Medicine and Health Sciences Commons^™

Letter By Horowitz Regarding Article, "Protein Interactions At Endothelial Junctions And Signaling Mechanisms Regulating Endothelial Permeability"., Arie Horowitz

Department of Cancer Biology Faculty Papers

No abstract provided.

Cool-Associated Tyrosine-Phosphorylated Protein 1 Is Required For The Anchorage-Independent Growth Of Cervical Carcinoma Cells By Binding Paxillin And Promoting Akt Activation., Sungsoo M. Yoo, Arash Latifkar, Richard A. Cerione, Marc A. Antonyak

Department of Biochemistry and Molecular Biology Faculty Papers

Cool-associated tyrosine-phosphorylated protein 1 (Cat-1) is a signaling scaffold as well as an ADP-ribosylation factor-GTPase-activating protein. Although best known for its role in cell migration, we recently showed that the ability of Cat-1 to bind paxillin, a major constituent of focal complexes, is also essential for the anchorage-independent growth of HeLa cervical carcinoma cells. Here we set out to learn more about the underlying mechanism by which Cat-paxillin interactions mediate this effect. We show that knocking down paxillin expression in HeLa cells promotes their ability to form colonies in soft agar, whereas ectopically expressing paxillin in these cells inhibits this …

Co-Targeting Hgf/Cmet Signaling With Mek Inhibitors In Metastatic Uveal Melanoma., Hanyin Cheng, Vivian Chua, Connie Liao, Timothy J. Purwin, Mizue Terai, Ken Kageyama, Michael A. Davies, Takami Sato, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Patients with metastatic uveal melanoma usually die within 1 year of diagnosis, emphasizing an urgent need to develop new treatment strategies. The liver is the most common site of metastasis. Mitogen-activated protein kinase kinase (MEK) inhibitors improve survival in V600 BRAF-mutated cutaneous melanoma patients but have limited efficacy in patients with uveal melanoma. Our previous work showed that hepatocyte growth factor (HGF) signaling elicits resistance to MEK inhibitors in metastatic uveal melanoma. In this study, we demonstrate that expression of two BH3-only family proteins, Bim-EL and Bmf, contributes to HGF-mediated resistance to MEK inhibitors. Targeting HGF/cMET signaling with LY2875358, a …

Clinical Pharmacology & Therapeutics: Past, Present, And Future., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation, and utilization continuum to catalyze, evolve, and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation, and application ushering therapeutic innovation into modern healthcare.

Surgical Site Infection And Transfusion Rates Are Higher In Underweight Total Knee Arthroplasty Patients., Jorge Manrique, Antonia F. Chen, Md, Mba, Miguel M. Gomez, Mitchell Maltenfort, Phd, William J. Hozack Md

Rothman Institute Papers

BACKGROUND: Underweight (UW) patients undergoing total hip arthroplasty have exhibited higher complication rates, including infection and transfusion. No study to our knowledge has evaluated UW total knee arthroplasty (TKA) patients. We, therefore, conducted a study to investigate if these patients are at increased risk for complications, including infection and transfusion.

METHODS: A case-control study was conducted using a prospectively collected institutional database. Twenty-seven TKA patients were identified as UW (body mass index [BMI] < 18.5 kg/m

RESULTS: The average BMI was 17.1 kg/m

CONCLUSIONS: Our study demonstrates that UW TKA patients have a higher likelihood of developing SSI and requiring blood transfusions. The …

Epidemiology And Impact Of Abdominal Oblique Injuries In Major And Minor League Baseball., Christopher L Camp, Stan Conte, Steven B. Cohen, Matthew Thompson, John D' Angelo, Joseph T Nguyen, Joshua S Dines

Rothman Institute Papers

BACKGROUND: Oblique injuries are known to be a common cause of time out of play for professional baseball players, and prior work has suggested that injury rates may be on the rise in Major League Baseball (MLB).

PURPOSE: To better understand the current incidence of oblique injuries, determine their impact based on time out of play, and to identify common injury patterns that may guide future injury prevention programs.

STUDY DESIGN: Descriptive epidemiological study.

METHODS: Using the MLB Health and Injury Tracking System, all oblique injuries that resulted in time out of play in MLB and Minor League Baseball (MiLB) …

Management Of Giant Retinal Tear Detachments, Maria H. Berrocal, Megan Chenworth, Luis A. Acaba

Student Papers, Posters & Projects

Giant retinal tears (GRTs) are full-thickness circumferential tears of more than 90 degrees of the retina that are associated with vitreous detachment. They are related to ocular trauma, high myopia, aphakia, pseudophakia, genetic mutations involving collagen and young age. GRTs comprise 1.5% of all rhegmatogenous retinal detachments and the average age of incidence is 42 years. GRTs are more common in males, as 72% of all cases occur in males. The incidence of GRTs in the general population is estimated to be 0.05 per 100,000 individuals. Common techniques used in the management of GRTs include fluid-air exchange, pneumatic retinopexy, scleral …

Efficacy And Tolerability Of Adjunctive Brivaracetam In Patients With Prior Antiepileptic Drug Exposure: A Post-Hoc Study., Ali A. Asadi-Pooya, Michael R. Sperling, Steve Chung, Pavel Klein, Anyzeila Diaz, Sami Elmoufti, Jimmy Schiemann, John Whitesides

Department of Neurology Faculty Papers

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV …

Feasibility, Safety, And Outcomes Of A Single-Step Endoscopic Ultrasonography-Guided Drainage Of Pancreatic Fluid Collections Without Fluoroscopy Using A Novel Electrocautery-Enhanced Lumen-Apposing, Self-Expanding Metal Stent., Joseph Yoo, Linda Yan, Raza Hasan, Sanaa Somalya, Jose Nieto, Ali A. Siddiqui

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND AND OBJECTIVES: There are currently limited data available regarding the safety of endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) using the lumen-apposing metal stent without fluoroscopic guidance. This study aims to evaluate clinical outcomes and safety of EUS-guided drainage of PFC using the electrocautery-enhanced lumen-apposing metal stents (EC-LAMSs) without fluoroscopic guidance.

METHODS: We conducted a retrospective study on patients with symptomatic PFC who underwent EUS-guided drainage using EC-LAMS without fluoroscopy. All patients were followed clinically until resolution of their PFC. Technical success (successful placement of EC-LAMS), number of patients who achieved complete resolution of PFC without additional …

A Word From The Writing Center (March 2017), Jennifer Wilson, Ms, Els

A Word From the Writing Team (Newsletter)

This issue includes:

• Learning Opportunity
• Books on writing
• Writing Cafe

Professional Practices, Training, And Funding Mechanisms: A Survey Of Pediatric Primary Care Psychologists, Kathryn W. Hoffses, Andrew R. Riley, Kathryn M. Menousek, Kriston B. Schellinger, Allison O. Grennan, Chrissy Cammarata, Jason L. Steadman

Department of Pediatrics Faculty Papers

The integration of mental health services in primary care settings has expanded rapidly in recent years with psychologists being at the forefront of efforts to promote healthy behaviors, reduce disease, and care for behavioral, emotional, and developmental needs to promote overall health and well-being for children and families (Asarnow, Kolko, Miranda,&Kazak, 2017; Stancin& Perrin, 2014). While there are many psychologists working in pediatric primary care (PPC), little is known about the specific activities that these psychologists engage in, the training they receive, or funding mechanisms that support their work. This study sought to address this gap in the literature through …

Spotlight On The Integrated Primary Care Special Interest Group, Kathryn W. Hoffses, Andrew R. Riley, Kathryn M. Menousek, Kriston B. Schellinger, Allison O. Grennan, Chrissy Cammarata, Jason L. Steadman

Department of Pediatrics Faculty Papers

No abstract provided.

Phosphorylation Of Prb: Mechanism For Rb Pathway Inactivation In Mycn-Amplified Retinoblastoma., Kathryn G. Ewens, Tricia R. Bhatti, Kimberly A. Moran, Jennifer Richards-Yutz, Carol L. Shields, Ralph C. Eagle Jr., Arupa Ganguly

Wills Eye Hospital Papers

A small, but unique subgroup of retinoblastoma has been identified with no detectable mutation in the retinoblastoma gene (RB1) and with high levels of MYCN gene amplification. This manuscript investigated alternate pathways of inactivating pRb, the encoded protein in these tumors. We analyzed the mutation status of the RB1 gene and MYCN copy number in a series of 245 unilateral retinoblastomas, and the phosphorylation status of pRb in a subset of five tumors using immunohistochemistry. There were 203 tumors with two mutations in RB1 (RB1(-/-) , 83%), 29 with one (RB1(+/-) , 12%) and 13 with no detectable mutations (RB1(+/+) …

Rehabilitation Therapy In Older Acute Heart Failure Patients (Rehab-Hf) Trial: Design And Rationale., Gordon R. Reeves, David J. Whellan, Pamela Duncan, Christopher M. O'Connor, Amy M. Pastva, Joel D. Eggebeen, Leigh Ann Hewston, Timothy M. Morgan, Shelby D. Reed, W. Jack Rejeski, Robert J. Mentz, Paul B. Rosenberg, Dalane W. Kitzman

Division of Cardiology Faculty Papers

BACKGROUND: Acute decompensated heart failure (ADHF) is a leading cause of hospitalization in older persons in the United States. Reduced physical function and frailty are major determinants of adverse outcomes in older patients with hospitalized ADHF. However, these are not addressed by current heart failure (HF) management strategies and there has been little study of exercise training in older, frail HF patients with recent ADHF.

HYPOTHESIS: Targeting physical frailty with a multi-domain structured physical rehabilitation intervention will improve physical function and reduce adverse outcomes among older patients experiencing a HF hospitalization.

STUDY DESIGN: REHAB-HF is a multi-center clinical trial in …

Functional Outcomes Of The Low Vision Depression Prevention Trial In Age-Related Macular Degeneration., Ashley D. Deemer, Robert W. Massof, Barry W. Rovner, Robin J. Casten, Catherine V. Piersol

Department of Psychiatry and Human Behavior Faculty Papers

Purpose: To compare the efficacy of behavioral activation (BA) plus low vision rehabilitation with an occupational therapist (OT-LVR) with supportive therapy (ST) on visual function in patients with age-related macular degeneration (AMD).

Methods: Single-masked, attention-controlled, randomized clinical trial with AMD patients with subsyndromal depressive symptoms (n = 188). All subjects had two outpatient low vision rehabilitation optometry visits, then were randomized to in-home BA + OT-LVR or ST. Behavioral activation is a structured behavioral treatment aiming to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. Functional …

Hypovolemic Shock And Hemoperitoneum From Spontaneous Avulsion Of A Large Pedunculated Uterine Leiomyoma, Daniel J. Mizrahi, Chhavi Kaushik, Robert Adamo

Department of Radiology Faculty Papers

Hemoperitoneum with hypovolemic shock from avulsion of a pedunculated leiomyoma is a rare but highly fatal condition that can occur spontaneously or as a result of trauma. We report a case of hemoperitoneum and hypovolemic shock secondary to a bleeding leiomyoma detected via computed tomography (CT) scan in a 39 year old premenopausal, gravida 0 female that presented with abdominal pain and became hemodynamically unstable in the emergency department. A preoperative bimanual exam revealed a mass consistent with a 20 week gestational uterus. Following fluid resuscitation, the patient underwent emergent myomectomy and ligation of the right uterine artery and was …

Influence Of Sex/Gender And Race On Responses To Raltegravir Combined With Tenofovir-Emtricitabine In Treatment-Naive Human Immunodeficiency Virus-1 Infected Patients: Pooled Analyses Of The Startmrk And Qdmrk Studies., Kathleen E. Squires, Linda-Gail Bekker, Christine Katlama, Yazdan Yazdanpanah, Yan Zhou, Anthony J Rodgers, Mark J Dinubile, Peter A Sklar, Randi Y Leavitt, Hedy Teppler

Department of Medicine Faculty Papers

BACKGROUND: Antiretroviral therapy in human immunodeficiency virus (HIV)-infected women and blacks merits particular scrutiny because these groups have been underrepresented in clinical trials.

METHODS: To document the effects of raltegravir across sex and racial lines, we conducted a pooled subgroup analysis of the efficacy and safety of raltegravir 400 mg BID plus tenofovir-emtricitabine by sex (women vs men) and self-identified race (black vs non-black) using phase 3 studies in treatment-naive patients.

RESULTS: Study participants included 42 black women, 102 non-black women, 48 black men, and 477 non-black men. Clade B infections were less common in women (43.8%) than men (84.6%) …

Use Of Theory To Plan Or Evaluate Guideline Implementation Among Physicians: A Scoping Review., Laurel Liang, Susanne Bernhardsson, Robin W.M. Vernooij, Melissa J. Armstrong, André Bussières, Melissa C. Brouwers, Anna R. Gagliardi, Samia Alhabib, Margot A.H. Fleuren, Margie Fortino, Daniele Mazza, Niamh O'Rourke, Melina L. Willson

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Guidelines support health care decision-making and high quality care and outcomes. However, their implementation is sub-optimal. Theory-informed, tailored implementation is associated with guideline use. Few guideline implementation studies published up to 1998 employed theory. This study aimed to describe if and how theory is now used to plan or evaluate guideline implementation among physicians.

METHODS: A scoping review was conducted. MEDLINE, EMBASE, and The Cochrane Library were searched from 2006 to April 2016. English language studies that planned or evaluated guideline implementation targeted to physicians based on explicitly named theory were eligible. Screening and data extraction were done in …

Using A Conformal Water Bolus To Adjust Heating Patterns Of Microwave Waveguide Applicators, Paul R. Stauffer, Dario B. Rodrigues, Randolph Sinahon, Lyndsey Sbarro, Valeria Beckhoff, Mark Hurwitz

Department of Radiation Oncology Faculty Papers

Background: Hyperthermia, i.e., raising tissue temperature to 40-45°C for 60 min, has been demonstrated to increase the effectiveness of radiation and chemotherapy for cancer. Although multi-element conformal heat applicators are under development to provide more adjustable heating of contoured anatomy, to date the most often used applicator to heat superficial disease is the simple microwave waveguide. With only a single power input, the operator must be resourceful to adjust heat treatment to accommodate variable size and shape tumors spreading across contoured anatomy. Methods: We used multiphysics simulation software that couples electromagnetic, thermal and fluid dynamics physics to simulate heating patterns …

Mintmap: Fast And Exhaustive Profiling Of Nuclear And Mitochondrial Trna Fragments From Short Rna-Seq Data., Phillipe Loher, Aristeidis G. Telonis, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

Transfer RNA fragments (tRFs) are an established class of constitutive regulatory molecules that arise from precursor and mature tRNAs. RNA deep sequencing (RNA-seq) has greatly facilitated the study of tRFs. However, the repeat nature of the tRNA templates and the idiosyncrasies of tRNA sequences necessitate the development and use of methodologies that differ markedly from those used to analyze RNA-seq data when studying microRNAs (miRNAs) or messenger RNAs (mRNAs). Here we present MINTmap (for MItochondrial and Nuclear TRF mapping), a method and a software package that was developed specifically for the quick, deterministic and exhaustive identification of tRFs in short …

Stones, Bones, Groans, Thrones, And Psychiatric Overtones: Systemic Associations Of Sclerochoroidal Calcification., Jordan A Sugarman, Alexzandra M Douglass, Emil Anthony T. Say, Carol L. Shields

Wills Eye Hospital Papers

Sclerochoroidal calcification (SCC) is a frequent masquerader of choroidal melanoma with important systemic associations such as hyperparathyroidism and parathyroid adenoma. Herein, we describe a case of a 67-year-old male who presented with an amelanotic choroidal lesion in the right eye (OD) and a history of kidney stones. Ultrasonography showed the lesion to be flat and calcified OD. Incidentally, a subclinical calcified plaque was also found in the fellow eye. Optical coherence tomography showed an elevated suprachoroidal mass in a table mountain configuration OD and flat configuration left eye, consistent with type 4 and type 1 SCC. The patient was referred …

A Comparison Of Colorimetric Assessment Of Vaginal Ph With Nugent Score For The Detection Of Bacterial Vaginosis., Matthew K. Hoffman, Mrutyunjaya B. Bellad, Umesh S. Charantimath, Avinash Kavi, Jyoti M. Nagmoti, Mahantesh B. Nagmoti, Ashalata A. Mallapur, Geetanjali M. Katageri, Umesh Y. Ramadurg, Sheshidhar G. Bannale, Amit P. Revankar, M. S. Ganachari, Richard J. Derman, Shivaprasad S. Goudar

Department of Obstetrics and Gynecology Faculty Papers

Background. A Nugent score > 7 has been defined as the gold standard for the diagnosis for bacterial vaginosis (BV), though it is resource intensive and impractical as point of care testing. We sought to determine if colorimetric assessment of vaginal pH can accurately predict the occurrence of BV. Methods. We performed a planned subanalysis of 1,216 pregnant women between 13 0/7 and 19 6/7 weeks who underwent vaginal examination as part of a randomized controlled trial. Using a standardized technique, specimens were obtained for colorimetric assessment and two separate slides for Gram staining. These slides were subsequently evaluated by two …

Mechanisms Of Modulation Of Brain Microvascular Endothelial Cells Function By Thrombin., Eugen Brailoiu, Megan M. Shipsky, Guang Yan, Mary E. Abood, G. Cristina Brailoiu

College of Pharmacy Faculty Papers

Brain microvascular endothelial cells are a critical component of the blood-brain barrier. They form a tight monolayer which is essential for maintaining the brain homeostasis. Blood-derived proteases such as thrombin may enter the brain during pathological conditions like trauma, stroke, and inflammation and further disrupts the permeability of the blood-brain barrier, via incompletely characterized mechanisms. We examined the underlying mechanisms evoked by thrombin in rat brain microvascular endothelial cells (RBMVEC). Our results indicate that thrombin, acting on protease-activated receptor 1 (PAR1) increases cytosolic Ca

Against The Odds: Making A Difference In Global Health

Global Health Events

Against the Odds: Making a Difference in Global Health is a banner traveling exhibition highlighting the role of communities in improving health at home and all around the world. The exhibition explores the shared basic needs required for a good quality of life, including nutritious food and clean water, a safe place to live, and affordable health care. Using historical and contemporary photographs, the banners tell stories of collaboration between families, scientists, advocates, governments, and international organizations, all taking up the challenge to prevent disease and improve medical care. This exhibition raises awareness of the sources and effects of health …

Serum Hypercoagulability States In Coats' Disease., Fariba Ghassemi, Carol L. Shields, Masoumeh Mohebbi, Mehdi Nili Ahmadabadi, Fatemeh Morsali, Siamak Sabour

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to investigate the serum hypercoagulability state and common viral and protozoan infections in Coats' disease versus a normal control group.

MATERIALS AND METHODS: In this comparative case series, 22 consecutive patients with Coats' disease and 19 non-Coats' patients undergoing lensectomy for congenital, traumatic, or senile cataract between January 2011 and June 2014 were included. Laboratory data for hypercoagulability states and common viral and protozoan infections were investigated.

RESULTS: The mean age for the Coats' group was 14.5 years (median 8 years, range: 2 months to 59 years), and for the control group it …

Map7 Regulates Axon Collateral Branch Development In Dorsal Root Ganglion Neurons., Stephen R Tymanskyj, Benjamin Yang, Aditi Falnikar, Angelo C Lepore, Le Ma

Department of Neuroscience Faculty Papers

Collateral branches from axons are key components of functional neural circuits that allow neurons to connect with multiple synaptic targets. Like axon growth and guidance, formation of collateral branches depends on the regulation of microtubules, but how such regulation is coordinated to ensure proper circuit development is not known. Based on microarray analysis, we have identified a role for microtubule-associated protein 7 (MAP7) during collateral branch development of dorsal root ganglion (DRG) sensory neurons. We show that MAP7 is expressed at the onset of collateral branch formation. Perturbation of its expression by overexpression or shRNA knockdown alters axon branching in …

Global Jefferson Day Presentation In The Jefferson Digital Commons, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

The first annual Global Jefferson Day, sponsored by the Office of Global Affairs, was held on Monday, January 30th. Presentations from the event–including the Keynote address “Evidence Based Interventions for Reducing Maternal and Neonatal Mortality: The Belgaum Experience”by Shivaprasad S. Goudar, MD, MHPE, KLE University’s Jawaharlal Nehru Medical College, India–are now available in the Jefferson Digital Commons.

Frequent Mild Head Injury Promotes Trigeminal Sensitivity Concomitant With Microglial Proliferation, Astrocytosis, And Increased Neuropeptide Levels In The Trigeminal Pain System., Ashley L. Tyburski, Lan Cheng, Soroush Assari, Kurosh Darvish, Melanie B Elliott

Department of Neurosurgery Faculty Papers

BACKGROUND: Frequent mild head injuries or concussion along with the presence of headache may contribute to the persistence of concussion symptoms.

METHODS: In this study, the acute effects of recovery between mild head injuries and the frequency of injuries on a headache behavior, trigeminal allodynia, was assessed using von Frey testing up to one week after injury, while histopathological changes in the trigeminal pain pathway were evaluated using western blot, ELISA and immunohistochemistry. RESULTS: A decreased recovery time combined with an increased mild closed head injury (CHI) frequency results in reduced trigeminal allodynia thresholds compared to controls. The repetitive CHI …

Targeting Cancer Stem Cell Propagation With Palbociclib, A Cdk4/6 Inhibitor: Telomerase Drives Tumor Cell Heterogeneity., Gloria Bonuccelli, Maria Peiris-Pages, Bela Ozsvari, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P Lisanti

Department of Medical Oncology Faculty Papers

In this report, we systematically examined the role of telomerase activity in lung and ovarian cancer stem cell (CSC) propagation. For this purpose, we indirectly gauged telomerase activity, by linking the hTERT-promoter to eGFP. Using lung (A549) and ovarian (SKOV3) cancer cells, transduced with the hTERT-GFP reporter, we then employed GFP-expression levels to fractionate these cell lines into GFP-high and GFP-low populations. We functionally compared the phenotype of these GFP-high and GFP-low populations. More specifically, we now show that the cancer cells with higher telomerase activity (GFP-high) are more energetically activated, with increased mitochondrial mass and function, as well as …

Bcl-W Has A Fundamental Role In B Cell Survival And Lymphomagenesis., Clare M. Adams, Annette S. Kim, Ramkrishna Mitra, John K Choi, Jerald Z. Gong, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types. Here, however, we have exposed a critical role for BCL-W in B cell survival and lymphomagenesis. Loss of Bcl-w conferred sensitivity to growth factor deprivation-induced …