Medicine and Health Sciences Commons^™

Pharmacologic And Clinical Evaluation Of Posaconazole., Jason N. Moore, Jason R. Healy, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. There is evidence of efficacy in the treatment and prevention of rarer, more difficult-to-treat fungal infections. Posaconazole oral suspension solution has shown limitations with respect to fasting state absorption, elevated gastrointestinal pH and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide an attractive treatment option by reducing interpatient variability and providing flexibility in critically ill patients. On the basis of clinical experience and further clinical studies, posaconazole was found to be …

Childhood Psychosocial Determinants Of Cardiovascular Health, Samuel S. Gidding, Erica D. Sood

Department of Medicine Faculty Papers

Understanding risk and protective factors that impact cardiovascular health is of utmost importance. There is ample evidence that cardiovascular health begins in childhood, tracks over time, and is subject to adverse social influences. This paper reviews key studies examining the relations of psychosocial factors in childhood to cardiovascular health in adulthood. The existing literature provides evidence for both individual and cumulative effects of childhood psychosocial factors on adult cardiovascular health across the population, although the specific mechanisms underlying these relationships are not yet fully understood. This paper also includes a discussion of evidence-based strategies for prevention and treatment of childhood …

Hospitalized Patients At High Risk For Obstructive Sleep Apnea Have More Rapid Response System Events And Intervention Is Associated With Reduced Events., Sunil Sharma, Md, Anindita Chowdhury, Lili Tang, Leslee Willes, Brian Glynn, Stuart F Quan

Department of Medicine Faculty Papers

BACKGROUND: Rapid response system (RRS) is a safety tool designed for early detection and intervention of a deteriorating patient on the general floor in the hospital. Obstructive sleep apnea (OSA) has been associated with significant cardiovascular complications. We hypothesized that patients with high-risk of OSA have higher rate of RRS events and intervention with positive airway pressure therapy in these patients can mitigate the RRS events.

METHODS: As part of a clinical pathway, during a 15 month period, patients with BMI ≥ 30 kg/m2 in select medical services were screened with a validated sleep questionnaire. Patients were characterized as high …

Jefferson Digital Commons: Proving That Jefferson Is An International Phenomenon!, Daniel G. Kipnis, Msi

Academic Commons and Scott Memorial Library Staff Papers and Presentations

Write-up about Jefferson Digital Commons for the SKMC Alumni Bulletin Spring 2016 Issue.

Endoscopic Ultrasound-Guided Pancreaticobiliary Intervention In Patients With Surgically Altered Anatomy And Inaccessible Papillae: A Review Of Current Literature., Aaron Martin, Charles Andrew Kistler, Piotr Wrobel, Juliana F. Yang, Ali A. Siddiqui

Division of Gastroenterology and Hepatology Faculty Papers

The management of pancreaticobiliary disease in patients with surgically altered anatomy is a growing problem for gastroenterologists today. Over the years, endoscopic ultrasound (EUS) has emerged as an important diagnostic and therapeutic modality in the treatment of pancreaticobiliary disease. Patient anatomy has become increasingly complex due to advances in surgical resection of pancreaticobiliary disease and EUS has emerged as the therapy of choice when endoscopic retrograde cholangiopancreatography failed cannulation or when the papilla is inaccessible such as in gastric obstruction or duodenal obstruction. The current article gives a comprehensive review of the current literature for EUS-guided intervention of the pancreaticobiliary …

Ips Cell Transplantation For Traumatic Spinal Cord Injury., Miguel Goulao, Angelo C Lepore

Farber Institute for Neuroscience Faculty Papers

A large body of work has been published on transplantation of a wide range of neural stem and progenitor cell types derived from the developing and adult CNS, as well as from pluripotent embryonic stem cells, in models of traumatic spinal cord injury (SCI). However, many of these cell-based approaches present practical issues for clinical translation such as ethical cell derivation, generation of potentially large numbers of homogenously prepared cells, and immune rejection. With the advent of induced Pluripotent Stem (iPS) cell technology, many of these issues may potentially be overcome. To date, a number of studies have demonstrated integration, …

The Impact Of Vascular Complications On Survival Of Patients On Venoarterial Extracorporeal Membrane Oxygenation., Daizo Tanaka, Hitoshi Hirose, Nicholas C. Cavarocchi, John W.C. Entwistle

Department of Surgery Faculty Papers

BACKGROUND: There are various factors that can influence the survival of patients receiving venoarterial extracorporeal membrane oxygenation (VA ECMO). Vascular complications from femoral cannulation are common and are potentially serious. We analyzed the impact of vascular complications on survival of patients receiving VA ECMO.

METHODS: Patients supported with VA ECMO by means of femoral cannulation from October 2010 to November 2014 were enrolled in this study. Data were gathered retrospectively by reviewing our institutional database. Patients were separated into two groups depending on the presence of major vascular complications, defined as patients who required surgical intervention. We evaluated predisposing factors …

Long-Term Effect Of Antiepileptic Drug Switch On Serum Lipids And C-Reactive Protein., Scott Mintzer, Rachael Miller, Krunal Shah, Inna Chervoneva, Maromi Nei, Christopher T. Skidmore, Michael R. Sperling

Department of Neurology Faculty Papers

BACKGROUND: Prior studies have shown that switching patients from inducing antiepileptic drugs (AEDs) to lamotrigine, levetiracetam, or topiramate reduces serum lipids and C-reactive protein (CRP). These studies were all of short duration, and some drugs, such as zonisamide, have not been investigated.

METHODS: We recruited 41 patients taking phenytoin or carbamazepine who were being switched to zonisamide, lamotrigine, or levetiracetam. We measured serum lipids and CRP before the switch, >6weeks after, and >6months after. An untreated control group (n=14) underwent similar measurement. We combined these data with those of our previous investigation (n=34 patients and 16 controls) of a very …

Gray Matter Abnormalities In Temporal Lobe Epilepsy: Relationships With Resting-State Functional Connectivity And Episodic Memory Performance., Gaelle Eve Doucet, Xiaosong He, Michael R Sperling, Ashwini Sharan Md, Joseph I Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, …

Induced Stem Cells As A Novel Multiple Sclerosis Therapy., Chong Xie, Yan-Qun Liu, Yang-Tai Guan, Guang-Xian Zhang

Department of Neurology Faculty Papers

Stem cell replacement is providing hope for many degenerative diseases that lack effective therapeutic methods including multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Transplantation of neural stem cells or mesenchymal stem cells is a potential therapy for MS thanks to their capacity for cell repopulation as well as for their immunomodulatory and neurotrophic properties. Induced pluripotent stem cell (iPSC), an emerging cell source in regenerative medicine, is also being tested for the treatment of MS. Remarkable improvement in mobility and robust remyelination have been observed after transplantation of iPSC-derived neural cells into demyelinated models. Direct …

Yy1 Is Required For Germinal Center B Cell Development., Anupam Banerjee, Vishal Sindhava, Raja Vuyyuru, Vibha Jha, Suchita Hodewadekar, Tim Manser, Michael L Atchison

Department of Microbiology and Immunology Faculty Papers

YY1 has been implicated as a master regulator of germinal center B cell development as YY1 binding sites are frequently present in promoters of germinal center-expressed genes. YY1 is known to be important for other stages of B cell development including the pro-B and pre-B cells stages. To determine if YY1 plays a critical role in germinal center development, we evaluated YY1 expression during B cell development, and used a YY1 conditional knock-out approach for deletion of YY1 in germinal center B cells (CRE driven by the immunoglobulin heavy chain γ1 switch region promoter; γ1-CRE). We found that YY1 is …

Thermoluminescence Study Of Mn Doped Lithium Tetraborate Powder And Pellet Samples Synthesized By Solution Combustion Synthesis, A. Özdemir, Zehra Yeǧingil, Necmettin Nur, Kasim Kurt, Tunç Tüken, Tolga Depçi, Gözde Tansuǧ, V. Altunal, V. Güçkan, Gökmen Sığırcık, Yan Yu, Muhammet Karataşlı, Y. Dolek

Department of Radiation Oncology Faculty Papers

In this paper, the thermoluminescence (TL) dosimetric characteristics under beta-ray, x-ray and gamma-ray excitations of powder and pellet Mn-doped lithium tetraborates (LTB) which were produced by solution combustion synthesis technique were investigated, and the results were compared with that of TLD-100 chips. The chemical composition and morphologies of the obtained LTB and Mn-doped LTB (LTB:Mn) were confirmed by X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) and scanning electron microscopy (SEM) with EDX. LTB:Mn was studied using luminescence spectroscopy. In addition, the effects of sintering and annealing temperatures and times on the thermoluminescence (TL) properties of LTB:Mn were investigated. The glow …

Circadian Factors Bmal1 And Rorα Control Hif-1Α Transcriptional Activity In Nucleus Pulposus Cells: Implications In Maintenance Of Intervertebral Disc Health., Kaori Suyama, Elizabeth S Silagi, Hyowon Choi, Kou Sakabe, Joji Mochida, Irving M Shapiro, Makarand V Risbud

Department of Orthopaedic Surgery Faculty Papers

BMAL1 and RORα are major regulators of the circadian molecular oscillator. Since previous work in other cell types has shown cross talk between circadian rhythm genes and hypoxic signaling, we investigated the role of BMAL1 and RORα in controlling HIF-1-dependent transcriptional responses in NP cells that exist in the physiologically hypoxic intervertebral disc. HIF-1-dependent HRE reporter activity was further promoted by co-transfection with either BMAL1 or RORα. In addition, stable silencing of BMAL1 or inhibition of RORα activity resulted in decreased HRE activation. Inhibition of RORα also modulated HIF1α-TAD activity. Interestingly, immunoprecipitation studies showed no evidence of BMAL1, CLOCK or …

A Parp1-Erk2 Synergism Is Required For The Induction Of Ltp., L Visochek, G Grigoryan, A Kalal, H Milshtein-Parush, N Gazit, I Slutsky, A Yeheskel, A Shainberg, A Castiel, R Seger, Marie-France Langelier, F Dantzer, Pascal Jabbour Md, M Segal, M Cohen-Armon

Department of Biochemistry and Molecular Biology Faculty Papers

Unexpectedly, a post-translational modification of DNA-binding proteins, initiating the cell response to single-strand DNA damage, was also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk synergism, which may underlie this phenomenon. A stimulation induced PARP1 binding to phosphorylated Erk2 in the chromatin of cerebral neurons caused Erk-induced PARP1 activation, rendering transcription factors and promoters of immediate early genes (IEG) accessible to PARP1-bound phosphorylated Erk2. Thus, Erk-induced PARP1 activation mediated IEG expression implicated in long-term memory. PARP1 inhibition, silencing, or genetic deletion abrogated stimulation-induced Erk-recruitment to IEG promoters, gene …

Integrating Correctional And Community Health Care: An Innovative Approach For Clinical Learning In A Baccalaureate Nursing Program., Mary T. Bouchaud, Beth Ann Swan

College of Nursing Faculty Papers & Presentations

PROBLEM: With an evolving focus on primary, community-based, and patient-centered care rather than acute, hospital-centric, disease-focused care, and recognition of the importance of coordinating care and managing transitions across providers and settings of care, registered nurses need to be prepared from a different and broader knowledge base and skills set. A culture change among nurse educators and administrators and in nursing education is needed to prepare competent registered nurses capable of practicing from a health promotion, disease prevention, community- and population-focused construct in caring for a population of patients who are presenting health problems and conditions that persist across decades …

Interventions For Improving Pregnancy Outcomes In Antenatally Diagnosed Or Suspected Morbidly Adherent Placenta, Rinku Sengupta, Alexis C. Gimovsky, Shuqin Wei, Anthony Akinloye Bamigboye, Vincenzo Berghella, Amanda R. Amorim Adegboye, William Donald Fraser

Department of Obstetrics and Gynecology Faculty Papers

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the benefits and harms associated with clinical interventions for improving outcomes in women with antenatally diagnosed or suspected MAP. We will compare conventional caesarean hysterectomy with uterine conservation treatments (together with adjunct measures) in women who have been diagnosed antenatally with, or suspected to have, MAP.

Treatment Of Dental Complications In Sickle Cell Disease., Priti Mulimani, Samir K. Ballas, Adinegara B L Abas, Laxminarayan Karanth

Cardeza Foundation for Hematologic Research

BACKGROUND: Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in …

A Direct Quantification Method For Measuring Plasma Micrornas Identified Potential Biomarkers For Detecting Metastatic Breast Cancer., Qian Zhao, Shengqiong Deng, Guangxue Wang, Cuicui Liu, Lingyu Meng, Shanshan Qiao, Lei Shen, Yue Zhang, Jinhui Lü, Yuzhen Zhang, Min Wang, Richard Pestell, Chunli Liang, Zuoren Yu, Wenshu Li

Department of Cancer Biology Faculty Papers

Circulating miRNAs are protected from ribonuclease degradation by assembly into microvesicles and exosomes. Releasing miRNAs completely from these particles is the key step to quantify the circulating miRNAs. Currently purified RNA-based quantitative analysis is widely used while it is time and cost consuming with high risk for those circulating miRNAs with low abundance due to partial loss of RNA during the steps of total RNA extraction and small RNA enrichment. Herein, we optimized a simple, effective and time-saving method to directly measure plasma miRNAs without RNA isolation. It is based on complete miRNA release from the protein complexes, followed by …

Brucker And Potter Lectures Posted In The Jdc, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

In case you missed these recent campus events, recordings are now available in the Jefferson Digital Commons for: 

Strangers in a Strange Land: Primary Care and Academic Medical Centers (24th Annual Paul C. Brucker, MD Lecture presented by Thomas L. Schwenk, MD, Dean, University of Nevada School of Medicine, Reno) – This annual series of lectures was established in 1990 to honor the former Dean’s important contributions to Thomas Jefferson University and to American medicine.

A Mitochondrial Etiology of Complex Diseases (2016 William Potter Lecturepresented by Douglas C. Wallace, PhD, University of Pennsylvania) – The Potter Lecture is sponsored …

Ictal Asystole In A Patient With Posterior Reversible Encephalopathy Syndrome (Pres) And Seizures: A Case Report, Joanna Suski, Md, Reginald T. Ho, Md, Maromi Nei, Md

Department of Neurology Posters

BACKGROUND

• Ictal asystole is rare, seen in less than 1% of patients with epilepsy, and typically seen in patients with temporal or frontal lobe seizures, rarely in occipital lobe seizures, and has never been described in a patient with PRES .
• PRES is a clinical-radiologic diagnosis in which there is a breakdown of the blood brain barrier caused by abrupt changes of blood pressure, or cytokines causing endothelial damage and this creates brain edema.
• The typical neurological symptoms of PRES include encephalopathy (50-80%), seizure (60-75%), headache (50%), and visual disturbance (35%).
• Brain imaging in PRES usually reveals vasogenic edema in …

Sonographic Findings Of A Semi-Professional Football Player With 1st Mtp Joint Pain: Gout Or Turf Toe?, David Jeong, Md, Caqsm, Cep, Rmsk, Danielle Snyderman, Md, Lauren Hersh, Md, Jeremy Close, Md

Department of Family & Community Medicine Posters

Purpose

Aim : To review the applications and indications of sonography for forefoot disorders, especially gout and plantar plate injury of 1^st MTP joint.

Introduction

• Forefoot disorders are common but forefoot ultrasound is underutilized.
• Point-of-Care Ultrasound was utilized in initial workup evaluating acute on chronic 1^st MTP joint pain in our case study.

Nitrilase 1 Modulates Lung Tumor Progression In Vitro And In Vivo., Yong Antican Wang, Yunguang Sun, Justin M Le Blanc, Charalambos C. Solomides, Md, Tingting Zhan, Bo Lu, Md

Department of Radiation Oncology Faculty Papers

Uncovering novel growth modulators for non-small cell lung cancer (NSCLC) may lead to new therapies for these patients. Previous studies suggest Nit1 suppresses chemically induced carcinogenesis of the foregut in a mouse model. In this study we aimed to determine the role of Nit1 in a transgenic mouse lung cancer model driven by a G12D Kras mutation. Nit1 knockout mice (Nit1-/-) were crossed with KrasG12D/+ mice to investigate whether a G12D Kras mutation and Nit1 inactivation interact to promote or inhibit the development of NSCLC. We found that lung tumorigenesis was suppressed in the Nit1-null background (Nit1-/-:KrasG12D/+). Micro-CT scans and …

Insights From Hur Biology Point To Potential Improvement For Second-Line Ovarian Cancer Therapy., Yu-Hung Huang, Weidan Peng, Narumi Furuuchi, James B Duhadaway, Masaya Jimbo, Andrea Pirritano, Charles J Dunton, Gary S Daum, Benjamin E Leiby, Jonathan Brody, Md, Janet A Sawicki

Kimmel Cancer Center Faculty Papers

This retrospective study aimed to investigate the role that an RNA-binding protein, HuR, plays in the response of high-grade serous ovarian tumors to chemotherapeutics. We immunohistochemically stained sections of 31 surgically-debulked chemo-naïve ovarian tumors for HuR and scored the degree of HuR cytoplasmic staining. We found no correlation between HuR intracellular localization in tumor sections and progression free survival (PFS) of these patients, 29 of whom underwent second-line gemcitabine/platin combination therapy for recurrent disease. Ribonucleoprotein immunoprecipitation (RNP-IP) analysis of ovarian cancer cells in culture showed that cytoplasmic HuR increases deoxycytidine kinase (dCK), a metabolic enzyme that activates gemcitabine. The effects …

Detection Of Circulating Tumor Cells In Uveal Melanoma By The Photoacoustic Method, Ryan M. Weight, Shingo Sato, Masahiro Ohara, Mizue Terai, Michael Mastrangelo, Marlana Orloff, Benjamin Goldschmidt, John Viator, Takami Sato

Department of Medical Oncology Posters

Abstract

Circulating tumor cells (CTCs) have been shown to be a prognostic marker in breast cancer¹. We hypothesize that circulating melanoma cell (CMC) detection could be utilized in the management of uveal melanoma, including early intervention. Prior methodologies for circulating uveal melanoma cell (CUMC) detection have been fraught with poor sensitivity, limiting their clinical utility². Development of an improved method is necessary to establish the clinical utility of CUMC monitoring. Photoacoustics, also referred to as laser-induced ultrasound, is a novel platform for the detection and capture of CMCs. Photoacoustics uses short duration pulsed light to create …

Molecular Treatment Effects Of Alemtuzumab In Skeletal Muscles Of Patients With Ibm., Karsten Schmidt, Konstanze Kleinschnitz, Goran Rakocevic, Marinos Dalakas, Jens Schmidt

Department of Neurology Faculty Papers

BACKGROUND: Mechanisms of inflammation and protein accumulation are crucial in inclusion body myositis (IBM). Recent evidence demonstrated that intravenous immunoglobulin failed to suppress cell-stress mediators in IBM. Here we studied the molecular changes in skeletal muscle biopsies from patients with IBM before and after treatment with alemtuzumab.

METHODS: Relevant inflammatory and degeneration-associated markers were assessed by quantitative-PCR and immunohistochemistry in repeated muscle biopsy specimens from patients with IBM, which had been treated in a previously published uncontrolled proof-of-concept trial with alemtuzumab.

RESULTS: There were no significant changes of the mRNA expression levels of the pro-inflammatory chemokines CXCL-9, CCL-4, and the …

Development Of A Temperature Sensitive Face Mask For Identification And Triage Of Febrile Patients, Annemarie Daecher, Flemming Forsberg, John R. Eisenbrey

Department of Radiology Posters

Abstract:

Many infectious diseases are most transmittable when the carrier is presenting with fever. We propose a disposable face mask that changes color as an indicator of fever to provide hospitals with a quick and inexpensive method for triaging infected patients while limiting exposure to others. Two blue thermochromatic dyes which transition to white at 89°F and 92°F were mixed with white paint and applied to 5 types of disposable face masks. During trials, a wearer either sat at rest or ran on a treadmill for 20 minutes and images were obtained every 5 minutes with a thermal camera to …

Dsg2 Increases Exosome Release And Enhances Egfr/C-Src Content: A Mechanism For Intercellular Mitogenic Effect, Andrew M. Overmiller, Jennifer A. Pierluissi, Peter J Wermuth, Ubaldo E. Martinez-Outshoorn, Md, Madalina Tuluc, Adam J. Luginbuhl, Joseph Curry, Larry A. Harshyne, James K. Wahl, Iii, Andrew P. South, M G Mahoney

Department of Dermatology and Cutaneous Biology Posters

Abstract:

Exosomes are nanoscale membrane-derived vesicles that are secreted by cancer cells and play a critical role in modulating the tumor microenvironment and disease pathogenesis. Dsg2, a desmosomal cadherin often overexpressed in skin malignancies including squamous cell carcinoma (SCC), can activate EGFR/c-Src signaling and promote oncogenesis. We sought to address the potential role of Dsg2 in exosome biogenesis and intercellular signaling in SCC. Here, purified exosomes from SCC cells and head/neck SCC patient sera were enriched with a processed 65 kDa membrane-associated C-terminal fragment of Dsg2. Cells overexpressing Dsg2 had increased exosome release and protein content and produced particles enriched …

Conducting A Systematic Review Using Prisma Guidelines From A Student's Perspective, Malinda Hawkins, June Horowitz, Phd, Rn, Faan, Kathleen Black, Phd, Rnc

College of Nursing Faculty Papers & Presentations

RESEARCH QUESTION

To understand how to conduct a systematic review using PRISMA guidelines.

INTRODUCTION

The purpose of this presentation is to depict a student’s point of view about conducting a systematic review using PRISMA guidelines. We sought to determine what inflammatory markers have been identified for preeclampsia.

** A faculty team is conducting this systematic review and invited the student to participate.

Healthy Living An In-Depth Look, Nina Radcliff, Md, Kristin Detterline

Jefferson Sleep Disorders Center in the News

Features Dr. Ritu Grewal, pulmonologist and attending physician at Jefferson Sleep Disorder Center Women's Program.

Endothelial To Mesenchymal Transition (Endomt) In The Pathogenesis Of Human Fibrotic Diseases., Sonsoles Piera-Velazquez, Fabian A. Mendoza, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Fibrotic diseases encompass a wide spectrum of clinical entities including systemic fibrotic diseases such as systemic sclerosis, sclerodermatous graft versus host disease, nephrogenic systemic fibrosis, and IgG₄-associated sclerosing disease, as well as numerous organ-specific disorders including radiation-induced fibrosis, and cardiac, pulmonary, liver, and kidney fibrosis. Although their causative mechanisms are quite diverse, these diseases share the common feature of an uncontrolled and progressive accumulation of fibrous tissue macromolecules in affected organs leading to their dysfunction and ultimate failure. The pathogenesis of fibrotic diseases is complex and despite extensive investigation has remained elusive. Numerous studies have identified myofibroblasts as the cells …