Medicine and Health Sciences Commons^™

Neural Crest Cell-Autonomous Roles Of Fibronectin In Cardiovascular Development., Xia Wang, Sophie Astrof

Department of Medicine Faculty Papers

The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (Fn1) is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1. We found that Fn1 synthesized by the NC mediated morphogenesis of the aortic arch artery and differentiation of NC cells into …

Bioinnovation Enterprise: An Engine Driving Breakthrough Therapies., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Biological advances have radically expanded our insights into the underpinnings of health and disease. New knowledge has formed the substrate for translation-expedited in turn by the biotechnology and pharmaceutical industry into novel therapeutic solutions impacting the management of patients and populations. Indeed, this Bioinnovation Enterprise has become the dominant growth sector in drug development and the engine driving the translation of breakthrough therapies worldwide. This annual Therapeutic Innovations issue highlights recent exceptional advances by the Bioinnovation Enterprise in translating molecular insights in pathobiology into transformative therapies.

Do Pressure Requirements Change Over Time With Auto Titrating Positive Airway Pressure Therapy For Obstructive Sleep Apnea?, Anupama Tiwari, Md, Karl Doghramji, Md, Ritu Grewal, Md

Department of Sleep Medicine Faculty Papers

Study Objective:

Prior studies have demonstrated reduced inflammation after chronic use of CPAP therapy. This may lead to reduced pressures over time as the upper airway becomes more compliant. We sought to determine if there was a reduction in 90th percentile pressure requirements in patients on Auto PAP for OSA.

Methods:

A retrospective chart review of 988 patients who underwent a sleep study at our sleep center was performed. Those with moderate to severe sleep apnea who were prescribed and compliant with Respironics Auto PAP were included, yielding a total of 46 patients for analysis. All statistical analysis analyses were …

Determinants Of Activity Levels In African Americans With Mild Cognitive Impairment., Barry W. Rovner, Md, Robin J. Casten, Phd, Benjamin E. Leiby, Phd

Department of Neurology Faculty Papers

Engaging in cognitive, social, and physical activities may prevent cognitive decline. In a sample of older African Americans with mild cognitive impairment (MCI; N=221), we investigated the cross-sectional relationships between activity levels and participants' demographic, clinical, and neuropsychological characteristics. The average age of participants was 75.4 years (SD, 7.0); 177 (80.1%) were women. Participation in cognitive/social activities was positively associated with education, depression, literacy, mobility, instrumental activities of daily living (IADL), verbal learning, and subcomponents of executive function. A linear regression identified IADLs, education, depression, and verbal learning as independent predictors. Participation in physical activities was positively associated with sex, …

Cogstate Computerized Memory Tests In Patients With Brain Metastases: Secondary Endpoint Results Of Nrg Oncology Rtog 0933., Chip Caine, Snehal Deshmukh, Vinai Gondi, Minesh Mehta, Wolfgang Tomé, Benjamin W. Corn, Andrew Kanner, Howard Rowley, Vijayananda Kundapur, Albert Denittis, Jeffrey Noah Greenspoon, Andre A. Konski, Glenn S. Bauman, Adam Raben, Wenyin Shi, Merideth Wendland, Lisa Kachnic

Department of Radiation Oncology Faculty Papers

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning …

Does A Short, Thick Neck Predict Obstructive Sleep Apnea?: The Role Of Physical Examination In Osa Screening, Ramya Punati, Md, Shivan Saxena, Md, Constantine Daskalakis, Sc.D., Salvatore Mangione, Md, Ritu G. Grewal, Md

Department of Sleep Medicine Faculty Papers

Purpose:

The purpose of this study was to determine whether a short neck, alone or together with a thick neck, can predict obstructive sleep apnea (OSA).

Methods:

The laryngeal heights of 169 new adult patients presenting to a sleep medicine physician were measured over a period of 5 months. Neck circumference, Mallampati score, and body-mass index (BMI) were also determined, together with medical history, smoking status, and serum bicarbonate. Lastly, patients’ polysomnograms were obtained in order to ascertain the presence or absence of OSA as indicated by the apnea-hypopnea index, as well as other sleep study parameters.

Results:

No association …

Severe Obesity Hypoventilation Syndrome Treated With Auto-Cpap, Zhanna Fast, Md, Ritu G. Grewal, Md

Department of Sleep Medicine Faculty Papers

Summary

Obesity hypoventilation syndrome (OHS) is a serious medical condition that remains undiagnosed in seriously ill hospitalized patients. Significant improvement of daytime hypercapnia can be achieved with positive airway pressure (PAP) therapy. Bi-level PAP is generally employed with the goal of improving ventilation. A 50-year-old woman with OHS and severe hypercapnia was successfully treated with an auto titrating continuous PAP (Auto-CPAP) device. The major role in the pathogenesis of daytime hypercapnia in patients with OHS, is the progressive accumulation of carbon dioxide (CO2) caused by repetitive obstructive events at night, which can be eliminated with the low cost approach of …

Racemose Neurocysticercosis., Kristin Krupa, Kelly Krupa, Bs, Mary L Pisculli, Deena M Athas, Christopher J Farrell, Md

Department of Neurosurgery Faculty Papers

BACKGROUND: Neurocysticercosis (NCC) is an invasive parasitic infection of the central nervous system caused by the larval stage of the tapeworm Taenia solium. The clinical manifestations of NCC depend on the parasitic load and location of infection, as well as the developmental stage of the cysticerci and host immune response, with symptoms ranging from subclinical headaches to seizures, cerebrovascular events, and life-threatening hydrocephalus. Racemose NCC represents a particularly severe variant of extraparenchymal NCC characterized by the presence of multiple confluent cysts within the subarachnoid space and is associated with increased morbidity and mortality, as well as a decreased response to …

Neurovascular Disorders: Novel Perspectives On Pathogenesis, Diagnosis, And Treatment., David Hasan, Nohra Chalouhi, Md, Aaron S Dumont, Robert M Starke, Pascal Jabbour Md

Department of Neurosurgery Faculty Papers

No abstract provided.

The Eff-1a Cytoplasmic Domain Influences Hypodermal Cell Fusions In C. Elegans But Is Not Dependent On 14-3-3 Proteins., Jessica H Shinn-Thomas, Jacob J Del Campo, Jianjun Wang, William A Mohler

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Regulatory and biophysical mechanisms of cell-cell fusion are largely unknown despite the fundamental requirement for fused cells in eukaryotic development. Only two cellular fusogens that are not of clear recent viral origin have been identified to date, both in nematodes. One of these, EFF-1, is necessary for most cell fusions in Caenorhabditis elegans. Unregulated EFF-1 expression causes lethality due to ectopic fusion between cells not developmentally programmed to fuse, highlighting the necessity of tight fusogen regulation for proper development. Identifying factors that regulate EFF-1 and its paralog AFF-1 could lead to discovery of molecular mechanisms that control cell fusion …

Surgical Intensivist And Global Critical Care: Is There A Role?, Jana B.A. Macleod, Orlando C. Kirton, Linda L. Maerz

Abington Jefferson Health Papers

No abstract provided.

Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).

METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed …

Anxiety And Depression In Patients With Advanced Macular Degeneration: Current Perspectives., Verena R Cimarolli, Robin J Casten, Barry W. Rovner, Vera Heyl, Silvia Sörensen, Amy Horowitz

Department of Medicine Faculty Papers

Age-related macular degeneration (AMD) - despite advances in prevention and medical treatment options - remains prevalent among older adults, often resulting in functional losses that negatively affect the mental health of older adults. In particular, the prevalence of both anxiety and depression in patients with AMD is high. Along with medical treatment options, low vision rehabilitation and AMD-specific behavioral and self-management programs have been developed and have demonstrated effectiveness in improving the mental health of AMD patients. This article reviews the prevalence of anxiety and depression in patients with advanced AMD, discusses potential mechanisms accounting for the development of depression …

Gliopathy Of Demyelinating And Non-Demyelinating Strains Of Mouse Hepatitis Virus., Lawrence C. Kenyon, Kaushiki Biswas, Kenneth S Shindler, Manasi Nabar, Marjorie Stout, Susan T Hingley, Judith B Grinspan, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Demyelination in the central nervous system induced by neurovirulent strains of Mouse Hepatitis Virus (MHV) is mediated by the viral spike glycoprotein, but it is not clear whether the mechanism of this disease pathology involves direct viral infection of oligodendrocytes. Detailed studies of glial cell tropism of MHV are presented, demonstrating that direct MHV infection of oligodendrocytes differs between demyelinating (RSA59) and non-demyelinating (RSMHV2) viral strains both in vitro and in vivo. Our results indicate that direct injury of mature oligodendrocytes is an important mechanism of virus-induced demyelination. In vivo, RSA59 infection was identified in spinal cord gray and white …

Dysregulation Of The Haem-Haemopexin Axis Is Associated With Severe Malaria In A Case-Control Study Of Ugandan Children., Robyn E Elphinstone, Frank Riley, Tian Lin, Sarah Higgins, Aggrey Dhabangi, Charles Musoke, Christine Cserti-Gazdewich, Raymond F. Regan, H Shaw Warren, Kevin C Kain

Department of Medicine Faculty Papers

BACKGROUND: Malaria is associated with haemolysis and the release of plasma haem. Plasma haem can cause endothelial injury and organ dysfunction, and is normally scavenged by haemopexin to limit toxicity. It was hypothesized that dysregulation of the haem-haemopexin pathway contributes to severe and fatal malaria infections.

METHODS: Plasma levels of haemin (oxidized haem), haemopexin, haptoglobin, and haemoglobin were quantified in a case-control study of Ugandan children with Plasmodium falciparum malaria. Levels at presentation were compared in children with uncomplicated malaria (UM; n = 29), severe malarial anaemia (SMA; n = 27) or cerebral malaria (CM; n = 31), and evaluated …

Download Entire Issue- Jefferson Interprofessional Education And Care Newsletter, Fall 2015, Volume 6, Issue 2

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

Download entire issue- Jefferson Interprofessional Education and Care Newsletter, Fall 2015, Volume 6, Issue 2

An Online Approach To Interprofessional Education, E. Adel Herge, Otd, Otr/L, Faota, Amber E. King, Pharmd, Bcps

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

Despite increasing interest in providing interprofessional education (IPE) opportunities for health profession students, the logistics of scheduling and integrating diverse curriculums remain challenging. Several models to address these potential barriers have been proposed and utilized (Blue et al, 2010). Faculty from three colleges within Thomas Jefferson University developed an asynchronous online interprofessional course as one solution to overcome logistical barriers to IPE.

Interprofessional Grand Rounds is offered to third year pharmacy students and second year occupational therapy (OT) students in the fall semester. The course utilizes a variety of learning activities to evaluate the influence of current public health and …

Examining Health Mentors’ Perceptions Of Student Teamwork, Deirdre Yarosh, Bs, Ma, Pharmd Student, Elena M. Umland, Pharmd

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

Statement of Issue:

With the increasing emphasis on interprofessional teamwork in healthcare, the need to train future health care professionals to work together as a functional team to provide patient-centered care is clear. Limited information exists regarding education of health care students and teamwork training.1,2 This research evaluates student team performance.

Background:

Thomas Jefferson University (TJU) offers a unique, two-year program emphasizing delivery of patient-centered care and providing valuable skill development by pairing interprofessional student teams with a Health Mentor (HM). The HM is an adult community volunteer with one or more chronic health condition(s). Student teams include representatives from …

In Addition To Checking Out A Book, You Can Check Out Your Health Too: A New Partnership Between Jefferson College Of Nursing And The Philadelphia Free Public Library, Kathryn Shaffer, Edd, Rn, Msn, Cne

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

At Jefferson Health is all we do, but at Jefferson College of Nursing (JCN), Health is H.E.R.E (humanistic, evidenced-based, reflective, excellence in clinical leaders). With a redesign of the undergraduate nursing curriculum, Jefferson College of Nursing (JCN) has transformed the way nurses of the 22nd century will practice, with a focus on caring for patients in all areas of the care continuum. The newly designed curriculum centers around four themes that are threaded throughout, Innovation, Practice Excellence, Interprofessional Collaboration, and Population Health. JCN believes that patients are partners in their health and that care is a collaborative effort.

To model …

From The Editors, Elizabeth Speakman, Edd, Rn, Anef, Fnap, Christine Arenson, Md, Lauren Collins, Md, Shoshana Sicks, Edm

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

This fall has seen a flurry of activity at the Jefferson Center for InterProfessional Education (JCIPE). In September, Lauren Collins, MD, Associate Director of JCIPE, was selected as one of five recipients of the prestigious Macy Faculty Scholars (MFS) program, a two-year career development award supported by the Josiah Macy Jr. Foundation. She now joins a national network of other MFS recipients in helping to re-envision training of health professions students and delivery of collaborative care. Elizabeth Speakman, EdD, RN, ANEF, FNAP, JCIPE Co-Director, completed her three-year Robert Wood Johnson Executive Nurse Fellowship and was recently selected to attend the …

Latest Jcph Capstones In The Jdc, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

A new batch of capstone presentations from the Jefferson College of Population Health have been loaded in the Jefferson Digital Commons.

Aileen Ishuin Macmillan, Aileen Ishuin Macmillan, Kelsey Duinkerken

Jefferson Nursing Oral Histories

Aileen Ishuin MacMillan did not grow up wanting to be a nurse, but after two years of college in Montclair not knowing what she wanted to do, Ms. MacMillan decided by chance to pursue nursing at Jefferson. After graduating in 1976 from the Diploma program she took a job as a nurse in the maternity ward of Thomas Jefferson University Hospital. During her forty year career at Jefferson Ms. MacMillan also completed her BSN at Gwynedd Mercy University. She remains very involved in Jefferson Nursing, serving on both the Jefferson Nursing College Alumni Board and, as president, on the Diploma …

Factors Associated With Tonic-Clonic Seizures In Patients With Drug-Resistant Mesial Temporal Epilepsy., Ali Akbar Asadi-Pooya, Cyrus Rostami, Amin H. Rabiei, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: Among different seizure types, tonic-clonic seizures are more significant because they are more often associated with morbidity. No prior study has been done to investigate risk factors associated with tonic-clonic seizures in patients with mesial temporal epilepsy.

METHODS: In this retrospective study, all drug-resistant mesial temporal epilepsy patients in the database of patients who underwent epilepsy surgery at Jefferson comprehensive epilepsy center were recruited. These patients were prospectively registered in a database from 1986 till 2014. Patients' age, gender, epilepsy risk factors, age at seizure onset, and preoperative seizure type(s) were registered routinely. Potential risk factors associated with experiencing …

Karen Jordan, Karen Jordan, Kelsey Duinkerken

Jefferson Nursing Oral Histories

Born and raised in Philadelphia, Karen Jordan was a member of the civil rights movement in Philadelphia during the 1960s, first becoming involved with the fight to desegregate Girard College. After a semester at Cheyney University Ms. Jordan took time away from school before deciding to study nursing. She enrolled in the Jefferson Diploma Nursing program in 1973 and graduated in 1976. She would later go on to also receive her Bachelor’s in Nursing Science, also from Thomas Jefferson University. Ms. Jordan has spent her long career at Jefferson working as a medical-surgical, oncology, and neonatal nurse. In her free …

Cyclin D1 Silencing Suppresses Tumorigenicity, Impairs Dna Double Strand Break Repair And Thus Radiosensitizes Androgenindependent Prostate Cancer Cells To Dna Damage., F Marampon, G L Gravina, Xiaoming Ju, A Vetuschi, R Sferra, Mathew C Casimiro, S Pompili, C Festuccia, A Colapietro, E Gaudio, E Di Cesare, V Tombolini, Richard Pestell

Department of Cancer Biology Faculty Papers

Patients with hormone-resistant prostate cancer (PCa) have higher biochemical failure rates following radiation therapy (RT). Cyclin D1 deregulated expression in PCa is associated with a more aggressive disease: however its role in radioresistance has not been determined. Cyclin D1 levels in the androgen-independent PC3 and 22Rv1 PCa cells were stably inhibited by infecting with cyclin D1-shRNA. Tumorigenicity and radiosensitivity were investigated using in vitro and in vivo experimental assays. Cyclin D1 silencing interfered with PCa oncogenic phenotype by inducing growth arrest in the G1 phase of cell cycle and reducing soft agar colony formation, migration, invasion in vitro and tumor …

Progtar: A Database Of Prognostically Inversely Correlated Mirnas And Genes (Pics) In Multiple Cancers, Chirayu Pankaj Goswami

Department of Pathology, Anatomy, and Cell Biology Posters

ABSTRACT

PROGTar is a database of Prognostically Inversely Correlated miRNA-mRNA pairs (PIC’s) in 23 cancer types. Partner miRNA and mRNA in a PIC show inverse correlation of expression and opposite hazards. We analyzed miRNA and mRNA expression data downloaded from The Cancer Genome Atlas (TCGA) in a 3 step approach to identify PICs in different cancer types. In first step we performed correlation analysis between miRNAs and mRNAs for each cancer type. This was followed by performing hazard analysis separately for miRNAs and mRNAs using expression data and survival related clinical variables. In the third step we merged the correlation …

Isosorbide Mononitrate In Heart Failure With Preserved Ejection Fraction., Margaret M. Redfield, Kevin J. Anstrom, James A. Levine, Gabe A. Koepp, Barry A. Borlaug, Horng H. Chen, Martin M. Lewinter, Susan M. Joseph, Sanjiv J. Shah, Marc J. Semigran, G. Michael Felker, Robert T. Cole, Gordon R. Reeves, Ryan J. Tedford, W.H. Wilson Tang, Steven E. Mcnulty, Eric J. Velazquez, Monica R Shah, Eugene Braunwald

Division of Cardiology Faculty Papers

BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients.

METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer …

New Podcast From Radiation Oncology, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

The Department of Radiation Oncology’s first podcast, FAQ: Special focus on the Radiation Oncology Residency Program at Thomas Jefferson University, features a discussion of what separates Jefferson from other residency program and answers commonly asked questions. The podcast is now archived in the Jefferson Digital Commons.

Igf-I Induces Upregulation Of Ddr1 Collagen Receptor In Breast Cancer Cells By Suppressing Mir-199a-5p Through The Pi3k/Akt Pathway., Roberta Matà, Chiara Palladino, Maria Luisa Nicolosi, Anna Rita Lo Presti, Roberta Malaguarnera, Marco Ragusa, Daniela Sciortino, Andrea Morrione, Marcello Maggiolini, Veronica Vella, Antonino Belfiore

Kimmel Cancer Center Faculty Papers

Discoidin Domain Receptor 1 (DDR1) is a collagen receptor tyrosine-kinase that contributes to epithelial-to-mesenchymal transition and enhances cancer progression. Our previous data indicate that, in breast cancer cells, DDR1 interacts with IGF-1R and positively modulates IGF-1R expression and biological responses, suggesting that the DDR1-IGF-IR cross-talk may play an important role in cancer.In this study, we set out to evaluate whether IGF-I stimulation may affect DDR1 expression. Indeed, in breast cancer cells (MCF-7 and MDA-MB-231) IGF-I induced significant increase of DDR1 protein expression, in a time and dose dependent manner. However, we did not observe parallel changes in DDR1 mRNA. DDR1 …

Comprehensive Profiling Of Metaplastic Breast Carcinoma Reveals Frequent Over-Expression Of Pd-L1, Zoran Gatalica, Upasana Joneja, Md, Anatole Ghazalpour, Jeffrey Swensen, Rebecca Feldman, Fred Cai, Sting Chen, Nick Xiao, Sandeep Reddy, Semir Vranić

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Background:

Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy relative to usual breast carcinomas such as ductal and lobular subtype. In molecular terms, MBC usually clusters with triple negative breast cancers (TNBC), but MBCs portray a worse prognosis in comparison with TNBC. Published studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches.

Methods:

297 samples [MBC (n=75), triple-negative breast cancer of no-special-type (TNBC-NOS, n=106), HER2-positive breast cancers (n=32) and luminal breast cancers (n=84)] were profiled using direct sequencing analysis [Illumina MiSeq Next Generation Sequencing …