Medicine and Health Sciences Commons^™

Purinergic Signaling During Porphyromonas Gingivalis Infection, C. Silva, A. C. Morandini, David M. Ojcius, R. Coutinho-Silva,

All Dugoni School of Dentistry Faculty Articles

Despite recent advances unraveling mechanisms of host–pathogen interactions in innate immunity, the participation of purinergic signaling in infection-driven inflammation remains an emerging research field with many unanswered questions. As one of the most-studied oral pathogens, Porphyromonas gingivalis is considered as a keystone pathogen with a central role in development of periodontal disease. This pathogen needs to evade immune-mediated defense mechanisms and tolerate inflammation in order to survive in the host. In this review, we summarize evidence showing that purinergic signaling modulates P. gingivalis survival and cellular immune responses, and discuss the role played by inflammasome activation and cell death during …

Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo

Electronic Theses and Dissertations

Sexually transmitted infections affect hundreds of millions of worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir …

Memory And Fine Motor Skill Test Performance Among Children Living Near Coal Ash Storage Sites., Lindsay Koloff Tompkins

Electronic Theses and Dissertations

Coal ash, a byproduct of coal combustion,is reduced in 47 U.S. states andfrequently contains heavy metals, some of which are known neurotoxins. An estimated 1.5 million children live near sites where coal ash is produced andstored, yet there have been no studies assessing coal ash exposure and children’s neuro behavioral health. This study is part of a larger cross-sectional study, Coal Ash and Neuro behavioral Symptoms in Children Aged 6- 14 Years Old, and aimed to determine the relationship between children’s memory and fine motor skill test performance and the proximity of the home to coal ash storage sites, the …

The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka

Electronic Theses and Dissertations

Global augmentation of protein O-GlcNAcylation occurs in response to a myriad of stressors and confers a survival advantage at the cellular level. This protective phenomenon has been demonstrated to mediate cardioprotection through various in vitro and in vivo studies during ischemia-reperfusion, myocardial infarction, and oxidative stress; however, relatively little is known of the regulation of protein O-GlcNAcylation. Protein O-GlcNAcylation is regulated by two antagonistic enzymes, namely, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ablation of cardiomyocyte OGT, the enzyme that catalyzes the addition of O-GlcNAc to proteins, exacerbates cardiac dysfunction during infarct-induced heart failure (HF). However, little is known of the …

Peptoanaerobacter Stomatis Interactions With Neutrophils., Emeri Jimenez Flores

Electronic Theses and Dissertations

Peptoanaerobacter stomatis is a newly appreciated taxon, present in high numbers in oral biofilms from periodontal patients. However, little is known about this organism’s potential virulence and its interaction with the host immune response. Therefore, to better understand the role of P. stomatis in periodontitis, we studied its interactions with neutrophils. Human neutrophils were challenged with P. stomatis strain CM2 or S. aureus AF488 (positive control) for 30 min. Bacterial internalization was examined by ImageStreamX imaging flow cytometry. Bacterial viability was assessed by colony-forming unit assays and Baclight assays. Phagocytosis-stimulated respiratory burst response was measured by flow cytometry. The fusion …

Type 2 Diabetes Mellitus (T2dm) Onset And "Remission"., Srikanth Tangelloju

Electronic Theses and Dissertations

Background: Type 2 diabetes mellitus (T2DM) is a progressive disease condition. As the disease progresses the function of beta (β) cells (cells which regulate insulin) decline, thereby increasing the circulating blood glucose levels. If left unmanaged the disease progresses from onset to development of T2DM related complications and eventually death. When managed, in certain individuals, T2DM onset can be prevented and/or slowed down and in certain T2DM individuals, remission is observed. There are some known modifiable risk factors such as diet and physical activities that are associated with the speed and direction of progression, but much is still unknown. In …

Carnosine, A Therapeutic Potential For Critical Limb Ischemic., Adjoa Agyemang Boakye

Electronic Theses and Dissertations

Critical Limb ischemia (CLI) is a serious manifestation of peripheral artery disease. Advanced CLI patients are poor candidates for vascular surgeries. Numerous studies have shown that hypoxia inducible factor 1α (HIF1-α) plays an important role in recovery from murine hindlimb ischemia (HLI). HIF1-α is regulated by oxygen dependent prolyl hydroxylases (PHDs). Previous studies have shown that inhibition of PHDs by metal quenchers and viral delivery of HIF1-α improves blood flow to the ischemic limb. However, clinical trials with these therapies are largely negative partly because they do not address the underlying chronic oxidative stress. Based on recent observations that endogenous …

The Impact Of The Patient Protection And Affordable Care Act’S Risk Adjustment Program On Adverse Selection : First Year Case Study., Steven K. Zimmerman

Electronic Theses and Dissertations

In 2014 the Patient Protection and Affordable Care Act (ACA) implemented a risk adjustment program to stabilize premiums and neutralize premiums in the individual health insurance marketplace. This dissertation will examine the impact of the ACA risk adjustment program on adverse selection for one insurer during 2014. This study utilized enrollment and claims data for one insurer and employs graphical analysis to test for adverse selection. Previous studies have been unable to utilize actual insurer data to test for adverse selection in under the ACA risk adjustment program. Until the implementation of the ACA, insurers relied on underwriting methods to …

Air Pollution, Pulmonary Oxidative Stress, And The Endothelin System In The Development Of Cardiovascular Injury., Jordan B. Finch

Electronic Theses and Dissertations

The goal of this project was to examine the role of endothelin-1 (ET-1) as a mediator in the pathway between air pollution exposure and the development of vascular injury. A human cohort and male mice (C57BL/6 and ecSOD-Tg) were used to evaluate changes in the ET-1 system in response to exposures of fine particulate matter (PM2.5). Human ET-1 levels were significantly associated with environmental factors and markers of vascular change, but were decreased with increased PM2.5. No association was seen between ET-1 and endothelial progenitor cells (EPCs) except for EPC-4, possibly indicating a regulatory relationship with this specific population. In …

Vinyl Chloride-Diet Interactions In Liver Disease : Potential Roles Of Autophagy And Energy Management., Anna L. Lang

Electronic Theses and Dissertations

Vinyl chloride (VC) is a prevalent environmental toxicant that has been shown to cause liver injury at high, occupational exposures. However, most studies have not addressed interactions of low doses with risk-modifying factors. This study aims to explore low-level VC metabolite exposure interactions with other potential risk-modifying factors and their effect on underlying liver disease. We examined sub-hepatotoxic effects of a VC metabolite (chloroethanol, CE) in two murine models of liver injury using ethanol and lipopolysaccharide (LPS). In both, CE significantly enhanced liver injury when compared to either ethanol or LPS alone. Previous studies have shown an increase in mTOR …

Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva

Electronic Theses and Dissertations

Background: Hyperhomocysteinemia (HHcy) has been observed to promote hypertension, but the mechanisms are unclear. Toll-like receptor 4 (TLR-4) is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. TLR-4 activation has been shown to promote inflammation that has been associated with pathogenesis of hypertension. In this study, we hypothesize that HHcy induces hypertension by TLR-4 activation that promotes inflammatory cytokine up-regulation (IL-1β, IL-6, TNF-α) and initiation of mitochondrial dysfunction leading to cell death and chronic vascular inflammation. Methods: To test this hypothesis, we used C57BL/6J mice (WT); Cystathionine-β-synthase deficient mice (CBS+/-) with genetic mild …

Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp

Electronic Theses and Dissertations

Cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury (AKI) in 30% of patients. Although recovery can occur after one episode of cisplatin-induced AKI, studies have indicated multiple episodes may lead to the development of chronic kidney disease (CKD), an irreversible disease with no current treatments. The standard mouse model of cisplatin-induced AKI consists of one, high dose of cisplatin (> 20 mg/kg) that is lethal to the animal three days later. This model doesn’t accurately reflect the repeated dosing regimen patients receive, and doesn’t allow for long-term outcome studies of pathologies associated with CKD. We have developed a …

Life Balance In Adult Healthy Siblings Of Individuals With Childhood Cancer., Yolanda Williams

Electronic Theses and Dissertations

Siblings of children who were diagnosed with cancer in childhood experience significant stress and psychological difficulties as a result of the cancer. Furthermore, the needs of siblings have often been overlooked in the cancer literature, prompting the need for more studies. The purpose of this dissertation is to examine the life balance and social support outcomes of adults who grew up in the household with a sibling that was diagnosed with cancer. The study sample consisted of 120 adult healthy siblings who grew up in a household with a sibling that was diagnosed with cancer prior to age 19. Participants …

Impact Of Luminance And Spatial Parameters On The Generation Of The Human Pattern Electroretinogram., Kate A. Godwin

Electronic Theses and Dissertations

The current work assessed some of the key hypotheses behind the generation of the pattern electroretinogram (PERG) response. The first of these hypotheses states that the PERG response is the result of linear cancellation of simultaneous increment and decrement retinal responses, as generated by the retinal ON- and OFF-pathways. Experiment 1 evaluated the possibility of simulating the PERG by summing the ERG responses elicited by increment and decrement flashes, and found that it was indeed possible to simulate the PERG from these responses. However, only the steady-state PERG could be modeled consistently. The second hypothesis evaluated a theory that the …

The Discovery Of A Novel, Ras-Mediated Nore1a/Pmliv Tumor Suppressor Complex., Jessica Mezzanotte Sharpe

Electronic Theses and Dissertations

Ras is the most commonly activated oncogene in human cancer. Activated Ras drives cell growth and proliferation by activating multiple mitogenic signaling pathways. However, Ras also has the paradoxical ability to promote anti-growth, pro-apoptotic, and pro-senescent signaling. The signaling pathways of many of these biological effectors remain poorly defined. One group of proteins capable of promoting Ras-induced apoptosis and cell cycle arrest is the RASSF family of tumor suppressors. Novel Ras Effector 1A, or NORE1A, was the first member of this family discovered and is a bona fide tumor suppressor that is lost or inactivated in a number of different …

Characterization Of Pg1604 (Porz) As An Essential Component Of Type 9 Secretion System In Porphyromonas Gingivalis., Apurva Tadimari Prabhakar

Electronic Theses and Dissertations

Background: The numerous virulence factors of Porphyromonas gingivalis are essential for the organism to invade host tissues while escaping immune responses [1, 2]. Some of these factors, like major proteases referred to as gingipains, are secreted by a unique secretion system called PerioGate or Type IX Secretion System (T9SS). T9SS consists of a number of membrane and periplasmic proteins, which provide transportation only for proteins that possess a conserved C-terminal domain (CTD). The CTD functions as a specific recognition signal for the T9SS. PG1604 of P. gingivalis W83 is a CTD-containing protein, which has been shown in our initial studies …

In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah

Electronic Theses and Dissertations

Klebsiella pneumoniae causes an acute respiratory infection in human with severe outcomes and high mortality rates even with antibiotic treatment. Even with its critical clinical importance, few virulence systems have been identified for K. pneumoniae limiting the development of new therapeutic strategies. Accordingly, we performed Next Generation sequencing for the strain ATCC 43816, a virulent strain in mouse respiratory disease models, and compared its genomic data with two previously sequenced strains NTUH-K2044 and MGH 78578 for the purpose of identifying genes required for colonizing host lungs. Furthermore, the virulence potential of the three K. pneumoniae strains were tested in a …

Β1 Integrin- And Jnk-Dependent Tumor Growth Upon Hypofractionated Radiation., Aejaz Sayeed, Huimin Lu, Qin Liu, David Deming, Alexander Duffy, Peter Mccue, Adam P. Dicker, Roger J. Davis, Dmitry Gabrilovich, Ulrich Rodeck, Dario C. Altieri, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Radiation therapy is an effective cancer treatment modality although tumors invariably become resistant. Using the transgenic adenocarcinoma of mouse prostate (TRAMP) model system, we report that a hypofractionated radiation schedule (10 Gy/day for 5 consecutive days) effectively blocks prostate tumor growth in wild type (β1wt /TRAMP) mice as well as in mice carrying a conditional ablation of β1 integrins in the prostatic epithelium (β1pc-/- /TRAMP). Since JNK is known to be suppressed by β1 integrins and mediates radiation-induced apoptosis, we tested the effect of SP600125, an inhibitor of c-Jun amino-terminal kinase (JNK) in the TRAMP model system. Our results show …

Type 1 Diabetes Mellitus Presenting With Diabetic Ketoacidosis (Dka) In A Neonate, Fareed Ahmed, Sayyeda Ghazala Kazi, Waqas Khan

Department of Emergency Medicine

Neonatal diabetes mellitus (NDM) is a rare manifestation with an incidence of one affected individual among 400000 live births. NDM can be divided into Transient (TNDM) and Permanent (PNDM) types. A significant overlap occurs between both groups, to an extent that TNDM cannot be distinguished from PNDM based solely on clinical features. Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). DKA at diagnosis is more common in young children near the age of five years. Neonatal DKA is a rare occurrence causing it to be missed in the differential …

“Let’S Work: Involving Nursing Students In The Care Of Elderly People At Nursing Home”, Mehtab Qutbuddin Jaffer, Shanaz Hussein Cassum

School of Nursing & Midwifery

Working in nursing homes is the most challenging task for a nursing staff, but at the same time it can be a spirit jarring experience for young nursing students. From the perspective of nursing students, often students find it difficult to deal with elderly people living in the nursing home. They feel stressed, depressed, and insecure when asked to communicate with elderly people. At the Aga Khan University School of Nursing and Midwifery (AKU-SONAM), baccalaureate nursing students chose an elective course on care of elderly clients, where theory is offered in a blended form and clinical experience is provided by …

Three Siblings With Familial Non-Medullary Thyroid Carcinoma: A Case Series, Owais Rashid, Naeemul Haque, Saad Farooq, Zareen Kiran,, Sabeeh Siddique, Shahid Pervez

Department of Biological & Biomedical Sciences

Abstract

BACKGROUND:

In 2015, thyroid carcinoma affected approximately 63,000 people in the USA, yet it remains one of the most treatable cancers. It is mainly classified into medullary and non-medullary types. Conventionally, medullary carcinoma was associated with heritability but increasing reports have now begun to associate non-medullary thyroid carcinoma with a genetic predisposition as well. It is important to identify a possible familial association in patients diagnosed with non-medullary thyroid carcinoma because these cancers behave more destructively than would otherwise be expected. Therefore, it is important to aggressively manage such patients and screening of close relatives might be justified. Our …

Analysis Of Rater Reliability Using A Faculty Developed, Revised Osce Evaluation Instrument, Tamara Andrews

Nursing Dissertations - Archive

Nurse educators need valid and reliable instruments to evaluate student performance during summative clinical experiences and Objective Structured Clinical Examinations (OSCEs). The purpose of this retrospective, secondary data analysis was to analyze existing data to determine whether there were differences between raters using a faculty-developed, revised OSCE instrument designed to evaluate student performance in a summative course OSCE. Data were extracted from an existing database collected during a prior study to compare OSCE instruments, within a large, urban college of nursing. Data were examined for a sample of 44 subjects whose OSCE performances were rated by faculty using the revised …

Quantitative Proteomic Analysis Of Stratum Corneum Dysfunction In Adult Chronic Atopic Dermatitis., Jason M Winget, Deborah Finlay, Kevin J Mills, Tom Huggins, Charles Bascom, Robert J Isfort, Robert L Moritz

Articles, Abstracts, and Reports

No abstract provided.

Daily Rhythms Of Physiological Parameters In The Dromedary Camel Under Natural And Laboratory Conditions, Ahmed A. Al-Haidary, Khalid A. Abdoun, Emad M. Samara, Aly B. Okab, Mamane Sani, Roberto Refinetti

Psychological Sciences Faculty Publications and Presentations

Camels are well adapted to hot arid environments and can contribute significantly to the economy of developing countries in arid regions of the world. Full understanding of the physiology of camels requires understanding of the internal temporal order of the body, as reflected in daily or circadian rhythms. In the current study, we investigated the daily rhythmicity of 20 physiological variables in camels exposed to natural oscillations of ambient temperature in a desert environment and compared the daily temporal courses of the variables. We also studied the rhythm of core body temperature under experimental conditions with constant ambient temperature in …

Reduced Motor Neuron Excitability Is An Important Contributor To Weakness In A Rat Model Of Sepsis, Paul Nardelli, Jacob A. Vincent, Randall K. Powers, Timothy C. Cope, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. We previously identified difficulty with motor unit recruitment in patients as a novel contributor to ICUAW. To study the mechanism underlying poor recruitment of motor units we used the rat cecal ligation and puncture model of sepsis. We identified striking dysfunction of alpha motor neurons during repetitive firing. Firing was more erratic, and often intermittent. Our data raised the possibility that reduced excitability of motor neurons was a significant contributor to weakness induced by sepsis. In this study we quantified the contribution of reduced motor neuron …

The Wooden Doctrine: Basketball, Moral Character, And The Successful Life, Janelle Dewitt

Center for the Study of Ethics in Society Papers

No abstract provided.

Crispr Humans: Ethics At The Edge Of Science, Insoo Hyun

Center for the Study of Ethics in Society Papers

No abstract provided.

Long-Term Clinical Outcome Of Peripheral Nerve Stimulation For Chronic Headache And Complication Prevention, Linqiu Zhou, Avi Ashkenazi, Joseph W. Smith, Na Jen, Timothy R. Deer, Chen Zhou

Department of Anesthesiology Faculty Papers

Background: Subcutaneous peripheral nerve stimulation (PNS) has emerged as a useful tool in the treatment of intractable headaches. However, complications such as skin erosion, infection and lead migration have adversely affected clinical outcome, and occasionally led to treatment cessation. Objectives: Here we report the results of peripheral nerve stimulator implantation performed on 24 patients with various chronic headaches at our center over a period of 9 years. We describe the complications of the procedure and their prevention with a modified surgical technique. Patients and Methods:We searched our database for patients with chronic refractory headacheswhohad undergone PNS. Patients were assessed before …

Induction Of Human Embryonic Stem Cell Derived Retinal Stem Cells In Vitro Using Transient Overexpression Of Messenger Rna For Blimp, Onecut1 And Otx2, Helen Cifuentes

Dissertations, Masters Theses, Capstones, and Culminating Projects

No abstract available

Extracorporeal Delivery Of A Therapeutic Enzyme, Chun Zhang, Jun Pu, Xiaolan Yang, Tao Feng, Fang Liu, Deqiang Wang, Xiaolei Hu, Ang Gao, Hongbo Liu, Chang-Guo Zhan, Fei Liao

Molecular Modeling and Biopharmaceutical Center Faculty Publications

To remove circulating harmful small biochemical(s)/substrates causing/deteriorating certain chronic disease, therapeutic enzyme(s) delivered via vein injection/infusion suffer(s) from immunoresponse after repeated administration at proper intervals for a long time and short half-lives since delivery. Accordingly, a novel, generally-applicable extracorporeal delivery of a therapeutic enzyme is proposed, by refitting a conventional hemodialysis device bearing a dialyzer, two pumps and connecting tubes, to build a routine extracorporeal blood circuit but a minimal dialysate circuit closed to circulate the therapeutic enzyme in dialysate. A special quantitative index was derived to reflect pharmacological action and thus pharmacodynamics of the delivered enzyme. With hyperuricemic blood …