequencing of exon 2. Standard quality control measures were implemented on the data. The strongest associations were in the intergenic region between the HLA-DRB1 and HLA-DQA1 loci. After conditioning on HLA-DRB1 alleles, the effect in the rest of the extended major histocompatibility (MHC) diminished. Non-HLA single …

Prolonged Survival In Metastatic Colorectal Cancer Following Chemotherapy, D. Paul, M. Gold, N. Nouraddin

Journal Articles

KEY CLINICAL MESSAGE: The cost of treating metastatic colorectal cancer has increased significantly after the introduction of targeted antivascular therapies. We report the unusual case of a patient with colorectal cancer with several large liver metastases at diagnosis, who was cured after removal of the primary tumor and treatment with 5-FU/LV only.

A Role For Noncoding Variation In Schizophrenia, P. Roussos, A. C. Mitchell, G. Voloudakis, J. F. Fullard, V. M. Pothula, J. Tsang, E. A. Stahl, A. Georgakopoulos, P. K. Gregersen, P. Sklar, +15 Additional Authors

Journal Articles

A large portion of common variant loci associated with genetic risk for schizophrenia reside within noncoding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from the human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci for a potential functional role, based on colocalization of a risk SNP, eQTL, and regulatory element sequence. We identified potential physical interactions of noncontiguous proximal and distal regulatory elements. This was verified in prefrontal …

Spla2 Ib Induces Human Podocyte Apoptosis Via The M-Type Phospholipase A2 Receptor, Y. B. Pan, J. X. Wan, Y. P. Liu, Q. Yang, W. Liang, P. C. Singhal, M. A. Saleem, G. H. Ding

Journal Articles

The M-type phospholipase A2 receptor (PLA2R) is expressed in podocytes in human glomeruli. Group IB secretory phospholipase A2 (sPLA2 IB), which is one of the ligands of the PLA2R, is more highly expressed in chronic renal failure patients than in controls. However, the roles of the PLA2R and sPLA2 IB in the pathogenesis of glomerular diseases are unknown. In the present study, we found that more podocyte apoptosis occurs in the kidneys of patients with higher PLA2R and serum sPLA2 IB levels. In vitro, we demonstrated that human podocyte cells expressed the PLA2R in the cell membrane. After binding with …

The Treatment-Naive Microbiome In New-Onset Crohn's Disease, D. Gevers, S. Kugathasan, L. A. Denson, Y. Vazquez-Baeza, W. Van Treuren, B. Y. Ren, E. Schwager, D. Knights, J. Markowitz, R. J. Xavier, +22 Additional Authors

Journal Articles

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with …

Randomized, Double-Blind, Placebo-Controlled Trial Of The Efficacy And Safety Of Rilonacept In The Treatment Of Systemic Juvenile Idiopathic Arthritis, N. T. Ilowite, K. Prather, Y. Lokhnygina, L. E. Schanberg, M. Elder, D. Milojevic, J. W. Verbsky, S. J. Spalding, B. S. Gottlieb, C. I. Sandborg, +12 Additional Authors

Journal Articles

OBJECTIVE: To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. METHODS: An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in >/=2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by …

A New System For Naming Ribosomal Proteins, N. Ban, R. Beckmann, J. H. D. Cate, J. D. Dinman, F. Dragon, S. R. Ellis, D. L. J. Lafontaine, L. Lindahl, J. M. Lipton, M. Yusupov, +15 Additional Authors

Journal Articles

A system for naming ribosomal proteins is described that the authors intend to use in the future. They urge others to adopt it. The objective is to eliminate the confusion caused by the assignment of identical names to ribosomal proteins from different species that are unrelated in structure and function. In the system proposed here, homologous ribosomal proteins are assigned the same name, regardless of species. It is designed so that new names are similar enough to old names to be easily recognized, but are written in a format that unambiguously identifies them as 'new system' names.

Newborn Screening For Scid In New York State: Experience From The First Two Years, B. H. Vogel, V. Bonagura, G. A. Weinberg, M. Ballow, J. Isabelle, L. Diantonio, A. Parker, A. Young, C. Cunningham-Rundles, M. Caggana, +8 Additional Authors

Journal Articles

PURPOSE: To describe the process and assess outcomes for the first 2 years of newborn screening for severe combined immunodeficiency (SCID NBS) in New York State (NYS). METHODS: The NYS algorithm utilizes a first-tier molecular screen for TRECs (T-cell receptor excision circles), the absence of which is indicative of increased risk of immunodeficiency. RESULTS: During the first 2 years, 485,912 infants were screened for SCID. Repeat specimens were requested from 561 premature and 746 non-premature infants with low or borderline TRECs. A total of 531 infants were referred for diagnostic evaluation leading to identification of 10 infants with SCID and …

Circulating Complexes Of The Vitamin D Binding Protein With G-Actin Induce Lung Inflammation By Targeting Endothelial Cells, L. Y. Ge, G. Trujillo, E. J. Miller, R. R. Kew

Journal Articles

This study investigated the actin scavenger function of the vitamin D binding protein (DBP) in vivo using DBP null (-/-) mice. Intravenous injection of G-actin into wild-type (DBP+/+) and DBP-/- mice showed that contrary to expectations, DBP+/+ mice developed more severe acute lung inflammation. Inflammation was restricted to the lung and pathological changes were clearly evident at 1.5 and 4 h post-injection but were largely resolved by 24 h. Histology of DBP+/+ lungs revealed noticeably more vascular leakage, hemorrhage and thickening of the alveolar wall. Flow cytometry analysis of whole lung homogenates showed significantly increased neutrophil infiltration into DBP+/+ mouse …

Approaching The Next Revolution? Evolutionary Integration Of Neural And Immune Pathogen Sensing And Response, K. J. Tracey

Journal Articles

Mammalian immunity evolved by the process of natural selection that produced differential survival and reproduction advantages through combinations of hereditary traits underlying the response to pathogens. Primitive animals sense the presence of microbial pathogens through recognition of pathogen-derived molecules in their rudimentary immune and nervous systems. No molecular biological mechanism assigns primacy of pathogen sensing mechanisms to immune cells over neurons. Rather, in animals as diverse as Caenorhabditis elegans to mammals, neural reflexes are activated by the presence of pathogens and transduce neural mechanisms that control the development of immunity. A coming revolution in immunological thinking will require immunologists to …

Central Cholinergic Activation Of A Vagus Nerve-To-Spleen Circuit Alleviates Experimental Colitis, H. Ji, M. F. Rabbi, B. Labis, V. A. Pavlov, K. J. Tracey, J. E. Ghia

Journal Articles

The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and alpha 7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility …

Lymphocyte Called Home: Beta2-Adreneric Neurotransmission Confines T Cells To Lymph Nodes To Suppress Inflammation, K J. Tracey

Journal Articles

No abstract provided.

Mapping Human Brain Networks With Cortico-Cortical Evoked Potentials, C. J. Keller, C. J. Honey, P. Megevand, L. Entz, I. Ulbert, A. D. Mehta

Journal Articles

The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode …

Nanocomposite Scaffold For Chondrocyte Growth And Cartilage Tissue Engineering: Effects Of Carbon Nanotube Surface Functionalization, N. O. Chahine, N. M. Collette, C. B. Thomas, D. C. Genetos, G. G. Loots

Journal Articles

The goal of this study was to assess the long-term biocompatibility of single-wall carbon nanotubes (SWNTs) for tissue engineering of articular cartilage. We hypothesized that SWNT nanocomposite scaffolds in cartilage tissue engineering can provide an improved molecular-sized substrate for stimulation of chondrocyte growth, as well as structural reinforcement of the scaffold's mechanical properties. The effect of SWNT surface functionalization (-COOH or -PEG) on chondrocyte viability and biochemical matrix deposition was examined in two-dimensional cultures, in three-dimensional (3D) pellet cultures, and in a 3D nanocomposite scaffold consisting of hydrogels + SWNTs. Outcome measures included cell viability, histological and SEM evaluation, GAG …

Do Hiv-Positive Women Receive Depression Treatment That Meets Best Practice Guidelines?, J. A. Cook, J. K. Burke-Miller, D. D. Grey, J. Cocohoba, C. L. Liu, R. M. Schwartz, E. T. Golub, K. Anastos, P. J. Steigman, M. H. Cohen

Journal Articles

This study addressed whether psychopharmacologic and psychotherapeutic treatment of depressed HIV+ women met standards defined in the best practice literature, and tested hypothesized predictors of standard-concordant care. 1,352 HIV-positive women in the multi-center Women's Interagency HIV Study were queried about depressive symptoms and mental health service utilization using standards published by the American Psychiatric Association and the Agency for Healthcare Research and Quality to define adequate depression treatment. We identified those who: (1) reported clinically significant depressive symptoms (CSDS) using Centers for Epidemiological Studies-Depression Scale scores of a parts per thousand yen16; or (2) had lifetime diagnoses of major depressive …

Low Vitamin D Level Is An Independent Predictor Of Poor Outcomes In Clostridium Difficile-Associated Diarrhea, W. J. Wang, S. Gray, C. Sison, S. Arramraju, B. K. John, S. A. Hussain, S. H. Kim, P. Mehta, M. Rubin

Journal Articles

Background: The incidence, recurrence, and all-cause mortality rate for Clostridium difficile-associated diarrhea (CDAD) has increased markedly over the past 10 years despite treatment. Low vitamin D levels are known to impair immune responses to infection and are associated with increased mortality. We compared the role of patient comorbidity measured by the Charlson Comorbidity Index (CCI) with vitamin D levels to ascertain whether vitamin D levels were an independent variable affecting the outcome of CDAD or a marker of overall comorbidity. Methods: A prospective cohort study studied 62 patients hospitalized between 2008 and 2009 with manifestations of CDAD and a positive …

Autoimmunity To Vimentin And Lupus Nephritis, A. Davidson

Journal Articles

No abstract provided.

Letter From Incoming Editor In Chief Of Molecular Medicine, Dr. Betty Diamond, B. Diamond

Journal Articles

No abstract provided.

Low-Dose T-3 Replacement Restores Depressed Cardiac T-3 Levels, Preserves Coronary Microvasculature And Attenuates Cardiac Dysfunction In Experimental Diabetes Mellitus, N. Y. Weltman, K. Ojamaa, E. H. Schlenker, Y. F. Chen, R. Zucchi, A. Saba, D. Colligiani, V. Rajagopalan, C. J. Pol, A. M. Gerdes

Journal Articles

Thyroid dysfunction is common in individuals with diabetes mellitus (DM) and may contribute to the associated cardiac dysfunction. However, little is known about the extent and pathophysiological consequences of low thyroid conditions on the heart in DM. DM was induced in adult female Sprague Dawley (SD) rats by injection of nicotinamide (N; 200 mg/kg) followed by streptozotocin (STZ; 65 mg/kg). One month after STZ/N, rats were randomized to the following groups (N = 10/group): STZ/N or STZ/N + 0.03 g/mL T-3; age-matched vehicle-treated rats served as nondiabetic controls (C). After 2 months of T-3 treatment (3 months post-DM induction), left …

Genotyping Of Immune-Related Genetic Variants Identifies Tyk2 As A Novel Associated Locus For Idiopathic Inflammatory Myopathies, M. Jani, J. Massey, L. R. Wedderburn, J. Vencovsky, K. Danko, I. E. Lundberg, L. Padyukov, A. Lee, P. K. Gregersen, Eumyonet, +10 Additional Authors

Journal Articles

No abstract provided.

Knowledge And Prevention Practices Before Breast Cancer Diagnosis In A Cross-Sectional Study Among Survivors: Impact On Patients' Involvement In The Decision Making Process, E. Taioli, G. R. Joseph, L. Robertson, S. Eckstein, C. Ragin

Journal Articles

Disparities exist in breast cancer knowledge and education, which tend to influence symptom interpretation and decision to seek screening/care. The present project describes a cohort of women's experiences, knowledge, and health behavior prior to and after a diagnosis of breast cancer. It also studies how knowledge and demographic factors are associated with level of involvement participants had in the treatment of their breast cancer. Women > 18 years who have been diagnosed and treated for breast cancer within 10 years were recruited in Pittsburgh, PA, through the Healthy People Cohort Registry, a database of volunteers from the community, and Brooklyn, NY, …

Spectral-Domain Optical Coherence Tomography Staging And Autofluorescence Imaging In Achromatopsia, J. P. Greenberg, J. Sherman, S. A. Zweifel, R. W. Chen, T. Duncker, S. Kohl, B. Baumann, B. Wissinger, L. A. Yannuzzi, S. H. Tsang

Journal Articles

IMPORTANCE Evidence is mounting that achromatopsia is a progressive retinal degeneration, and treatments for this condition are on the horizon. OBJECTIVES To categorize achromatopsia into clinically identifiable stages using spectral-domain optical coherence tomography and to describe fundus autofluorescence imaging in this condition. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study was performed between 2010 and 2012 at the Edward S. Harkness Eye Institute, New York-Presbyterian Hospital. Participants included 17 patients (aged 10-62 years) with full-field electroretinography-confirmed achromatopsia. MAIN OUTCOMES AND MEASURES Spectral-domain optical coherence tomography features and staging system, fundus autofluorescence and near-infrared reflectance features and their correlation to optical …

Physician Assistant Fort Lauderdale 2014, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Masters Of Public Health Overview, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

A Capability Maturity Model For Research Data Management., Jian Qin, Kevin Crowston, Arden Kirkland

School of Information Studies - Faculty Scholarship

Objective: To support the assessment and improvement of research data management (RDM) practices to increase its reliability, this paper describes the development of a capability maturity model (CMM) for RDM. Improved RDM is now a critical need, but low awareness of – or lack of – data management is still common among research projects.

Methods: A CMM includes four key elements: key practices, key process areas, maturity levels, and generic processes. These elements were determined for RDM by a review and synthesis of the published literature on and best practices for RDM.

Results: The RDM CMM includes …

Intramolecular Arylation Of Benzimidazoles Via Pd(Ii)/Cu(I) Catalyzed Cross-Dehydrogenative Coupling, Kyle C. Pereira, Ashley L. Porter, Brenton Deboef

Chemistry Faculty Publications

Electron poor benzimidazole substrates were arylated via an intramolecular cross-dehydrogenative coupling (CDC) reaction. These CDC reactions were catalyzed by a Pd(II)/Cu(I) catalyst system, capable of producing moderate yields on a large library of substrates. The substrate scope consisted of tethered arene-benzimidazoles that upon coupling, produced a fused polycyclic motif.

[Refer to PDF for graphical abstract]

Disability Awareness : Creating A Better Tomorrow, Marlina Massagli

Capstone Projects and Master's Theses

Many students in schools do not know that some of their peers in the classroom, or out in the community have or could have a disability. Understanding that their peers may have a disability is extremely important. Some disabilities are visible, however learning disabilities are naked to the eye. It is thus the teacher's responsibility to create a positive environment for all children, by creating a conscious awareness inside the classroom for all students. Through a series of interviews given to special education instructors and regular education teachers several trends emerged. The trend that was stressed most by educators was, …