Medicine and Health Sciences Commons^™

Vertebral Body Stapling Versus Bracing For Patients With High-Risk Moderate Idiopathic Scoliosis., Laury Cuddihy, Aina J Danielsson, Patrick J Cahill, Amer F Samdani, Harsh Grewal, John M Richmond, M J Mulcahey, John P Gaughan, M Darryl Antonacci, Randal R Betz

Department of Medicine Faculty Papers

Purpose. We report a comparison study of vertebral body stapling (VBS) versus a matched bracing cohort for immature patients with moderate (25 to 44°) idiopathic scoliosis (IS). Methods. 42 of 49 consecutive patients (86%) with IS were treated with VBS and followed for a minimum of 2 years. They were compared to 121 braced patients meeting identical inclusion criteria. 52 patients (66 curves) were matched according to age at start of treatment (10.6 years versus 11.1 years, resp. [P = 0.07]) and gender. Results. For thoracic curves 25-34°, VBS had a success rate (defined as curve progression

Interactions Of L-3,5,3′-Triiodothyronine, Allopregnanolone, And Ivermectin With The Gabaa Receptor: Evidence For Overlapping Intersubunit Binding Modes, Thomas Westergard, Reza Salari, Joseph V. Martin, Grace Brannigan

Department of Neuroscience Faculty Papers

No abstract provided.

Positive Allosteric Modulation Of Kv Channels By Sevoflurane: Insights Into The Structural Basis Of Inhaled Anesthetic Action., Qiansheng Liang, Warren D Anderson, Shelly T Jones, Caio S Souza, Juliana M Hosoume, Werner Treptow, Manuel Covarrubias

Department of Neuroscience Faculty Papers

Inhalational general anesthesia results from the poorly understood interactions of haloethers with multiple protein targets, which prominently includes ion channels in the nervous system. Previously, we reported that the commonly used inhaled anesthetic sevoflurane potentiates the activity of voltage-gated K+ (Kv) channels, specifically, several mammalian Kv1 channels and the Drosophila K-Shaw2 channel. Also, previous work suggested that the S4-S5 linker of K-Shaw2 plays a role in the inhibition of this Kv channel by n-alcohols and inhaled anesthetics. Here, we hypothesized that the S4-S5 linker is also a determinant of the potentiation of Kv1.2 and K-Shaw2 by sevoflurane. Following functional expression …

Deletion Of Cyclophilin D Impairs Β-Oxidation And Promotes Glucose Metabolism., Michele Tavecchio, Sofia Lisanti, Michael J Bennett, Lucia R Languino, Dario C Altieri

Department of Cancer Biology Faculty Papers

Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulin-producing β-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver …

Dna-Repair Defects And Olaparib In Metastatic Prostate Cancer., Joaquin Mateo, Suzanne Carreira, Shahneen Sandhu, Susana Miranda, Helen Mossop, Raquel Perez-Lopez, Daniel Nava Rodrigues, Dan Robinson, Aurelius Omlin, Nina Tunariu, Gunther Boysen, Nuria Porta, Penny Flohr, Alexa Gillman, Ines Figueiredo, Claire Paulding, George Seed, Suneil Jain, Christy Ralph, Andrew Protheroe, Syed Hussain, Robert Jones, Tony Elliott, Ursula Mcgovern, Diletta Bianchini, Jane Goodall, Zafeiris Zafeiriou, Chris T Williamson, Roberta Ferraldeschi, Ruth Riisnaes, Bernardette Ebbs, Gemma Fowler, Desamparados Roda, Wei Yuan, Yi-Mi Wu, Xuhong Cao, Rachel Brough, Helen Pemberton, Roger A'Hern, Amanda Swain, Lakshmi P Kunju, Rosalind Eeles, Gerhardt Attard, Christopher J Lord, Alan Ashworth, Mark A Rubin, Karen E Knudsen, Felix Y Feng, Arul M Chinnaiyan, Emma Hall, Johann S De Bono

Department of Medicine Faculty Papers

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the …

Does Metal Transfer Differ On Retrieved Ceramic And Cocr Femoral Heads?, Eliza K Fredette, Daniel W Macdonald, Richard J Underwood, Antonia F. Chen, Md, Mba, Michael A Mont, Gwo-Chin Lee, Gregg R Klein, Clare M Rimnac, Steven M Kurtz

Rothman Institute Faculty Papers

Metal transfer has been observed on retrieved THA femoral heads for both CoCr and ceramic bearing materials. In vitro wear testing has shown increased wear to polyethylene acetabular liners with the presence of metal transfer. This study sought to investigate the extent of metal transfer on the bearing surface of CoCr and ceramic femoral heads and identify prevalent morphologies. Three bearing couple cohorts: M-PE (n = 50), C-PE (n = 35), and C-C (n = 15), were derived from two previously matched collections (n = 50/group) of CoCr and ceramic femoral heads. From the three cohorts, 75% of the femoral …

Palbociclib In Hormone-Receptor-Positive Advanced Breast Cancer., Nicholas C Turner, Cynthia Huang Bartlett, Massimo Cristofanilli

Department of Medicine Faculty Papers

No abstract provided.

Emerging Novel Therapies For Heart Failure., Anthony M Szema, Sophia Dang, Jonathan C Li

Department of Medicine Faculty Papers

Heart function fails when the organ is unable to pump blood at a rate proportional to the body's need for oxygen or when this function leads to elevated cardiac chamber filling pressures (cardiogenic pulmonary edema). Despite our sophisticated knowledge of heart failure, even so-called ejection fraction-preserved heart failure has high rates of mortality and morbidity. So, novel therapies are sorely needed. This review discusses current standard therapies for heart failure and launches an exploration into emerging novel treatments on the heels of recently-approved sacubitril and ivbradine. For example, Vasoactive Intestinal Peptide (VIP) is protective of the heart, so in the …

Orphan Nuclear Receptor Nur77 Inhibits Cardiac Hypertrophic Response To Beta-Adrenergic Stimulation., Guijun Yan, Ni Zhu, Shengdong Huang, Bing Yi, Xiying Shang, Ming Chen, Nadan Wang, Guan-Xin Zhang, Jennifer A Talarico, Douglas G Tilley, Erhe Gao, Jianxin Sun

Center for Translational Medicine Faculty Papers

The orphan nuclear receptor Nur77 plays critical roles in cardiovascular diseases, and its expression is markedly induced in the heart after beta-adrenergic receptor (β-AR) activation. However, the functional significance of Nur77 in β-AR signaling in the heart remains unclear. By using Northern blot, Western blot, and immunofluorescent staining assays, we showed that Nur77 expression was markedly upregulated in cardiomyocytes in response to multiple hypertrophic stimuli, including isoproterenol (ISO), phenylephrine (PE), and endothelin-1 (ET-1). In a time- and dose-dependent manner, ISO increases Nur77 expression in the nuclei of cardiomyocytes. Overexpression of Nur77 markedly inhibited ISO-induced cardiac hypertrophy by inducing nuclear translocation …

Targeting The Mrna-Binding Protein Hur Impairs Malignant Characteristics Of Pancreatic Ductal Adenocarcinoma Cells., Masaya Jimbo, Fernando F Blanco, Yu-Hung Huang, Aristeidis G Telonis, Brad A Screnci, Gabriela L Cosma, Vitali Alexeev, Gregory E Gonye, Charles Yeo, Janet A Sawicki, Jordan M Winter, Jonathan Brody, Md

Computational Medicine Center Faculty Papers

Post-transcriptional regulation is a powerful mediator of gene expression, and can rapidly alter the expression of numerous transcripts involved in tumorigenesis. We have previously shown that the mRNA-binding protein HuR (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens compared to normal pancreatic tissues, and its cytoplasmic localization is associated with increased tumor stage. To gain a better insight into HuR's role in PDA biology and to assess it as a candidate therapeutic target, we altered HuR expression in PDA cell lines and characterized the resulting phenotype in preclinical models. HuR silencing by short hairpin and small interfering RNAs …

Novel Targeted Sirna-Loaded Hybrid Nanoparticles: Preparation, Characterization And In Vitro Evaluation., Nneka Dim, Maryna Perepelyuk, Olukayode Gomes, Chellappagounder Thangavel, Yi Liu, Robert Den, Ashakumary Lakshmikuttyamma, Sunday A Shoyele

Department of Radiation Oncology Faculty Papers

BACKGROUND: siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production …

Computerized Adaptive Tests Detect Change Following Orthopaedic Surgery In Youth With Cerebral Palsy., M J Mulcahey, Mary D Slavin, Pengsheng Ni, Lawrence C Vogel, Scott H Kozin, Stephen M Haley, Alan M Jette

Department of Occupational Therapy Faculty Papers

BACKGROUND: The Cerebral Palsy Computerized Adaptive Test (CP-CAT) is a parent-reported outcomes instrument for measuring lower and upper-extremity function, activity, and global health across impairment levels and a broad age range of children with cerebral palsy (CP). This study was performed to examine whether the Lower Extremity/Mobility (LE) CP-CAT detects change in mobility following orthopaedic surgery in children with CP.

METHODS: This multicenter, longitudinal study involved administration of the LE CP-CAT, the Pediatric Outcomes Data Collection Instrument (PODCI) Transfer/Mobility and Sports/Physical Functioning domains, and the Timed "Up & Go" test (TUG) before and after elective orthopaedic surgery in a convenience …

A Prospective Highlight On Exosomal Nanoshuttles And Cancer Immunotherapy And Vaccination., Mohammad Rafi, Yadollah Omidi

Department of Neurology Faculty Papers

INTRODUCTION: Exosomes (EXOs) and ectosomes (ECTOs) are nanoscale membranous extracellular vesicles (EVs) derived from different cells mediating various cellular communications. EXOs are liberated based on the exocytosis of multivesicular bodies, while ECTOs are ubiquitously released from the plasma membranes.

METHODS: Here, in this paper, we go over the extracellular vesicular machineries and concisely highlight their clinical importance in solid tumors and their possible applications in cancer immunotherapy/vaccination.

RESULTS: In various types of cancers, these vesicles play central roles delivering cancer cell messages to the target cells, as a result both of them seem to provide a novel useful means for …

Chimeric Cells Of Maternal Origin Do Not Appear To Be Pathogenic In The Juvenile Idiopathic Inflammatory Myopathies Or Muscular Dystrophy., Carol M Artlett, Sihem Sassi-Gaha, Ronald C Ramos, Frederick W Miller, Lisa G Rider

Department of Medicine Faculty Papers

INTRODUCTION: Microchimeric cells have been studied for over a decade, with conflicting reports on their presence and role in autoimmune and other inflammatory diseases. To determine whether microchimeric cells were pathogenic or mediating tissue repair in inflammatory myopathies, we phenotyped and quantified microchimeric cells in juvenile idiopathic inflammatory myopathies (JIIM), muscular dystrophy (MD), and noninflammatory control muscle tissues.

METHOD: Fluorescence immunophenotyping for infiltrating cells with sequential fluorescence in situ hybridization was performed on muscle biopsies from ten patients with JIIM, nine with MD and ten controls.

RESULTS: Microchimeric cells were significantly increased in MD muscle (0.079 ± 0.024 microchimeric cells/mm(2) …

Developments In Neurovascular Diseases And Treatments., Robert M Starke, Stephen J Monteith, Andrew M Southerland, R Webster Crowley, Nohra Chalouhi, Dale Ding, David M Hasan, Aaron S Dumont

Department of Neurosurgery Faculty Papers

No abstract provided.

Differential Host Immune Responses After Infection With Wild-Type Or Lab-Attenuated Rabies Viruses In Dogs., Clement W Gnanadurai, Yang Yang, Ying Huang, Zhenguang Li, Christina M Leyson, Tanya L Cooper, Simon R Platt, Stephen B Harvey, D Craig Hooper, Milosz Faber, Zhen F Fu

Department of Medical Genetics Faculty Papers

METHODOLOGY/PRINCIPAL FINDINGS: The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N) and not the glycoprotein (G). We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and …

Inflammatory Muscle Diseases., Marinos Dalakas

Department of Medicine Faculty Papers

No abstract provided.

Trna-Derived Short Non-Coding Rna As Interacting Partners Of Argonaute Proteins., Megumi Shigematsu, Yohei Kirino, Phd

Computational Medicine Center Faculty Papers

The advent of next-generation sequencing technologies has not only accelerated findings on various novel non-coding RNA (ncRNA) species but also led to the revision of the biological significance and versatility of fundamental RNA species with canonical function, such as transfer RNAs (tRNAs). Although tRNAs are best known as adapter components of translational machinery, recent studies suggest that tRNAs are not always end products but can further serve as a source for short ncRNAs. In many organisms, various tRNA-derived ncRNA species are produced from mature tRNAs or their precursor transcripts as functional molecules involved in various biological processes beyond translation. In …

Pleiotropic Effects Of Bitter Taste Receptors On [Ca2+]I Mobilization, Hyperpolarization, And Relaxation Of Human Airway Smooth Muscle Cells., Blanca Camoretti-Mercado, Susan H Pauer, Hwan Mee Yong, Dan'elle C Smith, Deepak A. Deshpande, Phd, Steven S An, Stephen B Liggett

Center for Translational Medicine Faculty Papers

Asthma is characterized by airway inflammation and airflow obstruction from human airway smooth muscle (HASM) constriction due to increased local bronchoconstrictive substances. We have recently found bitter taste receptors (TAS2Rs) on HASM, which increase [Ca2+]i and relax the muscle. We report here that some, but not all, TAS2R agonists decrease [Ca2+]i and relax HASM contracted by G-protein coupled receptors (GPCRs) that stimulate [Ca2+]i. This suggests both a second pathway by which TAS2Rs relax, and, a heterogeneity of the response phenotype. We utilized eight TAS2R agonists and five procontractile GPCR agonists in cultured HASM cells. We find that heterogeneity in the …

Flattening Filter-Free Accelerators: A Report From The Aapm Therapy Emerging Technology Assessment Work Group., Ying Xiao, Stephen F Kry, Richard Popple, Ellen Yorke, Niko Papanikolaou, Sotirios Stathakis, Ping Xia, Saiful Huq, John Bayouth, James Galvin Phd, Fang-Fang Yin

Department of Medicine Faculty Papers

This report describes the current state of flattening filter-free (FFF) radiotherapy beams implemented on conventional linear accelerators, and is aimed primarily at practicing medical physicists. The Therapy Emerging Technology Assessment Work Group of the American Association of Physicists in Medicine (AAPM) formed a writing group to assess FFF technology. The published literature on FFF technology was reviewed, along with technical specifications provided by vendors. Based on this information, supplemented by the clinical experience of the group members, consensus guidelines and recommendations for implementation of FFF technology were developed. Areas in need of further investigation were identified. Removing the flattening filter …

Successful Isolation Of Viable Adipose-Derived Stem Cells From Human Adipose Tissue Subject To Long-Term Cryopreservation: Positive Implications For Adult Stem Cell-Based Therapeutics In Patients Of Advanced Age., Sean Devitt, Md, Cynthia M Carter, Raia Dierov, Scott Weiss, Robert P Gersch, Ivona Percec

Jefferson Hospital Staff Papers and Presentations

We examined cell isolation, viability, and growth in adipose-derived stem cells harvested from whole adipose tissue subject to different cryopreservation lengths (2-1159 days) from patients of varying ages (26-62 years). Subcutaneous abdominal adipose tissue was excised during abdominoplasties and was cryopreserved. The viability and number of adipose-derived stem cells isolated were measured after initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with respect to cryopreservation duration and patient age. Significantly more viable cells were initially isolated from tissue cryopreserved2 years, irrespective of patient age. However, this difference did not persist with continued growth and …

Evaluation Of The American-English Quality Of Life In Short Stature Youth (Qolissy) Questionnaire In The United States., Monika Bullinger, Rachel Sommer, Andreas Pleil, Nelly Mauras, Judith L. Ross, Ron Newfield, Lawrence Silverman, Anja Rohenkohl, Janet Fox, Julia Quitmann

Department of Medical Genetics Faculty Papers

BACKGROUND: The European Quality of Life in Short Stature Youth (QoLISSY) is a novel condition-specific instrument developed to assess health related quality of life (HrQoL) in children/adolescents with short stature from patient and parent perspectives. Study objective was to linguistically validate and psychometrically test the American-English version of the QoLISSY instrument.

METHODS: Upon conversion of the British-English version to American-English, content validity and acceptance of the questionnaire were examined through focus group discussions with cognitive debriefing in 28 children/adolescents with growth hormone deficiency (GHD) or idiopathic short stature (ISS) and their parents. In the subsequent field test with 51 families …

State Law Mandates For Reporting Of Healthcare-Associated Clostridium Difficile Infections In Hospitals., Julie Reagan, Carolyn T A Herzig, Monika Pogorzelska-Maziarz, Andrew W Dick, Patricia W Stone, Jd Divya Srinath

Department of Nursing papers and presentations

US state and territorial laws were reviewed to identify Clostridium difficile infection reporting mandates. Twenty states require reporting either under state law or by incorporating federal Centers for Medicare & Medicaid Services' reporting requirements. Although state law mandates are more common, the incorporation of federal reporting requirements has been increasing.

Implementation Of Antimicrobial Stewardship Policies In U.S. Hospitals: Findings From A National Survey., Monika Pogorzelska-Maziarz, Carolyn T A Herzig, Elaine L Larson, E Yoko Furuya, Eli N Perencevich, Patricia W Stone

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To describe the use of antimicrobial stewardship policies and to investigate factors associated with implementation in a national sample of acute care hospitals.

DESIGN: Cross-sectional survey.

PARTICIPANTS: Infection Control Directors from acute care hospitals participating in the National Healthcare Safety Network (NHSN).

METHODS: An online survey was conducted in the Fall of 2011. A subset of hospitals also provided access to their 2011 NHSN annual survey data.

RESULTS: Responses were received from 1,015 hospitals (30% response rate). The majority of hospitals (64%) reported the presence of a policy; use of antibiograms and antimicrobial restriction policies were most frequently utilized …

Population Health: Where's The Beef?, David B. Nash

College of Population Health Faculty Papers

No abstract provided.

What Is Translational Bioinformatics?, Eric R. Londin, Carol I. Barash

Computational Medicine Center Faculty Papers

No abstract provided.