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Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

Genomic Characterization Of Sickle Cell Mouse Models For Therapeutic Genome Editing Applications, Kaitly Jensen Woodard

Theses and Dissertations (ETD)

Sickle cell disease (SCD) is caused by a mutation of the β-globin gene (HBB), resulting in abnormal hemoglobin molecules that polymerize when deoxygenated, forming “sickle” shaped red blood cells (RBCs). Sickle RBCs lead to anemia, multi-organ damage and pain crises, beginning the first year of life. The onset of symptoms coincides with the developmental switch of β-like globin gene expression from fetal stage γ-globin to adult stage β-globin, resulting in a shift from fetal hemoglobin (HbF, α2γ2) to adult hemoglobin (HbA, α2β2). Some individuals harbor rare genetic variants in the extended β-globin gene cluster that cause constitutively elevated postnatal HbF, …

Utility Of Cognitive Behavioral Therapy To Reduce Pain In Children With Sickle Cell Disease, Abigail Radomsky

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Schatz J, Schlenz AM, McClellan CB, et al. Changes in coping, pain, and activity after cognitive-behavioral training. The Clinical Journal of Pain 2015;31(6):536-47 https://doi.org/10.1097/ajp.0000000000000183

for a child with sickle cell disease.

Luspatercept Diminishes The Need For Red Blood Cell Replacement In Transfusion-Dependent Β-Thalassemia Patients, Joudeh B. Freij

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2020;382(13):1219-1231. https://doi.org/10.1056/NEJMoa1910182

for a patient with transfusion-dependent beta-thalassemia.

Laser-Assisted Tooth Extraction In Patients With Impaired Hemostasis, Elena Larionova Dr., Ekaterina Diachkova Dr., Elena Morozova Prof., Albert Davtyan Dr., Svetlana Tarasenko Prof.

BioMedicine

Introduction: The provision of efficient dental care to patients with hemostatic disorders is tied to difficulties and problems such as prolonged bleeding after or during surgical manipulation.

Aim: This study aims to increase the efficiency of oral surgery in patients with thrombocytopenia with the use of erbium laser on different stages of tooth extraction.

Methods: Patients (n = 96) were selected for tooth extraction on an outpatient basis: patients with confirmed thrombocytopenia (age 44 ± 15.4, 19–74) were included in the 1st group, and patients without impaired hemostasis (age 47.6 ± 15.3, 19¬81) were included in the …

A Study Examining The Safety And Efficacy Of Ferric Carboxymaltose In A Large Pediatric Cohort, Chandni Dargan Md, David Simon Do

Research Days

Background: Iron deficiency anemia (IDA) is common in the pediatric population with varying high-risk factors. Intravenous (IV) iron supplementation has become more desirable in patients with moderate to severe anemia and in patients who are either unresponsive to or have adverse side-effects secondary to oral iron. Iron sucrose and Iron dextran have been traditionally used in pediatrics while ferric carboxymaltose (FCM) has only been FDA approved in adults. One of the major advantages of FCM is the ease of dosing and efficacy. Though FCM was approved for adults in 2013 and there have been no safety concerns, it is not …

Bleeding Disorder Referrals To Hematology Clinic: A Single Institution Experience, Zuri Hudson

Research Days

Background: Our center receives hundreds of referrals yearly for bleeding disorder evaluation both due to bleeding symptoms and secondary to routine preoperative laboratory testing. The evaluation for a bleeding disorder can be challenging due to the wide variability of symptoms as well as the need for accurately interpreting lab results. Bhasin et al showed that 4% of patients referred to hematology based on a preoperative coagulation evaluation had a clinically relevant bleeding disorder. Currently there is little published about the referral patterns to pediatric hematology and the outcomes of these referrals.

Objectives/Goal: To characterize our hematology referrals for bleeding disorder …

The Effect Of Carfilzomib And Bortezomib Based Regimes On Cardiotoxicity In Multiple Myeloma Patients At Cooper University Hospital, Ami Patel, Tulin Budak-Alpdogan, Stalam Tapati

Rowan-Virtua Research Day

Introduction

• Multiple myeloma (MM) is a cancer of plasma cells, which is a white blood cell that normally produces antibodies
• Treatment in patients younger than 65 years old is typically high dose chemotherapy, usually with bortezomib based regimens or lenalidomide dexamethasone, followed by a stem cell transplant
• For patients with relapsed myeloma, carfilzomib is usually the treatment of choice
• Carfilzomib is a highly selective, irreversible proteasome inhibitor that binds to the 20 S proteasome. Several studies have illustrated that carfilzomib has been associated with cardiovascular adverse events (CVAE).
• Current literature on the role and effect of bortezomib on cardiotoxicity is …

Multiple Myeloma With Dual Expression Of Kappa And Lambda Light Chains, Monica Patel, Akash Patel, Yvette Wang

Rowan-Virtua Research Day

Multiple myeloma (MM) is a malignancy of plasma cells that accounts for approximately 1 to 2 percent of all cancers and about 17% of all hematologic malignancies.

Plasma cells normally produce antibodies and provide a defense mechanism for the body to fight infections.

Antibodies typically consist of two heavy chains (IgG, IgA, IgM, IgD and IgE) and two light chains (kappa and lambda).

Most cases of MM have malignant plasma cells producing monoclonal (M) proteins, most common being IgG about 52% of the time (1).

Only about 2% of these myeloma cases were also found to secrete more than one …

Spontaneous Splenic Laceration Presenting As Stable Angina In The Ed, Lea Rowson, James Baird

Rowan-Virtua Research Day

We present a case of a 62-year-old female who presented to the emergency department complaining of classic cardiac chest pain and was ultimately diagnosed with hemoperitoneum due to a splenic laceration sustained during recent colonoscopy. The signs and symptoms between these two diagnoses can be vaguely similar, and a missed diagnosis of either leads to increased morbidity and mortality. To make an appropriate diagnosis, a thorough history and physical examination is imperative. Observation of non-musculoskeletal left shoulder pain in addition to abdominal tenderness should lead the astute clinician down a different path towards diagnosis. Kehr’s sign is present in many …

Optimizing Empiric Vancomycin Use In Febrile Neutropenia Patients, Nicole Tadros, Erika Dittmar, Radhan Gopalani

All Publications

Introduction: Febrile neutropenia (FN) is a complication of chemotherapy resulting in a temperature 100.4⁰F or greater plus an absolute neutrophil count (ANC) below 500 cells/mm³ or an ANC below 1000 cells/mm³ and expected to decrease below 500 cells/mm³ within 48 hours. Timely administration of broad-spectrum antimicrobial therapy is a cornerstone for the initial management of FN. However, prolonged empiric antimicrobial treatment can lead to resistance and toxicity. National guidelines and published literature do not support vancomycin as a routine part of empiric antimicrobial regimens in FN; it is only recommended in patients with specific clinical indications. This …

The Heme-Regulated Inhibitor Pathway Modulates Susceptibility Of Poor Prognosis B-Lineage Acute Leukemia To Bh3-Mimetics, Kaitlyn Hill Smith

Theses and Dissertations (ETD)

Anti-apoptotic MCL1 is one of the most frequently amplified genes in human cancers and its elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes with BH3-mimetics. To explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+ B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation of Eif2ak1, which encodes HRI, blocks MCL-1 repression in …

Genetic Mechanisms Of Transcriptional Regulation In Childhood Acute Lymphoblastic Leukemia, Xujie Zhao

Theses and Dissertations (ETD)

Introduction. Advances in genomic profiling and sequencing studies have identified germline and somatic variations that are associated with childhood ALL, improving our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL). Recent genome-wide association studies (GWAS) have identified germline genetic variations of ARID5B and, more recently, IGF2BP1 that are associated with susceptibility to ALL. Genome-wide sequencing studies also discovered a new ALL subtype characterized of ZNF384-mediated chromosomal translocations, providing new insights into genetic heterogeneity in childhood ALL. However, the underlying mechanism by which these genetic variants contribute to the transcriptional regulatory circuitries of ALL is still poorly understood. …

Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson

Theses and Dissertations (ETD)

Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …

Do Needle Exchange Programs Cause More Harm To Injection Drug Users And Compromise The Safety Of The Communities In Which They Are In Place?, Amber L. Payne

Theses, Dissertations and Capstones

Needle Exchange Programs (NEP) are put in place in regions in the US, where illegal injectable drug use is prevalent, in order to decrease the amount of blood borne diseases by at least 10%, such as Hepatitis C and Human Immunodeficiency Virus (HIV), being spread throughout the drug-using community. People and Healthcare Professionals in these communities have questioned if NEPs have caused more harm to the drug users and if they have compromised public safety due to incorrect disposal of syringes.

During a study in 2011, the spread of blood borne diseases in areas where NEPs were present, decreased among …

Effects Of The Needle Exchange Program Implemented In West Virginia, Amber Graves, Anthony B. Uriarte, Katherine Duty

Theses, Dissertations and Capstones

Introduction: West Virginia has had a recent spike in infectious diseases such as HIV and hepatitis due to increased rates of injectable drug use. The rising costs associated with such diseases have been a cause for concern in the sector of healthcare and public health. In the state, the exchanging of dirty needles has resulted in the spread of bloodborne pathogens, however, the implementation of needle exchange programs has sought to decrease the rates of infection, improve health outcomes, and lower healthcare costs. However, there is a question as to the effectiveness of such programs.

Purpose of Study: …

The Epigenetic Effects Of Omega-3 Fatty Acids In Diffuse Large B-Cell Lymphoma, Tanner Jeffrey Bakhshi

Theses, Dissertations and Capstones

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. It is an aggressive cancer, with 50-70% of patients diagnosed at an advanced stage and 30-50% of patients not cured by chemoimmunotherapy. DLBCL is almost always caused by genetic damage sustained during the germinal center (GC) reaction. The mechanisms that govern the GC reaction bear a striking resemblance to those that drive DLBCL. Genomic studies have shown that some of its most common mutations occur in genes that encode epigenetic modifiers, including the lysine (histone) acetyltransferases CREBBP and p300. These mutations prevent the acetylation of multiple histone residues, …

Targeting Calcium Homeostasis For The Treatment Of Multiple Myeloma, Osama M. Elzamzamy

Graduate Theses, Dissertations, and Problem Reports

Multiple myeloma (MM) is a hematological malignancy characterized by the neoplastic proliferation of the plasma cells. MM is a relatively rare cancer that accounts for about 1.8% of all cancers and is the second most common hematologic malignancies, and despite the advancement from untreatable to treatable malignancy, it is yet incurable. Calcium ions (Ca²⁺) play an important role as second messengers in regulating a plethora of physiological and pathological processes, hence cytoplasmic Ca²⁺ is tightly regulated with strict spatial and temporal control to initiate, maintain, and terminate appropriate signaling pathways and phenotypes including cellular proliferation, cell cycle …

Efficacy Of The Nutritional Supplement, Evenflo, In The Management Of Sickle Cell Disease: A Randomized Controlled Trial, Richard Muga, Arthur Ajwang, James Ouma, Josephine Ojigo, Juliana Otieno, Peter Okoth, Caroline Wafula, Sophia Ajwang, David Ogolla, Abraham Hollist, James Adefisoye

Nursing & Health Sciences Research Journal

Background: In this study, we investigated if a combination of the nutraceutical supplement, EvenFlo and folic acid will be superior to the standard stand-alone use of folic acid.

Methods: We conducted a randomized double-blind, active-controlled, clinical trial. A total of 70 subjects with SCD ages 5-12 years were enrolled into the study with 35 in the intervention group and 35 in the control group; 61 completed the trial (32 from the intervention group and 29 from the control group).

Results: Participants in the intervention group were significantly less likely to experience crises compared to subjects in the control group. None …

Vitamin D Levels Affect Survival In A Bcr-Abl Acute Lymphoblastic Leukemia Mouse Model But Do Not Cause Vitamin-Drug Interactions, Kavya Annu

Theses and Dissertations (ETD)

It is a well-established phenomenon that dietary components containing CYP3A inducers or inhibitors if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an important role in pre-systemic metabolism of CYP3A drugs, we determined the impact of vitamin D (VD3) status on systemic exposure and efficacy of chemotherapeutic agents that are CYP3A substrates. We employed VD3 sufficient and deficient mice to perform pharmacokinetics (PK) and anti-leukemic efficacy studies.

First, using hCYP3A4 transgenic mouse model we evaluated the intestinal, hepatic and renal expression …