Medicine and Health Sciences Commons^™

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

Pharmacy Faculty Articles and Research

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

Development Of A Financial Literacy Component For A Comprehensive Secondary Transition Program For Diploma-Bound Students With Learning Differences, Rose Marie Borillo

Student Capstone Papers

Under the Individuals with Disabilities Education Act (IDEA), schools are required to provide transition planning for students with disabilities and mental illness by age 16 (Eismann et al, 2017). Occupational therapists have been underutilized in secondary transition planning, despite their expertise in targeting functional abilities, comprehension, and health using activity analysis to promote skill attainment and achieve independence (Mankey 2012; Eismann et al, 2017).

At the Winston School, there was no formal transition program aside from the individual college counseling provided by a staff member. A coordinated transition program was indicated to prepare students for life after high school to …

A Drive To Driven Model Of Mapping Intraspecific Interaction Networks., Libo Jiang, Jian Xu, Mengmeng Sang, Yan Zhang, Meixia Ye, Hanyuan Zhang, Biyin Wu, Youxiu Zhu, Peng Xu, Ruyu Tai, Zixia Zhao, Yanliang Jiang, Chuanju Dong, Lidan Sun, Christopher H. Griffin, Claudia Gragnoli, Rongling Wu

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Community ecology theory suggests that an individual's phenotype is determined by the phenotypes of its coexisting members to the extent at which this process can shape community evolution. Here, we develop a mapping theory to identify interaction quantitative trait loci (QTL) governing inter-individual dependence. We mathematically formulate the decision-making strategy of interacting individuals. We integrate these mathematical descriptors into a statistical procedure, enabling the joint characterization of how QTL drive the strengths of ecological interactions and how the genetic architecture of QTL is driven by ecological networks. In three fish full-sib mapping experiments, we identify a set of genome-wide QTL …

Design, Synthesis, & Biological Evaluation Of Novel Het-Aromatic/Aromatic Analogs For The Treatment Of Hiv, Cancer, & Cognitive Dysfunctions, Mohit Gupta

Electronic Theses and Dissertations

Cyclophilin A are a class of peptidyl-prolyl isomerases that catalyzes isomerization of the proline residue within a protein. Cyclophilin A plays an instrumental role in the pathogenesis of HIV and HCV virus. Using structure-based drug we designed and synthesized small molecule inhibitors of cyclophilin A. These inhibitors were biologically evaluated for their ability to inhibit WT HIV-1 inhibition.

Mitogen-Activated Protein Kinase signaling cascades plays a critical role in cancer cell survival, metastasis, and chemo-resistance. The MEK5/ERK5 pathway, which is a member of MAPK signaling cascade, is involved in cell survival, anti-apoptotic signaling, angiogenesis, and cell motility. It is found to …

Precarity Beyond Food: How The Closure Of An Independent Grocery Store Shed Light On The Limitations Of Food Access Efforts In Syracuse, New York, Katherine Louisa Ravene Mott

Theses - ALL

On September 11, 2017, the owner of an independent grocery store in Syracuse, New York’s Near Westside neighborhood announced that the store would close within the month. The Near Westside is often characterized by its high levels of concentrated poverty for African American and Hispanic neighborhood residents. Nojaim Brothers Supermarket opened in 1919 and persisted for 97 years amidst an unfavorable political and economic landscape marked by the creation of both chain grocery stores and supermarkets as well as the effects of urban renewal and disinvestment. I argue that Nojaim’s endurance can be attributed to the embeddedness of the grocery …

Mta3 Represses Cancer Stemness By Targeting The Sox2ot/Sox2 Axis, Liang Du, Lu Wang, Jinfeng Gan, Zhimeng Yao, Wan Lin, Junkuo Li, Yi Guo, Yuping Chen, Fuyou Zhou, Sai-Ching Jim Yeung, Robert P Coppes, Dianzheng Zhang, Hao Zhang

PCOM Scholarly Works

Cancer cell stemness (CCS) plays critical roles in both malignancy maintenance and metastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA3

Microbial Communities In Human Milk Relate To Measures Of Maternal Weight, Sara N. Lundgren, Juliette C. Madan, Margaret R. Karagas, Hilary G. Morrison, Anne G. Hoen, Brock C. Christensen

Dartmouth Scholarship

The process of breastfeeding exposes infants to bioactive substances including a diversity of bacteria from breast milk as well as maternal skin. Knowledge of the character of and variation in these microbial communities, as well as the factors that influence them, is limited. We aimed to identify profiles of breastfeeding-associated microbial communities and their association with maternal and infant factors. Bilateral milk samples were collected from women in the New Hampshire Birth Cohort Study at approximately 6 weeks postpartum without sterilization of the skin in order to capture the infant-relevant exposure. We sequenced the V4–V5 hypervariable region of the bacterial …

Patient Satisfaction With Substance Use Disorder Rehabilitation Services, Trupti Dhumal

Electronic Theses and Dissertations

Background: Patient satisfaction is considered as an important indicator in the evaluation of healthcare quality across an array of treatments and services. It is deemed vital especially in the field of substance use disorder (SUD) research due to an increased emphasis on understanding patients’ perceptions regarding their treatment and the attributes that drive their progress towards recovery. Despite the potential value, gaps have been recognized in the exploration of these satisfaction-related assessments among patients undergoing SUD treatment in residential rehabilitative settings. Thus, there is a need for understanding the dimensions contributing to satisfaction which would facilitate the development of …

Determining Nurse Practitioner Core Competencies Utilizing A Delphi Approach, Tracey Chan

Electronic Theses and Dissertations

Background: Competency-based education (CBE) has been recommended for nurse practitioner (NP) education. To implement CBE, existing NP core competencies need to be reduced in number and refined.

Purpose: This study refined and reduced redundancy in the National Organization of Nurse Practitioner Faculties (NONPF) and American Association of Colleges of Nursing (AACN) NP core competencies through the consensus of experts in NP practice. This study used the current NP Core Competencies (NONPF, 2017), the Essentials of Doctoral Education for Advanced Nursing Practice (AACN, 2006), and the Common Advanced Practice Registered Nurse Doctoral-Level Competencies,(AACN, 2017a) …

Characterization Of The Effect Of Exercise Dose And Integrative Nonpharmacological Therapies In The Treatment Of Chronic Pain, Anna M. Polaski

Electronic Theses and Dissertations

Chronic pain includes debilitating conditions affecting large populations of people throughout the world. These diseases are further complicated by comorbid psychological disorders which make chronic pain conditions difficult to treat. Nonpharmacological treatment options have more recently become an important mainstay of effective therapies and are currently being used to supplement or replace traditional pharmacological treatment methods. Exercise-based therapies in particular are of interest due to their demonstrated success in reducing pain symptoms as well as improving psychological outcomes. Dose is an important factor in being able to effectively prescribe treatments in the context of specific exercise interventions and specific pain …

Caregiver Perspectives On Telehealth: A Service Delivery For Occupational Therapy, Rebecca Johnston

Student Capstone Papers

Telehealth; also known as telerehabilitation, telecare, telemedicine, teletherapy, and telepractice; is an emerging healthcare service that is utilized in various healthcare facilities with a span of ages, conditions, and locations (World Federation of Occupational Therapy [WFOT], 2014). Telehealth utilizes information and communication technologies to deliver services to a patient when the healthcare provider is not in the same location (WFOT, 2014). Telehealth can provide an online platform for evaluations, consultations, monitoring, supervision, and intervention with patients and other professionals (WFOT, 2014).

Telehealth is an emerging method of delivering occupational therapy (OT) services to various populations, including: children and youth; productive …

Lifestyle Management For Vestibular Disorders, Michelle Pock

Student Capstone Papers

Individuals with vestibular disorders have concerns that impact lifestyle including limiting activities of daily living, limiting participation in social events, difficulty driving, and difficulty working (Cohen, 2014). Occupational therapists are able to help individuals with vestibular disorders by task analyzing symptom provoking activities, assessing the impact of symptoms on occupations, providing adaptations, and providing ways to modify environments (Gronski, Neville, Kannenberg, & Cohen, 2017). While occupational therapists are qualified to provide services to sustain and improve the occupational performance of individuals with vestibular disorders, occupational therapy is not well represented in this area particularly in addressing lifestyle components for vestibular …

Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes, Yang Peng

Theses & Dissertations

Type 1 diabetes is one of the most challenging chronic autoimmune diseases. The destruction and dysfunction of insulin-secreting β cells are the results of inflammatory infiltration and the synergistic effect of multiple immune cells. The aim of this dissertation is to develop novel and reliable therapeutic approaches to advance the treatment of T1D: including chemical modification of a broad-spectrum immunosuppressant, co-application of small molecule based immune intervention and siRNA based β cell preservative therapy, and administration of a PI3K-δ/γ dual inhibitor to specifically target immune cells, utilizing synthetic polymeric micelles or natural produced multi-functional exosomes derived from human bone marrow …

Charge-Based Optimization Of Neurotensin For Neurotensin-Receptor-1 Targeting Utilizing A One-Bead One-Compound Peptide Library Approach, Trey Neeley

Theses & Dissertations

Neurotensin-receptor-1 (NTSR1) is regularly overexpressed in various cancers and contributes to the proliferation, survival, migration, invasion, and angiogenesis of tumors. NTSR1-targeting vectors have demonstrated promise in both diagnostic and therapeutic aspects. Unfortunately, the relatively poor in vivo metabolic stability and high renal uptake and retention of NTSR1-targeted compounds have hampered the translation to the clinic. In this research, we utilized a one-bead one-compound (OBOC) peptide library approach to make targeted modifications at the naturally charged residues of an NTS (4-13) sequence to discover an NTS derivative with comparable affinity to NTSR1, acceptable in vivo stability, and tolerable renal retention. Subsequent …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

The Role Of Histone Chaperone Fact Complex In Base Excision Repair Pathway And Its Therapeutic Potential In Colon Cancer And Medulloblastoma, Heyu Song

Theses & Dissertations

Base excision repair (BER) pathway is required for the removal of damaged bases caused by alkylation, oxidation and ring-saturation. Human apurinic/apyrimidinic endonuclease 1 (APE1) plays a central role in BER pathway. Although repair of damaged bases by recombinant APE1 has been well investigated in vitro, how APE1 gains access to damaged bases in the context of chromatin is largely unknown. A prominent member of the histone chaperone family, FACT (Facilitates Chromatin Transcription) is thought to reorganize nucleosomes through the destabilization of multiple intra-nucleosome contacts. FACT complex is composed of two polypeptides identified as SPT16 (Suppressor of Ty 16) and SSRP1 …

Enhancing The Identification Of Rheumatoid Arthritis-Associated Lung Disease, Bryant England

Theses & Dissertations

Rheumatoid arthritis (RA) is a systemic autoimmune disease that predisposes afflicted individuals to reduced quality of life, physical disability, and premature mortality. While joint involvement is the primary manifestation of RA, extra-articular features including lung disease are responsible for a significant portion of the excess mortality. In this dissertation I demonstrate the contribution of chronic lung diseases to premature mortality in RA, contrasting with the more widely recognized comorbidity in RA of cardiovascular disease. Then, I establish that a novel serum biomarker, anti-malondialdehyde-acetaldehyde adduct (MAA) antibody, is associated with the presence of interstitial lung disease (ILD) in RA subjects. Further …

The Development Of Hyaluronan-Based Contract Agents For The Intraoperative Detection Of Pancreatic Tumors, Bowen Qi

Theses & Dissertations

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. Tumor-specific intraoperative fluorescence imaging could improve staging and surgical resection, thereby improving prognosis. In the first study, hyaluronic acid derived NPs with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG accumulated significantly in an orthotopic pancreatic ductal adenocarcinoma model with safety profile both in vitro and in vivo. To maximize tumor signal, while minimizing signal in healthy pancreas and RES capture of macromolecules, in the next study, we describe the rational …

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 …

Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya

Theses & Dissertations

This work presents research using the naturally available non- sulfated carbohydrate glycosaminoglycan hyaluronic acid (HA) for the synthesis of different chemical derivatives of HA for evaluation of binding kinetics with CD44 and P- selectin proteins for applications in fluorescence image-guided surgery. Chemical derivatives of HA such as deacetylated HA (deHA), sulfated HA (sHA), and deacetylated and sulfated HA (s-deHA) were synthesized by modulating sulfating and deacetylating reagents to alter binding specificities to CD44. Modified HA derivatives and CD44 biophysical interactions were assessed by fluorescence polarization. In silico techniques were also used to determine binding using molecular docking and MM-PBSA approaches. …

Orthodontically Induced External Root Resorption In Extraction Versus Non-Extraction Treatment Modalities – A Retrospective Cone-Beam Computed Tomography (Cbct) Study, Jaykishan Patel

Theses & Dissertations

Purpose of this study was to evaluate orthodontically induced external apical root resorption using cone beam computed tomography in patients receiving orthodontic treatment with or without extractions. Records of 188 consecutively treated patients who received orthodontic treatment with or without extractions were evaluated. Pre-and post-treatment root lengths of maxillary incisors, volumes of maxillary central incisors, and apex displacement of either right or left maxillary central incisors were measured using Invivo 5.4 or ITK-SNAP 3.8.0 software. After adjusting for initial length, treatment duration, tooth, sex, race, bracket type, and malocclusion, maxillary incisor reduction of root length in extraction group was 0.37 …

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. …

Identification Of More Potent And Efficacious Analogs Of The Novel Host-Derived Immunostimulant Ep67, Abdul Alshammari

Theses & Dissertations

EP67 is a human C5a-derived decapeptide agonist of C5a Receptor 1 (C5aR1/CD88) that selectively activates mononuclear phagocytes over neutrophils to stimulate protective innate and adaptive immune responses while potentially minimizing neutrophil-mediated toxicity. Two N-alkyl amino acids Pro⁷ and N-methyl-Leu⁸ (nme-Leu⁸) within EP67 induce structural changes that increase potency and selective activation of mononuclear phagocytes over neutrophils. Cis/trans isomerization at these positions, however, likely limits the activity of EP67 and low coupling efficiency between Pro⁷ and nme-Leu⁸ increases scale-up costs for clinical use. Thus, the goals of this study were to …

Evaluation Of A Technology-Based Survivor Care Plan For Breast Cancer Survivors: Pre-Post Pilot Study., Talya Laufer, Bryan Lerner, Anett Petrich, Anna Quinn, Leah Ernst, Alicin Roop, Janet Knoblauch, Nick C. Leasure, Rebecca J. Jaslow, Sarah Hegarty, Amy Leader, Andrea Barsevick

Department of Medical Oncology Faculty Papers

BACKGROUND: As of 2016, almost 16 million individuals were cancer survivors, including over 3.5 million survivors of breast cancer. Because cancer survivors are living longer and have unique health care needs, the Institute of Medicine proposed a survivor care plan as a way to alleviate the many medical, emotional, and care coordination problems of survivors.

OBJECTIVE: This pilot study for breast cancer survivors was undertaken to: (1) examine self-reported changes in knowledge, confidence, and activation from before receipt to after receipt of a survivor care plan; and (2) describe survivor preferences for, and satisfaction with, a technology-based survivor care plan. …

: Examining How Factors Associated With Patients, Physicians, Hospitals, And Surrounding Communities Affect Primary And Repeat Cesarean Delivery Through A Social-Ecological Lens, Christina Ventura-Dipersia

Dissertations and Theses

Background: Childbirth is one of the most common reasons for hospitalization in the U.S., and Cesarean delivery (i.e., surgical childbirth) is costlier and has a higher likelihood of birth-related complications, maternal rehospitalization, and postpartum medical care utilization than vaginal delivery. The rate of Cesarean delivery in the United States (U.S.) has increased in recent years by over 60%, from 20.7% of all births in 1996 to 32.9% of all births in 2011. As Although this increasing trend of Cesarean delivery incidence has also been seen in other countries, the rate of Cesarean delivery has been rising more steadily within …

Leader At The Bedside: A Mixed Methods Study Establishing Clinical Staff Nurse Leadership Competencies, Sherron Denise Franks-Meeks

Nursing Theses and Dissertations

Significance and Background

Leadership competencies were established for formal nursing roles (i.e. nurse executives), but not for informal nurse leader roles (i.e. clinical staff nurse leader). A set of comprehensive clinical staff nurse leader (CSNL) competencies would facilitate evaluation of the CSNL role in providing safe, quality, and efficient patient care.

Purpose

The purpose of this pilot was to establish a preliminary set of CSNL competencies with associated set of knowledge, skills, and attitudes (KSAs) for each competency identified through the CSNL’s voice. Theory & Design Underpinned by the Authentic Leadership Theory, this pilot was a multiphase sequential explanatory mixed …

Computational Studies And Design Of Pparγ And Glut1 Inhibitors, Suliman Almahmoud

Theses & Dissertations

The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor of the nuclear receptor superfamily that controls the expression of a variety of genes involved in fatty acid metabolism, adipogenesis, and insulin sensitivity. PPARγ is a target for insulin-sensitizing drugs, and it plays a significant function in prostate cancer. PPARγ antagonists have anti-proliferative effects in a broad range of hematopoietic and epithelial cell lines. The ligand binding domain (LBD) of PPARγ is large and has orthosteric and allosteric binding sites. Several PPARγ-ligand co-crystal structures show two bound molecules, one to the orthosteric pocket and a second to the allosteric …

The Effectiveness Of Resin-Modified Glass Ionomer Varnish In Preventing White Spot Lesions During Fixed Appliance Orthodontic Therapy: An In Vitro Study, Bradley Herman

Theses & Dissertations

The purpose of this investigation was to evaluate the efficacy of a glass ionomer varnish in preventing demineralization of enamel adjacent to and some distance away from an orthodontic bracket. Forty extracted human molars were divided into four different treatment groups (varnish in distilled water, varnish in acetic acid, enamel in acetic acid, and enamel in distilled water). Two 3 x 3 mm graphite windows were drawn on the tooth, one adjacent to the bracket and one 3 mm away from the first window, indicating the scanning area. Varnish was applied to the teeth in the varnish groups and all …

The Ethical Justification Of Increasing Awareness Of Preventive Medicine Among Healthcare Professionals, Patients And The General Public In The United States, Karishma Ether Moazzam

Electronic Theses and Dissertations

While practiced for centuries, preventive medicine has received increased attention during the recent times. Preventive medicine has a distinct mission to protect, promote, and maintain health as well as to prevent diseases, disabilities, and premature deaths. It aims to fulfill its mission through the combined form of clinical intervention and health promotion. In the recent years, preventive medicine has begun to lean more towards the clinical interventions, taking away from the health promotion. This imbalance has caused preventive medicine to lose its effectiveness in fulfilling its mission. One of the leading causes for such imbalance is the lack of proper …