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Proteoglycan-4 Regulates Fibroblast To Myofibroblast Transition And Expression Of Fibrotic Genes In The Synovium, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Holly Richendrfer, Tannin A. Schmidt, Khaled A. Elsaid 2020 Chapman University

Proteoglycan-4 Regulates Fibroblast To Myofibroblast Transition And Expression Of Fibrotic Genes In The Synovium, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Holly Richendrfer, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo.

Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or isotype control antibodies and ...


Composite Quantitative Knee Structure Metrics Predict The Development Of Accelerated Knee Osteoarthritis: Data From The Osteoarthritis Initiative, Matthew S. Harkey, Julie E. Davis, Lori Lyn. Price, Robert J. Ward, James W. MacKay, Charles B. Eaton, Grace H. Lo, Mary F. Barbe, Ming Zhang, Jincheng Pang, Alina C. Stout, Bing Lu, Timothy E. McAlindon, Jeffrey B. Driban 2020 University of Massachusetts Medical School

Composite Quantitative Knee Structure Metrics Predict The Development Of Accelerated Knee Osteoarthritis: Data From The Osteoarthritis Initiative, Matthew S. Harkey, Julie E. Davis, Lori Lyn. Price, Robert J. Ward, James W. Mackay, Charles B. Eaton, Grace H. Lo, Mary F. Barbe, Ming Zhang, Jincheng Pang, Alina C. Stout, Bing Lu, Timothy E. Mcalindon, Jeffrey B. Driban

UMass Center for Clinical and Translational Science Supported Publications

BACKGROUND: We aimed to determine if composite structural measures of knee osteoarthritis (KOA) progression on magnetic resonance (MR) imaging can predict the radiographic onset of accelerated knee osteoarthritis.

METHODS: We used data from a nested case-control study among participants from the Osteoarthritis Initiative without radiographic KOA at baseline. Participants were separated into three groups based on radiographic disease progression over 4 years: 1) accelerated (Kellgren-Lawrence grades [KL] 0/1 to 3/4), 2) typical (increase in KL, excluding accelerated osteoarthritis), or 3) no KOA (no change in KL). We assessed tibiofemoral cartilage damage (four regions: medial/lateral tibia/femur), bone ...


Frequency Of Complications Following Spinal Fusion In Children With Cerebral Palsy, Nili S. Amir 2020 University of Massachusetts Medical School

Frequency Of Complications Following Spinal Fusion In Children With Cerebral Palsy, Nili S. Amir

GSBS Dissertations and Theses

Background:

Neuromuscular Scoliosis is a frequent complication of Cerebral Palsy that requires surgical management including spinal fusion. The objective of this observational study was to describe differences in the frequency of postoperative complications in children with Cerebral Palsy following spinal fusion surgery compared to children with Idiopathic Scoliosis.

Methods:

The 2016 Kids’ Inpatient Database was queried to identify pediatric patients (old) with concurrent diagnoses of Cerebral Palsy and Neuromuscular Scoliosis undergoing spinal fusion surgery. Cases were compared to children without Cerebral Palsy and with a diagnosis of Idiopathic Scoliosis undergoing the same procedure. Fitted Poisson regression analysis with robust variance ...


Global Fkrp Registry: Observations In More Than 300 Patients With Limb Girdle Muscular Dystrophy R9, Lindsay B. Murphy, John Herbert Stevenson, Volker Straub 2020 Newcastle University

Global Fkrp Registry: Observations In More Than 300 Patients With Limb Girdle Muscular Dystrophy R9, Lindsay B. Murphy, John Herbert Stevenson, Volker Straub

Open Access Articles

OBJECTIVE: The Global FKRP Registry is a database for individuals with conditions caused by mutations in the Fukutin-Related Protein (FKRP) gene: limb girdle muscular dystrophy R9 (LGMDR9, formerly LGMD2I) and congenital muscular dystrophies MDC1C, Muscle-Eye-Brain Disease and Walker-Warburg Syndrome. The registry seeks to further understand the natural history and prevalence of FKRP-related conditions; aid the rapid identification of eligible patients for clinical studies; and provide a source of information to clinical and academic communities.

METHODS: Registration is patient-initiated through a secure online portal. Data, reported by both patients and their clinicians, include: age of onset, presenting symptoms, family history, motor ...


Assessment Of Intrinsic Hand Neuromuscular Physiology, Philemon Tsang 2020 The University of Western Ontario

Assessment Of Intrinsic Hand Neuromuscular Physiology, Philemon Tsang

Electronic Thesis and Dissertation Repository

Alterations to the peripheral nervous system and neuromuscular physiology may impact hand function in a typical or clinical population, such as individuals with ulnar neuropathy. The mechanisms that influence these positive and negative changes are still not well understood. The three studies within my thesis aim to validate the reliability of decomposition-based quantitative electromyography (DQEMG) measurements and explore the changes in intrinsic hand neuromuscular physiology in a typical aging population and individuals recovering from a surgical intervention for severe ulnar neuropathy.

The purpose of the first study was to determine the test-retest reliability of near-fibre (NF) jiggle, a measure of ...


What Outcomes Matter To Patients After Joint Or Spine Surgery?, Robin R. Whitebird, Leif I. Solberg, Christine K. Norton, Jeanette Y. Ziegenfuss, Stephen E. Asche, Elizabeth S. Grossman 2020 University of St. Thomas

What Outcomes Matter To Patients After Joint Or Spine Surgery?, Robin R. Whitebird, Leif I. Solberg, Christine K. Norton, Jeanette Y. Ziegenfuss, Stephen E. Asche, Elizabeth S. Grossman

Journal of Patient-Centered Research and Reviews

Purpose: Patient-reported outcome measures (PROMs) are increasingly used in clinical care, but there have been few studies of what patients identify as the most important outcomes.

Methods: Semi-structured interviews were conducted with 65 patients undergoing hip or knee replacement, spinal discectomy/laminotomy, or a spinal fusion. Interviews focused on outcomes patients identified as important, perceived usefulness of standardized PROMs measures, and contextual situations important to their care. Data were analyzed using a directed content analysis approach.

Results: Patients identified desired outcomes that were unique and important to them. Their preferred outcomes focused in the areas of freedom from pain, getting ...


A Closer Look At Muscle Breakdown: An Overview Of The Causes, Complications, And Diagnostics Of Rhabdomyolysis, Jamie Holchin 2020 Liberty University

A Closer Look At Muscle Breakdown: An Overview Of The Causes, Complications, And Diagnostics Of Rhabdomyolysis, Jamie Holchin

Senior Honors Theses

Rhabdomyolysis is the rapid breakdown of myocytes in skeletal muscle. This condition can be triggered by a variety of things including crush injury, drugs, prolonged exercise, and venom. Although the causes can vary, the general pathophysiology of rhabdomyolysis is similar. Increased intracellular calcium ion levels instigate the breakdown of cellular and certain organelle membranes of muscle cells. Reactive oxygen species form, ATP is depleted, and the sarcoplasmic reticulum, which regulates muscle contraction, is also damaged. Necrosis ensues, leading to toxic intracellular components spreading throughout the body. Rhabdomyolysis can then lead to several complications including acute renal injury and heart arrhythmias ...


An Ergonomic Assessment Of Healthcare Rehabilitation Workers, William Shepherd, Laramie Locke, Katherine Archibong 2020 Murray State University

An Ergonomic Assessment Of Healthcare Rehabilitation Workers, William Shepherd, Laramie Locke, Katherine Archibong

Scholars Week

Patient handling is a common task within the healthcare industry. Rehabilitation Therapists (RTs) and Rehabilitation Therapist Assistants (RTAs) report a significantly high incidence rate of low-back injuries and other musculoskeletal disorders (MSDs). The purpose of this study was to characterize the ergonomic risks associated with patient transfers and assisted gait therapy. Exposure to ergonomic risk factors were assessed using the Strain Index (SI), Rapid Entire Body Assessment (REBA), and 3-Dimensional Static Strength Prediction Program (3DSSPP). Subjects included three RTs and one RTA at a local assisted living and rehabilitation healthcare facility. Preliminary results indicate a high risk of developing MSDs ...


Cd44 Receptor Mediates Urate Crystal Phagocytosis By Macrophages And Regulates Inflammation In A Murine Peritoneal Model Of Acute Gout, Emira Bousoik, Marwa Qadri, Khaled A. Elsaid 2020 Chapman University

Cd44 Receptor Mediates Urate Crystal Phagocytosis By Macrophages And Regulates Inflammation In A Murine Peritoneal Model Of Acute Gout, Emira Bousoik, Marwa Qadri, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is a chronic arthritis caused by the deposition of poorly soluble monosodium urate monohydrate (MSU) crystals in peripheral joints. Resident macrophages initiate inflammation in response to MSU mediated by NF-κB nuclear translocation and NLRP3 inflammasome activation. We investigated the role of CD44, a transmembrane receptor, in mediating MSU phagocytosis by macrophages. We used an antibody that sheds the extracellular domain (ECD) of CD44 to study the role of the receptor and its associated protein phosphatase 2A (PP2A) in macrophage activation. We also studied the significance of CD44 in mediating MSU inflammation in-vivo. Cd44−/− BMDMs showed reduced MSU phagocytosis, LDH ...


Comparison Of Pre- And Post-Operative Shoulder Muscle Emg Profiles In Reverse Total Shoulder Arthroplasty Patients, Emily Lau, Sreten Franovic, Noah Kuhlmann, Eric C. Makhni MD, Stephanie Muh MD 2020 Henry Ford Health System

Comparison Of Pre- And Post-Operative Shoulder Muscle Emg Profiles In Reverse Total Shoulder Arthroplasty Patients, Emily Lau, Sreten Franovic, Noah Kuhlmann, Eric C. Makhni Md, Stephanie Muh Md

Medical Student Research Symposium

Background: Deltoid muscle function is central in reverse total shoulder arthroplasty (RTSA) function; however, there is limited information available regarding changes in deltoid activity before and after surgery. Few tests exist to evaluate specific muscle metrics pre and post operatively. Surface Electromyographic (EMG) is non-invasive and allows for observation of motions with multifaceted analysis of movement with minimal patient demand. Understanding the changes in shoulder muscle activation, namely in the deltoid, in patients pre and post-RTSA can further advance understanding of the procedure and rehabilitation efforts.

Methods: Nine individuals were recruited for this study: all patients underwent RTSA by a ...


Canine Models Of Inherited Musculoskeletal And Neurodegenerative Diseases, Brett D. Story, Matthew E. Miller, Allison M. Bradbury, Emily D. Million, Dongsheng Duan, Toloo Taghian, Dominik Faissler, Deborah Fernau, Sidney J. Beecy, Heather Gray-Edwards 2020 Auburn University

Canine Models Of Inherited Musculoskeletal And Neurodegenerative Diseases, Brett D. Story, Matthew E. Miller, Allison M. Bradbury, Emily D. Million, Dongsheng Duan, Toloo Taghian, Dominik Faissler, Deborah Fernau, Sidney J. Beecy, Heather Gray-Edwards

Open Access Articles

Mouse models of human disease remain the bread and butter of modern biology and therapeutic discovery. Nonetheless, more often than not mouse models do not reproduce the pathophysiology of the human conditions they are designed to mimic. Naturally occurring large animal models have predominantly been found in companion animals or livestock because of their emotional or economic value to modern society and, unlike mice, often recapitulate the human disease state. In particular, numerous models have been discovered in dogs and have a fundamental role in bridging proof of concept studies in mice to human clinical trials. The present article is ...


Does Dna Methylation Matter In Fshd, Valentina Salsi, Frederique Magdinier, Rossella Ginevra Tupler 2020 University of Modena and Reggio Emilia

Does Dna Methylation Matter In Fshd, Valentina Salsi, Frederique Magdinier, Rossella Ginevra Tupler

Open Access Articles

Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the genetic and epigenetic molecular features of the CpG-rich D4Z4 repeat tandem array at 4q35. Reduced DNA methylation of D4Z4 repeats is considered part of the FSHD mechanism and has been proposed as a reliable marker in the FSHD diagnostic procedure. We considered the assessment of D4Z4 DNA methylation status conducted on distinct cohorts using different methodologies. On the basis of the reported results we conclude that the percentage of DNA methylation detected at D4Z4 does not correlate with the disease status. Overall, data suggest that in the case of FSHD1, D4Z4 ...


Syllabus For Clinical Exercise Physiology (Kine 4700), Phillip Drouet 2020 California State University, San Bernardino

Syllabus For Clinical Exercise Physiology (Kine 4700), Phillip Drouet

Q2S Enhancing Pedagogy

The syllabus has newly developed learning objectives that will prepare students entering the field of clinical exercise physiology. This course will cover the etiology and pathophysiology of many chronic diseases that plague the population. Assessments of chronic diseases include but are not limited to understanding symptomology will also be covered. Due to the limitations in time the most prevalent chronic disease will be covered and students will have to present on a disease that was not presented in class. The practical application portion of this course will take place during a lab section. Here students will have the opportunity to ...


Real-World Outcomes Of Long-Term Prednisone And Deflazacort Use In Patients With Duchenne Muscular Dystrophy: Experience At A Single, Large Care Center, Jessica R. Marden, Jonathan Freimark, Zhiwen Yao, James Signorovitch, Cuixia Tian, Brenda L. Wong 2020 Analysis Group, Inc.

Real-World Outcomes Of Long-Term Prednisone And Deflazacort Use In Patients With Duchenne Muscular Dystrophy: Experience At A Single, Large Care Center, Jessica R. Marden, Jonathan Freimark, Zhiwen Yao, James Signorovitch, Cuixia Tian, Brenda L. Wong

Open Access Articles

Aim: To assess outcomes among patients with Duchenne muscular dystrophy receiving deflazacort or prednisone in real-world practice.

Methods: Clinical data for 435 boys with Duchenne muscular dystrophy from Cincinnati Children's Hospital Medical Center were studied retrospectively using time-to-event and regression analyses.

Results: Median ages at loss of ambulation were 15.6 and 13.5 years among deflazacort- and prednisone-initiated patients, respectively. Deflazacort was also associated with a lower risk of scoliosis and better ambulatory function, greater % lean body mass, shorter stature and lower weight, after adjusting for age and steroid duration. No differences were observed in whole body bone ...


Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer 2020 Arcadia University

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey ...


The Effectiveness Of Cannabidiol In Rheumatic Disease Pain: A Systematic Review, Mary C. Wiczek 2020 Minnesota State University, Mankato

The Effectiveness Of Cannabidiol In Rheumatic Disease Pain: A Systematic Review, Mary C. Wiczek

All Theses, Dissertations, and Other Capstone Projects

Cannabinoids have long been a part of human culture and medicine, and more recently have been rediscovered for their potential use in the management of rheumatic disease pain. The objective of this review was to evaluate the known clinical effectiveness of cannabidiol treatment for rheumatic disease related pain. The legality and current regulation of these products was also reviewed to establish the current status of federal and state rules regarding their clinical use. Basic definitions of the terms used to differentiate cannabidiol from other cannabinoid products was also outlined. A systematic literature search was then conducted to explore the current ...


Electrical Impedance Myography For Reducing Sample Size In Duchenne Muscular Dystrophy Trials, Melanie L. Leitner, Kush Kapur, Basil T. Darras, Michele Yang, Brenda Wong, Laura Dalle Pazze, Julaine Florence, Martin Buck, Laura Freedman, Jose Bohorquez, Seward Rutkove, Craig Zaidman 2019 Accelerating NeuroVentures, LLC

Electrical Impedance Myography For Reducing Sample Size In Duchenne Muscular Dystrophy Trials, Melanie L. Leitner, Kush Kapur, Basil T. Darras, Michele Yang, Brenda Wong, Laura Dalle Pazze, Julaine Florence, Martin Buck, Laura Freedman, Jose Bohorquez, Seward Rutkove, Craig Zaidman

Open Access Articles

OBJECTIVE: To evaluate the sensitivity of electrical impedance myography (EIM) to disease progression in both ambulatory and non-ambulatory boys with DMD.

METHODS AND PARTICIPANTS: A non-blinded, longitudinal cohort study of 29 ambulatory and 15 non-ambulatory boys with DMD and age-similar healthy boys. Subjects were followed for up to 1 year and assessed using the Myolex((R)) mView(TM) EIM system as part of a multicenter study.

RESULTS: In the ambulatory group, EIM 100 kHz resistance values showed significant change compared to the healthy boys. For example, in lower extremity muscles, the average change in EIM 100 kHz resistance values over ...


Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid 2019 Chapman University

Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect ...


Identification Of The Hyaluronic Acid Pathway As A Therapeutic Target For Facioscapulohumeral Muscular Dystrophy, Alec M. DeSimone, John D. Leszyk, Kathryn Wagner, Charles P. Emerson, Jr. 2019 University of Massachusetts Medical School

Identification Of The Hyaluronic Acid Pathway As A Therapeutic Target For Facioscapulohumeral Muscular Dystrophy, Alec M. Desimone, John D. Leszyk, Kathryn Wagner, Charles P. Emerson, Jr.

Open Access Articles

Facioscapulohumeral muscular dystrophy (FSHD) is linked to epigenetic derepression of the germline/embryonic transcription factor DUX4 in skeletal muscle. However, the etiology of muscle pathology is not fully understood, as DUX4 misexpression is not tightly correlated with disease severity. Using a DUX4-inducible cell model, we show that multiple DUX4-induced molecular pathologies that have been observed in patient-derived disease models are mediated by the signaling molecule hyaluronic acid (HA), which accumulates following DUX4 induction. These pathologies include formation of RNA granules, FUS aggregation, DNA damage, caspase activation, and cell death. We also observe previously unidentified pathologies including mislocalization of mitochondria and ...


Will Savings From Biosimilars Offset Increased Costs Related To Dose Escalation? A Comparison Of Infliximab And Golimumab For Rheumatoid Arthritis, Jeffrey R. Curtis, Fenglong Xie, Jonathan Kay, Joel D. Kallich 2019 University of Alabama, Birmingham

Will Savings From Biosimilars Offset Increased Costs Related To Dose Escalation? A Comparison Of Infliximab And Golimumab For Rheumatoid Arthritis, Jeffrey R. Curtis, Fenglong Xie, Jonathan Kay, Joel D. Kallich

Open Access Articles

INTRODUCTION: Biosimilar infliximab has the potential for appreciable cost savings compared to its reference biologic, but dose escalation is common and increases costs. We compared frequency of dose escalation and associated Medicare-approved amount so as to determine the break-even point at which infliximab dose escalation would offset the cost savings of using a biosimilar, referent to alternatively using golimumab.

METHODS: We studied Medicare enrollees with rheumatoid arthritis (RA) initiating infliximab or golimumab. Frequency of dose escalation was summarized descriptively over 18 months, as were Medicare-approved amounts for reimbursement. Analyses were repeated conditioning on high adherence (i.e., non-discontinuation, > 10-week gap ...


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