Medicine and Health Sciences Commons^™

Polθ Promotes The Repair Of 5'-Dna-Protein Crosslinks By Microhomology-Mediated End-Joining, Gurushankar Chandramouly, Shuren Liao, Timur Rusanov, Nikita Borisonnik, Marissa L Calbert, Tatiana Kent, Katherine Sullivan-Reed, Umeshkumar Vekariya, Ekaterina Kashkina, Tomasz Skorski, Hong Yan, Richard T Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase θ (Polθ) confers resistance to chemotherapy agents that cause DNA-protein crosslinks (DPCs) at double-strand breaks (DSBs), such as topoisomerase inhibitors. This suggests Polθ might facilitate DPC repair by microhomology-mediated end-joining (MMEJ). Here, we investigate Polθ repair of DSBs carrying DPCs by monitoring MMEJ in Xenopus egg extracts. MMEJ in extracts is dependent on Polθ, exhibits the MMEJ repair signature, and efficiently repairs 5' terminal DPCs independently of non-homologous end-joining and the replisome. We demonstrate that Polθ promotes the repair of 5' terminal DPCs in mammalian cells by using an MMEJ reporter and find that Polθ confers resistance to …

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 …

Pctp Contributes To Human Platelet Activation By Enhancing Dense Granule Secretion, Shaji Abraham, Lin Ma, Xianguo Kong, Shayan Askari, Leonard Edelstein, Steven Mckenzie

Cardeza Foundation for Hematologic Research

PCTP (phosphatidylcholine transfer protein) was discovered recently to regulate aggregation of human platelets stimulated with PAR4 activating peptide (PAR4AP). However, the role of PCTP following thrombin stimulation, the mechanisms by which PCTP contributes to platelet activation, and the role of PCTP with other receptors remained unknown. As mouse platelets do not express PCTP, we treated human platelets with various agonists in the presence of the specific PCTP inhibitor A1. We observed that PCTP inhibition significantly reduced dense granule secretion in response to thrombin, PAR1AP, PAR4AP, convulxin (GPVI agonist) and FcγRIIA crosslinking. In contrast, among these agonists, PCTP inhibition reduced aggregation …

Cardiovascular Disease Risk, Awareness, And Treatment In People With Epilepsy, Samuel W Terman, Carole E Aubert, Chloe E Hill, Jeremy Skvarce, James F Burke, Scott Mintzer

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate whether cardiovascular risk, risk awareness, and guideline concordant treatment differ in individuals with versus without epilepsy.

METHODS: This was a retrospective cross-sectional study using the National Health and Nutrition Examination Survey. We included participants ≥18 years for 2013-2018. We classified participants as having epilepsy if reporting ≥1 medication treating seizures. We calculated 10-year atherosclerotic cardiovascular disease (ASCVD) risk using the revised pooled cohort equation. We compared unadjusted and adjusted risk for participants with versus without epilepsy. We then assessed hypertension and diabetes disease awareness and control, plus statin guideline-concordance. We assessed mediators for both ASCVD risk and …

Effects Of Combining Meditation Techniques On Short-Term Memory, Attention, And Affect In Healthy College Students., Samani Unnata Pragya, Neelam D Mehta, Bassam Abomoelak, Parvin Uddin, Pushya Veeramachaneni, Naina Mehta, Stephanie Moore, Melissa Jean-Francois, Stephanie Garcia, Samani Chaitanya Pragya, Devendra I Mehta

Department of Medicine Faculty Papers

Meditation refers to a family of self-regulation practices that focuses on training attention and awareness to foster psycho-emotional well-being and to develop specific capacities such as calmness, clarity, and concentration. We report a prospective convenience-controlled study in which we analyzed the effect of two components of Preksha Dhyāna – buzzing bee sound meditation (Mahapran dhvani) and color meditation (leśyā dhyāna) on healthy college students. Mahapran and leśya dhyāna are two Preksha Dhyāna practices that are based on sound and green color, respectively. The study population represents a suitable target as college students experience different stress factors during the school year. …

Historical Perspective Of The G Protein-Coupled Receptor Kinase Family., Jeffrey L Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

Agonist activation of G protein-coupled receptors promotes sequential interaction of the receptor with heterotrimeric G proteins, G protein-coupled receptor kinases (GRKs), and arrestins. GRKs play a central role in mediating the switch from G protein to arrestin interaction and thereby control processes such as receptor desensitization and trafficking and arrestin-mediated signaling. In this review, I provide a historical perspective on some of the early studies that identified the family of GRKs with a primary focus on the non-visual GRKs. These studies included identification, purification, and cloning of the β-adrenergic receptor kinase in the mid- to late-1980s and subsequent cloning and …

Monitoring Tissue Oxygenation Index Using Near-Infrared Spectroscopy During Pre-Hospital Resuscitation Among Out-Of-Hospital Cardiac Arrest Patients: A Pilot Study, Jumpei Tsukuda, Shigeki Fujitani, Mahbubur Rahman, Kenichiro Morisawa, Takeshi Kawaguchi, Yasuhiko Taira

Department of Emergency Medicine Faculty Papers

BACKGROUND: Tissue oxygenation index (TOI) using the near infrared spectroscopy (NIRS) has been demonstrated as a useful indicator to predict return of spontaneous circulation (ROSC) among out-of-hospital cardiac arrest (OHCA) patients in hospital setting. However, it has not been widely examined based on pre-hospital setting.

METHODS: In this prospective observational study, we measured TOI in pre-hospital setting among OHCA patients receiving cardio-pulmonary resuscitation (CPR) during ambulance transportation between 2017 and 2018. Throughout the pre-hospital CPR procedure, TOI was continuously measured. The study population was divided into two subgroups: ROSC group and non-ROSC group.

RESULTS: Of the 81 patients included in …

Identification Of A Ctrp9 C-Terminal Polypeptide Capable Of Enhancing Bone-Derived Mesenchymal Stem Cell Cardioprotection Through Promoting Angiogenic Exosome Production., Demin Liu, Guoqiang Gu, Lu Gan, Wenjun Yan, Zhen Zhang, Peng Yao, Di Zhu, Wayne Bond Lau, Dina Xie, Sisi Wu, Zhijun Meng, Jumpei Tsukuda, Theodore Christopher, Bernard Lopez, Jianli Zhao, Erhe Gao, Walter Koch, Xin-Liang Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

BACKGROUND: Mesenchymal stem cell therapy improves ischemic heart failure via incompletely understood mechanisms. C1q-TNFα related protein-9 (CTRP9) is a novel anti-oxidative cardiokine capable of improving the local microenvironment and cell survival by its c-terminal active globular domain (gCTRP9). The current study attempted to: 1) identify active gCTRP9 c-terminal polypeptides with stem cell protective function; 2) determine whether a lead polypeptide may enable/enhance cortical bone-derived mesenchymal stem cell (CBSC) cardioprotection against post-myocardial infarction (post-MI) remodeling; and 3) define the responsible underlying cellular/molecular mechanisms.

METHODS AND RESULTS: Utilizing I-TASSER structure prediction and 3-D active site modeling, we cloned and purified 3 gCTRP9 …

From Theory To Practice: What Global Health Practitioners Need To Know About Social Norms And Narrative Interventions, Amy Henderson Riley, Kriss Barker, Rebecka Lundgren

College of Population Health Faculty Papers

There has been a marked increase in the literature in recent years about social norms, what they are, and how to measure them. New theoretical connections indicate specific significance for those working with global health programs that use narrative interventions, such as mass, print, and community media. The literature is dense, however. Different terms describe similar constructs, and the sheer number of new articles and emerging academic frameworks can be overwhelming. In this letter, we briefly summarize current social norms and narrative theorizing and provide examples of global programs that have effectively applied these theories. In so doing, we hope …

The Evolutionary Conserved Swi/Snf Subunits Arid1a And Arid1b Are Key Modulators Of Pluripotency And Cell-Fate Determination, Luca Pagliaroli, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Organismal development is a process that requires a fine-tuned control of cell fate and identity, through timely regulation of lineage-specific genes. These processes are mediated by the concerted action of transcription factors and protein complexes that orchestrate the interaction between cis-regulatory elements (enhancers, promoters) and RNA Polymerase II to elicit transcription. A proper understanding of these dynamics is essential to elucidate the mechanisms underlying developmental diseases. Many developmental disorders, such as Coffin-Siris Syndrome, characterized by growth impairment and intellectual disability are associated with mutations in subunits of the SWI/SNF chromatin remodeler complex, which is an essential regulator of transcription. ARID1B …

Capturing Initial Understanding And Impressions Of Surgical Therapy For Parkinson's Disease, Somnath Das, Caio Matias, Sunihidi Ramesh, Lohit Velagapudi, Julie Barbera, Samantha Katz, Michael Baldassari, Mohammad Rasool, Daniel Kremens, Jeffrey Ratliff, Md, Tsao-Wei Liang, Chengyuan Wu

Department of Neurosurgery Faculty Papers

Background: Deep Brain Stimulation (DBS) is an underutilized surgical therapy for Parkinson's Disease (PD). Both physician and patient hesitancies have been described as potential barriers to DBS, but the specifics of patient perceptions of DBS have not been well-characterized in the general PD population. Objective: To characterize the understanding and impressions of surgical therapy in PD patients prior to formal surgical evaluation. Methods: A 30-question survey assessing impressions of surgical therapy for PD and understanding of DBS for PD was administered to PD patients seen at an urban movement disorders clinic. Results: One hundred and two patients completed the survey. …

Dual Targeting Of Cdk4/6 And Cmet In Metastatic Uveal Melanoma., Masahiro Ohara, Kengo Saito, Ken Kageyama, Mizue Terai, Hanyin Cheng, A E Aplin, Takami Sato

Department of Medical Oncology Faculty Papers

Uveal melanoma (UM) is the most common cancer of the eye in adults. Up to 50% of UM patients subsequently develop metastases, especially in the liver. It has been reported that the retinoblastoma (RB) pathway is deregulated in more than 90% of UM despite the rarity of mutations in the RB1 gene itself. CDK4/6 inhibition (CDK4/6i) is a rational strategy for treatment of UM. In this report, we investigated the antiproliferative activity of a selective CDK4/6 inhibitor on metastatic UM. A CDK4/6 inhibitor suppressed UM cell lines growth in in vitro and in vivo experiments. Hepatocyte growth factor (HGF) decreased …

Smoking Cessation, Julita Mitchell, Md

Department of Family & Community Medicine Presentations and Grand Rounds

Learning Objectives

● Appreciate the significance of addressing smoking cessation

● Learn a brief interventional model for cessation counseling

● How to structure a quit plan

● Understand the role/risks/benefits of

• Pharmacologic therapy
• Behavioral therapy
• Electronic cigarettes

● Learn practical tips and hear sample language

● Watch a sample intervention

Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Aortic Occlusion: A Case Report, Artem Minalyan, Franklin L. Thelmo, Vincent Chan, Stephanie Tzarnas, Faizan Ahmed

Department of Medicine Faculty Papers

Background: Severe acute respiratory syndrome coronavirus 2 infection can lead to a constellation of viral and immune symptoms called coronavirus disease 2019. Emerging literature increasingly supports the premise that severe acute respiratory syndrome coronavirus 2 promotes a prothrombotic milieu. However, to date there have been no reports of acute aortic occlusion, itself a rare phenomenon. We report a case of fatal acute aortic occlusion in a patient with coronavirus disease 2019.

Case report: A 59-year-old Caucasian male with past medical history of peripheral vascular disease presented to the emergency department for evaluation of shortness of breath, fevers, and dry cough. …

Racial Disparities In Post-Acute Home Health Care Referral And Utilization Among Older Adults With Diabetes, Jamie Smith, Olga Jarrín, Haiqun Lin, Tina Dharamdasani, Jennifer Tsui, Charlotte Thomas-Hawkins

College of Nursing Faculty Papers & Presentations

Racial and ethnic disparities exist in diabetes prevalence, health services utilization, and outcomes including disabling and life-threatening complications among patients with diabetes. Home health care may especially benefit older adults with diabetes through individualized education, advocacy, care coordination, and psychosocial support for patients and their caregivers. The purpose of this study was to examine the association between race/ethnicity and hospital discharge to home health care and subsequent utilization of home health care among a cohort of adults (age 50 and older) who experienced a diabetes-related hospitalization. The study was limited to patients who were continuously enrolled in Medicare for at …

Declining Intensive Care Unit Mortality Of Covid-19: A Multi-Center Study, Sohaib Roomi, Syed Omar Shah, Waqas Ullah, Shan Abedin, Karyn L. Butler, Chiers, Kelly, Benjamin A. Kohl, Erika J. Yoo, Matthew Vibbert, Jack Jallo

Department of Surgery Faculty Papers

Background: Coronavirus disease 2019 (COVID-19) mortality has waned significantly over time; however, factors contributing towards this reduction largely remain unidentified. The purpose of this study was to evaluate the trend in mortality at our large tertiary academic health system and factors contributing to this trend. Methods: This is a retrospective cohort study of intensive care unit (ICU) patients diagnosed with COVID-19 between March and August 2020 admitted across 14 hospitals in the Philadelphia area. Collected data included demographics, comorbidities, admission risk of mortality score, laboratory values, medical interventions, survival outcomes, hospital and ICU length of stay (LOS) and discharge disposition. …

Stereotactic Body Radiation Therapy (Sbrt) For Patients With Stage I Non-Small Cell Lung Cancer Is Applicable To More Tumors Than Sublobar Resection, Andrew Song, Nathaniel R. Evans Iii, Scott W. Cowan, Jenny Guo, Tingting Zhan, Bo Lu, Maria Werner-Wasik

Department of Radiation Oncology Faculty Papers

Background: Virtually all patients with medically inoperable stage I non-small cell lung cancer (NSCLC) can receive stereotactic body radiation therapy. However, the percentage of such patients in whom sublobar resection is technically feasible is unknown. This discrepancy can confound clinical trial eligibility and designs comparing stereotactic body radiation therapy vs. sublobar resection.

Methods: A total of 137 patients treated with stereotactic body radiation therapy for lung lesions (3/2013-11/2017) underwent retrospective review. Diagnostic CT chest and PET/CT images, stereotactic body radiation therapy dates, and demographic data were collected on 100 of 137 patients. Two experienced board-certified thoracic surgeons independently reviewed anonymized …

Management Of Iatrogenic Coronary Artery Dissections Failing To Prepare Is Preparing To Fail, David L. Fischman, Alec Vishnevsky, Md

Division of Cardiology Faculty Papers

CICAD is a rare but important complication of coronary angiography and PCI. Careful attention to preventative techniques and knowledge of effective treatment strategies will prepare operators well and facilitate successful outcomes in this potentially life-threatening complication.

Coronary Vasospasm: Not Gone But Often Forgotten, Michael Savage, Tabitha Moe

Division of Cardiology Faculty Papers

No abstract provided.

Symptomatic Presentation Of Acute Myocardial Infarction In Heart Transplantation Patients, Shashank Jain, Dexter Jacob, Mahek Shah, David L. Fischman

Division of Cardiology Faculty Papers

Patients with acute myocardial infarction with a history of an orthotopic heart transplantation rarely present with classic anginal symptoms, secondary to cardiac denervation. We present 2 cases, the first of a patient with a ST-segment elevation myocardial infarction and the second who presented with a non-ST-segment elevation myocardial infarction. Both patients presented with typical symptoms and were treated with percutaneous coronary intervention.

Will The Covid-19 Pandemic Finally Fuel Drug Repurposing Efforts?, Anna Chen, Shivangi Patel, Matthew Alcusky, Vittorio Maio

College of Population Health Faculty Papers

No abstract provided.

A Brazilian National Preparedness Survey Of Anesthesiologists During The Coronavirus Pandemic, Vinícius Caldeira Quintão, Claudia Marquez Simões, Gibran Elias Harcha Munoz, Paul Barach, Maria José Carvalho Carmona, Brazilian Network For Research On Complications In Anesthesia Branca

College of Population Health Faculty Papers

No abstract provided.

High-Dose-Rate Brachytherapy For The Treatment Of Basal And Squamous Cell Carcinomas On Sensitive Areas Of The Face: A Report Of Clinical Outcomes And Acute And Subacute Toxicities, James M. Taylor, Bahar Dasgeb, Spencer Liem, Ayesha Ali, Amy Harrison, Mitchell Finkelstein, Jisun Cha, Rani Anne, Steven Greenbaum, William Sherwin, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Purpose Basal cell and cutaneous squamous cell carcinoma are common malignancies (keratinocyte carcinomas [KCs]). Surgical resection is the standard of care. Radiation using high-dose rate brachytherapy (HDR-BT) may serve as a superior alternative where surgical scars may be of cosmetic concern or in elderly patients with significant comorbidity. We aim to describe the clinical and cosmetic outcomes as well as posttreatment radiation toxicities associated with HDR-BT in patients who were treated for KCs of the face.

Methods and Materials Patients with KCs treated with HDR-BT from 2015 to 2018 were included in the study. Patient medical records and clinical photos …

C1q Complement/Tumor Necrosis Factor-Associated Proteins In Cardiovascular Disease And Covid-19, Yaoli Xie, Zhijun Meng, Jia Gao, Caihong Liu, Jing Wang, Rui Guo, Jianli Zhao, Bernard Lopez, Theodore Christopher, Daniel Lee, Xin-Liang Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

With continually improving treatment strategies and patient care, the overall mortality of cardiovascular disease (CVD) has been significantly reduced. However, this success is a double-edged sword, as many patients who survive cardiovascular complications will progress towards a chronic disorder over time. A family of adiponectin paralogs designated as C1q complement/tumor necrosis factor (TNF)-associated proteins (CTRPs) has been found to play a role in the development of CVD. CTRPs, which are comprised of 15 members, CTRP1 to CTRP15, are secreted from different organs/tissues and exhibit diverse functions, have attracted increasing attention because of their roles in maintaining inner homeostasis by regulating …

Atg16l1 As A Novel Biomarker And Autophagy Gene For Diabetic Retinopathy., Xinxiao Gao, Yunhui Du, Wayne Bond Lau, Yu Li, Siquan Zhu, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Objective: Accumulating evidence suggests the critical role of autophagy in the pathogenesis of diabetic retinopathy (DR). In the current study, we aim to identify autophagy genes involved in DR via microarray analyses.

Methods: Gene microarrays were performed to identify differentially expressed lncRNAs/mRNAs between normal and DR retinas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of lncRNA-coexpressed mRNAs were used to determine the related pathological pathways and biological modules. Real-time polymerase chain reactions (PCR) were conducted to validate the microarray analyses.

Results: A total of 2474 significantly dysregulated lncRNAs and 959 differentially expressed mRNAs were identified in the …

Safety And Efficacy Of Catheter Directed Thrombolysis (Cdt) In Elderly With Pulmonary Embolism (Pe)., Eneida Harrison, Jin Sun Kim, Vladimir Lakhter, Ka U Lio, Rami Alashram, Huaqing Zhao, Rohit Gupta, Maulin Patel, James Harrison, Joseph Panaro, Kerry Mohrien, Riyaz Bashir, Gary Cohen, Gerard Criner, Parth Rali

Department of Psychiatry and Human Behavior Faculty Papers

INTRODUCTION: Acute pulmonary embolism (PE) remains a common cause for morbidity and mortality in patients over 65 years. Given the increased risk of bleeding in the elderly population with the use of systemic thrombolysis, catheter-directed therapy (CDT) is being increasingly used for the treatment of submassive PE. Nevertheless, the safety of CDT in the elderly population is not well studied. We, therefore, aimed to evaluate the safety of CDT in our elderly patients.

METHODS: We conducted a retrospective observational study of consecutive patients aged >65 years with a diagnosis of PE from our Pulmonary Embolism Response Team database. We compared …

Preliminary Data On The Potential For Unintentional Antidoping Rule Violations By Permitted Cannabidiol (Cbd) Use., Ute Mareck, Gregor Fusshöller, Hans Geyer, Marilyn A. Huestis, Anja B Scheiff, Mario Thevis

Institute of Emerging Health Professions Faculty Papers

According to the World Anti-Doping Agency (WADA) regulations, cannabinoids use is prohibited in competition except for cannabidiol (CBD) use. For an adverse analytical finding (AAF) in doping control, cannabinoid misuse is based on identification of the pharmacologically inactive metabolite 11-nor-delta-9-carboxy-tetrahydrocannabinol-9-carboxylic acid (carboxy-THC) in urine at a concentration greater than 180 ng/ml. All other (minor) cannabinoids are reported as AAF when identified, except for CBD that has been explicitly excluded from the class of cannabinoids on WADA's Prohibited List since 2018. However, due to the fact that CBD isolated from cannabis plants may contain additional minor cannabinoids, the permissible use of …

Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.

Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …

Phenotype Expression Variability In Children With Gabrb3 Heterozygous Mutations., Abdulhafeez M. Khair, Alana E. Salvucci

Department of Pediatrics Faculty Papers

GABRB3 gene is a recently identified gene located in 15q12 chromosome and encodes for gamma-aminobutyric acid (GABA) receptor subunit beta-3 protein, which is linked to the GABAA receptor. The gene is believed to share a role in inhibitory GABAergic synapses, GABA iron-gated channel function, and possible cellular response to histamine. The β3 subunit is expressed in cerebral grey matter, thalami, hippocampi, and cerebellum, among other structures. Faulty GABRB3 function is linked to several neurological disorders and clinical syndromes. However, the spectrum of such disorders is not yet well known. We present three case reports highlighting the potentially expanding clinical phenotype …

Figo (International Federation Of Gynecology And Obstetrics) Initiative On Fetal Growth: Best Practice Advice For Screening, Diagnosis, And Management Of Fetal Growth Restriction, Nir Melamed, Ahmet Baschat, Yoav Yinon, Apostolos Athanasiadis, Federico Mecacci, Francesc Figueras, Vincenzo Berghella, Amala Nazareth, Muna Tahlak, H David Mcintyre, Fabrício Da Silva Costa, Anne B Kihara, Eran Hadar, Fionnuala Mcauliffe, Mark Hanson, Ronald C Ma, Rachel Gooden, Eyal Sheiner, Anil Kapur, Hema Divakar, Diogo Ayres-De-Campos, Liran Hiersch, Liona C Poon, John Kingdom, Roberto Romero, Moshe Hod

Department of Obstetrics and Gynecology Faculty Papers

No abstract provided.