Digital Commons Network^™

Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Trm5 is a eukaryal and archaeal tRNA methyltransferase that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to the N(1) position of G37 directly 3' to the anticodon. While the biological role of m(1)G37 in enhancing translational fidelity is well established, the catalytic mechanism of Trm5 has remained obscure. To address the mechanism of Trm5 and more broadly the mechanism of N-methylation to nucleobases, we examined the pH-activity profile of an archaeal Trm5 enzyme, and performed structure-guided mutational analysis. The data reveal a marked dependence of enzyme-catalyzed methyl transfer on hydrogen ion equilibria: the single-turnover rate constant for methylation increases by one …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Biological Rationale For The Use Of Dna Methyltransferase Inhibitors As New Strategy For Modulation Of Tumor Response To Chemotherapy And Radiation., Giovanni L Gravina, Claudio Festuccia, Francesco Marampon, Vladimir M Popov, Richard G Pestell, Bianca M Zani, Vincenzo Tombolini

Kimmel Cancer Center Faculty Papers

Epigenetic modifications play a key role in the patho-physiology of many tumors and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. DNA methyltransferase (DNMT) inhibitors represent a promising class of epigenetic modulators. Research performed yielded promising anti-tumorigenic activity for these agents in vitro and in vivo against a variety of hematologic and solid tumors. These epigenetic modulators cause cell cycle and growth arrest, differentiation and apoptosis. Rationale for combining these agents with cytotoxic therapy or radiation is straightforward since the use of DNMT inhibitor offers greatly improved access for cytotoxic …

Self-Protecting Bactericidal Titanium Alloy Surface Formed By Covalent Bonding Of Daptomycin Bisphosphonates., Chang-Po Chen, Eric Wickstrom

Department of Biochemistry and Molecular Biology Faculty Papers

Infections are a devastating complication of titanium alloy orthopedic implants. Current therapy includes antibiotic-impregnated bone cement and antibiotic-containing coatings. We hypothesized that daptomycin, a Gram-positive peptide antibiotic, could prevent bacterial colonization on titanium alloy surfaces if covalently bonded via a flexible, hydrophilic spacer. We designed and synthesized a series of daptomycin conjugates for bonding to the surface of 1.0 cm² Ti6Al4V foils through bisphosphonate groups, reaching a maximum yield of 180 pmol/cm². Daptomycin-bonded foils killed 53 ± 5% of a high challenge dose of 3 × 10⁵ cfu Staphylococcus aureus ATCC 29213.

What's Going On Here? Deconstructing The Interactive Encounter., Janice P Burke

Department of Occupational Therapy Faculty Papers

Eleanor Clarke Sagle Lecture

Nfκb Activation And Stimulation Of Chemokine Production In Normal Human Macrophages By The Gadolinium-Based Magnetic Resonance Contrast Agent Omniscan: Possible Role In The Pathogenesis Of Nephrogenic Systemic Fibrosis., Francesco Del Galdo, Peter J Wermuth, Sankar Addya, Paolo Fortina, Sergio A Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: Nephrogenic systemic fibrosis (NSF) is a generalised fibrotic disorder occurring in certain individuals with renal insufficiency exposed to gadolinium-based contrast agents (GdBCA) for MRI. Histopathological examination of affected tissues shows increased numbers of activated macrophages. To elucidate the mechanisms responsible for macrophage activation, the effects of the GdBCA Omniscan on normal human macrophage global gene expression, chemokine production and nuclear factor κB (NFκB) activation was examined.

METHODS: Normal human monocyte-derived macrophages were incubated with Omniscan (50 mM) and their gene expression analysed by microarrays and real-time PCR. Macrophage chemokine production was assayed by multiplex ELISA. NFκB activation was assessed …

Subglottic Secretion Aspiration In The Prevention Of Ventilator-Associated Pneumonia: A Review Of The Literature., Rachel Scherzer

Jefferson Hospital Staff Papers and Presentations

Ventilator-associated pneumonia is a common nosocomial infection that results in both negative patient outcomes and increased health care costs. Recently, many efforts have been targeted at ventilator-associated pneumonia prevention, including the practice of subglottic secretion aspiration. Six randomized control studies examining the effectiveness of subglottic secretion aspiration in the prevention of ventilator-associated pneumonia were reviewed for this article. Results consistently show that subglottic secretion aspiration significantly reduces the incidence of ventilator-associated pneumonia in a variety of patient populations. Despite these findings, this practice is limited in clinical settings. This clinical practice should be implemented in individuals requiring mechanical ventilation to …

Chart Rounds In The Digital Age: A Survey Of North American Institutions, M. A. Whiton, A. P. Dicker, E. J. Wuthrick, L. Doyle, A. S. Harrison, Y. R. Lawrence

Department of Radiation Oncology Faculty Papers

Purpose:

Recent reports of medical errors in radiaKon treatment delivery have emphasized the importance of quality assurance (QA) pracKces. Strict guidelines exist for medical physics QA, but not for QA procedures as applied to clinicians. We sought to document how clinical quality assurance (QA) meeKngs or “chart rounds” are performed across academic North American RadiaKon Oncology departments.

Wild-Type And Mutant Sod1 Share An Aberrant Conformation And A Common Pathogenic Pathway In Als., Daryl A Bosco, Gerardo Morfini, N Murat Karabacak, Yuyu Song, Francois Gros-Louis, Piera Pasinelli, Holly Goolsby, Benjamin A Fontaine, Nathan Lemay, Diane Mckenna-Yasek, Matthew P Frosch, Jeffrey N Agar, Jean-Pierre Julien, Scott T Brady, Robert H Brown

Farber Institute for Neuroscience Faculty Papers

Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wild-type SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal …

Pp32 (Anp32a) Expression Inhibits Pancreatic Cancer Cell Growth And Induces Gemcitabine Resistance By Disrupting Hur Binding To Mrnas., Timothy K Williams, Christina L Costantino, Nikolai A Bildzukewicz, Nathan G Richards, David W Rittenhouse, Lisa Einstein, Joseph A Cozzitorto, Judith C Keen, Abhijit Dasgupta, Myriam Gorospe, Gregory E Gonye, Charles J Yeo, Agnieszka K Witkiewicz, Jonathan R Brody

Department of Surgery Faculty Papers

The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, …

Knowledge, Attitudes, And Practice Behaviors Of Oncology Advanced Practice Nurses Regarding Advanced Care Planning For Patients With Cancer., Guiyun Zhou, Dnp, Crnp, Aocns, Jill C Stoltzfus, Phd, Arlene D Houldin, Phd, Pmhcns-Bc, Susan M Parks, Md, Beth Ann Swan, Phd, Crnp, Faan

College of Nursing Faculty Papers & Presentations

Purpose/Objectives: To establish initial reliability and validity of a Web-based survey focused on oncology advanced practice nurses' (APNs') knowledge, attitudes, and practice behaviors regarding advanced care planning, and to obtain preliminary understanding of APNs' knowledge, attitudes, and practice behaviors and perceived barriers to advanced care planning.

Design: Descriptive, cross-sectional, pilot survey study.

Setting: The eastern United States.Sample: 300 oncology APNs.Methods: Guided by the Theory of Planned Behavior, a knowledge, attitudes, and practice behaviors survey was developed and reviewed for content validity. The survey was distributed to 300 APNs via e-mail and sent again to the 89 APNs who responded to …

The Addition Of Rituximab To Fludarabine And Cyclophosphamide Improves Progression-Free Survival In Patients With Previously Treated Chronic Lymphocytic Leukemia., Amit Mahipal, Mark Weiss

Department of Medical Oncology Faculty Papers

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. There has been considerable progress in understanding the biology and treatment of CLL in last 20 years. The introduction of purine analogs (pentostatin, fludarabine, and cladribine) dramatically increased the response rates compared to alkylating agents. Combination chemoimmunotherapy has further improved the overall frequency of response to over 80% in treatment-naïve and over 60% in relapsed/ refractory disease, respectively.

Effects Of High Intraoperative Inspired Oxygen On Postoperative Nausea And Vomiting In Gynecologic Laparoscopic Surgery, Tatjana Šimurina, Md, Msc, Boris Mraović, Md, Simon Mikulandra, Md, Msc, Zdenko Sonicki, Md, Phd, Nina Sulen, Md, Branko Dukić, Md, Tong J. Gan, M.D

Department of Anesthesiology Faculty Papers

Study objective: To assess the efficacy of intraoperative different inspired oxygen fractions (FIO2) of 0.8 and 0.5 when compared with standard FIO2 0.3 in prevention of postoperative nausea and vomiting (PONV).

Design: A prospective, controlled, randomized, double-blind study.

Setting: General hospital, postanesthesia care unit (PACU) and gynecologic floor room. Patients: 120 ASA physical status I and II women, aged 21 to 76 y, undergoing elective gynecologic laparoscopic surgery.

Interventions: Patients were randomized to receive gas mixture of 30% oxygen in air (FI O2=0.3, group G30), 50% oxygen in air (FIO2=0.5, group G50) or 80% oxygen in air (FIO2=0.8, group G80), …

Obstructive Sleep Apnea And Ocular Disorders., Deepak P. Grover

Wills Eye Hospital Papers

PURPOSE OF REVIEW: Obstructive sleep apnea is a diagnosis that ophthalmologists can screen for when a patient presents with certain risk factors. Recent literature provides strong data for associations between sleep apnea and ocular disorders.

RECENT FINDINGS: A potentially serious disorder, sleep apnea can lead to many systemic and ocular complications. Recent findings provide data on the prevalence of sleep apnea with various disorders. Adequate treatment of sleep apnea has also shown to reverse both systemic and eye-related complications.

SUMMARY: Early diagnosis and management of sleep apnea is critical for reducing the risk of devastating systemic complications and preserving ocular …

Biosynthesis: A New (Old) Way Of Hijacking Trna., Georges Lahoud, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Aminoacylation of tRNA is the cellular process for providing aminoacyl donors for the ribosome synthesis of polypeptides. New research highlights an unexpected structural overlap between enzymes involved in this process and those involved in the biosynthesis of cyclodipeptides, an important class of bioactive molecules.

J. Graham Smith Jr, Md (November 22, 1926-May 18, 2010)., Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

With the passing of J. Graham Smith, Jr. on May 18, 2010, following a short illness, dermatology lost one of its most distinguished envoys. (Figure 1) Skee*, as he was known by his many friends, held the important offices in American dermatology for which he made many significant contributions.

Ms4a4b, A Cd20 Homologue In T Cells, Inhibits T Cell Propagation By Modulation Of Cell Cycle., Hui Xu, Yaping Yan, Mark S Williams, Gregory B Carey, Jingxian Yang, Hongmei Li, Guang-Xian Zhang, Abdolmohamad Rostami

Department of Neurology Faculty Papers

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural …

Sepsis-Induced Cardiomyopathy: A Review Of Pathophysiologic Mechanisms., Anthony Flynn, Bhalaghuru Chokkalingam Mani, Paul J Mather

Department of Medicine Faculty Papers

Cardiac dysfunction is a well-recognized complication of severe sepsis and septic shock. Cardiac dysfunction in sepsis is characterized by ventricular dilatation, reduction in ejection fraction and reduced contractility. Initially, cardiac dysfunction was considered to occur only during the "hypodynamic" phase of shock. But we now know that it occurs very early in sepsis even during the "hyperdynamic" phase of septic shock. Circulating blood-borne factors were suspected to be involved in the evolution of sepsis induced cardiomyopathy, but it is not until recently that the cellular and molecular events are being targeted by researchers in a quest to understand this enigmatic …

Role Of Growth Factors In The Pathogenesis Of Tissue Fibrosis In Systemic Sclerosis., Sergio A. Jimenez, Susan V. Castro, Sonsoles Piera-Velazquez

Department of Medicine Faculty Papers

The most severe clinical and pathologic manifestations of systemic sclerosis (SSc) are the result of a fibrotic process characterized by the excessive and often progressive deposition of collagen and other connective tissue macromolecules in skin and numerous internal organs. The mechanisms involved in the initiation and progression of the remarkable fibrotic process in SSc remain largely unknown. Extensive recent studies have indicated that a variety of polypeptide growth factors play a crucial role in this process. The most commonly implicated growth factors include transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), platelet derived growth factor (PDGF), and vascular …

Jcipe Hosted Its First International Interprofessional Education And Care Conference

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

One hundred and thirty two (132) individuals from Canada and the US gathered at Thomas Jefferson University, Dorrance H. Hamilton Building on March 12-13, 2010 for JCIPE’s first annual conference. The 2010 conference theme was ‘Interprofessional Care for the 21st Century: Redefining Education and Practice’ and brought a wide range of expertise on interprofessional education, learning and practice.

Jefferson Award For Excellence In Interprofessional Education

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

In recognition for outstanding contributions to interprofessional education two faculty awards were given by JCIPE to Christine Jerpbak, MD, Department of Family and Community Medicine on May 23, 2010 and E. Adel Herge, OTD, OTR/L , Department of Occupational Therapy on June 1, 2010.

The Patient Centered Medical Home: Federal, State And Local Initiatives To Transform Primary Care. The First Of An Occasional Series In Interprofessional Education And Care In The Patient-Centered Medical Home, Brooke Salzman

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

The Patient Centered Medical Home (PCMH) is rapidly emerging as one prototype for redesigning health care delivery, restructuring reimbursement, and reestablishing the critical value of primary care. The actual term “medical home” was introduced by the American Academy of Pediatrics, (AAP) in 1967, initially referring to a central location for archiving a child’s medical record. In 2002, the AAP expanded the medical home concept to include care characterized as accessible, continuous, comprehensive, patient-centered, coordinated, compassionate, and culturally effective. In 2004, the American Academy of Family Physicians (AAFP) embraced the model in its Future of Family Medicine project report, and in …

Clinical Care Plan, Interprofessional Course, Marcia Levinson, Kathryn Shaffer, Amy Egras

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

Evidence suggests interprofessional collaborative practice significantly improves patient outcomes, reduces mortality and enhances quality-of-life.1 Person-focused care demands collaboration among professions in a team approach to address multiple issues including illness, prevention, and health promotion activities. Key elements of successful implementation of interprofessional education are supported in Thomas Jefferson University’s Clinical Care Plan, Interprofessional Course (CCPIC) that includes increasing knowledge of the roles, responsibilities, and competencies of other health professions, collaborating in teams, recognizing the patient as the expert, and communicating effectively.

Developing Interprofessional Teams Using High Fidelity Resuscitation, Ksenia Zukowsky, Kevin Dysart, Brian Glynn, Tara Berman, Judi Ondik, Patricia Constanty, Debbie Cruz

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

Interprofessional simulations using scenarios, megacodes, algorithms, and high fidelity equipment provide a closer approximation to what clinicians are likely to face as a team in the actual resuscitation of a newborn infant.

From The Editors, Christine Arenson, Md, Molly Rose, Rn, Phd

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

Welcome to the latest edition of the Jefferson Interprofessional Education and Care Newsletter. In this issue, Dr. Zukowsky and colleagues describe the value of high-fidelity simulation to train interprofessional teams in high-risk high-stakes care. Their successful model has important implications for preparing teams to perform optimally during critical, and often stressful, clinical situations where expertise in both technical and team skills is imperative for best patient outcomes. Dr. Levinson and colleagues describe an exciting interprofessional care planning course which, for the first time at Jefferson, has brought senior Occupational Therapy (OT), Physical Therapy (PT), Nursing, Pharmacy and Medical students together …

Download Entire Pdf Interprofessional Education And Care Newsletter, Vol. 2, No. 1, Fall 2010

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

This issue includes articles on:

Developing Interprofessional Teams using High Fidelity Resuscitation

Clinical Care Plan, Interprofessional Course

The Patient Centered Medical Home: Federal, State and Local Initiatives to Transform Primary Care The First of an Occasional Series in Interprofessional Education and Care in the Patient-Centered Medical Home

JCIPE hosted its First International Interprofessional Education and Care Conference

Interprofessional Geriatric Education: Team-Based Care For Chronic Conditions, Christine Hsieh, Chrstine A. Arenson, Tarae Waddell-Terry

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

The Eastern Pennsylvania-Delaware Geriatric Education Center (EPaD GEC) mission is to provide interprofessional geriatric education in Northeast and Southeast Pennsylvania and Delaware. EPaD GEC consortium members (Thomas Jefferson University (TJU), Christiana Care Health System (CCHS), Marywood University (MU) and Philadelphia Senior Center (PSC)) are committed to improving the health and quality of life of older adults and their caregivers by translating new evidence and innovative practice models into practical curricula and programs. One of our educational goals is to develop a structured curriculum on geriatric topics that can be integrated into the educational curricula of multiple health disciplines.

An Innovative Interprofessional Course: Cultural Humility And Competence, Nancy L. Chernett, Elaine Yuen, Susan Toth-Cohen, Robert Simmons

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

As we tackle the disproportionate burden of chronic illness and access to quality health care of an increasingly diverse population, it is critical to infuse cultural and linguistic competence in all sectors of health care training. To reach the Healthy People 2020 goal of eliminating health disparities, health and human services education must provide the knowledge and experience to understand the root causes of health disparities, as well as strategies to advance ongoing cultural and linguistic competence.

Advanced Physical Diagnosis: An Innovative Interprofessional Approach For Teaching Clinical Skills To Senior Medical Students, Dale Berg, Ann Barr, E.Adel Herge, Audrey Zapletal, Katherine Berg

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

Conclusions: This interprofessional education session, employing a case-based videotape, was successful in illustrating to senior medical students the roles of OT and PT in patient management, and in increasing their awareness of the types of patient problems that would warrant referral for OT and PT services. The team is developing learning activities for future modules for medical students to teach the role of occupational and physical therapies in interprofessional health care.

From The Editors, Christine Arenson, Md, Molly Rose, Rn, Phd

Collaborative Healthcare: Interprofessional Practice, Education and Evaluation (JCIPE)

Welcome to this inaugural edition of the Jefferson InterProfessional Education and Care Newsletter. We are delighted to launch this new vehicle to share the exciting programs advancing interprofessional care and education that are happening here at Jefferson and beyond. The Newsletter will be a biannual on-line peer-reviewed publication, which will showcase a range of innovative courses, experiential, simulation, and clinical instruction, and new models of team-based care, all designed to enhance the ability of the healthcare team to meet the mandates of the Institute of Medicine to provide safe, effective, efficient, equitable, timely, patientcentered care. Interprofessional team-based care has been …