Medicine and Health Sciences Commons^™

Theta And High-Frequency Activity Mark Spontaneous Recall Of Episodic Memories., John F Burke, Ashwini D Sharan, Michael R Sperling, Ashwin G Ramayya, James J. Evans, M Karl Healey, Erin N Beck, Kathryn A Davis, Timothy H Lucas, Michael J Kahana

Department of Neurology Faculty Papers

Humans possess the remarkable ability to search their memory, allowing specific past episodes to be re-experienced spontaneously. Here, we administered a free recall test to 114 neurosurgical patients and used intracranial theta and high-frequency activity (HFA) to identify the spatiotemporal pattern of neural activity underlying spontaneous episodic retrieval. We found that retrieval evolved in three electrophysiological stages composed of: (1) early theta oscillations in the right temporal cortex, (2) increased HFA in the left hemisphere including the medial temporal lobe (MTL), left inferior frontal gyrus, as well as the ventrolateral temporal cortex, and (3) motor/language activation during vocalization of the …

Diverseot: Increasing Diversity Within The Field Of Occupational Therapy, Jocelyn Dressel, Ots, Erin Shervinskie, Ots, Lauren Yaker, Ots

Collaborative Research and Evidence shared Among Therapists and Educators (CREATE Day)

Objectives of Presentation:

At the end of this session, participants will be able to:

1. Describe the need to increase diversity among occupational therapy professionals

2. Recognize the impact of the absence of diversity within health professions

3. Discuss strategies utilized by other health professions to increase diversity in their student and professional workforce

4. Analyze and adapt effective strategies to increase diversity in the occupational therapy workforce

PICO What are effective strategies to increase diversity among OT students in order to create a diverse workforce?

Note: Handout only, no audio

Letters From 1841 Jefferson Medical College Graduate In Jdc, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

The Jefferson Digital Commons team is hard at work loading the letters of John Plimpton Green (1819-1892). Green graduated from Jefferson Medical College in 1841 and he practiced medicine in Whampoa, China and then Caopaipo, Chile, where he lived most of his life.

Epithelial Immunization Induces Polyfunctional Cd8+ T Cells And Optimal Mousepox Protection., Adam R Hersperger, Nicholas A Siciliano, Brian C Dehaven, Adam E. Snook, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

We assessed several routes of immunization with vaccinia virus (VACV) in protecting mice against ectromelia virus (ECTV). By a wide margin, skin scarification provided the greatest protection. Humoral immunity and resident-memory T cells notwithstanding, several approaches revealed that circulating, memory CD8(+) T cells primed via scarification were functionally superior and conferred enhanced virus control. Immunization via the epithelial route warrants further investigation, as it may also provide enhanced defense against other infectious agents.

Blau Syndrome, The Prototypic Auto-Inflammatory Granulomatous Disease., Carine H Wouters, Anne Maes, Kevin P Foley, John Bertin, Carlos D Rose

Department of Medicine Faculty Papers

Blau syndrome is a monogenic disease resulting from mutations in the pattern recognition receptor NOD2, and is phenotypically characterized by the triad of granulomatous polyarthritis, dermatitis and uveitis. This paper reviews briefly the classical clinical features of the disease, as well as more recently described extra-triad symptoms. From an ongoing prospective multicenter study, we provide new data on the natural history of Blau syndrome, focusing on functional status and visual outcome. We also present an update of the range of different NOD2 mutations found in Blau syndrome as well as recent data on morphologic and immunohistochemical characteristics of the Blau …

Breach Of Tolerance: Primary Biliary Cirrhosis., Lifeng Wang, Fu-Sheng Wang, Christopher Chang, M Eric Gershwin

Department of Medical Genetics Faculty Papers

In primary biliary cirrhosis (PBC), the breach of tolerance that leads to active disease involves a disruption in several layers of control, including central tolerance, peripheral anergy, a "liver tolerance effect," and the action of T regulatory cells and their related cytokines. Each of these control mechanisms plays a role in preventing an immune response against self, but all of them act in concert to generate effective protection against autoimmunity without compromising the ability of the host immune system to mount an effective response to pathogens. At the same time, genetic susceptibility, environmental factors, including infection agents and xenobiotics, play …

Obesity And Mortality: Are The Risks Declining? Evidence From Multiple Prospective Studies In The United States., Tapan S. Mehta, Kevin R. Fontaine, Scott W. Keith, Sripal S. Bangalore, Gustavo De Los Campos, Alfred Bartolucci, Nicholas M. Pajewski, David B. Allison

Department of Pharmacology and Experimental Therapeutics Faculty Papers

We evaluated whether the obesity-associated years of life lost (YLL) have decreased over calendar time. We implemented a meta-analysis including only studies with two or more serial body mass index (BMI) assessments at different calendar years. For each BMI category (normal weight: BMI 18.5 to <25 >[reference]; overweight: BMI 25 to60, YLL for grade 1 obesity decreased by 1.02 years (P < 0.001) and increased by 0.63 years for grade 2-3 obesity (P = 0.63). Among women aged ≤60, YLL for grade 1 obesity decreased by 4.21 years (P < 0.001) and by 4.97 years (P < 0.001) for grade 2-3 obesity. In women aged >60, YLL for grade 1 obesity decreased by 3.98 years (P < 0.001) and by 2.64 years (P = 0.001) for grade 2-3 obesity. Grade 1 obesity's association with decreased longevity has reduced for older Caucasian men. For Caucasian women, there is evidence of a decline in the obesity YLL association across all ages.

Vaccines To Combat River Blindness: Expression, Selection And Formulation Of Vaccines Against Infection With Onchocerca Volvulus In A Mouse Model., Jessica A. Hess, Bin Zhan, Sandra Bonne-Annee, Jessica M. Deckman, Maria Elena Bottazzi, Peter J. Hotez, Thomas R R. Klei, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation …

Dexa-Measured Vat Robustly Predicts Impaired Glucose Tolerance And Metabolic Syndrome In Obese Women, Xia Bi, C. D. Keil, L. Seabolt, R. Tyree, M. Buchowski, H. Kang, C. Shibao, H. J. Silver

Sigma Xi Student Research Day

Abdominal visceral adiposity (VAT) has been shown to be an independent risk factor for metabolic and cardiovascular disease. Using enCORE analysis version 13.6 on a GE Lunar iDXA, a new fully automated analysis software to measure VAT, we determined the strength of associations between DEXA-derived VAT and other known indicators for diabetes and cardiovascular disease risk in Caucasian and African American obese women. We collected anthropometrics, vital signs, lipid profile, and DXA whole body composition scan for 229 subjects with BMI 30.0 – 49.9 kg/m2 & age 21 to 69 y. We then performed the non-parametric Spearman correlation analysis and …

Differentiation State-Specific Mitochondrial Dynamic Regulatory Networks Are Revealed By Global Transcriptional Analysis Of The Developing Chicken Lens., Daniel Chauss, Subhasree Basu, Suren Rajakaruna, Zhiwei Ma, Victoria Gau, Sara Anastas, Lisa A. Brennan, J. Fielding Hejtmancik, A. Sue Menko, Marc Kantorow

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that requires a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium …

Intravitreal Triamcinolone Acetonide Injection For Macular Edema Due To Central Retinal Vein Occlusion Persisting Despite Multiple Intravitreal Bevacizumab Injections., Rayan A Alshareef, Sunir Garg, Jason Hsu, James Vander, Carl Park, Marc J Spirn

Wills Eye Hospital Papers

PURPOSE: To evaluate the response to intravitreal triamcinolone acetonide for macular edema persisting or recurring despite multiple intravitreal bevacizumab (IVB) treatments for central retinal vein occlusion (CRVO).

METHODS: Retrospective interventional case series of 21 eyes with CRVO from 21 patients who were diagnosed with persistent or recurrent macular edema secondary to CRVO and treated with 0.1mL (4mg) intravitreal triamcinolone acetonide (IVTA) after initial treatment with 3 or more IVB injections. Anatomic and visual responses were the study primary outcomes.

RESULTS: Mean logarithm of the minimum angle of resolution visual acuity was 1.19 (20/316) immediately before IVTA injection, and improved to …

Parp-2 And Parp-3 Are Selectively Activated By 5' Phosphorylated Dna Breaks Through An Allosteric Regulatory Mechanism Shared With Parp-1., Marie-France Langelier, Amanda A Riccio, John M Pascal

Department of Biochemistry and Molecular Biology Faculty Papers

PARP-1, PARP-2 and PARP-3 are DNA-dependent PARPs that localize to DNA damage, synthesize poly(ADP-ribose) (PAR) covalently attached to target proteins including themselves, and thereby recruit repair factors to DNA breaks to increase repair efficiency. PARP-1, PARP-2 and PARP-3 have in common two C-terminal domains-Trp-Gly-Arg (WGR) and catalytic (CAT). In contrast, the N-terminal region (NTR) of PARP-1 is over 500 residues and includes four regulatory domains, whereas PARP-2 and PARP-3 have smaller NTRs (70 and 40 residues, respectively) of unknown structural composition and function. Here, we show that PARP-2 and PARP-3 are preferentially activated by DNA breaks harboring a 5' phosphate …

Tumour-Stroma Crosstalk In The Development Of Squamous Cell Carcinoma., Yok Zuan Lim, Andrew P South

Department of Dermatology and Cutaneous Biology Faculty Papers

Squamous cell carcinoma (SCC) represents one of the most frequently diagnosed tumours and contributes significant mortality worldwide. Recent deep sequencing of cancer genomes has identified common mutations in SCC arising across different tissues highlighting perturbation of squamous differentiation as a key event. At the same time significant data have been accumulating to show that common tumour-stroma interactions capable of driving disease progression are also evident when comparing SCC arising in different tissues. We and others have shown altered matrix composition surrounding SCC can promote tumour development. This review focuses on some of the emerging data with particular emphasis on SCC …

Regulation Of L1 Expression And Retrotransposition By Melatonin And Its Receptor: Implications For Cancer Risk Associated With Light Exposure At Night., Dawn Deharo, Kristine J Kines, Mark Sokolowski, Robert T Dauchy, Vincent A Streva, Steven M Hill, John P Hanifin, George Brainard, David E Blask, Victoria P Belancio

Department of Neurology Faculty Papers

Expression of long interspersed element-1 (L1) is upregulated in many human malignancies. L1 can introduce genomic instability via insertional mutagenesis and DNA double-strand breaks, both of which may promote cancer. Light exposure at night, a recently recognized carcinogen, is associated with an increased risk of cancer in shift workers. We report that melatonin receptor 1 inhibits mobilization of L1 in cultured cells through downregulation of L1 mRNA and ORF1 protein. The addition of melatonin receptor antagonists abolishes the MT1 effect on retrotransposition in a dose-dependent manner. Furthermore, melatonin-rich, but not melatonin-poor, human blood collected at different times during the circadian …

Mir-143 Acts As A Tumor Suppressor By Targeting N-Ras And Enhances Temozolomide-Induced Apoptosis In Glioma., Lin Wang, Zhu-Mei Shi, Cheng-Fei Jiang, Xue Liu, Qiu-Dan Chen, Xu Qian, Dong-Mei Li, Xin Ge, Xie-Feng Wang, Ling-Zhi Liu, Yong-Ping You, Ning Liu, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Therapeutic applications of microRNAs (miRNAs) in RAS-driven glioma were valuable, but their specific roles and functions have yet to be fully elucidated. Here, we firstly report that miR-143 directly targets the neuroblastoma RAS viral oncogene homolog (N-RAS) and functions as a tumor-suppressor in glioma. Overexpression of miR-143 decreased the expression of N-RAS, inhibited PI3K/AKT, MAPK/ERK signaling, and attenuated the accumulation of p65 in nucleus of glioma cells. In human clinical specimens, miR-143 was downregulated where an adverse with N-RAS expression was observed. Furthermore, overexpression of miR-143 decreased glioma cell migration, invasion, tube formation and slowed tumor growth and angiogenesis in …

In The Jdc: John Heysham Gibbon, Jr. Memorial Service, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

The latest addition to the Jefferson Digital Commons historical biographies is from a memorial service for Dr. John Heysham Gibbon, Jr. Read the transcript or listen to an audio file.

Optimal Duration Of Holter Recordings: Is There Additional Yield From 48 Versus 24 Hours?, Amanda Trang, Md, Behzad B. Pavri, Md

Department of Medicine Faculty Papers

INTRODUCTION

• Holter monitors are often used for evaluation of palpitations, syncope, heart rate, and detection of arrhythmias
• The duration of a typical Holter recording is either 24 or 48 hours
• Little research has been targeted at determining the ideal duration of monitoring
• We examined the yield of 24 versus 48 hours of Holter monitoring

Nut Midline Carcinoma In A Pregnant Woman, Jill N. D'Souza, Md, David M. Cognetti, Md, Ryan N. Heffelfinger, Md, James J. Evans, Md, Madalina Tuluc, Md, Jurij R. Bilyk, Marc R. Rosen, Md

Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds

NUT midline carcinoma is a rare, highly aggressive tumor that involves midline structures, particularly in the head, neck and mediastinum. It is characterized by NUT gene translocations on chromosome 15. It typically impacts teenagers or young adults, and has a fulminant course leading to death in less than a year in most cases despite aggressive chemoradiotherapy. Due to its location, this tumor is frequently considered inoperable. We present a case of a sinonasal NUT midline carcinoma with orbital invasion discovered during the workup of sinusitis in a young, pregnant woman. The tumor was managed with definitive excision to negative margins …

Cervical Spine Osteomyelitis After Esophageal Dilation In Patients With A History Of Laryngectomy Or Pharyngectomy And Pharyngeal Irradiation, Richard A. Goldman, Md, Jill N. D'Souza, Md, Adam J. Luginbuhl, Md, Joshua E. Heller, Md, Joseph M. Curry, Md, David M. Cognetti, Md

Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds

Dysphagia is a common sequela of the treatment of head and neck cancer and is frequently managed with esophageal dilation in patients with dysphagia secondary to hypopharyngeal stenosis. Reported complications of esophageal dilation include bleeding, esophageal perforation, and mediastinitis. We examine four cases of cervical spine osteomyelitis presenting as a delayed complication of esophageal dilation for hypopharyngeal stenosis in patients with a history of laryngectomy or pharyngectomy and radiation with or without chemotherapy. The history of head and neck surgery and radiation in these patients further complicates the management of the cervical spine osteomyelitis.

Direct Comparison Of Apremilast And Best Supportive Care Using A Discrete Event Simulation, Zoe Clancy, Pharmd

Master of Science in Applied Health Economics and Outcomes Research Capstone Presentations

Apremilast is compared to best supportive care (BSC), and response to treatment is assessed after a trial period of 16 weeks, which corresponds to the primary efficacy endpoint in the apremilast clinical trials. DES is a technique that is event-based and models a population at the individual level in terms of utility, costs, and resource use. The DES was implemented as a series of input, calculation, and output flowcharts in Arena®. The DES reported an incremental QALY per patient of 0.16 and incremental cost per patient of $17,325. The Markov model reported an incremental QALY of 0.18 and incremental cost …

Microrna Expression Differences In Human Hematopoietic Cell Lineages Enable Regulated Transgene Expression., Raúl Teruel Montoya, Xianguo Kong, Shaji Abraham, Lin Ma, Satya P Kunapuli, Michael Holinstat, Chad A Shaw, Steven E. Mckenzie, Leonard Edelstein, Paul Bray

Cardeza Foundation for Hematologic Research

Blood microRNA (miRNA) levels have been associated with and shown to participate in disease pathophysiology. However, the hematopoietic cell of origin of blood miRNAs and the individual blood cell miRNA profiles are poorly understood. We report the miRNA content of highly purified normal hematopoietic cells from the same individuals. Although T-cells, B-cells and granulocytes had the highest miRNA content per cell, erythrocytes contributed more cellular miRNA to the blood, followed by granulocytes and platelets. miRNA profiling revealed different patterns and different expression levels of miRNA specific for each lineage. miR-30c-5p was determined to be an appropriate reference normalizer for cross-cell …

A Survey Of Expert Opinion Regarding Rotator Cuff Repair., Daniel C Acevedo, E Scott Paxton, Gerald R Williams, Joseph A Abboud

Rothman Institute Papers

Many patients with rotator cuff tears have questions for their surgeons regarding the surgical procedure, perioperative management, restrictions, therapy, and ability to work after a rotator cuff repair. The purpose of our study was to determine common clinical practices among experts regarding rotator cuff repair and to assist them in counseling patients. We surveyed 372 members of the American Shoulder and Elbow Surgeons (ASES) and the Association of Clinical Elbow and Shoulder Surgeons (ACESS); 111 members (29.8%) completed all or part of the survey, and 92.8% of the respondents answered every question. A consensus response (>50% agreement) was achieved …

Shape And Position Of The Node And Notochord Along The Bilateral Plane Of Symmetry Are Regulated By Cell-Extracellular Matrix Interactions., Maria Pulina, Dong Liang, Sophie Astrof

Center for Translational Medicine Faculty Papers

The node and notochord (and their equivalents in other species) are essential signaling centers, positioned along the plane of bilateral symmetry in developing vertebrate embryos. However, genes and mechanisms regulating morphogenesis of these structures and their placement along the embryonic midline are not well understood. In this work, we provide the first evidence that the position of the node and the notochord along the bilateral plane of symmetry are under genetic control and are regulated by integrin α5β1 and fibronectin in mice. We found that the shape of the node is often inverted in integrin α5-null and fibronectin-null mutants, and …

Transcribing And Digitizing Eighteenth And Nineteenth Century Letters For A Historical Digital Repository, Emily Dunster, Ms, Daniel G. Kipnis, Msi, F. Michael Angelo, Ma

Academic Commons and Scott Memorial Library Staff Papers and Presentations

In the fall of 2011 the Scott Memorial Library purchased 53 letters belonging to an 1841 graduate of Jefferson Medical College, John Plimpton Green. The library staff transcribed and digitized the letters creating an online collection in the University institutional repository, Jefferson Digital Commons. This article will detail the process of transcribing and digitizing the collection along with sharing statistics and benefits of this project to global researchers.

Molecular And Functional Identification Of A Mitochondrial Ryanodine Receptor In Neurons., Regina Jakob, Gisela Beutner, Virendra K Sharma, Yuntao Duan, Robert A Gross, Stephen Hurst, Bong Sook Jhun, Jin O-Uchi, Shey-Shing Sheu

Department of Medicine Faculty Papers

Mitochondrial Ca(2+) controls numerous cell functions, such as energy metabolism, reactive oxygen species generation, spatiotemporal dynamics of Ca(2+) signaling, cell growth and death in various cell types including neurons. Mitochondrial Ca(2+) accumulation is mainly mediated by the mitochondrial Ca(2+) uniporter (MCU), but recent reports also indicate that mitochondrial Ca(2+)-influx mechanisms are regulated not only by MCU, but also by multiple channels/transporters. We previously reported that ryanodine receptor (RyR), which is a one of the main Ca(2+)-release channels at endoplasmic/sarcoplasmic reticulum (SR/ER) in excitable cells, is expressed at the mitochondrial inner membrane (IMM) and serves as a part of the Ca(2+) …

New Mph Capstone Presentations In The Jdc, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

The latest MPH capstone presentations have been loaded in the Jefferson Digital Commons

Jefferson Digital Commons Quarterly Report: Apr-Jun 2014, Daniel G. Kipnis, Msi, Kelsey Duinkerken, Msi

Jefferson Digital Commons Reports

Contents for this quarterly report:

• A few numbers
• 6th Annual Faculty Days
• Data Management and the Jefferson Digital Commons
• Two new handouts
• Announcing New Grand Rounds-Department of Medicine
• Assorted new assets deposited in the JDC, including: faculty posters, MPH student capstones, Grand rounds, lectures and podcasts
• Jefferson Medical College yearbooks scanned 1950-1960
• Meet Sumner Waldron Jackson, JMC graduate of 1914, hero martyr of the French Resistance during WWII.
• What is being said about the Jefferson Digital Commons

Lessons Learned Through Leadership, John L. Melvin, Md, Mmsc

Department of Rehabilitation Medicine Faculty Papers

This paper identifies a number of principles I have adopted when assuming leadership roles. They evolved from experiences that suggested they would help me be more effective in these roles. I have found through using them that they are indeed helpful to me as a leader and to the organizations I lead. When comparing notes with other leaders, I find they seem to apply to others as well.

Succinate Dehydrogenase Deficiency In Sporadic Pituitary Adenomas: A Potential Mechanism For Tumorigenesis, Edward Andrews, Md, Stacey K. Mardekian, Md, Markku Miettinen, Mark T. Curtis, Md

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

In order to determine whether succinate dehydrogenase (SDH) deficiency plays a role in spor-adic, non-familial pituitary adenomas, we analyzed 80 pituitary adenomas for SDH deficiency from patients without familial tumor syndromes or without known SDH deficiency-associated neoplasms. SDH deficiency was determined by immunohistochemical (IHC) stains for SDHB since the loss of any of the four SDH subunits results in the loss of SDHB expression. Three pituitary adenomas showed complete loss of SDHB staining, and of these two also showed loss of SDHA staining. We further characterized these adenomas by looking at Ki67, IGF1R, and 5-hmC levels via IHC. SDHx …

Partnerships For Health - Jeff Health And The Rwanda Village Concept Project – A Model Of Interdisciplinary Health Professions Student Global Education, James D. Plumb, Md, Mph, Ellen J. Plumb, Md, Komal Soin, Md-Cugh 2014, Edmond Bagazini, Md, Mph, Remy Muhire Manzi, Md, Mph, Jean Christoph Rusatira, Md

College of Population Health Lectures, Presentations, Workshops

Background

The Rwanda Health and Healing Project (RHHP)

• Started in 2006: Barefoot Artists and TJU Department of Family and Community Medicine

– Global health immersion experience

– Interdisciplinary

– Focus: team-based, sustainable public health programming,

economic development, community empowerment

• Public-Health Programming: Akarambi, Rugerero

– Hygiene and Sanitation

– Childhood Nutrition

– Helminth Prevention

– HIV Education

– Income Generation: chicken coop, rabbit rearing, mushroom farming, bee keeping, pig farming