Medicine and Health Sciences Commons^™

Seeing Is Believing: Optical Computed Tomography (Oct) And Histologic Analysis To Define Pathophysiology Of “Very”, Very Late Stent Thrombosis Occurring More Than 7 Years After Drug Eluting Stent Implantation, Antony G. Kaliyadan, Md, Alec Vishnevsky, Md, Henry Siu, Md, David Fishman, Md, John Farber, Md, Nicholas Ruggiero Ii, Md, Michael P. Savage, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Case Presentation

• 58-year-old male with prior non-ST elevation MI with PCI performed using a sirolimus eluting stent placed in a large OM1 branch 86 months prior presented with five hours chest pain similar to prior MI >7 years earlier.
• Additional history of hypertension, hyperlipidemia, non-compliance with antiplatelet therapy and active tobacco abuse at time of presentation.
• Patient reported self-discontinuation of medications (aspirin (time unknown), statin, beta blocker) and resumed smoking.
• Clopidogrel was discontinued by his primary physician 97 days prior to presentation
• Initial electrocardiogram revealed a lateral ST elevation MI and the patient was taken to the cardiac catheterization lab …

Dr. R. Tait Mckenzie: Pioneer And Legacy To Physiatry., John F. Ditunno, Jr, Richard E. Verville

Department of Rehabilitation Medicine Faculty Papers

No abstract provided.

A Comparison Of The Who 2004 And 2010 Classification Systems In Pancreatic Neuroendocrine Tumors (Pancreatic Net), James P. Casey, Md, Aakanksha Asija, Md, Anthony J. Prestipino, M.D., Jocelyn A. Sendecki, Md, Jonathan Brody, Md, Harish Lavu, Md, Jordan M. Winter, Md, Charles Yeo, Md, Ashwin R. Sama, Md, Madhaven V. Pillai, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pancreatic NETs are rare tumors with multiple classification systems. Previous classification systems included tumor size, histologic grade, mitoses, Ki67, and metastases. The current WHO 2010 system utilizes mitotic rate and Ki67% to assign a grade. We compared the WHO 2004 and 2010 classification systems in predicting mortality and metastasis.

Pathologic parameters were used to classify 50 cases of Pancreatic NET according to the WHO 2004 and WHO 2010 systems. The relationship between the WHO 2004 and WHO 2010 grading was investigated using an exact Chi squared test. WHO grade categorization was next explored by vital status, by the exact method, …

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 …

Ethanol Pharmacokinetics In Neonates And Infants, Elizabeth Marek, Pharmd., Walter K. Kraft, Md

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Introduction:

Ethanol has been used for years in neonatal and infant liquid medications, yet the pharmacokinetics, pharmacodynamics, and safety of ethanol in this vulnerable population have not been well characterized. The purpose of this review is to raise awareness of ethanol use as an excipient in neonatal and infant medications and to provide insight, based on the available evidence, into clearance rates of ethanol in babies. We also discuss ethanol pharmacokinetics in adults, theoretical pharmaco-kinetic changes in neonates and infants as it may apply to ethanol disposition, and case reports involving ethanol exposure in neonates and infants.

Materials and methods: …

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 …

Defining The Clinical Role Of Adapted Digital Light Field Photography In The Treatment Of Hiv-Induced Kaposi's Sarcoma Lesions, Jacquelyn Knapp, Gabriel Prager, Rui Bastos, Md, Susannah K. Graves, Md, Rolanda Carmen Manuel, Md, Yu-Tsueng Liu, Md, Phd

CwiC-PH

Kaposi’s sarcoma (KS): a vascular tumor associated with HHV8 and HIV infection

KS burden at Maputo Central Hospital (MCH):

•Referral center for all of southern Mozambique, 1500 beds, >65% HIV+ patients on medical services

•Dermatology ward: 50 beds, >30% of admitted patients suffer from Kaposi’s sarcoma and its complications

•10-15 cases/month admitted with advanced KS; additional 15-20 cases/month treated outpatient

•KS is the most common form of malignancy seen at MCH among men, second most frequent among women

Current KS standard of care:

•First line treatment: chemo- and concomitant antiretroviral-therapy

•Pre-treatment photographs rarely taken to establish a baseline for therapeutic …

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 …

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 …

The Patient Burden Of Screening Mammography Recall., Matthew Alcusky, Liane Philpotts, Machaon Bonafede, Janice L. Clarke, Alexandria Skoufalos

College of Population Health Faculty Papers

OBJECTIVE: The aim of this article is to evaluate the burden of direct and indirect costs borne by recalled patients after a false positive screening mammogram.

METHODS: Women aged 40-75 years undergoing screening mammography were identified from a U.S. commercial claims database. Women were required to have 12 months pre- and 6 months post-index enrollment to identify utilization and exclude patients with subsequent cancer diagnoses. Recall was defined as the use of diagnostic mammography or breast ultrasound during 6 months post-index. Descriptive statistics were presented for recalled and non-recalled patients; differences were compared using the chi square test. Out-of-pocket costs …

Randomised Clinical Trial: Polyethylene Glycol 3350 With Sports Drink Vs. Polyethylene Glycol With Electrolyte Solution As Purgatives For Colonoscopy--The Incidence Of Hyponatraemia., Rebecca Matro, Constantine Daskalakis, Dan Negoianu, Leo Katz, Cassandra Henry, Michael Share, David Kastenberg

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Polyethylene glycol 3350 plus sports drink (PEG-SD) is a hypo-osmotic purgative commonly used for colonoscopy, though little safety data are available.

AIM: To evaluate the effect of PEG-SD on serum sodium (Na) and other electrolytes compared with PEG-electrolyte solution (PEG-ELS).

METHODS: We performed a single center, prospective, randomised, investigator-blind comparison of PEG-ELS to PEG-SD in out-patients undergoing colonoscopy. Laboratories were obtained at baseline and immediately before and after colonoscopy. The primary endpoint was development of hyponatraemia (Na/L) the day of colonoscopy. Changes in electrolyte levels were computed as the difference between the lowest value on the day of colonoscopy …

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 ≤ …

The Effects Of Fatigue On Robotic Surgical Skill Training In Urology Residents, James R. Mark, Douglas C. Kelly, Edouard J. Trabulsi, Patrick J. Shenot, Costas D. Lallas

Department of Urology Faculty Papers

This study reports on the effect of fatigue on Urology residents using the daVinci surgical skills simulator (dVSS). Seven Urology residents performed a series of selected exercises on the dVSS while pre-call and post-call. Prior to dVSS performance a survey of subjective fatigue was taken and residents were tested with the Epworth Sleepiness Scale (ESS). Using the metrics available in the dVSS software, the performance of each resident was evaluated. The Urology residents slept an average of 4.07 h (range 2.5-6 h) while on call compared to an average of 5.43 h while not on call (range 3-7 h, p …

Safety Of Topiramate For Treating Migraines., Michael J. Marmura

Department of Jefferson Headache Center Papers and Presentations

INTRODUCTION: Migraine is a very common medical disorder characterized by attacks of moderate-severe headache, nausea and disability. Topiramate is an effective, popular prophylactic migraine treatment, which is approved for use in adults and adolescents. Due to its multiple mechanisms of action, topiramate has multiple potential safety issues, including systemic and CNS adverse events, which may complicate therapy.

AREAS COVERED: This review evaluates common adverse events as seen in the pivotal trials of topiramate for migraine as well as those observed in postmarketing studies. These include weight loss, metabolic acidosis, renal calculi, acute angle closure glaucoma, visual distortions and cognitive slowing. …

Return To Work After Stroke: A Nursing State Of The Science., Catherine Harris, Phd, Mba, Crnp

College of Nursing Faculty Papers & Presentations

There is a lack of research related to return to work (RTW) after acute ischemic stroke. Historically considered a disease of the elderly, acute ischemic stroke studies have not routinely used return to work as an outcome. Major stroke trials have not routinely collected this data as an endpoint. However, the mean age for acute ischemic stroke (AIS) has declined to 69 years of age, while the incidence in patients under the age of 55 has increased to 19%^1-3. Changes in retirement age have also affected RTW as a consideration in stroke patients. Failure to RTW after recovery …

Vaccination With A Genetically Modified Brugia Malayi Cysteine Protease Inhibitor-2 Reduces Adult Parasite Numbers And Affects The Fertility Of Female Worms Following A Subcutaneous Challenge Of Mongolian Gerbils (Meriones Unguiculatus) With B. Malayi Infective Larvae., Sridhar Arumugam, Junfei Wei, Danielle Ward, David Abraham, Sara Lustigman, Bin Zhan, Thomas R. Klei

Department of Microbiology and Immunology Faculty Papers

Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0% at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.

Mir-103a-3p Targets The 5' Utr Of Gprc5a In Pancreatic Cells., Honglei Zhou, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

MicroRNAs (miRNAs) are short noncoding RNAs that regulate the expression of their targets in a sequence-dependent manner. For protein-coding transcripts, miRNAs regulate expression levels through binding sites in either the 3' untranslated region (3' UTR) or the amino acid coding sequence (CDS) of the targeted messenger RNA (mRNA). Currently, for the 5' untranslated region (5' UTR) of mRNAs, very few naturally occurring examples exist whereby the targeting miRNA down-regulates the expression of the corresponding mRNA in a seed-dependent manner. Here we describe and characterize two miR-103a-3p target sites in the 5' UTR of GPRC5A, a gene that acts as a …

A Double-Blind Randomized Trial Of Fish Oil To Lower Triglycerides And Improve Cardiometabolic Risk In Adolescents., Samuel S. Gidding, Carol Prospero, Jobayer Hossain, Frances Zappalla, Prabhakaran Babu Balagopal, Bonita Falkner, Peter Kwiterovich

Department of Pediatrics Faculty Papers

OBJECTIVES: To determine the efficacy of 4 g/day fish oil to lower triglycerides and impact lipoprotein particles, inflammation, insulin resistance, coagulation, and thrombosis.

STUDY DESIGN: Participants (n = 42, age 14 ± 2 years) with hypertriglyceridemia and low-density lipoprotein (LDL) cholesterol/dL were enrolled in a randomized, double-blind, crossover trial comparing 4 g of fish oil daily with placebo. Treatment interval was 8 weeks with a 4-week washout. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, fibrinogen, plasminogen activator inhibitor-1, and thrombin generation were measured.

RESULTS: Baseline lipid profile was total cholesterol 194 (5.4) mg/dL (mean …

Steatocystoma Multiplex: Those Little Tumours., Ellen H. De Moll, W. Clark Lambert, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

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 …

Philadelphia Healthier Generation Summit, Lauren Puzen Msw,Mph

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Patient Engagement: The Missing Measure In The Patient-Centered Medical Home, Manisha Verma Md, Mph

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Quest: Creating A Biotechnology Workforce Pipeline, Lynette Hazleton Mph

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Teaching Us Healthcare Organization And Delivery: Two Models Of Instruction, Juan Leon Phd, Laura T. Pizzi Pharmd, Mph, Deon Steele Mph

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

The Medical Reserve Corps: Volunteers Making A Difference, Mary Lou Manning Phd, Crnp, Cic, Faan, Neale Batra Ba

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Educating Leaders In Healthcare Quality And Safety, James Pelegano Md, Ms

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Scitech News- 68(3)-2014

Sci-Tech News

No abstract provided.

Mitochondrial Ion Channels/Transporters As Sensors And Regulators Of Cellular Redox Signaling., Jin O-Uchi, Shin-Young Ryu, Bong Sook Jhun, Stephen Hurst, Shey-Shing Sheu

Department of Medicine Faculty Papers

SIGNIFICANCE: Mitochondrial ion channels/transporters and the electron transport chain (ETC) serve as key sensors and regulators for cellular redox signaling, the production of reactive oxygen species (ROS) and nitrogen species (RNS) in mitochondria, and balancing cell survival and death. Although the functional and pharmacological characteristics of mitochondrial ion transport mechanisms have been extensively studied for several decades, the majority of the molecular identities that are responsible for these channels/transporters have remained a mystery until very recently.

RECENT ADVANCES: Recent breakthrough studies uncovered the molecular identities of the diverse array of major mitochondrial ion channels/transporters, including the mitochondrial Ca2+ uniporter pore, …

Adrenergic Signaling Regulates Mitochondrial Ca2+ Uptake Through Pyk2-Dependent Tyrosine Phosphorylation Of The Mitochondrial Ca2+ Uniporter., Jin O-Uchi, Bong Sook Jhun, Shangcheng Xu, Stephen Hurst, Anna Raffaello, Xiaoyun Liu, Bing Yi, Huiliang Zhang, Polina Gross, Jyotsna Mishra, Alina Ainbinder, Sarah Kettlewell, Godfrey L Smith, Robert T Dirksen, Wang Wang, Rosario Rizzuto, Shey-Shing Sheu

Department of Medicine Faculty Papers

AIMS: Mitochondrial Ca2+ homeostasis is crucial for balancing cell survival and death. The recent discovery of the molecular identity of the mitochondrial Ca2+ uniporter pore (MCU) opens new possibilities for applying genetic approaches to study mitochondrial Ca2+ regulation in various cell types, including cardiac myocytes. Basal tyrosine phosphorylation of MCU was reported from mass spectroscopy of human and mouse tissues, but the signaling pathways that regulate mitochondrial Ca2+ entry through posttranslational modifications of MCU are completely unknown. Therefore, we investigated α1-adrenergic-mediated signal transduction of MCU posttranslational modification and function in cardiac cells.

RESULTS: α1-adrenoceptor (α1-AR) signaling translocated activated proline-rich tyrosine …