Medicine and Health Sciences Commons^™

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Characterizing The Combination Of Rpa Inhibitors With Parp Inhibitors In High-Grade Serous Ovarian Cancer, Yat Tang

Theses & Dissertations

High-grade serous ovarian cancer (HGSC) is the most common and deadly gynecologic malignancy. HGSC patients with BRCA1/2 mutations have homologous recombination deficiency (HRD), requiring parallel pathways to maintain genome integrity (e.g., PARP1, PARP2). Approximately 50% of ovarian carcinomas are estimated to exhibit HRD. For the remaining 50% and the large percentage of HRD patients with acquired or innate resistance to single-agent PARP inhibitors, there is a need to develop alternative therapeutic strategies.

Replication Protein A (RPA) is a heterotrimeric protein crucial for genome maintenance. Phosphorylation of RPA in DNA damage response (DDR) is a negative regulator of DNA end resection. …

Hiv-1 Elimination In Humanized Mice, Hang Su

Theses & Dissertations

Human immunodeficiency virus type one (HIV-1) exclusively infects humans and chimpanzees. Therefore, animal models are required for all investigations of viral pathogenesis, therapy and cure. Immunodeficient mice transplanted with human hematopoietic stem cells, termed humanized mice, support the development of multiple human cell lineages throughout the cell’s life span. To this end, we used humanized mice to evaluate the dynamic changes of host immunologic and viral profiles during both acute and chronic HIV-1 infection. We identified the temporal and spatial distribution of HIV-1 cell and tissue compartment infections and outlined correlations made between viral progression and host immunity by comparing …

Targeted Inhibition Of Histone Deacetyltransferases For Pancreatic Cancer Therapy, Richard Laschanzky

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a dismal five-year survival rate of less than 10%. One major obstacle in PDAC treatment is acquired drug resistance. Pan-histone deacetylase inhibitors (pan-HDACi) are a relatively new class of anti-cancer drugs, with demonstrated ability to overcome drug resistance and re-sensitize PDAC tumors to Gemcitabine (Gem). These agents target HDACs, a family of 18 enzymes (divided into four classes, I-IV) that catalyze the deacetylation of histones and other cellular proteins and have multiple effects on cell growth, differentiation, survival, and tumorigenesis. Although pan-HDACi have shown significant efficacy in preclinical analysis, and some …

Defining The Role Of Tyrosine Phosphorylation In The Regulation Of Connexin43 In Cardiac Diseases, Li Zheng

Theses & Dissertations

Connexins are integral membrane proteins that oligomerize to form gap junction channels. Ions and small molecules diffuse intercellularly through these channels, allowing individual cellular events to synchronize into the functional response of an entire organ. Gap junction channels composed of Connexin43 (Cx43) mediate electrical coupling and impulse propagation in the normal working myocardium. In the failing heart, Cx43 remodeling (decreased expression, altered phosphorylation state, loss at intercalated discs, and increased presence at lateral membranes) contributes to rhythm disturbances and contractile dysfunction. While there is considerable information regarding key interactions of Cx43 in the regulation of gap junction channels, unfortunately, the …

Anticipation, Accompaniment, And A Good Death In Perinatal Care., Bryanna S. Moore, Brian S. Carter, Bryan Beaven, Katie House, Joel House

Manuscripts, Articles, Book Chapters and Other Papers

The ethics of perinatal care, and the experiences of families who receive such care, remains a nascent area of inquiry. It can be hard to see how existing "good death" constructs apply to the experiences of fetal patients and their families. In this paper, we explore two themes raised by a case at our fetal health center: anticipation and accompaniment. In this case, a mother presented to our fetal health center; her unborn son, our fetal patient, was diagnosed with life-threatening hypoplastic left heart syndrome and endocardial fibroelastosis. The parents were told that their son's life expectancy, upon birth, was …

The Development Of Novel Apurinic/Aprymidinic Endonuclease/Redox-Factor 1 Inhibitors For The Treatment Of Human Melanoma, Bella Sharifi

Pharmaceutical Sciences (MS) Theses

Apurinic/apyrimidinic DNA repair endonuclease-1 (APE1), first recognized as an important DNA excision repair enzyme, is also known as Redox Factor-1 (Ref-1) involved in the activation of many nuclear transcription factors in both redox-dependent and independent manner. It has been well-documented that the overexpression of APE/Ref-1 contributes to the development of chemo-resistance and is associated with tumor progression in many human malignancies [1].

Our previous study in melanoma demonstrated that the development of novel inhibitors targeting the redox regulation domain of APE/Ref-1 is a promising strategy for melanoma treatment. To date, limited successes have been reported in developing novel …

The Feasibility Of Vigorous Resistance Exercise Training In Adults With Intellectual Disabilities With Cardiovascular Disease Risk Factors, Stijn Wetering, Alyt Oppewal, Thessa I. M. Hilgenkamp

Physical Therapy Faculty Research

Background The cardiovascular disease (CVD) risk is high in adults with intellectual disabilities. This CVD risk can potentially be decreased with a resistance training (RT) programme at vigorous intensity, following previous research on successful High‐Intensity Training programmes. Our aim was to explore the feasibility of a vigorous RT‐programme for adults with intellectual disabilities with CVD risk factors. Method Twenty‐four adults with intellectual disabilities with at least one CVD risk factor participated in a 24‐week RT‐programme. The training intensity was increased from novice (50%1RM) to vigorous (75%–80%1RM). Feasibility was based on the achieved training intensity at the end of the RT‐programme. …

Altered Central Hemodynamics In Individuals With Down Syndrome, Thessa Irena Maria Hilgenkamp, Elizabeth Cornellia Schroeder, Sang Ouk Wee, Georgios Grigoriadis, Alexander Jacob Rosenberg, Tracy Baynard, Bo Fernhall

Physical Therapy Faculty Research

Background: Individuals with Down Syndrome (DS) have autonomic dysfunction impacting regulation of heart rate, Blood Pressure (BP), and peripheral vasoconstriction. This may alter central hemodynamics through different wave reflections. We investigated central hemodynamics including wave reflection during rest and a sympathoexcitatory stimulus [Lower Body Negative Pressure (LBNP)] in individuals with DS and controls. Methods: Radial applanation tonometry was performed on participants with and without DS before and during 5-min LBNP stimulus of −20 mmHg. Waveforms were calibrated to mean and diastolic BP. Generalized transfer function was used to estimate aortic pressures [Systolic Blood Pressure (aSBP), Diastolic Blood Pressure (aDBP), mean …

Multitex Rct - A Multifaceted Intervention Package For Protection Against Cotton Dust Exposure Among Textile Workers - A Cluster Randomized Controlled Trial In Pakistan: Study Protocol, Asaad Ahmed Nafees, Sara De Matteis, Muhammad Masood Kadir, Peter Burney, David Coggon, Sean Semple, Paul Cullinan

Community Health Sciences

Background: In the Pakistani textile industry the prevalence of workplace respiratory illnesses, including byssinosis, is high. The MultiTex RCT study aims to determine the effectiveness of a multifaceted intervention package in reducing dust levels in cotton mills, decreasing the frequency of respiratory symptoms among cotton textile workers, and improving their lung function.
Methods/design: We will conduct a cluster-randomized controlled trial at 28 textile mills in Karachi. The intervention will comprise: training in occupational health for all workers and managers reinforced by regular refresher sessions; the formation of workplace committees to draw up, agree and promote a health and safety plan …

Putting A Face To Cancer, Lenn Robbins

Capstones

About one month after I began my studies at the Craig Newmark Graduate School of Journalism, I was diagnosed with a rare form of cancer, Langerhans Cell Histiocytosis (LCH). Three years and three relapses later, I have my MA, I defiant will to fight this disease and the hope that by chronicling my experience I might help others. If this project helps just one person, it's been worth the ride.

https://lennrobbins.wixsite.com/facetocancer

Liver Cancer: Current And Future Trends Using Biomaterials, Sue Anne Chew, Stefania Moscato, Sachin George, Bahareh Azimi, Serena Danti

Health & Biomedical Sciences Faculty Publications

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer diagnosed and the second leading cause of death worldwide. Despite advancement in current treatments for HCC, the prognosis for this cancer is still unfavorable. This comprehensive review article focuses on all the current technology that applies biomaterials to treat and study liver cancer, thus showing the versatility of biomaterials to be used as smart tools in this complex pathologic scenario. Specifically, after introducing the liver anatomy and pathology by focusing on the available treatments for HCC, this review summarizes the current biomaterial-based approaches for systemic delivery and implantable tools …

Long Term Outcomes Of Surgical And Clinical Symptoms Following Minimally Invasive Heller Myotomy: A Retrospective Clinical Database Review, Laura E. Flores, Priscila Rodrigues Armijo, Bhavani Pokala, Sarah Samreen, Dmitry Oleynikov

Graduate Medical Education Research Journal

I

Introduction

Minimally invasive Heller myotomy rates have increased, but little evidence is available regarding long term clinical and surgical outcomes. Our aim was to evaluate long term symptom improvement and medication resolution for patients undergoing minimally invasive Heller myotomy.

Methods

A single-institution database was retrospectively reviewed for patients undergoing laparoscopic Heller myotomy (LHM) or robotic Heller myotomy (RHM) during 2007-2018. Patients with primary HM followed by a Dor fundoplication were included. Demographics and surgical data were analyzed. Esophageal symptoms, testing, and medication use were collected preoperatively (pre-op), at 6-month (6-mo), 12-month (12-mo), and long-term (LT; 12-mo+) follow-up. Analysis was …

Effects Of Stem Cell Therapy On 6-Minute Walk Test Distance And Left Ventricular Ejection Fraction In Patients With Nonischemic Cardiomyopathy, Kayleigh Hunt, Alexa Maziuk

Physician Assistant Capstones, 2016 to 2019

Objective

To assess the efficacy of stem cells in the improvement of functional capacity and quality of life in the setting of nonischemic dilated cardiomyopathy.

Design

Systematic literature review

Methods

A literature search of PubMed was conducted utilizing the following search terms: “stem,” “cell,” “nonischemic,” and “cardiomyopathy.” The following limits were used: “2015-2018,” nonischemic cardiomyopathy, results of LVEF and 6MWT, randomized controlled trials, pilot studies, and sample size >22.

Results

Butler et al. found that within the itMSC group, 6MWD increased by an average of 27.40 m (95% CI 0.28–54.52; P=0.05), but it decreased by an average of 10.83 m …

Subanesthetic Iv Ketamine Reduces Acute Suicidal Ideation In Patients With Mood Disorders, Kimberly Jenko, Jack Anzilotti

Physician Assistant Capstones, 2016 to 2019

Background. Depression and suicide are common in the United States and present a significant problem in the healthcare landscape. Currently, there are few options that can rapidly reduce suicidal ideation in patients with depression. Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to reduce acute suicidality in patients with depression. Previous studies have a reduction of suicidal ideation compared to saline placebo, but few studies have shown a significant effect compared to a similar psychoactive drug such as midazolam.

Method. A search of PubMed and PsychNET was performed in September 2018 using the terms “ketamine,” “suicide,” …

Effect Of Postpartum Protocols On Maternal Outcomes, Kelsey Grimm, Emily Harnish

Physician Assistant Capstones, 2016 to 2019

Objective: To determine whether postpartum hemorrhage (PPH) protocols lead to decreases in maternal morbidity and mortality.

Design: Systemic literature review.

Methods: The clinical question investigated is whether the implementation of PPH protocols has measurable impact on maternal morbidity and mortality. Searches were done through PubMed using the keywords: “maternal hemorrhage postpartum protocol.” Studies were eliminated if they were more than 10 years old, conducted outside the United States, published in a non-English language, used other animal subjects besides humans, used non-female subjects, if they did not answer the clinical question, or were review articles. Eventually, three cohort …

Exposition Aux Bioaérosols Dans Les Centres De Traitement Des Eaux Usées : Application D’Approches Moléculaires Et Risque Viral, Caroline Duchaine, Marc Veillette, Vanessa Dion Dupont, Hamza Mbareche, Évelyne Brisebois, Jacques Lavoie, Yves Beaudet

Rapports de recherche scientifique

Le traitement des eaux usées comporte plusieurs étapes susceptibles de générer des bioaérosols auxquels des travailleurs peuvent être exposés. Bien que la littérature à ce sujet soit relativement abondante, les connaissances relatives au risque, à l’exposition et à la fréquence de certaines maladies chez cette population demeurent mal documentées. L’environnement des centres de traitement des eaux usées est complexe à plusieurs égards. En effet, les différents sites de traitement représentent des risques variables en ce qui a trait à la nature et à la concentration des bioaérosols, ainsi qu’au type de travail effectué. La majorité des études s’intéressant à cette …

Retour Et Maintien Durable En Emploi Après Un Trouble Musculosquelettique : Pistes D’Action Pour Le Superviseur, Iuliana Nastasia, Marie-France Coutu, Romain Rives, Jessica Dubé, Sarah Gaspard, Audrey Quilicot

Rapports de recherche scientifique

Les troubles musculosquelettiques (TMS) demeurent un problème majeur de santé au travail dans les pays industrialisés. Les conséquences de l’incapacité au travail représentent un fardeau important pour les travailleurs et leurs familles, mais aussi pour les organisations. Même si plusieurs études sur l’incapacité au travail soulignent le rôle important du superviseur dans le contexte de différents programmes de retour au travail, peu se sont intéressées spécifiquement au rôle de celui-ci, à ses responsabilités ainsi qu’à ses actions pour faciliter la réintégration des travailleurs qui ont eu une blessure musculosquelettique reliée au travail.

L’objectif général de cette étude est de proposer …

Diet-Induced Leukocyte Telomere Shortening In A Baboon Model For Early Stage Atherosclerosis, Genesio M. Karere, Michael C. Mahaney, Deborah E. Newman, Angelica M. Riojas, Clint Christensen, Shifra Birnbaum, John L. Vandeberg, Laura Cox

School of Medicine Publications

Reported associations between leukocyte telomere length (LTL) attrition, diet and cardiovascular disease (CVD) are inconsistent. This study explores effects of prolonged exposure to a high cholesterol high fat (HCHF) diet on LTL in a baboon model of atherosclerosis. We measured LTL by qPCR in pedigreed baboons fed a chow (n = 105) or HCHF (n = 106) diet for 2 years, tested for effects of diet on LTL, and association between CVD risk factors and atherosclerotic lesions with LTL. Though not different at baseline, after 2 years median LTL is shorter in HCHF fed baboons (P < 0.0001). Diet predicts sex- and age-adjusted LTL and LTL attrition (P = 0.0009 and 0.0156, respectively). Serum concentrations of CVD biomarkers are associated with LTL at the 2-year endpoint and LTL accounts approximately 6% of the variance in aortic lesions (P = 0.04). Although heritable at baseline (h2 = 0.27, P = 0.027) and after 2 years (h2 = 0.46, P = 0.0038), baseline LTL does not predict lesion extent after 2 years. Atherogenic diet influences LTL, and LTL is a potential biomarker for early atherosclerosis. Prolonged exposure to an atherogenic diet decreases LTL and increases LTL attrition, and shortened LTL is associated with early-stage atherosclerosis in pedigreed baboons.

Does Dispensing Naloxone Kits To High-Risk Patients At The Time Of Emergency Department (Ed) Discharge Reduce The Burden Of Subsequent Overdose-Related Care?, Steven D. Perry, Charleen Gnisci, Rachel Beham

Emergency Medicine

Purpose: The rates of opioid-related overdose and death have remained at or near historically high levels despite reform in pharmaceutical opioid prescribing trends. This study will determine if a recently implemented protocol which aims to provide high-risk patients with naloxone emergency kits at the time of ED discharge has reduced the need for subsequent overdose-related care to a greater degree than providing the same patients with written outpatient naloxone prescriptions. Patients currently receive either intervention upon discharge from the ED based on a protocolized, criteria-based, provider-implemented decision-making tree that identifies patients at high risk for subsequent overdose.

Methods: This study …

Impact Of Required Antibiotic Stop Dates And Indications On Length Of Treatment In Hospitalized Patients With Pneumonia, Amanda Haddad, Kathryn Hernando, Kayihura Manigaba, Abigail Antigua

Infectious Disease

Purpose: The CDC Core Elements of Hospital Antibiotic Stewardship Programs recommends implementing policies to support optimal antibiotic prescribing including documentation of dose, duration and indication. On January 31, 2017, the study institution implemented new physician order entry screens in the electronic health record requiring the input of indication and duration on all antibiotic orders. The objective of this study is to determine if implementation of mandatory indication and duration for antibiotic orders decreases antibiotic duration of therapy in hospitalized patients with pneumonia.

Methods: This study was submitted to the Institutional Review Committee for approval. The clinical pharmacy surveillance platform, …

Impact Of Methicillin-Resistant Staphylococcus Aureus (Mrsa) Nasal Swab On Total Duration Of Mrsa Therapy For Pneumonia Patients, Darren D. Yum, Kayihura Manigaba, Danielle Gagne, Heather Ellis

Infectious Disease

Purpose: Recent literature has highlighted MRSA nasal screening as a possible antimicrobial stewardship program tool for avoiding unnecessary empiric anti-MRSA therapy for pneumonia. MRSA is an important cause of pneumonia and clinicians must determine when empiric antimicrobial therapy directed toward this pathogen is needed. Negative MRSA nasal swab has been shown to have a high negative predictive value ( >95%) across different types of pneumonia. The objective of this study is to assess the impact of negative MRSA nasal swabs on the duration of anti-MRSA therapy in a community hospital setting.

Methods: This study will be submitted to the institutional …

An In-Depth Review Of Retinitis Pigmentosa Development And Pathologies Overtime In Patients, Abdul Harris

Honors College Theses

Retinitis Pigmentosa is a disease which can cause blindness and affects around 2.5 million people worldwide. It is a disorder that has a multitude of ways of being inherited, such as autosomal dominant, autosomal recessive as well as X-linked and mitochondrial linked disorder. While some versions of RP may be syndromic (20%-30%), a majority of cases are in fact non-syndromic. The majority of non-syndromic cases inherited via autosomal dominant RP having RHO gene mutations, and X-linked means of inheritance having majority of patients with RPGR gene mutations. Ushers Syndrome, a syndromic version of retinitis pigmentosa and autosomal recessive RP having …

Air Pollution & Asthma Prevalence: Hotspot Analysis On Environmental Injustice In Buffalo, New York, Zuveria Shaguphta

Graduate Dissertations and Theses

This research aims to focus on the historical impacts of segregation in these communities (with Census Bureau data) and whether we see that these are the areas with continued segregation and a disproportionate number of TRI facilities. The third part of this research will be to investigate the presence of asthma in these neighborhoods as documented by the New York State Health Department. Asthma is a chronic disease in which the airways are inflamed due to some kind of external factor causing this reaction. Literature shows that there is a relationship between outdoor air pollution from combustion of fossil fuels …

Postpartum Endometritis And Infection Following Incomplete Or Complete Abortion: Case Definition & Guidelines For Data Collection, Analysis, And Presentation Of Maternal Immunization Safety Data, C E. Rouse, L O. Eckert, F M. Muñoz, J S A. Stringer, S Kochhar, L Bartlett, M Sanicas, D J. Dudley, D M. Harper, Fyezah Jehan

Department of Paediatrics and Child Health

Abstract are not provided by the author/publisher

Ramucirumab: A New Agent For Advanced Or Metastatic Gastric Junction Adenocarcinoma, Adam Smith, Rebecca Worden, Jessica Hoffert, Brendon Rasor, Hannah Stewart, David Koh

Pharmacy and Wellness Review

Ramucirumab (Cyramza®), approved April 21, 2014, is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist with a U.S. Food and Drug Administration (FDA) indication for the treatment of advanced or metastatic gastric/gastroesophageal junction adenocarcinoma. Gastric cancer is a prevalent cancer in the United States with a poor prognosis. The phase 3 trial, REGARD, shows that ramucirumab, when used within four months after the last dose of first-line chemotherapy or six months after the last dose of adjuvant chemotherapy, increases overall survival. Also, ramucirumab has been included in combination therapy, such as in the RAINBOW trial, which demonstrated its effectiveness …

Outbreak Of Ebola Virus Disease, Alexandra Dimit, Tiffany Kneuss, Joelle Farano, Haley Armstrong, Jodi Otte, Andrew M. Roecker

Pharmacy and Wellness Review

Ebola virus disease (EVD) has existed as a major health concern with devastating and, many times, fatal symptoms. The recent outbreaks of EVD in West Africa and the Democratic Republic of the Congo (DRC) have incited international concern. In this article, the implications of EVD will be discussed including the etiology, transmission, signs and symptoms, diagnosis and treatment of the disease. In addition to this discussion, the manner in which major health care organizations, including the World Health Organization (WHO), are dealing with treating infected patients and containing spread of the disease will be covered.

Cannabinoids For The Treatment Of Chronic Headaches, Kevin Krivanek, Lucy K. Wagala, Brian Heilbronner, Kimberly Loughlin, David Kinder

Pharmacy and Wellness Review

Species of the Cannabis plant genus were among the earliest medicinal plants cultivated by man, with historical accounts of their medicinal uses dating back before the Common Era. Despite its current legal status, Cannabis has garnered nationwide attention as a therapeutic agent for various disease states, including chronic headaches, due to its medical indications as an antispastic, analgesic, antiemetic, neuroprotective and anti-inflammatory agent. Since headaches have a high prevalence in the American population and greatly impair simple daily aspects of living, chronic headaches have become a particular point of interest in regard to the therapeutic potential of Cannabis. Clinical trials …

Marijuana And Its Cardiovascular Implications, Albert Bui, Daniel Powell, Victoria Cho, Kelsey Lindsley, Lindsey Peters

Pharmacy and Wellness Review

As marijuana becomes legalized for medical use, it is important for prescribers and pharmacists to be knowledgeable about the important aspects of marijuana such as mechanism of action, indications and abuse potential. Although marijuana's medicinal benefits are frequently reported, the risks, namely cardiovascular risks, associated with its utilization are often overlooked. Use of marijuana has been reported to increase the risk of myocardial infarction, tachycardia and hypotension, among others. Health care providers must determine if marijuana's benefits outweigh such risks when marijuana therapy is an option. It is also important for pharmacists to understand how to successfully counsel patients using …

Fda Approves New Inhaled Insulin: Afrezza® (Technosphere® Insulin), Benjamin Finley, Christina Ciccone, Kimberly Loughlin, Michelle Musser

Pharmacy and Wellness Review

Diabetes is an endocrine disease caused by deficiency or malfunction of insulin that results in high blood glucose levels and places patients at higher risk for a number of complications. This chronic disease is difficult to manage and affects millions of people in the United States, costing the health care system billions of dollars a year. Of a variety of antidiabetic agents used to control blood glucose, insulin is perhaps the most effective, but until recently it was only available in injectable form. As of June 27, 2014, a new inhaled insulin called Afrezza® (Technosphere® insulin) was approved by the …