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Week Of November 11, 2019, New York Medical College

InTouch

• NYMC Opens Family Health Center to Provide Primary Care to Community, Create Learning Opportunities for Students
• Department of Pediatrics Hosts Ninth Annual Assistant Professor Pediatric Research Symposium
• StuHE Fights Against Breast Cancer

Changes In Ventricular Depolarisation Vectors During Exercise Caused By Regional Myocardial Ischaemia, Cameruddin Vellani, Satwat Hashmi, Sadia Mahmud, Mohammad Yusuf, Safia Awan, Khawar Kazmi

Section of Cardiology

Research at the Aga Khan University for several years has been directed to find a reliable, low-cost, portable, non-invasive method for identification of coronary artery disease, its location and extent. A new method has been devised to measure the magnitude and direction of cardiac electrical vectors in three perpendicular planes during physical exercise to identify reduction in myocardial excitability as the electrophysiological marker of hypoxia. This report shows that changes in electrical forces due to exercise-induced regional hypoxia serve as indicators of reversible myocardial ischaemia. Changes in the magnitude and direction of vectors at stages of the Bruce protocol were …

Macrophage-Associated Wound Healing Contributes To African Green Monkey Siv Pathogenesis Control, Fredrik Barrenas, Kevin Raehtz, Cuiling Xu, Lynn Law, Richard R. Green, Guido Silvestri, Steven E. Bosinger, Andrew Nishida, Qingsheng Li, Wuxun Lu, Jianshui Zhang, Matthew J. Thomas, Jean Chang, Elise Smith, Jeffrey M. Weiss, Reem A. Dawoud, George H. Richter, Anita Trichel, Dongzhu Ma, Xinxia Peng, Jan Komorowski, Cristian Apetrei, Ivona Pandrea, Michael Gale Jr.

Nebraska Center for Virology: Faculty Publications

Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection. Here, we examined how this outcome is achieved by comparing a natural SIV host, African green monkey (AGM) to an AIDS susceptible species, rhesus macaque (RM). To asses gene expression profiles from acutely SIV infected AGMs and RMs, we developed a systems biology approach termed Conserved Gene Signature Analysis (CGSA), which compared RNA sequencing data from rectal AGM and RM tissues to various other species. We found that AGMs rapidly activate, and then maintain, evolutionarily conserved regenerative wound healing mechanisms in mucosal tissue. The wound healing protein fibronectin …

Clpc Affects The Intracellular Survival Capacity Of Staphylococcus Aureus In Non-Professional Phagocytic Cells, Gubesh Gunaratnam, Lorena Tuchscherr, Mohamed I. Elhawy, Ralph Bertram, Janina Eisenbeis, Christian Spengler, Thomas Tschernig, Bettina Löffler, Greg A. Somerville, Karin Jacobs, Mathias Herrmann, Markus Bischoff

School of Veterinary and Biomedical Sciences: Faculty Publications

Invasion and persistence of bacteria within host cells requires that they adapt to life in an intracellular environment. This adaptation induces bacterial stress through events such as phagocytosis and enhanced nutrient-restriction. During stress, bacteria synthesize a family of proteins known as heat shock proteins (HSPs) to facilitate adaptation and survival. Previously, we determined the Staphylococcus aureus HSP ClpC temporally alters bacterial metabolism and persistence. This led us to hypothesize that ClpC might alter intracellular survival. Inactivation of clpC in S. aureus strain DSM20231 significantly enhanced long-term intracellular survival in human epithelial (HaCaT) and endothelial (EA.hy926) cell lines, without markedly affecting …

Sign And Speech Share Partially Overlapping Conceptual Representations, Samuel Evans, Cathy J. Price, Jörn Diedrichsen, Eva Gutierrez-Sigut, Mairéad Macsweeney

Brain and Mind Institute Researchers' Publications

© 2019 The Author(s) Conceptual knowledge is fundamental to human cognition. Yet, the extent to which it is influenced by language is unclear. Studies of semantic processing show that similar neural patterns are evoked by the same concepts presented in different modalities (e.g., spoken words and pictures or text) [1–3]. This suggests that conceptual representations are “modality independent.” However, an alternative possibility is that the similarity reflects retrieval of common spoken language representations. Indeed, in hearing spoken language users, text and spoken language are co-dependent [4, 5], and pictures are encoded via visual and verbal routes [6]. A parallel approach …

Week Of November 4, 2019, New York Medical College

InTouch

• SOM Class of 2023 Marks Medical School Milestone: The White Coat Ceremony
• BioInc@NYMC Celebrates Five-Year Anniversary and Expansion
• NYMC Shines a Spotlight on Autism
• NYMC Supports Breast Cancer Awareness Month

Incorporating B Cell Activating Factor (Baff) Into The Membrane Of Rabies Virus (Rabv) Particles Improves The Speed And Magnitude Of Vaccine-Induced Antibody Responses., Joseph R Plummer, James P Mcgettigan

Department of Microbiology and Immunology Faculty Papers

B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) superfamily of cytokines that links innate with adaptive immunity. BAFF signals through receptors on B cells, making it an attractive molecule to potentiate vaccine-induced B cell responses. We hypothesized that a rabies virus (RABV)-based vaccine displaying both antigen and BAFF on the surface of the same virus particle would target antigen-specific B cells for activation and improve RABV-specific antibody responses. To test this hypothesis, we constructed a recombinant RABV-based vector expressing virus membrane-anchored murine BAFF (RABV-ED51-mBAFF). BAFF was incorporated into the RABV particle and determined to …

Delineating The Mechanisms Of Misfolded Endoplasmic Reticulum (Er) Luminal Protein Retrotranslocation For Er-Associated Degradation, Christina Oikonomou

Theses and Dissertations (ETD)

Secreted, plasma membrane, and resident proteins of the secretory pathway are synthesized in the endoplasmic reticulum (ER) where they undergo post-translational modifications, oxidative folding, and subunit assembly in tightly monitored processes. An ER quality control (ERQC) system oversees protein maturation and ensures that only those reaching their native state will continue trafficking into the secretory pathway to reach their final destinations. Proteins that fail quality control must be recognized and eliminated to maintain ER proteostasis. The ER-associated degradation (ERAD) was discovered nearly 30 years ago and entails the identification of improperly matured secretory pathway proteins and their retrotranslocation to the …

Targeting Parp-1 With Metronomic Therapy As A New Approach To Modulate Mdsc Function And Enhance Anti-Pd1 Immunotherapy In Colon Cancer, Salome Valentina Ibba, Mohamed Ghonim, Abdelmetalab Tarhuni, Matthew Dean, Hamid Boulares, Augusto Ochoa, Youssef Errami, Ali Elbahraway, Ilyes Benslimane, Dorota Wyczechowska, Luis Del Valle, Amir Al-Khami, Hanh Luu

School of Medicine Faculty Publications

34th Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer - Part 1, November 6 - 10, 2019, National Harbor, MD

A Physiologically-Based Pharmacokinetic Model For Targeting Calcitriol-Conjugated Quantum Dots To Inflammatory Breast Cancer Cells., James Forder, Mallory Smith, Margot Wagner, Rachel J. Schaefer, Jonathan Gorky, Kenneth L. Van Golen, Anja Nohe, Prasad Dhurjati

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Quantum dots (QDs) conjugated with 1,25 dihydroxyvitamin D3 (calcitriol) and Mucin-1 (MUC-1) antibodies (SM3) have been found to target inflammatory breast cancer (IBC) tumors and reduce proliferation, migration, and differentiation of these tumors in mice. A physiologically-based pharmacokinetic model has been constructed and optimized to match experimental data for multiple QDs: control QDs, QDs conjugated with calcitriol, and QDs conjugated with both calcitriol and SM3 MUC1 antibodies. The model predicts continuous QD concentration for key tissues in mice distinguished by IBC stage (healthy, early-stage, and late-stage). Experimental and clinical efforts in QD treatment of IBC can be augmented by in …

Acute Diagnosis Of Wilson’S Disease In A Teenage Patient, Sarah Irvin, Ryan Mccarthy

Marshall Journal of Medicine

Wilson’s Disease, a rare autosomal recessive genetic disease, is caused by a mutation in the ATP7B enzyme gene. Without this enzyme, copper builds up in the brain, liver, and cornea causing a multitude of symptoms. It is important to consider Wilson’s disease because the prognosis is dependent on timely diagnosis. This is an interesting case of a 19-year-old male who presented with suicidal thoughts and rapid weight loss. After many months and an extensive work-up, Wilson’s Disease was diagnosed. Due to his rapid decline, he was transferred to a larger university healthcare center where he is currently enrolled in clinical …

Deepcon-Pre: Improved Protein Contact Map Prediction Using Inverse Covariance And Deep Residual Networks, Nachammai Palaniappan

Theses

As with most domains where machine learning methods are applied, correct feature engineering is critical when developing deep learning algorithms for solving the protein folding problem. Unlike the domains such as computer vision and natural language processing, feature engineering is not rigorously studied towards solving the protein folding problem. A recent research has highlighted that input features known as precision matrix are most informative for predicting inter-residue contact map, the key for building three-dimensional models. In this work, we study the significance of the precision matrix feature when very deep residual networks are trained. Using a standard dataset of 3456 …

Characterizing The Roles Of Nuclear Proteins Dbc1, G9a, And Glp In Adipocyte Function And Metabolic Health, Ashley Ann Able

LSU Doctoral Dissertations

Obesity is a metabolic disorder characterized by excess energy storage in adipose tissue and it increases the risk for Type 2 diabetes. Impaired or altered adipocyte function during obesity can contribute to metabolic dysfunction. DBC1 (deleted in breast cancer 1) and EHMTs 1 and 2 (euchromatic histone lysine methyltransferases 1 and 2) have been shown to have a role in fat cell development and function. DBC1 is typically localized in the nucleus and can regulate a variety of epigenetic modifiers, transcription factors, and nuclear receptors. EHMTs 1 and 2, also known respectively as GLP and G9a, were initially classified as …

Week Of October 28, 2019, New York Medical College

InTouch

• The NYMC Family Health Center is Now Open
• Jane M. Ponterio, M.D. '81, Is Named Senior Associate Dean for Student Affairs of the School of Medicine
• Race for Rehab Is Still Running Strong After Twenty-One Years
• NYMC Study Identifies Effective Treatment for Individuals with POTS
• NYMC Makes an Impact at the Heart Walk
• From the Collection of Edward C. Halperin, M.D., M.A.

Phenylethynyl-Substituted Benzenes And Heterocycles For The Treatment Of Cancer, David S. Watt, Chunming Liu, Vitaliy M. Sviripa, Wen Zhang, Markos Leggas

Molecular and Cellular Biochemistry Faculty Patents

Halogenated phenylethynyl-substituted heterocycles that possess either an N-alkylamino or N,N-dialkylamino group attached to the heterocycle or halogenated phenylethynyl-substituted benzenes that a nitrogen-containing heterocycle attached to the benzene inhibit the proliferation cancer cells and are useful antineoplastic agents.

Characterization Of Resistance To A Potent D-Peptide Hiv Entry Inhibitor., Amanda R Smith, Matthew T Weinstock, Amanda E Siglin, Frank G Whitby, J Nicholas Francis, Christopher P Hill, Debra M Eckert, Michael J Root, Michael S Kay

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: PIE12-trimer is a highly potent D-peptide HIV-1 entry inhibitor that broadly targets group M isolates. It specifically binds the three identical conserved hydrophobic pockets at the base of the gp41 N-trimer with sub-femtomolar affinity. This extremely high affinity for the transiently exposed gp41 trimer provides a reserve of binding energy (resistance capacitor) to prevent the viral resistance pathway of stepwise accumulation of modest affinity-disrupting mutations. Such modest mutations would not affect PIE12-trimer potency and therefore not confer a selective advantage. Viral passaging in the presence of escalating PIE12-trimer concentrations ultimately selected for PIE12-trimer resistant populations, but required an extremely …

Metformin And Cancer: Pharmacoepidemiology Considerations, Sarah Kradel, Christina Spinaris, Victoria Pennington, Adam Trimble, Lara Long, Natalie Dipietro

Pharmacy and Wellness Review

No abstract provided.

Nlrp6 In Gram-Positive Pneumonia And Sepsis, Laxman Ghimire

LSU Doctoral Dissertations

Acute lower respiratory infections (pneumonia) and pneumonia-derived sepsis are among the leading causes of death in the world causing 7.8 million deaths annually. In this regard, Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in the US and implicated for causing high mortality-associated necrotizing pneumonia and aggravating viral pneumonia with superinfection. Additionally, sepsis is the 7^th leading cause of death among newborns in the US and is responsible for more than 750,000 hospitalization cases every year. Although there is a plethora of research in both pneumonia and sepsis, the detailed pathophysiology still remains elusive. Understanding the host defense mechanism will help …

Antidepressant Dosing In Major Depression: A Pharmacogenomic Approach, Morgan Homan, Haval Norman, Victoria Cho, Yousif Rojeab

Pharmacy and Wellness Review

Major depressive disorder (MDD) is the most predominant mental disorder in the United States, with serious and costly health risks if not successfully managed. Pharmacotherapy is a standard option for MDD treatment, but patients often require extensive therapy adjustments to find a suitable regimen. Pharmacogenomics may enable greater precision in antidepressant therapy. Genotypic variations in CYP2D6 and CYP2C19 metabolic enzymes are reliable predictors of serum drug concentration, but the complex dose-response relationship of antidepressants prevents such variations from predicting therapy success. Additionally, ABCBl has been examined for its role in P-glycoprotein efflux of antidepressants in the brain, yet it is …

Use Of Botulinum Toxin In Central Nervous System Disorders, Julie Puvogel, Paige Torbet, Jourdan Ujlaki, Rebecca Worden, Lindsey Peters

Pharmacy and Wellness Review

Botulinum toxin is a neurotoxin that is produced by Clostridium botulinum. At one time, this toxin was only seen as a lethal substance, but now scientists have found many medical uses for it. There are eight distinctive toxins (A-H), but only A and B currently have clinical uses. Botulinum toxin A has three different versions that are U.S. Food and Drug Administration (FDA) approved: onabotulinumtoxinA (Botox®), abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®). Botulinum toxin B is also FDA approved as rimabotulinumtoxinB (Myobloc®). The toxins work by inducing reversible, local, dose-dependent chemodenervation by inhibiting acetylcholine release from presynaptic terminals. These drugs are approved …

Prevention And Treatment Of Glucocorticoid-Induced Osteoporosis, Mackenzie Devine, Anh Dao Le, Julie Puvogel, Victoria Cho, Michelle Musser

Pharmacy and Wellness Review

Osteoporosis is a disease state resulting in decreased bone mineral density (BMD) and increased risk of fracture, specifically of the vertebrae, spine and hip. Risk factors and high risk populations for developing osteoporosis include low BMD, long-term glucocorticoid therapy, genetics, diet, postmenopausal women and patients with inflammatory or chronic disease states. A variety of signaling pathways involving hormones, cytokines and other signaling molecules are involved in bone formation and are affected by long-term glucocorticoid therapy, leading to the development of glucocorticoid-induced osteoporosis (GIO).

There are a variety of drugs that work efficaciously to prevent and treat GIO. Alendronate is a …

The Effect Of Cyp3a5 Polymorphism On Kidney Transplant Recipients Given Tacrolimus, Samia Alam, Sunitha Johns, Haval Norman, Brian Heilbronner, Yousif Rojeab

Pharmacy and Wellness Review

Tacrolimus, an immunosuppressant agent indicated for organ transplants, is commonly administered to reduce the risk of renal graft rejection in patients with chronic kidney disease (CKD) and end stage renal disease (ESRD). Due to its narrow therapeutic index and high inter-patient variability, studies have suggested that CYP3A5-based dosing provides specialized regimens which may significantly improve the chances of achieving therapeutic concentrations. According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendations, extensive (CYP3A5*1/*1) and intermediate metabolizers (CYP3A5*1/*3) require a higher initial dose while poor metabolizers (CYP3A5*3/*3) require a lower initial dose in order to achieve target tacrolimus concentrations. Studies concluded that …

Dose Effects Of Recombinant Adenovirus Immunization In Rodents, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Recombinant adenovirus type 5 (rAd) has been used as a vaccine platform against many infectious diseases and has been shown to be an effective vaccine vector. The dose of the vaccine varies significantly from study to study, making it very diffcult to compare immune responses and vaccine effcacy. This study determined the immune correlates induced by serial dilutions of rAd vaccines delivered intramuscularly (IM) and intranasally (IN) to mice and rats. When immunized IM, mice had substantially higher antibody responses at the higher vaccine doses, whereas, the IN immunized mice showed a lower response to the higher rAd vaccine doses. …

Potential Use Of Dopamine And Dopamine Agonists As Angiogenesis Inhibitors In The Treatment Of Cancer, Benjamin Finley, Katherine Liu, Daniel Powell, Jamie Kellner, David H. Kinder

Pharmacy and Wellness Review

In recent years, there have been numerous developments in monoclonal antibodies used as anticancer drugs with a focus on reducing the ability of cancers to metastasize and produce new vasculature. These agents are called angiogenesis inhibitors and although these agents have been proven effective in treating certain types of cancers, production and administration of monoclonal antibodies comes at a steep cost with a severe side effect profile. Under normal physiologic conditions, angiogenesis is an important mechanism to create new blood vessels from preexisting vessels, usually occurring in adults. Tumor cells can hijack the angiogenesis pathway to produce new distant tumors …

New Cholesterol Guidelines: An Update For Pharmacists, Emily Limberg, Benjamin Finley, Stacy Henthorne, Sarah Kradel, David Bright

Pharmacy and Wellness Review

The American College of Cardiology and American Heart Association published new blood cholesterol guidelines in November 2013. The new guidelines place an emphasis on evidence-based treatment of dyslipidemias and primarily use randomized controlled trials to create recommendations for health care providers. Major changes from the previous guidelines include eliminating low-density lipoprotein goals, the classification of statins by lipid-lowering potential and the creation of four major statin benefit groups. The new guidelines also establish the role of non-statins in dyslipidemias and use the Pooled Cohort Risk Assessment Equations to calculate patients' risk for cardiovascular events and the need for cholesterol-lowering medications. …

Crohn's Disease: Management, Emerging Therapies And The Role Of The Pharmacist, Sarah Turley, Tiffany Kneuss, Lydia Suchecki, Alison Steinbrunner, Kristen Timperman

Pharmacy and Wellness Review

Crohn's disease is a relapsing-remitting disorder of the gastrointestinal tract caused by a mixture of genetic and environmental factors. Pharmacologic treatment of Crohn's disease is patient-specific, and regimens vary widely between individuals. Drug regimens are typically based on 5-aminosalicylate therapy and may include a combination of steroids, histamine 2 receptor antagonists, proton pump inhibitors, immunomodulators, antibiotics, biologic agents and other medications aimed at symptom relief. A new medication, vedolizumab, is currently in phase III clinical trials awaiting U.S. Food and Drug Administration (FDA) approval for use in Crohn's disease. Vedolizumab is an alpha-integrin inhibitor, which is anticipated to have a …

Lbrutinib (Lmbruvica™) For Treatment Of Mantle Cell Lymphoma, Brittany Crowe, Joy Hoffman, Hannah Stewart, Alison Steinbrunner, Mark E. Olah

Pharmacy and Wellness Review

Mantle cell lymphoma (MCL) is a rare and moderately aggressive form of non-Hodgkin's lymphoma (NHL) that predominantly presents at an advanced stage in older males. Patients often present with multiple involvement in the lymph nodes, blood, spleen, bone marrow and gastrointestinal tract (GIT). Some patients may be asymptomatic in early stages or present with an incurable, indolent (slow progressing) form, while other patients display rapid growth of more aggressive lymphomas. Overall survival for patients diagnosed with MCL is four to five years and treatment should be initiated in those who are symptomatic. Mantle cell lymphoma responds well to first-line treatment, …

Drugs Of Abuse: A Review Of Tramadol Abuse, Brittany Crowe, Tiffany Kneuss, Benjamin Finley, Kelsey Fink, Manoranjan S. D'Souza

Pharmacy and Wellness Review

Prescription drug abuse is the fastest growing drug problem in America. Among the different prescription drugs being abused, analgesics are the most commonly abused group of drugs. In the last few years, there is increasing evidence of abuse of tramadol, which is an atypical, centrally acting opioid analgesic. The increasing abuse of tramadol has prompted regulatory authorities to strengthen the product labeling of tramadol with respect to its abuse potential. Furthermore, several states have added tramadol to their controlled substances list. In this article, we will review the pharmacology of tramadol and some of the preclinical and clinical studies that …

Ado-Trastuzumab Emtansine For Her2 Positive Breast Cancer, Kimberly Baucher, Taylor Beale, Maria Laikos, Eric Stack, Mary Ellen Hethcox

Pharmacy and Wellness Review

No abstract provided.

Antidepressant Therapy: A Review Of Current Treatment Options And A Glance At The Future, Brittany Dye, Stacy Henthorne, Molly Kulp, Tristan Maiers, Zachary Crawford, Erin Petersen

Pharmacy and Wellness Review

Depression and anxiety disorders are two of the most common mental illnesses experienced by people within the United States, affecting 6.7 percent of the adult population per year. This article will focus on one specific type of depression, major depressive disorder (MDD), characterized by two or more weeks of depressed mood and/or decreased interest in normally enjoyed activities. Depression complicates treatment of other disease state(s), making successful treatment of depression essential in the management of a patient's overall health. This review will evaluate the pathophysiology, antidepressant treatment, and new approaches to treatment, specifically vortioxetine, for MDD.