Medicine and Health Sciences Commons^™

A Plausible Mechanism, Based Upon Short-Root Movement, For Regulating The Number Of Cortex Cell Layers In Roots., Shuang Wu, Chin-Mei Lee, Tomomi Hayashi, Simara Price, Fanchon Divol, Sophia Henry, Germain Pauluzzi, Christophe Perin, Kimberly L Gallagher

Department of Medical Laboratory Sciences & Biotechnology Faculty Papers

Formation of specialized cells and tissues at defined times and in specific positions is essential for the development of multicellular organisms. Often this developmental precision is achieved through intercellular signaling networks, which establish patterns of differential gene expression and ultimately the specification of distinct cell fates. Here we address the question of how the SHORT-ROOT (SHR) proteins from Arabidopsis thaliana (AtSHR), Brachypodium distachyon (BdSHR), and Oryza sativa (OsSHR1 and OsSHR2) function in patterning the root ground tissue. We find that all of the SHR proteins function as mobile signals in A. thaliana and all of the SHR homologs physically interact …

Ido2 In Immunomodulation And Autoimmune Disease., George C Prendergast, Richard Metz, Alexander J Muller, Lauren M F Merlo, Laura Mandik-Nayak

Department of Microbiology and Immunology Faculty Papers

IDO2 is a relative of IDO1 implicated in tryptophan catabolism and immune modulation but its specific contributions to normal physiology and pathophysiology are not known. Evolutionary genetic studies suggest that IDO2 has a unique function ancestral to IDO1. In mice, IDO2 gene deletion does not appreciably affect embryonic development or hematopoiesis, but it leads to defects in allergic or autoimmune responses and in the ability of IDO1 to influence the generation of T regulatory cells. Gene expression studies indicate that IDO2 is a basally and more narrowly expressed gene than IDO1 and that IDO2 is uniquely regulated by AhR, which …

New Posters Added To The Jefferson Digital Commons, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

15 new posters have been deposited in the Jefferson Digital Commons

Screen Time Overtime: Should A “Screen Time Diet” Be Part Of Healthy Everyday Activities And Routines For Families And Their Young Children?, Sarah Jamieson, Ots, Mary Muhlenhaupt, Otd, Otr/L, Faota

Department of Occupational Therapy Posters and Presentations

Introduction:

Though television is still the primary form of media for children, almost one-third of TV programming is accessed through smart phones, tablets, and computers (Strasburger et al., 2013).

•Families do not adhere to AAP’s guidelines (Brown, 2011)

•Research suggests detrimental effect on young children

OT’s are an integral resource to help families design healthy recreational “screen time diets.”

Mouse Hepatitis Virus Infection Upregulates Genes Involved In Innate Immune Responses., Dhriti Chatterjee, Sankar Addya, Reas S Khan, Lawrence C. Kenyon, Alexander Choe, Randall J Cohrs, Kenneth S Shindler, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Neurotropic recombinant strain of Mouse Hepatitis Virus, RSA59, induces meningo-encephalitis, myelitis and demyelination following intracranial inoculation. RSA59 induced neuropathology is partially caused by activation of CNS resident microglia, as demonstrated by changes in cellular morphology and increased expression of a microglia/macrophage specific calcium ion binding factor, Iba1. Affymetrix Microarray analysis for mRNA expression data reveals expression of inflammatory mediators that are known to be released by activated microglia. Microglia-specific cell surface molecules, including CD11b, CD74, CD52 and CD68, are significantly upregulated in contrast to CD4, CD8 and CD19. Protein analysis of spinal cord extracts taken from mice 6 days post-inoculation, …

Bronchial Thermoplasty – Principles And Controversies, David Manoff, Md

Division of Pulmonary, Allergy, and Critical Care Medicine Presentations and Grand Rounds

Objectives:

1) Learn the indications and contraindications to bronchial thermoplasty.

2) Develop a basic understanding of the controversies about, and the barriers to, the use of thermoplasty.

3) Understand the peri-procedural care and follow-up of patients who receive bronchial thermoplasty.

No Audio. PowerPoint slides only.

Management Of Head And Neck Pseudoaneurysms: A Review Of 33 Consecutive Cases., Eliza Anderson, Nohra Chalouhi, Md, Aaron Dumont, Stavropoula Tjoumakaris, Mario Zanaty, Robert H. Rosenwasswer Md, Robert M Starke, Pascal Jabbour Md

Department of Neurosurgery Faculty Papers

Background. Endosaccular coiling, vessel occlusion, stenting, stent-assisted coiling, and flow diversion are all endovascular treatment options for pseudoaneurysms (PAs) of the head and neck. We explore different clinical situations in which these were selected for PA management at a single institution. Methods. Over a period of ten years, 33 patients presented to our hospital with PAs of the head and neck. Their outcomes and procedural complications are discussed. Results. We observed a complication rate of 18.2% (6 of 33), consisting predominantly of infarcts following vessel occlusion. As measured by the modified Rankin Scale, 25 (75.8%) patients had achieved favorable outcomes …

Predictors Of Infections Following Cranioplasty: A Retrospective Review Of A Large Single Center Study., Mario Zanaty, Nohra Chalouhi, Md, Robert M Starke, Rohan Chitale, Md, Shannon Hann, Md, Cory D Bovenzi, Mark P Saigh, Eric W Schwartz, Emily S I Kunkel, Alexandra S Efthimiadis-Budike, Pascal Jabbour Md, Richard Dalyai, Robert H. Rosenwasswer Md, Stavropoula Tjoumakaris

Department of Neurosurgery Faculty Papers

Introduction. The variables that predispose to postcranioplasty infections are poorly described in the literature. We formulated a multivariate model that predicts the risk of infection in patients undergoing cranioplasty. Method. Retrospective review of all patients who underwent cranioplasty following craniectomy from January, 2000, to December, 2011. Tested predictors were age, sex, diabetic status, hypertensive status, reason for craniectomy, urgency status of craniectomy, location of cranioplasty, reoperation for hematoma, hydrocephalus postcranioplasty, and material type. A multivariate logistic regression analysis was performed. Results. Three hundred forty-eight patients met the study criteria. Infection rate was 26.43% (92/348). Of these cases with infection, 56.52% …

Loss Of Hif-1Α In The Notochord Results In Cell Death And Complete Disappearance Of The Nucleus Pulposus., Christophe Merceron, Laura Mangiavini, Alexander Robling, Tremika Leshan Wilson, Amato J Giaccia, Irving Shapiro, Ernestina Schipani, Makarand V Risbud

Department of Orthopaedic Surgery Faculty Papers

The intervertebral disc (IVD) is one of the largest avascular organs in vertebrates. The nucleus pulposus (NP), a highly hydrated and proteoglycan-enriched tissue, forms the inner portion of the IVD. The NP is surrounded by a multi-lamellar fibrocartilaginous structure, the annulus fibrosus (AF). This structure is covered superior and inferior side by cartilaginous endplates (CEP). The NP is a unique tissue within the IVD as it results from the differentiation of notochordal cells, whereas, AF and CEP derive from the sclerotome. The hypoxia inducible factor-1α (HIF-1α) is expressed in NP cells but its function in NP development and homeostasis is …

Tp53 Mutations Detected In Circulating Tumor Cells Present In The Blood Of Metastatic Triple Negative Breast Cancer Patients., Sandra V Fernandez, Catherine Bingham, Patricia Fittipaldi, Laura Austin, Juan P. Palazzo, Gary Palmer, Katherine Alpaugh, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Circulating tumor cells (CTCs) are tumor cells shed from either primary tumors or its metastases that circulate in the peripheral blood of patients with metastatic cancers. The molecular characterization of the CTCs is critical to identifying the key drivers of cancer metastasis and devising therapeutic approaches. However, the molecular characterization of CTCs is difficult to achieve because their isolation is a major technological challenge.

METHODS: CTCs from two triple negative breast cancer patients were enriched using CellSearch and single cells selected by DEPArray™. A TP53 R110 fs*13 mutation identified by next generation sequencing in the breast and chest skin …

Curcumin-Induced Heme Oxygenase-1 Expression Prevents H2o2-Induced Cell Death In Wild Type And Heme Oxygenase-2 Knockout Adipose-Derived Mesenchymal Stem Cells., Niels A J Cremers, Ditte M S Lundvig, Stephanie C M Van Dalen, Rik F Schelbergen, Peter L E M Van Lent, Walter A Szarek, Raymond F. Regan, Carine E Carels, Frank A D T G Wagener

Department of Emergency Medicine Faculty Papers

Mesenchymal stem cell (MSC) administration is a promising adjuvant therapy to treat tissue injury. However, MSC survival after administration is often hampered by oxidative stress at the site of injury. Heme oxygenase (HO) generates the cytoprotective effector molecules biliverdin/bilirubin, carbon monoxide (CO) and iron/ferritin by breaking down heme. Since HO-activity mediates anti-apoptotic, anti-inflammatory, and anti-oxidative effects, we hypothesized that modulation of the HO-system affects MSC survival. Adipose-derived MSCs (ASCs) from wild type (WT) and HO-2 knockout (KO) mice were isolated and characterized with respect to ASC marker expression. In order to analyze potential modulatory effects of the HO-system on ASC …

Jefferson Digital Commons Quarterly Report: July-September 2014, Daniel G. Kipnis, Msi, Kelsey Duinkerken, Msi

Jefferson Digital Commons Reports

This Jefferson Digital Commons quarterly report will cover the following:

• Milestone: 2 million downloads for the Jefferson Digital Commons
• Some statistics
• New assets added to the JDC
• Historical Materials
• What people are saying about the JDC

Persistent At-Level Thermal Hyperalgesia And Tactile Allodynia Accompany Chronic Neuronal And Astrocyte Activation In Superficial Dorsal Horn Following Mouse Cervical Contusion Spinal Cord Injury., Jaime L Watson, Tamara J Hala, Rajarshi Putatunda, Daniel Sannie, Angelo C Lepore

Department of Neuroscience Faculty Papers

In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal …

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, …

Association Of Leukocyte Mitochondrial Dna Content With Glioma Risk: Evidence From A Chinese Case-Control Study., Jie Zhang, Deyang Li, Falin Qu, Yibing Chen, Gang Li, Hequn Jiang, Xiaojun Huang, Hushan Yang, Jinliang Xing

Department of Cancer Biology Faculty Papers

BACKGROUND: Increasing evidence suggests that alterations in mitochondrial DNA (mtDNA) content may be implicated in the tumorigenesis of several malignancies. However, the association between mtDNA content in peripheral blood lymphocytes (PBLs) and glioma risk has not been investigated.

METHODS: Real-time PCR was used to examine the mtDNA content in PBLs of 414 glioma patients and 414 matched controls in a hospital-based case-control study. The association between mtDNA content and glioma risk was evaluated using an unconditional multivariate logistic regression model.

RESULTS: We found that glioma patients exhibited a significantly higher median mtDNA content than healthy controls (0.99 vs. 0.71, P …

Risk Factors For Surgical Site Infection Following Total Joint Arthroplasty., Mohammad R Rasouli, Camilo Restrepo, Mitchell Maltenfort, Phd, James J Purtill, Javad Parvizi

Rothman Institute Papers

BACKGROUND: Currently, most hospitals in the United States are obliged to report infections that occur following total joint arthroplasty to the Centers for Disease Control and Prevention through the National Healthcare Safety Network surveillance. The objective of this study was to identify the risk factors of surgical site infections that were reported to the Centers for Disease Control and Prevention from a single institution.

METHODS: For this study, 6111 primary and revision total joint arthroplasties performed from April 2010 to June 2012 were identified. Surgical site infection cases captured by infection surveillance staff on the basis of the Centers for …

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

Rothman Institute Papers

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

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

Two Million Downloads For The Jefferson Digital Commons, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

Strike up the band, turn up the tunes, and break out your dancing shoes! On September 14, 2014 the Jefferson Digital Commons surpassed 2 million downloads. As of Monday September 15, 2014 the JDC has 2,000,842 total downloads.

Acetylation-Defective Mutant Of Pparγ Is Associated With Decreased Lipid Synthesis In Breast Cancer Cells., Lifeng Tian, Chenguang Wang, Fred K Hagen, Michael Gormley, Sankar Addya, Raymond Soccio, Mathew C Casimiro, Jie Zhou, Michael J Powell, Ping Xu, Haiteng Deng, Anthony A Sauve, Richard Pestell

Department of Cancer Biology Faculty Papers

In our prior publications we characterized a conserved acetylation motif (K(R)xxKK) of evolutionarily related nuclear receptors. Recent reports showed that peroxisome proliferator activated receptor gamma (PPARγ) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue. However, it still remains unknown whether lysyl residues 154 and 155 (K154/155) of the conserved acetylation motif (RIHKK) in Pparγ1 are acetylated. Herein, we demonstrate that Pparγ1 is acetylated and regulated by both endogenous TSA-sensitive and NAD-dependent deacetylases. Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was …

Transcriptome Profiling Of Spinal Muscular Atrophy Motor Neurons Derived From Mouse Embryonic Stem Cells., Miho Maeda, Ashlee W Harris, Brewster F Kingham, Casey J Lumpkin, Lynn M Opdenaker, Suzanne M Mccahan, Wenlan Wang, Matthew E R Butchbach

Department of Pediatrics Faculty Papers

Proximal spinal muscular atrophy (SMA) is an early onset, autosomal recessive motor neuron disease caused by loss of or mutation in SMN1 (survival motor neuron 1). Despite understanding the genetic basis underlying this disease, it is still not known why motor neurons (MNs) are selectively affected by the loss of the ubiquitously expressed SMN protein. Using a mouse embryonic stem cell (mESC) model for severe SMA, the RNA transcript profiles (transcriptomes) between control and severe SMA (SMN2+/+;mSmn-/-) mESC-derived MNs were compared in this study using massively parallel RNA sequencing (RNA-Seq). The MN differentiation efficiencies between control and severe SMA mESCs …

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

Center for Translational Medicine Faculty Papers

No abstract provided.

Loss Of Miro1-Directed Mitochondrial Movement Results In A Novel Murine Model For Neuron Disease., Tammy T Nguyen, Sang S Oh, David Weaver, Agnieszka Lewandowska, Dane Maxfield, Max-Hinderk Schuler, Nathan K Smith, Jane Macfarlane, Gerald Saunders, Cheryl A Palmer, Valentina Debattisti, Takumi Koshiba, Stefan Pulst, Eva L Feldman, György Hajnóczky, Janet M Shaw

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring …

Impact Of Distinct Poxvirus Infections On The Specificities And Functionalities Of Cd4+ T Cell Responses., Nicholas A Siciliano, Adam R Hersperger, Aimee M Lacuanan, Ren-Huan Xu, John Sidney, Alessandro Sette, Luis J Sigal, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: The factors that determine CD4+ T cell (TCD4+) specificities, functional capacity, and memory persistence in response to complex pathogens remain unclear. We explored these parameters in the C57BL/6 mouse through comparison of two highly related (>92% homology) poxviruses: ectromelia virus (ECTV), a natural mouse pathogen, and vaccinia virus (VACV), a heterologous virus that nevertheless elicits potent immune responses. In addition to elucidating several previously unidentified major histocompatibility complex class II (MHC-II)-restricted epitopes, we observed many qualitative and quantitative differences between the TCD4+ repertoires, including responses not elicited by VACV despite complete sequence conservation. In addition, we observed functional …

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 …

Neuroprotective Effect Of Heme Oxygenase-2 Knockout In The Blood Injection Model Of Intracerebral Hemorrhage., Jing Chen-Roetling, Ying Cai, Raymond F Regan

Department of Emergency Medicine Faculty Papers

BACKGROUND: The toxicity of heme breakdown products may contribute to the pathogenesis of intracerebral hemorrhage (ICH). Heme catabolism is catalyzed by the heme oxygenase enzymes. We have previously reported that heme oxygenase-2 (HO-2), the constitutive isoform, protects neurons from hemin in vitro and reduces oxidative stress after striatal blood injection. In order to further evaluate HO-2 as a therapeutic target, we tested the hypothesis that HO-2 gene deletion protects neurons and attenuates behavioral deficits after ICH.

FINDINGS: Injection of 20 μl blood into the right striatum of HO-2 wild-type mice resulted in loss of approximately one third of striatal neurons …

Letters From 1841 Jefferson Medical College Graduate In Jdc, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

The Jefferson Digital Commons team is hard at work loading the letters of John Plimpton Green (1819-1892). Green graduated from Jefferson Medical College in 1841 and he practiced medicine in Whampoa, China and then Caopaipo, Chile, where he lived most of his life.

Epithelial Immunization Induces Polyfunctional Cd8+ T Cells And Optimal Mousepox Protection., Adam R Hersperger, Nicholas A Siciliano, Brian C Dehaven, Adam E. Snook, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

We assessed several routes of immunization with vaccinia virus (VACV) in protecting mice against ectromelia virus (ECTV). By a wide margin, skin scarification provided the greatest protection. Humoral immunity and resident-memory T cells notwithstanding, several approaches revealed that circulating, memory CD8(+) T cells primed via scarification were functionally superior and conferred enhanced virus control. Immunization via the epithelial route warrants further investigation, as it may also provide enhanced defense against other infectious agents.

Blau Syndrome, The Prototypic Auto-Inflammatory Granulomatous Disease., Carine H Wouters, Anne Maes, Kevin P Foley, John Bertin, Carlos D Rose

Department of Medicine Faculty Papers

Blau syndrome is a monogenic disease resulting from mutations in the pattern recognition receptor NOD2, and is phenotypically characterized by the triad of granulomatous polyarthritis, dermatitis and uveitis. This paper reviews briefly the classical clinical features of the disease, as well as more recently described extra-triad symptoms. From an ongoing prospective multicenter study, we provide new data on the natural history of Blau syndrome, focusing on functional status and visual outcome. We also present an update of the range of different NOD2 mutations found in Blau syndrome as well as recent data on morphologic and immunohistochemical characteristics of the Blau …