Digital Commons Network^™

Comparing Record Linkage Software Programs And Algorithms Using Real-World Data., Alan F. Karr, Matthew T. Taylor, Suzanne L. West, Soko Setoguchi, Tzuyung D. Kou, Tobias Gerhard, Daniel B. Horton

Student Papers, Posters & Projects

Linkage of medical databases, including insurer claims and electronic health records (EHRs), is increasingly common. However, few studies have investigated the behavior and output of linkage software. To determine how linkage quality is affected by different algorithms, blocking variables, methods for string matching and weight determination, and decision rules, we compared the performance of 4 nonproprietary linkage software packages linking patient identifiers from noninteroperable inpatient and outpatient EHRs. We linked datasets using first and last name, gender, and date of birth (DOB). We evaluated DOB and year of birth (YOB) as blocking variables and used exact and inexact matching methods. …

Conceptualization Of A Parasympathetic Endocrine System., Jonathan Gorky, James Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We here propose a parasympathetic endocrine system (PES) comprised of circulating peptides released from secretory cells in the gut, significantly modulated by vagal projections from the dorsal motor nucleus of the vagus (DMV). While most of these gut peptides mediate well-described satiety and digestive effects that increase parasympathetic control of digestion (Lee et al., 1994; Gutzwiller et al., 1999; Klok et al., 2007), they also have actions that are far-reaching and increase parasympathetic signaling broadly throughout the body. The actions beyond satiety that peptides like somatostatin, cholecystokinin, glucagon-like peptide 1, and vasoactive intestinal peptide have been well-examined, but not in …

Silymarin In Non-Cirrhotics With Non-Alcoholic Steatohepatitis: A Randomized, Double-Blind, Placebo Controlled Trial., Victor J. Navarro, Steven H. Belle, Massimo D'Amato, Nezam Adfhal, Elizabeth M. Brunt, Michael W. Fried, K. Rajender Reddy, Abdus S. Wahed, Stephen Harrison

Division of Gastroenterology and Hepatology Faculty Papers

The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its antioxidant properties. We aimed to assess the safety and efficacy of higher than customary doses of silymarin in non-cirrhotic patients with NASH. This exploratory randomized double-blind placebo controlled multicenter Phase II trial tested a proprietary standardized silymarin preparation (Legalon®, Rottapharm|Madaus, Mylan) and was conducted at 5 medical centers in the United States. Eligible adult patients had liver biopsy within 12 months showing NASH without cirrhosis with NAFLD Activity Score (NAS) ≥4 …

Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée De Leeuw, Karen E. Knudsen, J. Alan Diehl

Department of Cancer Biology Faculty Papers

The cyclin-dependent kinase 4/6 (CDK4/6) kinase is dysregulated in melanoma, highlighting it as a potential therapeutic target. CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. While beneficial, resistance to therapy is a concern, and the molecular mechanisms of such resistance remain undefined. We demonstrate that reactivation of mammalian target of rapamycin 1 (mTORC1) signaling through increased expression of the amino acid transporter, solute carrier family 36 member 1 (SLC36A1), drives resistance to CDK4/6 inhibitors. Increased expression of SLC36A1 reflects two distinct mechanisms: (i) Rb loss, which drives SLC36A1 via reduced suppression of E2f; (ii) fragile X …

Heme And Hemoglobin Utilization By Mycobacterium Tuberculosis., Avishek Mitra, Ying-Hui Ko, Gino Cingolani, Michael Niederweis

Department of Biochemistry and Molecular Biology Faculty Papers

Iron is essential for growth of Mycobacterium tuberculosis (Mtb), but most iron in the human body is stored in heme within hemoglobin. Here, we demonstrate that the substrate-binding protein DppA of the inner membrane Dpp transporter is required for heme and hemoglobin utilization by Mtb. The 1.27 Å crystal structure of DppA shows a tetrapeptide bound in the protein core and a large solvent-exposed crevice for heme binding. Mutation of arginine 179 in this cleft eliminates heme binding to DppA and prevents heme utilization by Mtb. The outer membrane proteins PPE36 and PPE62 are also required for heme and hemoglobin …

The Presence Of A Cmv Immunodominant Allele In The Recipient Is Associated With Increased Survival In Cmv Positive Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation, Dolores Grosso, Benjamin Leiby, Matthew Carabasi, Joanne Filicko-O'Hara, Sameh Gaballa, William O'Hara, John L Wagner, Neal Flomenberg

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Specific major histocompatibility (MHC) class I alleles dominate anti-CMV responses in a hierarchal manner. These CMV immunodominant (IMD) alleles are associated with a higher magnitude and frequency of cytotoxic lymphocyte responses as compared to other human leukocyte antigen (HLA) alleles. CMV reactivation has been associated with an increased incidence of graft-vs.-host disease and non-relapse mortality, as well as protection from relapse in HLA-matched HSCT settings. Less is known about the impact of CMV reactivation on these major outcomes after haploidentical (HI) HSCT, an increasingly applied therapeutic option. In HI HSCT, the efficiency of the immune response is decreased due …

Endovascular Management And The Risk Of Late Failure In The Treatment Of Ureteroarterial Fistulas, George Titomihelakis, Anthony Feghali, Tuong Nguyen, Dawn Salvatore, Paul Dimuzio, Babak Abai

Department of Medicine Faculty Papers

Ureteroarterial fistula (UAF) is a rare and life-threatening source of hematuria. A high index of suspicion is warranted for early diagnosis and timely intervention. Because of high perioperative risk and comorbidities in UAF patients, the endovascular approach has become preferred for repair. Infection can complicate this mode of therapy, and treatment with antibiotics is important. Herein we present five cases of secondary UAFs treated with stent graft alone or stent graft and embolization.

Excision Repair Cross-Complementing Group-1 (Ercc1) Induction Kinetics And Polymorphism Are Markers Of Inferior Outcome In Patients With Colorectal Cancer Treated With Oxaliplatin., Devika Rao, Atrayee Basu Mallick, Titto Augustine, Cecilia Daroqui, Jeeshan Jiffry, Amartej Merla, Imran Chaudhary, Raviraja Seetharam, Arjun Sood, Srikanth Gajavelli, Santiago Aparo, Lakshmi Rajdev, Andreas Kaubisch, Jennifer Chuy, Abdissa Negassa, John M. Mariadason, Radhashree Maitra, Sanjay Goel

Department of Medical Oncology Faculty Papers

Background: ERCC1, a component of nucleotide excision repair pathway, is known to repair DNA breaks induced by platinum drugs. We sought to ascertain if ERCC1 expression dynamics and a single nucleotide polymorphism (SNP) rs11615 are biomarkers of sensitivity to oxaliplatin therapy in patients with colorectal cancer (CRC).

Methods: Western blot and qPCR for ERCC1 expression was performed from PBMCs isolated from patients receiving oxaliplatin-based therapy at specified timepoints. DNA was also isolated from 59 biorepository specimens for SNP analysis. Clinical benefit was determined using progression free survival (PFS) for metastatic CRC.

Results: ERCC1 was induced in PBMC in response to …

Continuation Of Angiotensin Converting Enzyme Inhibitors On The Day Of Surgery Is Not Associated With Increased Risk Of Hypotension Upon Induction Of General Anesthesia In Elective Non-Cardiac Surgeries., U. Yoon, A. J. Setren, A. Chen, T. Nguyen, M. C. Torjman, T. L. Kennedy

Department of Anesthesiology Faculty Papers

No abstract provided.

Perioperative Use Of Renin-Angiotensin System Inhibitors And Outcomes In Patients Undergoing Cardiac Surgery., Qian Ding, Zugui Zhang, Hong Liu, Huang Nie, Mark Berguson, Jordan E. Goldhammer, Nilas Young, Douglas Boyd, Rohinton Morris, Jianzhong Sun

Department of Anesthesiology Faculty Papers

It remains disputable about perioperative use of renin-angiotensin system inhibitors (RASi) and their outcome effects. This multicenter retrospective cohort study examines association between use of perioperative RASi and outcomes in patients undergoing coronary artery bypass graft and/or valve surgery. After the exclusion, the patients are divided into 2 groups with or without preoperative RASi (PreRASi, n = 8581), or 2 groups with or without postoperative RASi (PostRASi, n = 8130). With using of propensity scores matching to reduce treatment selection bias, the study shows that PreRASi is associated with a significant reduction in postoperative 30-day mortality compared with without one …

Neurological Conditions Associated With Spinal Cord Injury, Man Amanat, Alexander R. Vaccaro, Mona Salehi, Vafa Rahimi-Movaghar

Rothman Institute Papers

Background: Comorbid neurological conditions associated with spinal cord injury (SCI) significantly affect an individual’s quality of life, yet they are often under-rated. Recent reports suggest that SCI may predispose patients to develop other neurological disorders. We aim at providing an overview of the evidence of neurological conditions which are or seem resultant of SCI.

Methods: We conducted a literature review using PUBMED and GOOGLE SCHOLAR to evaluate the occurrence of different neurological disorders in people with SCI.

Results: Individuals with SCI seem at an increased risk of stroke, cognitive impairment, dementia, multiple sclerosis, Parkinson’s disease, restless leg syndrome, and seizures. …

Comparison Of Two Commercial Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry (Maldi-Tof Ms) Systems For Identification Of Nontuberculous Mycobacteria., Barbara A. Brown-Elliott, Thomas R. Fritsche, Brooke J. Olson, Sruthi Vasireddy, Ravikiran Vasireddy, Elena Iakhiaeva, Diana Alame, Richard J. Wallace, John A. Branda

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Objectives: This multi-center study’s aim was to assess the performance of two commercially-available matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems in identifying a challenge collection of clinically-relevant nontuberculous mycobacteria (NTM).

Methods: NTM clinical isolates (N=244) belonging to 23 species/subspecies were identified by gene sequencing and analyzed using the Bruker Biotyper with Mycobacterial Library v5.0.0 and the bioMérieux VITEK MS with v3.0 database.

Results: Using the Bruker or bioMérieux systems, 92% or 95% of NTM strains, respectively, were identified at least to the complex/group level; 62% and 57%, respectively, were identified to the highest taxonomic level. Differentiation between members …

Commentary: Using Directional Deep Brain Stimulation To Co-Activate The Subthalamic Nucleus And Zona Incerta For Overlapping Essential Tremor/Parkinson's Disease Symptoms., Chengyuan Wu, Caio Matias

Department of Radiology Faculty Papers

We have read with interest the article titled “Using Directional Deep Brain Stimulation to Co-activate the Subthalamic Nucleus and Zona Incerta for Overlapping Essential Tremor/Parkinson's Disease Symptoms” by Falconer et al. (1). In this case report, the authors present a patient treated with unilateral left-sided deep brain stimulation (DBS) after medical management alone proved to be ineffective. The stereotactic target was described as being “3 mm lateral to the most lateral point of the red nucleus” at the Bejjani line (2); and implantation of the electrode at this target was confirmed with microelectrode recordings, intraoperative macrostimulation …

Map7 Prevents Axonal Branch Retraction By Creating A Stable Microtubule Boundary To Rescue Polymerization., Stephen R. Tymanskyj, Le Ma

Farber Institute for Neuroscience Faculty Papers

Complex neural circuits are built from axonal branches that allow each neuron to connect with multiple targets. During development, maturation of nascent branches depends on stabilization of newly assembled or transported microtubules, which are thought to be regulated by microtubule-associated proteins (MAPs). However, because many known MAPs inhibit branch formation, it is not clear which MAP is responsible for regulating microtubule stability during branch development. Here, we show that MAP7, a less-well understood MAP that is localized to branch junctions, provides a key molecular mechanism to regulate microtubule stability during branch formation. In developing rodent sensory neurons of mixed sex, …

Insights Into The Hiv Latency And The Role Of Cytokines., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Manjari Dimri, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Human immunodeficiency virus-1 (HIV-1) has the ability to infect latently at the level of individual CD4+ cells. Latent HIV-1 proviruses are transcriptionally silent and immunologically inert, but are still capable of reactivating productive lytic infection following cellular activation. These latent viruses are the main obstacle in the eradication of HIV-1, because current HIV-1 treatment regimens are ineffective against them. Normal immunological response against an antigen activates CD4+ naïve T cells. The activated CD4+ naïve T cells undergo cell cycle, resulting in further transformation and profound proliferation to form effector CD4+ T-cells. Notably, in HIV-1 infected individuals, some of the effector …

Irisin Functions To Inhibit Malignant Growth Of Human Pancreatic Cancer Cells Via Downregulation Of The Pi3k/Akt Signaling Pathway., Deguo Zhang, Ping Zhang, Luan Li, Nan Tang, Fei Huang, Xianguo Kong, Xueying Tan, Guangjun Shi

Department of Medicine Faculty Papers

Introduction: Irisin is a newly identified cytokine that has gained increasing attention because of its potential therapeutic applications in metabolic diseases and human cancers. Recently, accumulating evidence indicates that irisin plays an important role in the development and metastasis of various tumors. The aim of this study was to evaluate the effects and underlying mechanisms of irisin on malignant growth of pancreatic cancer cells.

Materials and methods: The anti-proliferative effect of irisin was examined using the CCK-8 assay. Irisin-induced apoptosis was determined by the annexin V-FITC/PI staining assay. The effects of irisin on cell migration and invasion were assessed using …

Identification Of Monocyte-Like Precursors Of Granulocytes In Cancer As A Mechanism For Accumulation Of Pmn-Mdscs., Jérôme Mastio, Thomas Condamine, George Dominguez, Andrew V Kossenkov, Laxminarasimha Donthireddy, Filippo Veglia, Cindy Lin, Fang Wang, Shuyu Fu, Jie Zhou, Patrick Viatour, Sergio Lavilla-Alonso, Alexander T. Polo, Evgenii N. Tcyganov, Charles Mulligan, Brian Nam, Joseph Bennett, Gregory Masters, Michael Guarino, Amit Kumar, Yulia Nefedova, Robert H. Vonderheide, Lucia R. Languino, Scott I. Abrams, Dmitry I. Gabrilovich

Department of Cancer Biology Faculty Papers

We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM). In contrast, these cells significantly expanded in tumor-bearing mice and differentiated to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Selective depletion of monocytic cells had no effect on the number of granulocytes in naive mice but decreased the population of PMN-MDSCs in tumor-bearing mice by 50%. The expansion of MLPGs was found to be …

Surgical Stress And Cancer Progression: The Twisted Tango., Zhiwei Chen, Peidong Zhang, Ya Xu, Jiahui Yan, Zixuan Liu, Wayne Bond Lau, Bonnie Lau, Ying Li, Xia Zhao, Yuquan Wei, Shengtao Zhou

Department of Emergency Medicine Faculty Papers

Surgical resection is an important avenue for cancer treatment, which, in most cases, can effectively alleviate the patient symptoms. However, accumulating evidence has documented that surgical resection potentially enhances metastatic seeding of tumor cells. In this review, we revisit the literature on surgical stress, and outline the mechanisms by which surgical stress, including ischemia/reperfusion injury, activation of sympathetic nervous system, inflammation, systemically hypercoagulable state, immune suppression and effects of anesthetic agents, promotes tumor metastasis. We also propose preventive strategies or resolution of tumor metastasis caused by surgical stress.

Eosinophilic Dermatosis Of Hematologic Malignancy Responding To Dupilumab In A Patient With Chronic Lymphocytic Leukemia., Annie Jin, Bobak T. Pousti, Kevin T. Savage, Nicholas K. Mollanazar, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

Leukemia cutis (LC) and eosinophilic dermatosis of hematologic malignancy (EDHM) are rare cutaneous manifestations of hematologic malignancies. Various therapeutic options have been reported, with largely underwhelming responses. We present a patient with chronic lymphocytic leukemia (CLL) with concomitant LC and EDHM who was treated with dupilumab.

Pioneers In Dermatology And Venereology: An Interview With Prof. Lawrence C. Parish., Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Medical Evaluation And Management Of Male And Female Voiding Dysfunction: A Review., Alana Murphy, Seth Teplitsky, Akhil K. Das, Joon Yau Leong, Andrew Margules, Costas D. Lallas

Department of Urology Faculty Papers

A significant workforce shortage of urologists available to serve the US population has been projected to occur over the next decade. Accordingly, much of the management of urologic patients will need to be assumed by other specialties and practitioners. Since primary care physicians are often first evaluate common urologic complaints, it makes sense that these physicians are in an excellent position to intervene in the management of these patients when appropriate. One of the most common complaints in urology is voiding dysfunction. The incidence of voiding dysfunction increases with age, with conservative estimates showing that over 50% of elderly patients …

Outcomes Of Bilateral Shoulder Arthroplasties: A Comparison Of Bilateral Total Shoulder Arthroplasties And Bilateral Reverse Shoulder Arthroplasties., Ryan Matthew Cox, Tyler James Brolin, Eric Michael Padegimas, Mark D. Lazarus, Charles Lonnie Getz, Matthew Lee Ramsey, Gerald Ross Williams, Joseph Albert Abboud

Rothman Institute Papers

Background: The purpose of this study was to compare outcomes of patients who underwent bilateral total shoulder arthroplasties (TSAs) for osteoarthritis (OA) versus bilateral reverse shoulder arthroplasties (RSAs) for cuff tear arthropathy (CTA).

Methods: Inclusion criteria were patients who underwent bilateral TSAs for OA or bilateral RSAs for CTA with at least 2 years of follow-up. Twenty-six TSA patients (52 shoulders) were matched 2 to 1 with 13 RSA patients (26 shoulders) by sex, age at first surgery, and time between surgeries. Outcomes measured were shoulder range of motion (ROM), complications, and patient-reported scores.

Results: Preoperatively, TSA patients had significantly …

Meta-Analysis A Myriad Of Data - Is It Helpful?, James Harrop

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

Long-Distance Axon Regeneration Promotes Recovery Of Diaphragmatic Respiratory Function After Spinal Cord Injury., Mark W. Urban, Biswarup Ghosh, Cole G. Block, Laura R. Strojny, Brittany A. Charsar, Miguel Goulão, Sreeya S. Komaravolu, George M. Smith, Megan C. Wright, Shuxin Li, Angelo C. Lepore

Farber Institute for Neuroscience Faculty Papers

Compromise in inspiratory breathing following cervical spinal cord injury (SCI) is caused by damage to descending bulbospinal axons originating in the rostral ventral respiratory group (rVRG) and consequent denervation and silencing of phrenic motor neurons (PhMNs) that directly control diaphragm activation. In a rat model of high-cervical hemisection SCI, we performed systemic administration of an antagonist peptide directed against phosphatase and tensin homolog (PTEN), a central inhibitor of neuron-intrinsic axon growth potential. PTEN antagonist peptide (PAP4) robustly restored diaphragm function, as determined with electromyography (EMG) recordings in living SCI animals. PAP4 promoted substantial, long-distance regeneration of injured rVRG axons through …

Clinical Outcome Assessments Toolbox For Radiopharmaceuticals., Charles A Kunos, Jacek Capala, Adam P Dicker, Benjamin Movsas, Susan Percy Ivy, Lori M Minasian

Department of Radiation Oncology Faculty Papers

For nearly 40 years, the U.S. National Cancer Institute (NCI) has funded health-related quality-of-life (HRQOL) and symptom management in oncology clinical trials as a method for including a cancer patient's experience during and after treatment. The NCI's planned scope for HRQOL, symptom and patient-reported outcomes management research is explained as it pertains to radiopharmaceutical clinical development. An effort already underway to support protocol authoring via an NCI Cancer Therapy Evaluation Program (CTEP) Centralized Protocol Writing Service (CPWS) is described as this service aids incorporation of HRQOL, symptom and patient-reported outcomes management research into sponsored protocols.

Ossification Of The Posterior Longitudinal Ligament: Surgical Approaches And Associated Complications., Jeffery Head, George Rymarczuk, Geoffrey Stricsek, Lohit Velagapudi, Christopher Maulucci, Christian Hoelscher, Md, James Harrop

Department of Neurosurgery Faculty Papers

Ossification of the posterior longitudinal ligament (OPLL) is a rare but potentially devastating cause of degenerative cervical myelopathy (DCM). Decompressive surgery is the standard of care for OPLL and can be achieved through anterior, posterior, or combined approaches to the cervical spine. Surgical correction of OPLL via any approach is associated with higher rates of complications and the presence of OPLL is considered a significant risk factor for perioperative complications in DCM surgeries. Potential complications include dural tear (DT) and subsequent cerebrospinal fluid leak, C5 palsy, hematoma, hardware failure, surgical site infections, and other neurological deficits. Anterior approaches are technically …

Antibody Responses Against The Vaccine Antigens Ov-103 And Ov-Ral-2 Are Associated With Protective Immunity To Onchocerca Volvulus Infection In Both Mice And Humans., Parakkal Jovvian George, Jessica A. Hess, Sonia Jain, John B. Patton, Tingting Zhan, Nancy Tricoche, Bin Zhan, Maria Elena Bottazzi, Peter J. Hotez, David Abraham, Sara Lustigman

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The current strategy for the elimination of onchocerciasis is based on annual or bi-annual mass drug administration with ivermectin. However, due to several limiting factors there is a growing concern that elimination of onchocerciasis cannot be achieved solely through the current strategy. Additional tools are critically needed including a prophylactic vaccine. Presently Ov-103 and Ov-RAL-2 are the most promising vaccine candidates against an Onchocerca volvulus infection.

METHODOLOGY/PRINCIPAL FINDINGS: Protection induced by immunization of mice with the alum-adjuvanted Ov-103 or Ov-RAL-2 vaccines appeared to be antibody dependent since AID-/- mice that could not mount antigen-specific IgG antibody responses were not …

Smart Lighting Clinical Testbed Pilot Study On Circadian Phase Advancement, Joseph D. Gleason, Meeko Oishi, Michelle Simkulet, Arunas Tuzikas, John P. Hanifin, George C. Brainard, S. R.J. Brueck, Robert F. Karlicek, Jr., Lee K. Brown

Department of Neurology Faculty Papers

Objective: Lighting is a strong synchronizer for circadian rhythms, which in turn drives a wide range of biological functions. The objective of our work is a) to construct a clinical in-patient testbed with smart lighting, and b) evaluate its feasibility for use in future clinical studies.

Methods: A feedback capable, variable spectrum lighting system was installed at the University of New Mexico Hospital. The system consists of variable spectrum lighting troffers, color sensors, occupancy sensors, and computing and communication infrastructure. We conducted a pilot study to demonstrate proof of principle, that 1) this new technology is capable of providing continuous …

Development Of Substrate Degradation Enzyme Therapy For Mucopolysaccharidosis Iva Murine Model., Kazuki Sawamoto, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is caused by a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Conventional enzyme replacement therapy (ERT) is approved for MPS IVA. However, the fact that the infused enzyme cannot penetrate avascular lesions in cartilage leads to minimal impact on the bone lesion. Moreover, short half-life, high cost, instability, and narrow optimal pH range remain unmet challenges in ERT. Thermostable keratanase, endo-β-N-acetylglucosaminidase, has a unique character of a wide optimal pH range of pH 5.0-7.0. We hypothesized that this endoglycosidase degrades keratan sulfate (KS) polymer in circulating blood and, therefore, ameliorates the accumulation of KS in …

Mechanisms Of Simvastatin Myotoxicity: The Role Of Autophagy Flux Inhibition., Arya Emami, Shahla Shojaei, Simone C. Da Silva Rosa, Mahmoud Aghaei, Ehsan Samiei, Amir Reza Vosoughi, Forouh Kalantari, Philip Kawalec, James Thliveris, Pawan Sharma, Amir A. Zeki, Mohsen Akbari, Joseph W. Gordon, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Statins are some of the most widely used drugs worldwide, but one of their major side effects is myotoxicity. Using mouse myoblast (C2C12) and human alveolar rhabdomyosarcoma cell lines (RH30) in both 2-dimensional (2D) and 3-dimensional (3D) cell culture, we investigated the mechanisms of simvastatin's myotoxicity. We found that simvastatin significantly reduced cell viability in C2C12 cells compared to RH30 cells. However, simvastatin induced greater apoptosis in RH30 compared to C2C12 cells. Simvastatin-induced cell death is dependent on geranylgeranyl pyrophosphate (GGPP) in C2C12 cells, while in RH30 cells it is dependent on both farnesyl pyrophosphate (FPP) and GGPP. Simvastatin inhibited …