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An Osteocalcin-Deficient Mouse Strain Without Endocrine Abnormalities, Cassandra R. Diegel, Steven Hann, Ugar M. Ayturk, Jennifer C. W. Hu, Kyungeun Lim, Casey J. Droscha, Zachary B. Madaj, Gabrielle E. Foxa, Isaac Izaguirre, Vai Vivarium And Transgenics Core, Noorulain Paracha, Bohdan Pidhaynyy, Terry L. Dowd, Alexandra G. Robling, Matthew L. Warman, Bart O. Williams May 2020

An Osteocalcin-Deficient Mouse Strain Without Endocrine Abnormalities, Cassandra R. Diegel, Steven Hann, Ugar M. Ayturk, Jennifer C. W. Hu, Kyungeun Lim, Casey J. Droscha, Zachary B. Madaj, Gabrielle E. Foxa, Isaac Izaguirre, Vai Vivarium And Transgenics Core, Noorulain Paracha, Bohdan Pidhaynyy, Terry L. Dowd, Alexandra G. Robling, Matthew L. Warman, Bart O. Williams

Publications and Research

Osteocalcin (OCN), the most abundant noncollagenous protein in the bone matrix, is reported to be a bone-derived endocrine hormone with wide-ranging effects on many aspects of physiology, including glucose metabolism and male fertility. Many of these observations were made using an OCN-deficient mouse allele (Osc– ) in which the 2 OCN-encoding genes in mice, Bglap and Bglap2, were deleted in ES cells by homologous recombination. Here we describe mice with a new Bglap and Bglap2 double-knockout (dko) allele (Bglap/2p.Pro25fs17Ter) that was generated by CRISPR/Cas9-mediated gene editing. Mice homozygous for this new allele do not express full-length Bglap or Bglap2 mRNA …


A Rare Case Report And Literature Review Of Anabolic-Androgenic Steroids (Aas)-Induced Acute Myocardial Infarction, Qian Zhang, Khine S. Shan, Ahmad Raza, Neelima Manda, Travis Nace May 2020

A Rare Case Report And Literature Review Of Anabolic-Androgenic Steroids (Aas)-Induced Acute Myocardial Infarction, Qian Zhang, Khine S. Shan, Ahmad Raza, Neelima Manda, Travis Nace

Abington Jefferson Health Papers

Anabolic-androgenic steroids (AAS) are synthetic drugs manufactured to mimic the male sex hormone testosterone [1]. They are usually prescribed for medical conditions including but not limited to impotence in males, endometriosis, hypogonadism, and aplastic anemia [2]. It has also been used historically by athletes and bodybuilders to enhance performance as it can stimulate protein synthesis leading to an increase in muscle size and strength [3]. However, the use of AAS has become a serious global public health dilemma as it has been used widely by the general population to improve physical strength and appearance [1]. In …


A Fatal Case Of Primary Amoebic Meningoencephalitis From Recreational Waters., Edward Hamaty, Saif Faiek, Minesh Nandi, David Stidd, Manish Trivedi, Hari Kandukuri May 2020

A Fatal Case Of Primary Amoebic Meningoencephalitis From Recreational Waters., Edward Hamaty, Saif Faiek, Minesh Nandi, David Stidd, Manish Trivedi, Hari Kandukuri

Department of Neurosurgery Faculty Papers

Background: Naegleria Fowleri is a single-cell, thermophilic amphizoid amoeba, and a rare known causative agent for primary amoebic meningoencephalitis with >97% mortality rate. The amoeba resides in freshwater lakes and ponds but can also survive in inadequately chlorinated pools and recreational waters. The mode of infection includes activities such as diving or jumping into freshwater or submerging the head under the water. Although most commonly seen in the southern United States, it is essential to keep this clinical suspicion in mind regardless of geography, as presenting symptoms can be very similar to classic bacterial meningitis.

Conclusion: As per the CDC, …


Prospective Trial Of Sacroiliac Joint Fusion Using 3d-Printed Triangular Titanium Implants, Vikas Patel, Don Kovalsky, S Craig Meyer, Abhineet Chowdhary, Harry Lockstadt, Fernando Techy, Casey Langel, Robert Limoni, Philip S. Yuan, Andy Kranenburg, Daniel Cher, Gabriel Tender, Travis J. Hillen May 2020

Prospective Trial Of Sacroiliac Joint Fusion Using 3d-Printed Triangular Titanium Implants, Vikas Patel, Don Kovalsky, S Craig Meyer, Abhineet Chowdhary, Harry Lockstadt, Fernando Techy, Casey Langel, Robert Limoni, Philip S. Yuan, Andy Kranenburg, Daniel Cher, Gabriel Tender, Travis J. Hillen

School of Medicine Faculty Publications

Background: Prior trials provide strong evidence supporting minimally invasive sacroiliac joint (SIJ) fusion using triangular titanium implants (TTI) for chronic SIJ dysfunction.

Objective: To assess the safety and effectiveness of SIJF using a 3D-printed TTI.

Methods: Fifty-one subjects with carefully diagnosed SIJ dysfunction underwent SIJF with 3D TTI. Subjects completed pain, disability and quality of life questionnaires at baseline and 3, 6 and 12 months postoperatively. Functional tests were performed in the clinic at each visit. Pelvic CT scans were independently evaluated for radiolucency, bridging bone and other endpoints.

Results: Ninety percent had 12-month follow-up. Dysfunction due to pain (Oswestry …


Nanoparticle-Mediated Drug Delivery For The Treatment Of Cardiovascular Diseases, Rajasekharreddy Pala, Vt Anju, Madhu Dyavaiah, Siddhardha Busi, Surya M. Nauli May 2020

Nanoparticle-Mediated Drug Delivery For The Treatment Of Cardiovascular Diseases, Rajasekharreddy Pala, Vt Anju, Madhu Dyavaiah, Siddhardha Busi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cardiovascular diseases (CVDs) are one of the foremost causes of high morbidity and mortality globally. Preventive, diagnostic, and treatment measures available for CVDs are not very useful, which demands promising alternative methods. Nanoscience and nanotechnology open a new window in the area of CVDs with an opportunity to achieve effective treatment, better prognosis, and less adverse effects on non-target tissues. The application of nanoparticles and nanocarriers in the area of cardiology has gathered much attention due to the properties such as passive and active targeting to the cardiac tissues, improved target specificity, and sensitivity. It has reported that more than …


Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang May 2020

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …


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, …


Regulation Of Myofilament Contractile Function In Human Donor And Failing Hearts, Kerry S. Mcdonald, Laurin M. Hanft, Joel C. Robinett, Maya Guglin, Kenneth S. Campbell May 2020

Regulation Of Myofilament Contractile Function In Human Donor And Failing Hearts, Kerry S. Mcdonald, Laurin M. Hanft, Joel C. Robinett, Maya Guglin, Kenneth S. Campbell

Internal Medicine Faculty Publications

Heart failure (HF) often includes changes in myocardial contractile function. This study addressed the myofibrillar basis for contractile dysfunction in failing human myocardium. Regulation of contractile properties was measured in cardiac myocyte preparations isolated from frozen, left ventricular mid-wall biopsies of donor (n = 7) and failing human hearts (n = 8). Permeabilized cardiac myocyte preparations were attached between a force transducer and a position motor, and both the Ca2+ dependence and sarcomere length (SL) dependence of force, rate of force, loaded shortening, and power output were measured at 15 ± 1°C. The myocyte preparation size was …


The Carpentier-Edwards Classic And Physio Annuloplasty Rings In Repair Of Degenerative Mitral Valve Disease: A Retrospective Study, Abubakari I. Sidiki Md, Alexandr G. Faybushevich Md, Phd, Alexandr N. Lishchuk Md, Phd, Alexandr N. Koltunov Md, Phd, Ekaterina A. Roshchina, Jonas Atulebire Akambase May 2020

The Carpentier-Edwards Classic And Physio Annuloplasty Rings In Repair Of Degenerative Mitral Valve Disease: A Retrospective Study, Abubakari I. Sidiki Md, Alexandr G. Faybushevich Md, Phd, Alexandr N. Lishchuk Md, Phd, Alexandr N. Koltunov Md, Phd, Ekaterina A. Roshchina, Jonas Atulebire Akambase

Journal of the Saudi Heart Association

Objectives. Physio ring (SR) is considered an improved version of the Classic rigid ring (RR). Today, SR is more widely used in mitral valve (MV) repair. We sought to compare the long-term outcomes of repair with RR and SR in degenerative mitral valve disease.

Methods. In a computerized registry of our institution, 306 patients had MV repair with either RR (139 patients) or SR (167 patients) ring between 2005 and 2015. Fifteen of them had concomitant tricuspid valve repair. Ninety-two (30.1%) had Barlow’s disease and 214 (69.9%) had fibroelastic deficiency. The patients had similar demographic and echocardiographic characteristics. …


Anti-Aggregation Effects Of Phenolic Compounds On Α-Synuclein, Kenjiro Ono, Mayumi Tsuji, Tritia R. Yamasaki, Giulio M. Pasinetti May 2020

Anti-Aggregation Effects Of Phenolic Compounds On Α-Synuclein, Kenjiro Ono, Mayumi Tsuji, Tritia R. Yamasaki, Giulio M. Pasinetti

Neurology Faculty Publications

The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson's disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that attenuate αS aggregation and propagation. Based on cumulative evidence that αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies, we and other groups reported that phenolic compounds inhibit αS aggregation including oligomerization, thereby ameliorating αS oligomer-induced cellular and synaptic toxicities. Heterogeneity in gut microbiota may influence the …


Skin And Soft Tissue Infections In The Emergency Department, Nicole Martinez May 2020

Skin And Soft Tissue Infections In The Emergency Department, Nicole Martinez

Dissertations

Background/Purpose: Skin and soft tissue infections (SSTI) represent a diverse group of infections varying in clinical presentation and degree of severity. The International Classification of Diseases codes for patients presenting with cellulitis or abscess account for $5.5 billion in annual health care costs and 1.4% of all hospital admissions nationally. Data are needed to inform admission and management decisions. The purpose of this study is to examine relationships among sociodemographic, physical examination findings, and treatment modality and management in patients with SSTIs.

Theoretical/Conceptual Framework: Web of Causation Theoretical Framework explores multiple causative factors treated with equal prominence, thus …


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.


Ccl2 Overexpression In The Brain Promotes Glial Activation And Accelerates Tau Pathology In A Mouse Model Of Tauopathy, Aurelie Joly-Amado, Jordan Hunter, Zainuddin Quadri, Frank Zamudio, Patricia V. Rocha-Rangel, Deanna Chan, Anisha Kesarwani, Kevin Nash, Daniel C. Lee, Dave Morgan, Marcia N. Gordon, Maj-Linda B. Selenica May 2020

Ccl2 Overexpression In The Brain Promotes Glial Activation And Accelerates Tau Pathology In A Mouse Model Of Tauopathy, Aurelie Joly-Amado, Jordan Hunter, Zainuddin Quadri, Frank Zamudio, Patricia V. Rocha-Rangel, Deanna Chan, Anisha Kesarwani, Kevin Nash, Daniel C. Lee, Dave Morgan, Marcia N. Gordon, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

Innate immune activation is a major contributor to Alzheimer’s Disease (AD) pathophysiology, although the mechanisms involved are poorly understood. Chemokine C-C motif ligand (CCL) 2 is produced by neurons and glial cells and is upregulated in the AD brain. Transgene expression of CCL2 in mouse models of amyloidosis produces microglia-induced amyloid β oligomerization, a strong indication of the role of these activation pathways in the amyloidogenic processes of AD. We have previously shown that CCL2 polarizes microglia in wild type mice. However, how CCL2 signaling contributes to tau pathogenesis remains unknown. To address this question, CCL2 was delivered via recombinant …


Challenges And Special Aspects Of Pulmonary Hypertension In Middle- To Low-Income Regions: Jacc State-Of-The-Art Review, Babar Hasan, Georg Hansmann, Werner Budts, Alexandra Heath, Zahra Hoodbhoy, Zhi-Cheng Jing, Martin Koestenberger, Katharina Meinel, Ana Olga Mocumbi, Ganna D. Radchenko May 2020

Challenges And Special Aspects Of Pulmonary Hypertension In Middle- To Low-Income Regions: Jacc State-Of-The-Art Review, Babar Hasan, Georg Hansmann, Werner Budts, Alexandra Heath, Zahra Hoodbhoy, Zhi-Cheng Jing, Martin Koestenberger, Katharina Meinel, Ana Olga Mocumbi, Ganna D. Radchenko

Department of Paediatrics and Child Health

Challenges and special aspects related to the management and prognosis of pulmonary hypertension (PH) in middle- to low-income regions (MLIRs) range from late presentation to comorbidities, lack of resources and expertise, cost, and rare options of lung transplantation. Expert consensus recommendations addressing the specific challenges for prevention and therapy of PH in MLIRs with limited resources have been lacking. To date, 6 MLIR-PH registries containing mostly adult patients with PH exist. Importantly, the global prevalence of PH is much higher in MLIRs compared with high-income regions: group 2 PH (left heart disease), pulmonary arterial hypertension associated with unrepaired congenital heart …


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 …


Age-Dependent Involvement Of Gut Mast Cells And Histamine In Post-Stroke Inflammation, Maria Pilar Blasco, Anjali Chauhan, Pedram Honarpisheh, Hilda Ahnstedt, John D'Aigle, Arunkumar Ganesan, Sriram Ayyaswamy, Frank Blixt, Susan Venable, Angela Major, David Durgan, Anthony Haag, Julia Kofler, Robert Bryan, Louise D Mccullough, Bhanu Priya Ganesh May 2020

Age-Dependent Involvement Of Gut Mast Cells And Histamine In Post-Stroke Inflammation, Maria Pilar Blasco, Anjali Chauhan, Pedram Honarpisheh, Hilda Ahnstedt, John D'Aigle, Arunkumar Ganesan, Sriram Ayyaswamy, Frank Blixt, Susan Venable, Angela Major, David Durgan, Anthony Haag, Julia Kofler, Robert Bryan, Louise D Mccullough, Bhanu Priya Ganesh

Faculty, Staff and Students Publications

BACKGROUND: Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation, and mast cells residing in the gut are a primary source of histamine.

METHODS: Stroke was induced in male C57BL/6 J mice at 3 months (young) and 20 months (aged) of age. Role of histamine after stroke was examined using young (Yg) and aged (Ag) mice; mice underwent MCAO surgery and were euthanized at 6 h, 24 h, …


Correlations Of Calf Muscle Macrophage Content With Muscle Properties And Walking Performance In Peripheral Artery Disease, Kate Kosmac, Marta Gonzalez-Freire, Mary M. Mcdermott, Sarah H. White, R. Grace Walton, Robert L. Sufit, Lu Tian, Lingyu Li, Melina R. Kibbe, Michael H Criqui, Jack M. Guralnik, Tamar S. Polonsky, Christiaan Leeuwenburgh, Luigi Ferrucci, Charlotte A. Peterson May 2020

Correlations Of Calf Muscle Macrophage Content With Muscle Properties And Walking Performance In Peripheral Artery Disease, Kate Kosmac, Marta Gonzalez-Freire, Mary M. Mcdermott, Sarah H. White, R. Grace Walton, Robert L. Sufit, Lu Tian, Lingyu Li, Melina R. Kibbe, Michael H Criqui, Jack M. Guralnik, Tamar S. Polonsky, Christiaan Leeuwenburgh, Luigi Ferrucci, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background

Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD.

Methods and Results

Macrophages, satellite cells, and extracellular matrix in gastrocnemius muscles from 25 patients with PAD and 7 patients without PAD were quantified using immunohistochemistry. Among patients …


Tfeb Regulates Murine Liver Cell Fate During Development And Regeneration, Nunzia Pastore, Tuong Huynh, Niculin J Herz, Alessia Calcagni', Tiemo J Klisch, Lorenzo Brunetti, Kangho Ho Kim, Marco De Giorgi, Ayrea Hurley, Annamaria Carissimo, Margherita Mutarelli, Niya Aleksieva, Luca D'Orsi, William R Lagor, David D Moore, Carmine Settembre, Milton J Finegold, Stuart J Forbes, Andrea Ballabio May 2020

Tfeb Regulates Murine Liver Cell Fate During Development And Regeneration, Nunzia Pastore, Tuong Huynh, Niculin J Herz, Alessia Calcagni', Tiemo J Klisch, Lorenzo Brunetti, Kangho Ho Kim, Marco De Giorgi, Ayrea Hurley, Annamaria Carissimo, Margherita Mutarelli, Niya Aleksieva, Luca D'Orsi, William R Lagor, David D Moore, Carmine Settembre, Milton J Finegold, Stuart J Forbes, Andrea Ballabio

Faculty, Staff and Students Publications

It is well established that pluripotent stem cells in fetal and postnatal liver (LPCs) can differentiate into both hepatocytes and cholangiocytes. However, the signaling pathways implicated in the differentiation of LPCs are still incompletely understood. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is known to be involved in osteoblast and myeloid differentiation, but its role in lineage commitment in the liver has not been investigated. Here we show that during development and upon regeneration TFEB drives the differentiation status of murine LPCs into the progenitor/cholangiocyte lineage while inhibiting hepatocyte differentiation. Genetic interaction studies show that …


Allosteric Inhibitor Of Β-Catenin Selectively Targets Oncogenic Wnt Signaling In Colon Cancer., Anton Cheltsov, Natsuko Nomura, Venkata Mahidhar Yenugonda, Jatin Roper, Rajesh Mukthavaram, Pengfei Jiang, Nam-Gu Her, Ivan Babic, Santosh Kesari, Elmar Nurmemmedov May 2020

Allosteric Inhibitor Of Β-Catenin Selectively Targets Oncogenic Wnt Signaling In Colon Cancer., Anton Cheltsov, Natsuko Nomura, Venkata Mahidhar Yenugonda, Jatin Roper, Rajesh Mukthavaram, Pengfei Jiang, Nam-Gu Her, Ivan Babic, Santosh Kesari, Elmar Nurmemmedov

Articles, Abstracts, and Reports

Abnormal regulation of β-catenin initiates an oncogenic program that serves as a main driver of many cancers. Albeit challenging, β-catenin is an attractive drug target due to its role in maintenance of cancer stem cells and potential to eliminate cancer relapse. We have identified C2, a novel β-catenin inhibitor, which is a small molecule that binds to a novel allosteric site on the surface of β-catenin. C2 selectively inhibits β-catenin, lowers its cellular load and significantly reduces viability of β-catenin-driven cancer cells. Through direct binding to β-catenin, C2 renders the target inactive that eventually activates proteasome system for its removal. …


Similac Special Care And Elecare Cause Neonatal Gut Injury In Mice, Karishma Rao, Heather L. Menden, Wei Yu, Inamul Haque, Susana Chavez-Bueno, Alain C. Cuna, Shahid Umar, Venkatesh Sampath May 2020

Similac Special Care And Elecare Cause Neonatal Gut Injury In Mice, Karishma Rao, Heather L. Menden, Wei Yu, Inamul Haque, Susana Chavez-Bueno, Alain C. Cuna, Shahid Umar, Venkatesh Sampath

Research Days

No abstract provided.


Proteolysis-Targeting Chimera (Protac) For Targeted Protein Degradation And Cancer Therapy, Xin Li, Yongcheng Song May 2020

Proteolysis-Targeting Chimera (Protac) For Targeted Protein Degradation And Cancer Therapy, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand (mostly small-molecule inhibitor) of the protein of interest (POI) and a covalently linked ligand of an E3 ubiquitin ligase (E3). Upon binding to the POI, the PROTAC can recruit E3 for POI ubiquitination, which is subjected to proteasome-mediated degradation. PROTAC complements nucleic acid-based gene knockdown/out technologies for targeted protein reduction and could mimic pharmacological protein inhibition. To date, PROTACs targeting ~ 50 proteins, many of which are clinically validated drug targets, have been successfully developed with several …


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 …


Safety And Activity Of Varlilumab, A Novel And First-In-Class Agonist Anti-Cd27 Antibody, For Hematologic Malignancies., Stephen M Ansell, Ian Flinn, Matthew H Taylor, Branimir I Sikic, Joshua Brody, John Nemunaitis, Andrew Feldman, Thomas R Hawthorne, Tracey Rawls, Tibor Keler, Michael J Yellin May 2020

Safety And Activity Of Varlilumab, A Novel And First-In-Class Agonist Anti-Cd27 Antibody, For Hematologic Malignancies., Stephen M Ansell, Ian Flinn, Matthew H Taylor, Branimir I Sikic, Joshua Brody, John Nemunaitis, Andrew Feldman, Thomas R Hawthorne, Tracey Rawls, Tibor Keler, Michael J Yellin

Articles, Abstracts, and Reports

CD27, a costimulatory molecule on T cells, induces intracellular signals mediating cellular activation, proliferation, effector function, and cell survival on binding to its ligand, CD70. Varlilumab, a novel, first-in-class, agonist immunoglobulin G1 anti-CD27 antibody, mediates antitumor immunity and direct killing of CD27+ tumor cells in animal models. This first-in-human, dose-escalation, and expansion study evaluated varlilumab in patients with hematologic malignancies. Primary objectives were to assess safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. In a 3 + 3 dose-escalation design, 30 patients with B-cell (n = …


Effects Of Acute Intracranial Pressure Changes On Optic Nerve Head Morphology In Humnans And Pig Model, Sachin Kedar May 2020

Effects Of Acute Intracranial Pressure Changes On Optic Nerve Head Morphology In Humnans And Pig Model, Sachin Kedar

Theses & Dissertations

The optic nerve head (ONH) is located at the interface of intracranial and intraocular compartments. It is comprised of lamina cribrosa (LC), a fenestrated connective tissue tethered to the posterior sclera across the scleral canal. Since LC is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) posteriorly, it is an ideal site for noninvasively detecting intracranial pressure (ICP) fluctuation. We hypothesized that the pressure differential between IOP and ICP across LC, will determine LC position and meridional diameter of scleral canal (also called Bruch’s membrane opening- BMOD). We tested our hypothesis in 19 human subjects undergoing medically necessary …


Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek May 2020

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …


Characterization Of A Plasmid-Based Dna Vaccine For Simian Immunodeficiency Virus, Priya Sanipara May 2020

Characterization Of A Plasmid-Based Dna Vaccine For Simian Immunodeficiency Virus, Priya Sanipara

Honors Theses

Described as one of the world’s worst pandemics, HIV (Human Immunodeficiency Virus) infects millions of people each year and is the cause for AIDS (Acquired Immunodeficiency Syndrome). Despite the development of vaccines for numerous infectious diseases such as polio, small pox, and influenza, a vaccine for HIV remains elusive due to the virus’s high mutation rate and ability to evade the immune system. HIV causes depletion of CD4+ lymphocytes, resulting in a weakened immune system. However, the development of a plasmid-based DNA vaccine approach may help revolutionize vaccine development for HIV due to its ability to confer cellular and humoral …


Correlation Of Inflammation In Arthritis With The Myelination In The Brain, Anna Spears May 2020

Correlation Of Inflammation In Arthritis With The Myelination In The Brain, Anna Spears

Honors Theses

This study was conducted to investigate whether the influence of arthritis has an effect on the cerebral white matter. The project was performed at the South Oxford Campus, where diffusion tensor imaging (DTI) data was obtained from the Nathan Kline Institute-Rockland Sample (NKI- RS). Image processing was conducted using Functional Magnetic Resonance Imaging of Brain Software Library in which we obtained raw data to formulate Apparent Diffusion Coefficient (ADC), Axial Diffusivity (AD), Radial Diffusivity (RD), and Fractional Anisotropy. A one way Analysis of Covariance (ANCOVA) was performed to determine the significant difference between the history of arthritis on each of …


Scald Injury-Induced T Cell Dysfunction Can Be Mitigated By Gr1+ Cell Depletion And Blockage Of Cd47/Cd172a Signaling, Nadine Beckmann, Franziska Huber, Marc Hanschen, Barbara St. Pierre Schneider, Vanessa Nomelli, Charles C. Caldwell May 2020

Scald Injury-Induced T Cell Dysfunction Can Be Mitigated By Gr1+ Cell Depletion And Blockage Of Cd47/Cd172a Signaling, Nadine Beckmann, Franziska Huber, Marc Hanschen, Barbara St. Pierre Schneider, Vanessa Nomelli, Charles C. Caldwell

Nursing Faculty Research

Infection is a common and severe complication of burn injury: Sepsis accounts for 47% of postburn mortality. Burn-induced T cell suppression likely contributes to the increased infection susceptibility in burn patients. However, little is known about the kinetics of T cell dysfunction after burn and its underlying mechanisms. In this study, we show in a murine scald injury model that T cell activation of both CD4+ and CD8+ T cells as well as T cell cytokine production is suppressed acutely and persistently for at least 11 days after burn injury. Purified T cells from scald-injured mice exhibit normal T cell …