Translational Medical Research Commons^™

Micro-Computed Tomographic Analysis Of The Shaping Ability Of Xp-Endo Shaper In Oval-Shaped Distal Root Canals Of Mandibular Molars, Ane Poly, Wei-Ju Louis Tseng, Fernando Marques, Frank Carsten Setzer, Bekir Karabucak

Center for Translational Medicine Faculty Papers

Objective: To compare the shaping ability of the XP-endo Shaper (XPS) system to the ProTaper Next (PTN) system in oval-shaped distal root canals.

Methods: From 12 mandibular molars, distal roots with moderately curved single oval canals were randomly assorted to be instrumented with XPS (experimental group) or PTN (control group) and then scanned using micro-computed tomography [Scan 1]. The root canals of the XPS samples were prepared following the manufacturer's instructions using 15 insertions (XPS15) and rescanned [Scan 2]. An additional 10 insertions to the working length were applied, totalling 25 insertions (XPS25), and the roots were rescanned again [Scan …

Ogr1-Dependent Regulation Of The Allergen-Induced Asthma Phenotype, Ajay P Nayak, Deepak A. Deshpande, Phd, Sushrut D. Shah, Dominic R Villalba, Roslyn Yi, Nadan Wang, Raymond B. Penn

Division of Pulmonary and Critical Care Medicine Faculty Papers

The proton-sensing receptor, ovarian cancer G protein-coupled receptor (OGR1), has been shown to be expressed in airway smooth muscle (ASM) cells and is capable of promoting ASM contraction in response to decreased extracellular pH. OGR1 knockout (OGR1KO) mice are reported to be resistant to the asthma features induced by inhaled allergen. We recently described certain benzodiazepines as OGR1 activators capable of mediating both procontractile and prorelaxant signaling in ASM cells. Here we assess the effect of treatment with the benzodiazepines lorazepam or sulazepam on the asthma phenotype in wild-type (WT) and OGR1KO mice subjected to inhaled house dust mite (HDM; …

Activation Of Crtc2/Creb1 In Skeletal Muscle Enhances Weight Loss During Intermittent Fasting, Nelson E Bruno, Jerome C Nwachukwu, David C Hughes, Sathish Srinivasan, Richard Hawkins, David Sturgill, Gordon L Hager, Stephen Hurst, Shey-Shing Sheu, Sue C Bodine, Michael D Conkright, Kendall W Nettles

Department of Medicine Faculty Papers

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, maintenance of higher energy expenditure during the fast and reduced binge-eating …

Human Immunodeficiency Virus Type-1 (Hiv-1) Transcriptional Regulation, Latency And Therapy In The Central Nervous System, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Priya Tyagi, Alok Bhushan, Mudit Tyagi

College of Pharmacy Faculty Papers

The central nervous system (CNS) is highly compartmentalized and serves as a specific site of human immunodeficiency virus (HIV) infection. Therefore, an understanding of the cellular populations that are infected by HIV or that harbor latent HIV proviruses is imperative in the attempts to address cure strategies, taking into account that HIV infection and latency in the CNS may differ considerably from those in the periphery. HIV replication in the CNS is reported to persist despite prolonged combination antiretroviral therapy due to the inability of the current antiretroviral drugs to penetrate and cross the blood–brain barrier. Consequently, as a result …

Lack Of Interferon (Ifn) Regulatory Factor 8 Associated With Restricted Ifn-Γ Response Augmented Japanese Encephalitis Virus Replication In The Mouse Brain, Aarti Tripathi, Bhupendra Singh Rawat, Sankar Addya, Milan Surjit, Prafullakumar Tailor, Sudhanshu Vrati, Arup Banerjee

Kimmel Cancer Center Faculty Papers

Interferon regulatory factor 8 (IRF8), a myeloid lineage transcription factor, emerges as an essential regulator for microglial activation. However, the precise role of IRF8 during Japanese encephalitis virus (JEV) infection in the brain remains elusive. Here, we report that JEV infection enhances IRF8 expression in the infected mouse brain. Comparative transcriptional profiling of whole-brain RNA analysis and validation by quantitative reverse transcription-PCR (qRT-PCR) reveals an impaired interferon gamma (IFN-g) and related gene expression in Irf8 knockout (Irf82/2)-infected mice. Further, Ifng knockout (Ifng2/2) mice exhibit a reduced level of Irf8. Both Ifng2/2 and Irf82/2 mice exhibit significantly reduced levels of activated …

Hiv-1 Persistence In The Cns: Mechanisms Of Latency, Pathogenesis And An Update On Eradication Strategies., Shilpa Sonti, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Despite four decades of research into the human immunodeficiency virus (HIV-1), a successful strategy to eradicate the virus post-infection is lacking. The major reason for this is the persistence of the virus in certain anatomical reservoirs where it can become latent and remain quiescent for as long as the cellular reservoir is alive. The Central Nervous System (CNS), in particular, is an intriguing anatomical compartment that is tightly regulated by the blood-brain barrier. Targeting the CNS viral reservoir is a major challenge owing to the decreased permeability of drugs into the CNS and the cellular microenvironment that facilitates the compartmentalization …

Autophagy, Apoptosis, The Unfolded Protein Response, And Lung Function In Idiopathic Pulmonary Fibrosis, Pawan Sharma, Javad Alizadeh, Maya Juarez, Afshin Samali, Andrew J Halayko, Nicholas J Kenyon, Saeid Ghavami, Amir A Zeki

Center for Translational Medicine Faculty Papers

Autophagy, apoptosis, and the unfolded protein response (UPR) are fundamental biological processes essential for manifold cellular functions in health and disease. Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disorder associated with aging that has limited therapies, reflecting our incomplete understanding. We conducted an observational study linking molecular markers of cell stress response pathways (UPR: BiP, XBP1; apoptosis: cleaved caspase-3; autophagy: LC3β) in lung tissues from IPF patients and correlated the expression of these protein markers to each subject's lung function measures. We hypothesized that changes in lung tissue expression of apoptosis, autophagy, and UPR markers correlate with …

Emerging Advances Of Nanotechnology In Drug And Vaccine Delivery Against Viral Associated Respiratory Infectious Diseases (Varid), Amir Seyfoori, Mahdieh Shokrollahi Barough, Pooneh Mokarram, Mazaher Ahmadi, Parvaneh Mehrbod, Alireza Sheidary, Tayyebeh Madrakian, Mohammad Kiumarsi, Tavia Walsh, Kielan D Mcalinden, Chandra C Ghosh, Pawan Sharma, Amir A Zeki, Saeid Ghavami, Mohsen Akbari

Center for Translational Medicine Faculty Papers

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and …

Circumcision As An Intervening Strategy Against Hiv Acquisition In The Male Genital Tract, Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Unsafe sex with HIV-infected individuals remains a major route for HIV transmission, and protective strategies, such as the distribution of free condoms and pre-or post-prophylaxis medication, have failed to control the spread of HIV, particularly in resource-limited settings and high HIV prevalence areas. An additional key strategy for HIV prevention is voluntary male circumcision (MC). International health organizations (e.g., the World Health Organization, UNAIDS) have recommended this strategy on a larger scale, however, there is a general lack of public understanding about how MC effectively protects against HIV infection. This review aims to discuss the acquisition of HIV through the …

An Update On The Hiv Dna Vaccine Strategy, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable …

Combinatorial Use Of Both Epigenetic And Non-Epigenetic Mechanisms To Efficiently Reactivate Hiv Latency, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

The persistence of latent HIV provirus pools in different resting CD4+ cell subsets remains the greatest obstacle in the current efforts to treat and cure HIV infection. Recent efforts to purge out latently infected memory CD4+ T-cells using latency-reversing agents have failed in clinical trials. This review discusses the epigenetic and non-epigenetic mechanisms of HIV latency control, major limitations of the current approaches of using latency-reversing agents to reactivate HIV latency in resting CD4+ T-cells, and potential solutions to these limitations.

Ap-1 And Nf-Κb Synergize To Transcriptionally Activate Latent Hiv Upon T-Cell Receptor Activation., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Latent HIV-1 proviruses are capable of reactivating productive lytic infection, but the precise molecular mechanisms underlying emergence from latency are poorly understood. In this study, we determined the contribution of the transcription factors NF-κB, NFAT, and AP-1 in the reactivation of latent HIV following T-cell receptor (TCR) activation using Jurkat T-cell clones harboring single latent HIV proviruses. Our findings demonstrate that during reactivation from latency, NF-κB enhances HIV transcription while NFAT inhibits it by competing with NF-κB for overlapping binding sites on the HIV long terminal repeat (LTR). We have also demonstrated for the first time the molecular contribution of …

Chloroquine: Autophagy Inhibitor, Antimalarial, Bitter Taste Receptor Agonist In Fight Against Covid-19, A Reality Check?, Pawan Sharma, Kielan D. Mcalinden, Saeid Ghavami, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate …

Establishing The Relationship Between Mendelian Nafld And Skin Pathology, Anthony Medvedev, Hassan Vahidnezhad, Phd, Leila Youssefian, Phd, Jouni Uitto, Md, Phd

Phase 1

Introduction:

It is estimated that 25% of the world’s population has some form of Nonalcoholic Fatty Liver Disease (NAFLD), a pathology associated with the development of cirrhosis, varices, and hepatocellular carcinoma. The discovery of a biallelic mutation in ABHD5 established the link between NAFLD and Chanarin-Dorfman syndrome. Consequently, it was hypothesized that additional NAFLD-inducing mutations could be associated with dermatologic manifestations.

Methods:

International NAFLD patients from consanguineous families underwent whole exome sequencing. These results were then filtered by frequency and pathogenicity prediction algorithms (e.g. Mutation Taster, Polyphen, CADD) to yield novel mutations. Concurrently, a literature review via PubMed identified …

Expanding The Whipple Accelerated Recovery Pathway (Warp) To All Patients Undergoing Pancreaticoduodenectomy (Pd), Ava Torjani, Clifford Yudkoff, Taylor R. Kavanagh, Wilbur Bowne, Geoffrey Krampitz, Hamza Rshaidat, Cyrus J. Sholevar, Alexandra C. Leto, William Preston, Elwin Tham, Mandeep Shergill, Shawnna Cannaday, Theresa Yeo, Harish Lavu, Charles J. Yeo

Phase 1

Introduction

Enhanced recovery after surgery constitutes a multi-disciplinary approach to reduce length of stay (LOS), post-operative complications (POCs), and readmission rate (RR). This not only improves patient outcomes, but also reduces hospital costs. The Whipple Accelerated Recovery Pathway (WARP) trial successfully reduced LOS without increasing the rate of POCs and RR in patients undergoing pancreaticoduodenectomy (PD). However, the study was limited to a highly selective group of patients. This study aimed to determine if WARP could be expanded to all patients undergoing PD.

Methods

A single-institution retrospective review of 281 patients who underwent PD between 2017-2020 was conducted. Patients were …

Differences In Clinical And Functional Outcomes Between Osteochondral Allograft Transplantation And Autologous Chondrocyte Implantation When Used In The Treatment Of Focal Grade 3 And Grade 4 Articular Cartilage Defects, Daniel Abraham, Joseph Brutico, Kashyap Chauhan, Anant Dixit, Fotios Tjoumakaris, Brad Tucker, Kevin Freedman

Phase 1

Introduction:

Grade 3 and 4 articular cartilage defects involve 50% of cartilage thickness without involvement of the underlying bone. There are several available options for the surgical repair of articular cartilage lesions including osteochondral allograft transplantation (OCA), a well-established procedure, and autologous chondrocyte implantation (ACI), an alternative developed more recently. Although there are studies examining ACI outcomes, there hasn’t been significant comparison of ACI outcomes to other procedures, including OCA. The inquiry question of this study was: how do clinical and functional outcomes differ between patients with focal articular cartilage defects treated with ACI and patients treated with OCA? …

Impact Of Medical Nutrition Therapy On Blood Pressure, Connor Mcelwee, Jessica Vitale, Cynthia Cheng, Md, Phd

Phase 1

Introduction:

We are studying how Jefferson’s Medical Nutrition Therapy (MNT) program has impacted biometric variables in program participants. These variables include body weight, HgA1C, lipids, and blood pressure (BP). My poster will focus on the impact of Jefferson’s MNT on blood pressure. My hypothesis is that participation in MNT will result in reduced blood pressure.

Methods:

The target population is patients who have participated in Jefferson’s MNT program. Study exclusion criteria included history of gastric bypass surgery, medical conditions or medication usage that might impact weight loss and other dependent variables. Data was abstracted from patients’ medical records, as …

Outcomes Following Open Reduction And Internal Fixation For Distal Humerus Fracture: Does Handedness Matter?, Charlotte N. Shields, Joseph R. Johnson, Jack M. Haglin, Sanjit R. Konda, Md, Kenneth A. Egol, Md

Phase 1

Introduction: No studies have assessed the relationship between extremity dominance and distal humerus fractures. This study sought to compare post-operative outcomes between patients with distal humerus fractures treated by open reduction and internal fixation (ORIF) of their non-dominant vs dominant arm.

Methods: A retrospective review of patients who sustained a distal humerus fracture treated with ORIF at one hospital between 2011-2015 was performed. Data collection included demographics, hand dominance, injury information, and surgical management. Post-operative outcomes included complications, time to fracture union, painful hardware, removal of hardware, Mayo Elbow Performance Index (MEPI), and range of motion.

Results: Of the …

The Use Of Imiquimod For The Treatment Of Empd From The Patients’ Perspective, Darren D'Mello, Paul Chung, Md

Phase 1

Introduction:

Imiquimod is a topical medication used to treat many dermatologic conditions, and it has been used to treat patients with Extra-Mammary Paget’s Disease. There have been case reports that described the effects and outcomes of patients who were treated with Imiquimod, but more research on its use for EMPD must be done. There have been no studies that gathered data from the patients themselves; this is what our study hopes to accomplish. We hypothesize that patients with EMPD who were treated with Imiquimod early after their diagnoses or after surgery had better outcomes than those who did not use …

Validation And Accuracy Of Synovial Alpha Defensin In A Suburban Academic Center After Implantation As Part Of The Workup For Periprosthetic Joint Infections, Donald Willier, Iii, Kenneth J. Mcalpine, Md, Anthony F. De Giacomo, Md, John S. Garfi, Ms, Lawrence M. Specht, Md, Michael S. Kain, Md

Phase 1

Introduction

Periprosthetic joint infection (PJI) is a leading cause of total hip and knee arthroplasty failure. The Musculoskeletal Infection Society (MSIS) criteria for PJI has allowed diagnosis standardization. To increase the MSIS criteria accuracy, synovial fluid biomarkers have been tested. Studies evaluating synovial alpha defensin have reported both sensitivity and specificity up to 100%. In this study, we report our analysis on the use of alpha defensin testing in a suburban academic tertiary referral center.

Methods

We performed a retrospective analysis of a prospectively collected database of 133 patients tested for PJI over a 6 year period. From 2014, our …

Effect Of Recipient Diabetes Status On Immune Rejection After Descemet Stripping Endothelial Keratoplasty, Elliot Cherkas, Zeba Syed, Michael Sulewski

Phase 1

This study seeks to determine whether recipient diabetes status relates to incidence of immune rejection following Descemet Stripping Endothelial Keratoplasty (DSEK). We hypothesized that patients with diabetes would have a greater risk of graft immune rejection.

This is a retrospective cohort study to compare recipient diabetes status in 794 DSEK surgeries at Wills Eye Hospital between January 2008 and July 2019. Kaplan-Meier functions of survival time until first immune rejection was compared between groups. Pearson’s chi square test and Wilcoxon test were used to test the null hypothesis.

During the study period, 146 of 794 DSEK recipients had diabetes. At …

The Impact Of Patient Characteristics On Quality Of Life In Keloid Patients, Jonathan Wang, Romsin Zaya, Rachel Zachian, Mary Metkus, Neda Nikbakht

Phase 1

Introduction: Quality of life (QoL) is an important metric in assessing dermatological diseases such as keloids. This study evaluated the effects of patient characteristics on QoL in keloid patients.

Methods: This was a cross-sectional study. 36 patients presenting to the keloid clinic at TJUH were surveyed. QoL subscale scores for emotion, symptom, and function were calculated in addition to a total score for each patient using a keloid-specific questionnaire. The association between the QoL scores and patient characteristics of sex, ethnicity, as well as keloid location, duration, visibility, size, number, pain score, and pruritis score were evaluated using t-tests. …

Total Knee Arthroplasty In Patients With Prior Meniscus Surgery: A Matched Case Control Study, Lasya Rangavajjula, Steven B. Cohen, Md, Meghan E. Bishop, Md, Shyam Brahmabhatt, Md, Michael G. Ciccotti, Md, Ashley Bassett, Md, Christopher Hadley

Phase 1

Introduction: Meniscus surgery is one of the most commonly performed orthopedic surgical procedures in the United States. However, outcomes following a Total Knee Arthroplasty (TKA) in patients with a history of prior knee arthroscopy are varied with small patient cohorts, warranting further research. The research question investigates how the clinical outcomes of TKA compare between patients with and without prior meniscectomy history. It is hypothesized that there will be no significant difference in clinical outcomes between the two cohorts.

Methods: The study design is a retrospective case-control study. The study population included patients from Rothman Institute with TKA and …

Predictors And Characteristics Of Rib Fracture Following Sbrt For Lung Tumors, Michael P. Carducci, Baskaran Sundaram, Md, Benjamin Greenberger, Md, Maria Werner-Wasik, Md, Gregory C. Kane, Md

Phase 1

See Additional Files section for the abstract.

Predictive Value Of Index Lesion Cross-Sectional Area In Diffuse Large B Cell Lymphoma Patients Treated With Chimeric Antigen Receptor T-Cells, Nicole Winchell, Drew Torigian, Md, Stephen Schuster, Md

Phase 1

No abstract provided.

A Meta-Analysis Of The Effects Of Sglt-2 Inhibitors On Serum Electrolytes, Mark Leibensperger, Jingjing Zhang, Md, Phd, Yonghong Huan, Md

Phase 1

Introduction: Previous studies have reported that sodium-glucose co-transporter 2 (SGLT2) inhibitors affect serum electrolytes levels, especially magnesium. This study aims to integrate direct and indirect trial evidence to evaluate the relative effects of all SGLT2 inhibitors against each other on electrolyte levels in patients with type 2 diabetes (T2D).

Methods: Electronic databases were systematically searched through December 2018 to identify eligible randomized controlled trials (RCTs) that reported mean changes in serum electrolyte levels, including magnesium, sodium, potassium, phosphate, calcium, and urate in patients with T2D. Random-effects pairwise and network meta-analyses were performed to calculate the weighted mean difference (WMD) …

Correlates Of Rem Sleep Without Atonia In Dream Enactment Behavior Associated With Parkinson’S Disease, Nisha Bagchi, Ritu Grewal, Abigail Quintos, Rohin Saroya

Phase 1

Introduction: Parkinson’s Disease (PD), a common neurodegenerative disease worldwide, has few reliable biomarkers. PD has been linked to REM Behavioral Disorder (RBD), a condition where patients abnormally experience REM sleep without atonia (RSWA). We aim to determine whether chin movements, a feature of RSWA, could serve as a PD biomarker. We hypothesize that those with higher RSWA are more likely to have PD.

Methods: Our study examined patients who underwent polysomnograms from 2015 onwards at the Jefferson Sleep Disorders Center. We did a retrospective EPIC chart review and compared 2 groups, those with RBD and PD (n=12) versus RBD …

Coronary Artery Disease And Nonalcoholic Fatty Liver Disease: Clinical Correlation Using Ct Coronary Calcium Scans, Richard S. Kirby, Dina Halegoua-De Marzio

Phase 1

Introduction: Nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) have been explored with coronary angiography which showed a link between severe NAFLD and CVD risk. This study’s aim is to determine if CT coronary artery calcium (CAC) scores used to determine CAD severity in asymptomatic populations can help predict presence of NAFLD.

Methods: Retrospective cross-sectional study of positive CT CAC scores and liver imaging with either CT, ultrasound, or MRI of the abdomen or CT of the chest. Drinking 7 or 14 drinks per week for a woman or man respectively and chronic viral hepatitis diagnosis …

Patient And Renal Allograft Outcomes Of Anticoagulation Therapy In Kidney Transplantation, Rachel Greene, Goni Katz-Greenberg, Md

Phase 1

Introduction: Kidney transplant recipients are often on anticoagulation or antiplatelet therapy, for a variety of indications. These medications are associated with increased risk of bleeding but may reduce risk of thrombosis and possible complications such as allograft loss. The aim of our study is to evaluate the effect of perioperative anticoagulation or antiplatelet therapy on patient and allograft outcomes.

Methods: Data collection was done by retrospective chart review of all patients who underwent a kidney or kidney/pancreas transplantation at Thomas Jefferson University Hospital (TJUH) from 2012-2019. We recorded perioperative anticoagulation and antiplatelet therapy, risk factors for bleeding and thrombosis, …

Treatment Of Distal Radius Fractures In Patients Over 80 Years Of Age: Functional Outcomes After Open Reduction And Internal Fixation Versus Nonoperative Treatment, Robert Gallivan, Lili E. Schindelar, Md, Mph, Richard Mcentee, Pedro K. Beredjiklian, Md

Phase 1

INTRODUCTION

Distal radius fractures are one of the most common fractures seen in the elderly. With the younger physiological age of patients over 60 years, the expectation of functional outcomes is changing. The management of distal radius fractures in the elderly patient, especially those over the age of 80, has not been well defined. The purpose of this study was to compare operative to nonoperative treatment of distal radius fractures in patients older than 80 years to determine if there is any difference in functional outcomes or complications.

METHODS

A retrospective review was performed to identify patients 80 years or …