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Articles 6151 - 6180 of 14928

Full-Text Articles in Medicine and Health Sciences

Shedding Light On The Role Of Extracellular Vesicles In Hiv Infection And Wound Healing., Aseel Alqatawni, Adhikarimayum Lakhikumar Sharma, Beatrice Attilus, Mudit Tyagi, Rene Daniel May 2020

Shedding Light On The Role Of Extracellular Vesicles In Hiv Infection And Wound Healing., Aseel Alqatawni, Adhikarimayum Lakhikumar Sharma, Beatrice Attilus, Mudit Tyagi, Rene Daniel

Center for Translational Medicine Faculty Papers

Extracellular vesicles (EVs) play an important role in intercellular communication. They are naturally released from cells into the extracellular environment. Based on their biogenesis, release pathways, size, content, and function, EVs are classified into exosomes, microvesicles (MVs), and apoptotic bodies (ApoBDs). Previous research has documented that EVs, specifically exosomes and MVs, play an important role in HIV infection, either by promoting HIV infection and pathogenesis or by inhibiting HIV-1 to a certain extent. We have also previously reported that EVs (particularly exosomes) from vaginal fluids inhibit HIV at the post-entry step (i.e., reverse transcription, integration). Besides the role that EVs …


Characteristics Of Nontuberculous Mycobacterial Infections At A Midwestern Tertiary Hospital: A Retrospective Study Of 365 Patients., Claire E Hannah, Bradley A Ford, Jina Chung, Dilek Ince, Karolyn A Wanat May 2020

Characteristics Of Nontuberculous Mycobacterial Infections At A Midwestern Tertiary Hospital: A Retrospective Study Of 365 Patients., Claire E Hannah, Bradley A Ford, Jina Chung, Dilek Ince, Karolyn A Wanat

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: The prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease.

Methods: We conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, …


Peptic Ulcer Perforation After Cesarean Section; Case Series And Literature Review, Mahboobeh Shirazi, Mehnoosh Tork Zaban, Sriharsha Gummadi, Marjan Ghaemi May 2020

Peptic Ulcer Perforation After Cesarean Section; Case Series And Literature Review, Mahboobeh Shirazi, Mehnoosh Tork Zaban, Sriharsha Gummadi, Marjan Ghaemi

Department of Radiology Faculty Papers

BACKGROUND: Peptic ulcer perforation in the early post-cesarean period is rare but may result in maternal mortality.

CASE PRESENTATION: Four cases of post-cesarean peptic ulcer perforation are presented. In all four patients, presentations include peritoneal signs such as acute abdominal pain and progressive distention, hemodynamic instability and intraperitoneal free fluid by ultrasound. Laparotomy and repair were done in all 4 cases. There were 2 maternal deaths. We also have reviewed English literature for the similar cases reported from 1940 to March 2019.

CONCLUSION: New onset tachycardia, abdominal pain and progressive distension after cesarean section without congruent changes in hemoglobin should …


Dosing Common Medications In Hospitalized Pediatric Patients With Obesity: A Review, Barbara Ameer, Michael Weintraub May 2020

Dosing Common Medications In Hospitalized Pediatric Patients With Obesity: A Review, Barbara Ameer, Michael Weintraub

Department of Medicine Faculty Papers

Medication management in children and adolescents with obesity is challenging since both developmental and pathophysiologic changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics, and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 U.S. medical centers. A PubMed search revealed 33 studies providing pharmacokinetic and/or effectiveness data for 23% (16/70) of medications, 44% of which have just one study and can be considered exploratory. This …


Adiponectin Inhibits Cardiac Arrest/Cardiopulmonary Resuscitation‑Induced Apoptosis In Brain By Increasing Autophagy Involved In Adipor1‑Ampk Signaling., Yarong He, Bofu Liu, Peng Yao, Yuming Shao, Yanwei Cheng, Jie Zhao, Jiang Wu, Zhi Wei Zhao, Wen Huang, Theodore A. Christopher, Bernard Lopez, Xin-Liang Ma, Yu Cao May 2020

Adiponectin Inhibits Cardiac Arrest/Cardiopulmonary Resuscitation‑Induced Apoptosis In Brain By Increasing Autophagy Involved In Adipor1‑Ampk Signaling., Yarong He, Bofu Liu, Peng Yao, Yuming Shao, Yanwei Cheng, Jie Zhao, Jiang Wu, Zhi Wei Zhao, Wen Huang, Theodore A. Christopher, Bernard Lopez, Xin-Liang Ma, Yu Cao

Department of Emergency Medicine Faculty Papers

Emerging evidence suggests that both apoptosis and autophagy contribute to global cerebral ischemia-reperfusion (GCIR)-induced neuronal death, which results from cardiac arrest (CA). However, the mechanism of how GCIR may affect the balance between apoptosis and autophagy resulting from CA remains to be elucidated. Additionally, the role of adiponectin (APN) in reversing the apoptosis and autophagy induced by GCIR following cardiac arrest-cardiopulmonary resuscitation (CA-C PR) is unclear. Thus, the aim of the present study was to investigate how GCIR affect the apoptosis and autophagy in response to CA and to clarify whether APN may alter the apoptosis and autophagy of neuronal …


The 2019-2020 Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2) Pandemic: A Joint American College Of Academic International Medicine-World Academic Council Of Emergency Medicine Multidisciplinary Covid-19 Working Group Consensus Paper., Stanislaw P. Stawicki, Rebecca Jeanmonod, Andrew C. Miller, Lorenzo Paladino, David F. Gaieski, Anna Q. Yaffee, Annelies De Wulf, Joydeep Grover, Thomas J. Papadimos, Christina Bloem, Sagar C. Galwankar, Vivek Chauhan, Michael S. Firstenberg, Salvatore Di Somma, Donald Jeanmonod, Sona M. Garg, Veronica Tucci, Harry L. Anderson, Lateef Fatimah, Tamara J. Worlton, Siddharth P Dubhashi, Krystal S. Glaze, Sagar Sinha, Ijeoma Nnodim Opara, Vikas Yellapu, Dhanashree Kelkar, Ayman El-Menyar, Vimal Krishnan, S. Venkataramanaiah, Yan Leyfman, Hassan Ali Saoud Al Thani, Prabath Wb Nanayakkara, Sudip Nanda, Eric Cioè-Peña, Indrani Sardesai, Shruti Chandra, Aruna Munasinghe, Vibha Dutta, Silvana Teixeira Dal Ponte, Ricardo Izurieta, Juan A. Asensio, Manish Garg May 2020

The 2019-2020 Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2) Pandemic: A Joint American College Of Academic International Medicine-World Academic Council Of Emergency Medicine Multidisciplinary Covid-19 Working Group Consensus Paper., Stanislaw P. Stawicki, Rebecca Jeanmonod, Andrew C. Miller, Lorenzo Paladino, David F. Gaieski, Anna Q. Yaffee, Annelies De Wulf, Joydeep Grover, Thomas J. Papadimos, Christina Bloem, Sagar C. Galwankar, Vivek Chauhan, Michael S. Firstenberg, Salvatore Di Somma, Donald Jeanmonod, Sona M. Garg, Veronica Tucci, Harry L. Anderson, Lateef Fatimah, Tamara J. Worlton, Siddharth P Dubhashi, Krystal S. Glaze, Sagar Sinha, Ijeoma Nnodim Opara, Vikas Yellapu, Dhanashree Kelkar, Ayman El-Menyar, Vimal Krishnan, S. Venkataramanaiah, Yan Leyfman, Hassan Ali Saoud Al Thani, Prabath Wb Nanayakkara, Sudip Nanda, Eric Cioè-Peña, Indrani Sardesai, Shruti Chandra, Aruna Munasinghe, Vibha Dutta, Silvana Teixeira Dal Ponte, Ricardo Izurieta, Juan A. Asensio, Manish Garg

Department of Emergency Medicine Faculty Papers

What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel Betacoronavirus, was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this …


A Rare Association Of Takotsubo Cardiomyopathy With Neuroleptic Malignant Syndrome, Waqas Ullah, Muhammad Arslan Cheema, Ammar Ashfaq, Maryam Mukhtar, Zain Ali, Mamoon Ur Rashid, Vincent Figueredo May 2020

A Rare Association Of Takotsubo Cardiomyopathy With Neuroleptic Malignant Syndrome, Waqas Ullah, Muhammad Arslan Cheema, Ammar Ashfaq, Maryam Mukhtar, Zain Ali, Mamoon Ur Rashid, Vincent Figueredo

Abington Jefferson Health Papers

Neuroleptic malignant syndrome is a potentially fatal neurological condition secondary toantipsychotic medication. It is characterized by distinctive clinical findings and autonomicdisturbances. NMS has not been associated with Takotsubo cardiomyopathy (TCM).

TCM is an abnormal response to physiological stressors resulting from the autonomicabnormalities which at times can mimic myocardial infarction (MI). We present a unique caseof a 54-year-old female with bipolar disease presenting with lithium and haloperidol-inducedNMS complicated by TCM. The purpose of this case is to make clinicians aware of this rareassociation.


Non-Obstetrical Robotic-Assisted Laparoscopic Surgery In Pregnancy: A Systematic Literature Review., Courtney Capella, Joseph Godovchik, Thenappan Chandrasekar, Huda B. Al-Kouatly May 2020

Non-Obstetrical Robotic-Assisted Laparoscopic Surgery In Pregnancy: A Systematic Literature Review., Courtney Capella, Joseph Godovchik, Thenappan Chandrasekar, Huda B. Al-Kouatly

Department of Urology Faculty Papers

Urologic and gynecologic surgeons are the top utilizers of robotic surgery; however, non-obstetrical robotic-assisted laparoscopic surgery (RALS) in pregnant patients is infrequent. A systematic literature review was performed to ascertain the frequency, indication and complications of RALS in pregnancy. Results showed thirty-eight pregnancies from eleven publications between 2008-2020. Five cases were for urologic indication and thirty-three for gynecologic indication. Minimal surgical alterations were required. Although no adverse maternal-fetal outcomes were reported, there are not enough cases published to determine safety. This review demonstrates the feasibility of RALS for the pregnant population in the hands of competent robotic surgeons.


Global Kidney Exchange Should Expand Wisely., Alvin E Roth, Ignazio R. Marino, Obi Ekwenna, Ty B Dunn, Siegfredo R Paloyo, Miguel Tan, Ricardo Correa-Rotter, Christian S Kuhr, Christopher L Marsh, Jorge Ortiz, Giuliano Testa, Puneet Sindhwani, Dorry L Segev, Jeffrey Rogers, Jeffrey D Punch, Rachel C Forbes, Michael A Zimmerman, Matthew J Ellis, Aparna Rege, Laura Basagoitia, Kimberly D Krawiec, Michael A Rees May 2020

Global Kidney Exchange Should Expand Wisely., Alvin E Roth, Ignazio R. Marino, Obi Ekwenna, Ty B Dunn, Siegfredo R Paloyo, Miguel Tan, Ricardo Correa-Rotter, Christian S Kuhr, Christopher L Marsh, Jorge Ortiz, Giuliano Testa, Puneet Sindhwani, Dorry L Segev, Jeffrey Rogers, Jeffrey D Punch, Rachel C Forbes, Michael A Zimmerman, Matthew J Ellis, Aparna Rege, Laura Basagoitia, Kimberly D Krawiec, Michael A Rees

Department of Surgery Faculty Papers

We read with great interest and appreciation the careful consideration and analysis by Ambagtsheer et al. of the most critical ethical objections to Global Kidney Exchange (GKE). Ambagtsheer et al. conclude that implementation of GKE is a means to increase access to transplantation ethically and effectively.


Zinc Finger Rna-Binding Protein Zn72d Regulates Adar-Mediated Rna Editing In Neurons., Anne L Sapiro, Emily C Freund, Lucas Restrepo, Huan-Huan Qiao, Amruta Bhate, Qin Li, Jian-Quan Ni, Timothy J Mosca, Jin Billy Li May 2020

Zinc Finger Rna-Binding Protein Zn72d Regulates Adar-Mediated Rna Editing In Neurons., Anne L Sapiro, Emily C Freund, Lucas Restrepo, Huan-Huan Qiao, Amruta Bhate, Qin Li, Jian-Quan Ni, Timothy J Mosca, Jin Billy Li

Department of Neurology Faculty Papers

Adenosine-to-inosine RNA editing, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, alters RNA sequences from those encoded by DNA. These editing events are dynamically regulated, but few trans regulators of ADARs are known in vivo. Here, we screen RNA-binding proteins for roles in editing regulation with knockdown experiments in the Drosophila brain. We identify zinc-finger protein at 72D (Zn72D) as a regulator of editing levels at a majority of editing sites in the brain. Zn72D both regulates ADAR protein levels and interacts with ADAR in an RNA-dependent fashion, and similar to ADAR, Zn72D is necessary to maintain proper neuromuscular …


Functionally Distinct High And Low Theta Oscillations In The Human Hippocampus., Abhinav Goyal, Jonathan Miller, Salman E Qasim, Andrew J Watrous, Honghui Zhang, Joel M Stein, Cory S Inman, Robert E Gross, Jon T Willie, Bradley Lega, Jui-Jui Lin, Ashwini Sharan, Chengyuan Wu, Michael R Sperling, Sameer A Sheth, Guy M Mckhann, Elliot H Smith, Catherine Schevon, Joshua Jacobs May 2020

Functionally Distinct High And Low Theta Oscillations In The Human Hippocampus., Abhinav Goyal, Jonathan Miller, Salman E Qasim, Andrew J Watrous, Honghui Zhang, Joel M Stein, Cory S Inman, Robert E Gross, Jon T Willie, Bradley Lega, Jui-Jui Lin, Ashwini Sharan, Chengyuan Wu, Michael R Sperling, Sameer A Sheth, Guy M Mckhann, Elliot H Smith, Catherine Schevon, Joshua Jacobs

Department of Neurosurgery Faculty Papers

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4-10 Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta's function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior-posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus …


Twice-Daily Doravirine Overcomes The Interaction Effect From Once-Weekly Rifapentine And Isoniazid In Healthy Volunteers., Edwin Lam, Joseph Schaefer, Richard Zheng, Tingting Zhan, Walter K. Kraft May 2020

Twice-Daily Doravirine Overcomes The Interaction Effect From Once-Weekly Rifapentine And Isoniazid In Healthy Volunteers., Edwin Lam, Joseph Schaefer, Richard Zheng, Tingting Zhan, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Doravirine (DOR) is a non‐nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus‐1 (HIV‐1). Its use in combination with rifapentine (RPT), an anti‐tuberculosis antibiotic, may reduce the exposure of DOR compromising viral suppression in those living with HIV‐1 co‐infected with tuberculosis. We conducted a prospective, phase I, open label, two‐period, fixed sequence, drug interaction study to evaluate the effect of once‐weekly RPT and isoniazid (INH) on the pharmacokinetics of DOR in healthy volunteers. DOR 100 mg was administered alone twice‐daily for 4 days in period 1. In period 2, once‐weekly RPT+INH was co‐administered with multiple doses of …


Cirrhosis For The Pcp, Krys Foster, Md, Mph May 2020

Cirrhosis For The Pcp, Krys Foster, Md, Mph

Department of Family & Community Medicine Presentations and Grand Rounds

Objectives:

  • Understand the morbidity and mortality associated with Cirrhosis in the United States
  • Recognize etiologies and clinical presentation of cirrhosis
  • Identify decompensated cirrhosis and approaches to treatment and monitoring

Agenda

  • Definition and Epidemiology
  • Etiologies
  • Clinical Presentation
  • Diagnosis and Evaluation/Classification
  • Management of Compensated Cirrhosis
  • Decompensated Cirrhosis & Complications
  • ○ Portal Hypertension ○ Varices ○ Ascites ○ SBP ○ Hepatorenal Syndrome ○ Hepatic Encephalopathy
  • Secondary Prevention and Long Term Management
  • Conclusions


Vaccines, Children, And The Public Health Trust, Christopher Chambers, Md May 2020

Vaccines, Children, And The Public Health Trust, Christopher Chambers, Md

Department of Family & Community Medicine Presentations and Grand Rounds

Objectives

  1. Review the impact of immunizations on the public health over the past 50 years.
  2. Childhood Vaccines Now
  3. Describe the challenges associated with trying to eliminate “immunizable” diseases. Examples: Invasive Pneumoccal Disease, Neisseria meningitis
  4. The Future


Accelerating Primary Care Transformation At Jefferson (Jeffapct): Reflections From A Five- Year Hrsa Grant, Christine A. Arenson, Md, Amy Cunningham, Phd, Mph, Samantha Kelly, Ma, Randa Sifri, Md May 2020

Accelerating Primary Care Transformation At Jefferson (Jeffapct): Reflections From A Five- Year Hrsa Grant, Christine A. Arenson, Md, Amy Cunningham, Phd, Mph, Samantha Kelly, Ma, Randa Sifri, Md

Department of Family & Community Medicine Presentations and Grand Rounds

JeffAPCT Overview

Five year HRSA-funded grant (7/1/15-6/30/20)

Leadership team from Family Medicine, Internal Medicine, Physician Assistant Program

  • Objective 1: To improve/ expand primary care and population health curriculum across the continuum of primary care providers and trainees (students, residents, and practitioners)
  • Objective 2: To create an enhanced, sustainable model of primary care physician faculty development for PCMH Transformation
  • Objective 3: To create a new, sustainable model of faculty development for community-based primary care preceptors (MD/DO, PA, NP, others)


A Rare Case Of Coronary Artery Thrombosis In A Patient With Recently Diagnosed Giant Cell Arteritis: Is Anticardiolipin Antibody Involved?, Khine S. Shan, Qian Zhang, Sharmila Bisaria, Anubha Tewary May 2020

A Rare Case Of Coronary Artery Thrombosis In A Patient With Recently Diagnosed Giant Cell Arteritis: Is Anticardiolipin Antibody Involved?, Khine S. Shan, Qian Zhang, Sharmila Bisaria, Anubha Tewary

Abington Jefferson Health Papers

Giant cell arteritis (GCA) is an immune-mediated systemic inflammation of large-sized arteries that predominantly affects elderly women. It may be considered as one of the risk factors for acute coronary syndrome (ACS). Moreover, patients with GCA may have increased anticardiolipin antibodies (aCL). However, its relationship with antiphospholipid syndrome (APS) is not clear. We present a case of a unique presentation of GCA with a connection to both ACS and APS. A 76-year-old woman who initially presented to the hospital with a chief complaint of intermittent unilateral headache, blurry vision along with transient aphasia was found to have a biopsy confirmed …


A Rare Presentation Of Coronavirus Disease 2019 (Covid-19) Induced Viral Myositis With Subsequent Rhabdomyolysis., Qian Zhang, Khine S. Shan, Artem Minalyan, Conor O'Sullivan, Travis Nace May 2020

A Rare Presentation Of Coronavirus Disease 2019 (Covid-19) Induced Viral Myositis With Subsequent Rhabdomyolysis., Qian Zhang, Khine S. Shan, Artem Minalyan, Conor O'Sullivan, Travis Nace

Abington Jefferson Health Papers

A 38-year-old gentleman with no significant past medical history but had recent COVID-19 exposure presented to the hospital with the chief complaints of fever, shortness of breath, and generalized myalgia. He was unfortunately found to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Laboratory findings showed creatine kinase (CK) >42,670 U/L along with elevated inflammatory markers and unremarkable creatinine, cardiac troponin level. The cause of his rhabdomyolysis was discovered to be due to COVID-19 as he had no evidence of other viral infections, strenuous exercise, seizure, or other nontraumatic exertional etiologies. He received aggressive fluid resuscitation while we trended …


Differences In Brain Morphometry Associated With Creative Performance In High- And Average-Creative Achievers., Evangelia G Chrysikou, Christopher Wertz, David B Yaden, Scott Barry Kaufman, Donna Bacon, Nancy Wintering, Rex E Jung, Andrew B. Newberg, Md May 2020

Differences In Brain Morphometry Associated With Creative Performance In High- And Average-Creative Achievers., Evangelia G Chrysikou, Christopher Wertz, David B Yaden, Scott Barry Kaufman, Donna Bacon, Nancy Wintering, Rex E Jung, Andrew B. Newberg, Md

Department of Medicine Faculty Papers

Nearly everyone has the ability for creative thought. Yet, certain individuals create works that propel their fields, challenge paradigms, and advance the world. What are the neurobiological factors that might underlie such prominent creative achievement? In this study, we focus on morphometric differences in brain structure between high creative achievers from diverse fields of expertise and a 'smart' comparison group of age-, intelligence-, and education-matched average creative achievers. Participants underwent a high-resolution structural brain imaging scan and completed a series of intelligence, creative thinking, personality, and creative achievement measures. We examined whether high and average creative achievers could be distinguished …


Diurnal Patterns Of Gene Expression In The Dorsal Vagal Complex And The Central Nucleus Of The Amygdala - Non-Rhythm-Generating Brain Regions, Mary M Staehle, Sean O'Sullivan, Rajanikanth Vadigepalli, Kate F Kernan, Gregory E Gonye, Babatunde A Ogunnaike, James S. Schwaber May 2020

Diurnal Patterns Of Gene Expression In The Dorsal Vagal Complex And The Central Nucleus Of The Amygdala - Non-Rhythm-Generating Brain Regions, Mary M Staehle, Sean O'Sullivan, Rajanikanth Vadigepalli, Kate F Kernan, Gregory E Gonye, Babatunde A Ogunnaike, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Genes that establish the circadian clock have differential expression with respect to solar time in central and peripheral tissues. Here, we find circadian-time-induced differential expression in a large number of genes not associated with circadian rhythms in two brain regions lacking overt circadian function: the dorsal vagal complex (DVC) and the central nucleus of the amygdala (CeA). These regions primarily engage in autonomic, homeostatic, and emotional regulation. However, we find striking diurnal shifts in gene expression in these regions of male Sprague Dawley rats with no obvious patterns that could be attributed to function or region. These findings have implications …


The Short Variant Of Optic Atrophy 1 (Opa1) Improves Cell Survival Under Oxidative Stress., Hakjoo Lee, Sylvia B Smith, Shey-Shing Sheu, Yisang Yoon May 2020

The Short Variant Of Optic Atrophy 1 (Opa1) Improves Cell Survival Under Oxidative Stress., Hakjoo Lee, Sylvia B Smith, Shey-Shing Sheu, Yisang Yoon

Center for Translational Medicine Faculty Papers

Optic atrophy 1 (OPA1) is a dynamin protein that mediates mitochondrial fusion at the inner membrane. OPA1 is also necessary for maintaining the cristae and thus essential for supporting cellular energetics. OPA1 exists as membrane-anchored long form (L-OPA1) and short form (S-OPA1) that lacks the transmembrane region and is generated by cleavage of L-OPA1. Mitochondrial dysfunction and cellular stresses activate the inner membrane-associated zinc metallopeptidase OMA1 that cleaves L-OPA1, causing S-OPA1 accumulation. The prevailing notion has been that L-OPA1 is the functional form, whereas S-OPA1 is an inactive cleavage product in mammals, and that stress-induced OPA1 cleavage causes mitochondrial fragmentation …


Endorepellin Evokes An Angiostatic Stress Signaling Cascade In Endothelial Cells., Aastha Kapoor, Carolyn G Chen, Renato V Iozzo May 2020

Endorepellin Evokes An Angiostatic Stress Signaling Cascade In Endothelial Cells., Aastha Kapoor, Carolyn G Chen, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan perlecan, influences various signaling pathways in endothelial cells by binding to VEGFR2. In this study, we discovered that soluble endorepellin activates the canonical stress signaling pathway consisting of PERK, eIF2α, ATF4, and GADD45α. Specifically, endorepellin evoked transient activation of VEGFR2, which, in turn, phosphorylated PERK at Thr980 Subsequently, PERK phosphorylated eIF2α at Ser51, upregulating its downstream effector proteins ATF4 and GADD45α. RNAi-mediated knockdown of PERK or eIF2α abrogated the endorepellin-mediated up-regulation of GADD45α, the ultimate effector protein of this stress signaling cascade. To functionally validate these findings, we utilized an ex …


Synaptic Dysfunction Induced By Glycine-Alanine Dipeptides In C9orf72-Als/Ftd Is Rescued By Sv2 Replenishment., Brigid K Jensen, Martin H Schuldi, Kevin Mcavoy, Katelyn A Russell, Ashley Boehringer, Bridget M Curran, Karthik Krishnamurthy, Xinmei Wen, Thomas Westergard, Le Ma, Aaron R. Haeusler, Dieter Edbauer, Piera Pasinelli, Davide Trotti May 2020

Synaptic Dysfunction Induced By Glycine-Alanine Dipeptides In C9orf72-Als/Ftd Is Rescued By Sv2 Replenishment., Brigid K Jensen, Martin H Schuldi, Kevin Mcavoy, Katelyn A Russell, Ashley Boehringer, Bridget M Curran, Karthik Krishnamurthy, Xinmei Wen, Thomas Westergard, Le Ma, Aaron R. Haeusler, Dieter Edbauer, Piera Pasinelli, Davide Trotti

Department of Neuroscience Faculty Papers

The most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an intronic hexanucleotide repeat expansion in the C9orf72 gene. In disease, RNA transcripts containing this expanded region undergo repeat-associated non-AUG translation to produce dipeptide repeat proteins (DPRs), which are detected in brain and spinal cord of patients and are neurotoxic both in vitro and in vivo paradigms. We reveal here a novel pathogenic mechanism for the most abundantly detected DPR in ALS/FTD autopsy tissues, poly-glycine-alanine (GA). Previously, we showed motor dysfunction in a GA mouse model without loss of motor neurons. Here, we demonstrate that mobile …


Goals Of Care 101, Alexandra Evans, Do, Adam Pennarola, Md, Elham Siddiqui, Md May 2020

Goals Of Care 101, Alexandra Evans, Do, Adam Pennarola, Md, Elham Siddiqui, Md

Department of Family & Community Medicine Presentations and Grand Rounds

Hospice and Palliative Medicine - Alexandra Evans, DO

Approaching Goals of Care in the Outpatient World - Elham Siddiqui, MD

Inpatient Goals of Care Discussion - Adam Pennarola, MD


Nk Cell-Derived Gm-Csf Potentiates Inflammatory Arthritis And Is Negatively Regulated By Cis, Cynthia Louis, Fernando Souza-Fonseca-Guimaraes, Yuyan Yang, Damian D'Silva, Tobias Kratina, Laura Dagley, Soroor Hediyeh-Zadeh, Jai Rautela, Seth Lucian Masters, Melissa J Davis, Jeffrey J Babon, Bogoljub Ciric, Eric Vivier, Warren S Alexander, Nicholas D Huntington, Ian P Wicks May 2020

Nk Cell-Derived Gm-Csf Potentiates Inflammatory Arthritis And Is Negatively Regulated By Cis, Cynthia Louis, Fernando Souza-Fonseca-Guimaraes, Yuyan Yang, Damian D'Silva, Tobias Kratina, Laura Dagley, Soroor Hediyeh-Zadeh, Jai Rautela, Seth Lucian Masters, Melissa J Davis, Jeffrey J Babon, Bogoljub Ciric, Eric Vivier, Warren S Alexander, Nicholas D Huntington, Ian P Wicks

Department of Neurology Faculty Papers

Despite increasing recognition of the importance of GM-CSF in autoimmune disease, it remains unclear how GM-CSF is regulated at sites of tissue inflammation. Using GM-CSF fate reporter mice, we show that synovial NK cells produce GM-CSF in autoantibody-mediated inflammatory arthritis. Synovial NK cells promote a neutrophilic inflammatory cell infiltrate, and persistent arthritis, via GM-CSF production, as deletion of NK cells, or specific ablation of GM-CSF production in NK cells, abrogated disease. Synovial NK cell production of GM-CSF is IL-18–dependent. Furthermore, we show that cytokine-inducible SH2-containing protein (CIS) is crucial in limiting GM-CSF signaling not only during inflammatory arthritis but also …


Apc-Β-Catenin-Tcf Signaling Silences The Intestinal Guanylin-Gucy2c Tumor Suppressor Axis., Erik S Blomain, Jeffrey A Rappaport, Amanda M Pattison, Babar Bashir, Ellen Caparosa, Jonathan Stem, Adam E Snook, Scott A Waldman May 2020

Apc-Β-Catenin-Tcf Signaling Silences The Intestinal Guanylin-Gucy2c Tumor Suppressor Axis., Erik S Blomain, Jeffrey A Rappaport, Amanda M Pattison, Babar Bashir, Ellen Caparosa, Jonathan Stem, Adam E Snook, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation …


What’S The Word? Defining Community Pharmacy Interventions, Elizabeth Laughlin, Bsps, Danielle C. Mayer, Pharmd, Bcacp, Sarah Lynch, Pharmd, Bcacp May 2020

What’S The Word? Defining Community Pharmacy Interventions, Elizabeth Laughlin, Bsps, Danielle C. Mayer, Pharmd, Bcacp, Sarah Lynch, Pharmd, Bcacp

College of Pharmacy Posters

Primary Objective: Determine whether student pharmacists & licensed pharmacists are consistently able to categorize interventions

Secondary Objective: Evaluate trends in themes for situations that are not easily categorized


Prospective Study Of Military Special Operations Medical Personnel And Lower Extremity Fracture Immobilization In An Austere Environment, Kevin Martin, Trevor Mcbride, Alicia Unangst, Jaime Chisholm May 2020

Prospective Study Of Military Special Operations Medical Personnel And Lower Extremity Fracture Immobilization In An Austere Environment, Kevin Martin, Trevor Mcbride, Alicia Unangst, Jaime Chisholm

Department of Orthopaedic Surgery Faculty Papers

Background: Austere fracture immobilization equipment and techniques are often overlooked, with few studies critically evaluating the process. The purpose of this study was to evaluate current austere splinting techniques and equipment used for lower extremity fractures while field testing a new 1-step spray-on foam splint.

Methods: This is a prospective analysis of austere splinting techniques. A cadaveric model with a distal third tibia-fibula fracture was used for testing. The specimens were placed in an austere environment and participants immobilized the injury with standard equipment (structural aluminum malleable [SAM] splint, 6-in. ACE wrap) while being critically evaluated. The specimens were also …


Anosmia And Ageusia As The Only Indicators Of Coronavirus Disease 2019 (Covid-19), Qian Zhang, Khine S. Shan, Shahrzad Abdollahi, Travis C. Nace May 2020

Anosmia And Ageusia As The Only Indicators Of Coronavirus Disease 2019 (Covid-19), Qian Zhang, Khine S. Shan, Shahrzad Abdollahi, Travis C. Nace

Abington Jefferson Health Papers

The patient is a 60-year-old woman with a history of vertigo and seasonal allergies who presented to the hospital with the chief complaint of headache. Radiological findings were negative for intracranial abnormalities. The headache was due to trigeminal neuralgia. She had concurrent complaints of anosmia and ageusia without fever, respiratory symptoms, or obvious risk factors. However, it was determined to test the patient for coronavirus disease 2019 (COVID-19) infection despite extremely low clinical suspicion. Unfortunately, she was found to be COVID-19 positive after she was discharged from the hospital while she remained asymptomatic. There is currently a lack of published …


Perceptions Of Risk For Stress Fractures: A Qualitative Study Of Female Runners With And Without Stress Fracture Histories., Therese E Johnston, Jeremy Close, Phil Jamora, Susan F Wainwright May 2020

Perceptions Of Risk For Stress Fractures: A Qualitative Study Of Female Runners With And Without Stress Fracture Histories., Therese E Johnston, Jeremy Close, Phil Jamora, Susan F Wainwright

Department of Physical Therapy Faculty Papers

OBJECTIVES: To gain insight into perceived factors related to bone health and stress fracture (SF) prevention for female runners and to understand their experiences within the medical community.

DESIGN: Cohort qualitative study.

SETTING: University health system.

PARTICIPANTS: Forty female runners, 20 who had SF histories and 20 age-and-running-distance matched women without SF.

MAIN OUTCOME MEASURES: Women participated in audiotaped qualitative semi-structured interviews. For women with a SF history, questions sought their perspectives on factors that they felt contributed to SF, experiences with the medical community, and changes made post SF. For women without a SF history, questions sought perspectives on …


Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo May 2020

Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion …