Medicine and Health Sciences Commons^™

Can Mirna Be The Missing Link Between Parkinson’S Disease And Pesticides?, Fatma Gobba

Theses and Dissertations

Parkinson’s disease (PD) is a common neurodegenerative condition that leads to significant morbidity and a decline in the quality of life. It develops as a consequence of the loss of dopaminergic neurons in the substantia nigra pars compacta. Nevertheless, the development of PD is influenced by environmental factors, and the intricate nature of these relationships is further complicated by a multitude of factors, including the genetic backgrounds that are specific to populations and variations in environmental exposures, such as pesticides. Pesticides, consisting of a diverse family of chemicals commonly used in both agricultural and household settings to protect crops against …

Sperm Dna Integrity In Absolute Teratozoospermia Patients And Its Impact On Assisted Reproductive Technology Outcome, Dina Faris

Theses and Dissertations

Sperm DNA Fragmentation (SDF) is a common cause of male infertility, although it is underdiagnosed due to lack of routine testing. High levels of SDF are reported in men with abnormal sperm morphology. However, the implications of such findings on live birth following Intracytoplasmic Sperm Injection (ICSI) have not been studied in absolute teratozoospermia men (100% abnormal sperm morphology). In this prospective study, the severity of DNA damage was evaluated in absolute teratozoospermia patients and its impact on ICSI outcomes, particularly live birth rate. My study included 36 men with absolute teratozoospermia and 30 men with normal sperm. Real-time assessment …

Differential Transcriptional Alterations In Detoxification Genes In Parkinson’S Disease In Egypt, Nourhan Shebl

Theses and Dissertations

PD is the most common motor neurodegenerative disease worldwide. The underlying cause of PD is still unknow, owingthis to the complexity of the disease. Often, genetics and environmental factors are collaborating in the initiation of the disease. Despite the diversity of its genetical and environmental profiles, the Egyptian population is one of the mostunderrepresented population in terms of PD research. In this study, we investigated PD through various perspectives tohighlight the complexity of the disease in Egypt, taking into consideration the diversity of the Egyptian population. We recruited PD patients and reference controls from 4 governorates: Cairo, Giza, Alexandria, and …

Investigating The Role Of Vasopressin Receptor 1a Expressing Neurons In Mouse Dorsal Raphe, Tirth Nimishbhai Patel

Theses and Dissertations

Human social interactions heavily impact our physical and mental wellbeing. Arginine-vasopressin (Avp) and serotonin have both been implicated in modulation of social behaviors ranging from affiliation to aggression. In male mice, Avp neurons in the bed nucleus of stria terminalis (BNST) show increased activity during prosocial behavior. BNST sends Avp afferents to the dorsal raphe (DR) in the midbrain, a home to a large portion of serotonin neurons in the mouse brain. Previous data suggests that DR is activated during male prosocial behavior with a female stimulus, and Avp indirectly excites serotonin neurons. We hypothesized that DR contains a population …

A Learning Health System For Radiation Oncology, Rishabh Kapoor

Theses and Dissertations

The proposed research aims to address the challenges faced by clinical data science researchers in radiation oncology accessing, integrating, and analyzing heterogeneous data from various sources. The research presents a scalable intelligent infrastructure, called the Health Information Gateway and Exchange (HINGE), which captures and structures data from multiple sources into a knowledge base with semantically interlinked entities. This infrastructure enables researchers to mine novel associations and gather relevant knowledge for personalized clinical outcomes.

The dissertation discusses the design framework and implementation of HINGE, which abstracts structured data from treatment planning systems, treatment management systems, and electronic health records. It utilizes …

Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky

Theses and Dissertations

Modern cancer treatment uses radiation therapy in over 50% of patient cases. It is an e↵ective way of treating tumors because the mechanisms of cell killing are well known through the damage that ionizing radiation does to DNA. The amount of radiation can be tracked through measuring the dose of the clinical photon or electron beam used. However, there are limitations in the usage of radiation therapy, for example, a tumor can create hypoxic areas that become radioresistant leading to complete ine↵ectiveness of further radiation treatment. This project looks into the application of cold atmospheric plasma as an adjuvant therapy …

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …

Contribution Of Metabolic Cell Swelling On Microcirculatory Perfusion In Septic Shock, Charles E. Payne

Theses and Dissertations

Sepsis, a systemic immunological response that leads to organ-dysfunction, the development of septic shock, and death has mortality rate of 15-25%. A subset of sepsis, septic shock, has an in-hospital mortality rate of 30-50%. Sepsis and its treatment are the most expensive healthcare problem in the United States with the US Agency for Healthcare Research and Quality estimating annual costs over $20 billion. Hypoxia experienced in septic shock induces metabolic cell and tissue swelling leading to further microcirculatory dysfunction and poor tissue perfusion. Reversing metabolic cell swelling corrects these perfusion defects. Two models were used in rats to induce septic …

Molecular Mechanisms Of Prdm16 As A Tumor Suppressor In Pancreatic Ductal Adenocarcinoma, Eric Hurwitz

Theses and Dissertations

The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-b) signaling, whose inactivation is deemed essential to the progression of pancreatic ductal adenocarcinoma (PDAC). Using the Kras^G12D-based mouse model of human PDAC, we surprisingly found that ablating Prdm16 did not block but instead accelerated PDAC formation and progression, suggesting that Prdm16 might function as a tumor suppressor in this malignancy. Subsequent genetic experiments showed that ablating Prdm16 along with Smad4 resulted in a shift from a well-differentiated and confined neoplasm to a highly aggressive and metastatic disease, which was associated with a striking deviation …

Role Of The Ormdls In Keratinocytes, Souad Hatmi

Theses and Dissertations

The epidermis, the outermost layer of the skin, serves as a vital barrier protecting the body from environmental stressors, pathogens, and dehydration. Keratinocytes, the predominant cell type in the epidermis, play a central role in maintaining skin integrity and barrier function. In normal human skin, keratinocytes move from the basal layer to the stratum corneum, the top layer of the epidermis. In their travel, keratinocytes undergo a process of terminal differentiation, loss their ability to proliferate, secrete sphingolipids into the extracellular space, and gradually loss their nucleus and organelles. Sphingolipids, particularly ceramides, are key components of the intercellular lipid lamellae …

Evaluation Of Spliceai For Improved Genetic Variant Classification In Inherited Ophthalmic Disease Genes, Melissa Reeves

Theses and Dissertations

ABSTRACT

EVALUATION OF SPLICEAI FOR IMPROVED GENETIC VARIANT CLASSIFICATION IN INHERITED OPHTHALMIC DISEASE GENES

By Melissa Jean Reeves, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2023

Major Director: Melissa Jamerson, PhD, MLS(ASCP)

Associate Professor, Department of Medical Laboratory Sciences

Inherited ophthalmic diseases impact individuals around the globe. Inherited retinal diseases (IRDs) are the leading cause of blindness in individuals aged 15 to 45. The personal, social, and economic impact of vision loss is profound. Due to individual differences, symptoms can be variable, and …

A Preliminary Investigation Of Neuroantibody Levels, Prevalence, And Environmental Factors In Patients With Neurological Dysfunction, Jihan Azar

Theses and Dissertations

Nervous system damage comprises a large proportion of diseases worldwide. It is also the most difficult to diagnose. Biomarkers for nervous system damage are needed in order to diagnose these diseases early enough to allow for intervention. In this study, we recruited patients from two Egyptian hospitals with MCI, ET and NMS and health references. Serum autoantibody levels against neural proteins and heavy metals were analyzed and compared. Immunoglobulin G (IgG) antibodies against neurofilament H (NFH), Glial Fibrillary Acidic Protein (GFAP), Myelin Basic Protein (MBP) and alpha synuclein (a-SYN) and Immunoglobulin M (IgM) antibody against neurofilament light (NFL) were among …

Assessing Identification Of Newly Diagnosed Breast Cancer Patients For Referral To Genetic Counseling, Corinne Marie Locke

Theses and Dissertations

Since 1998, the National Comprehensive Cancer Network (NCCN) guidelines have specified clinical indications for genetic testing for breast cancer susceptibility genes, but retrospective studies have shown that, despite meeting the NCCN criteria, patients are not always advised of the option of genetic testing. Further compounding this issue, studies have shown that cancer family history intake and documented family history can be incomplete even when taken by oncology providers. At this study site and other cancer centers in the country, patients with a new diagnosis of breast cancer are referred for genetic counseling by their cancer care team if they are …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Modeling Of Patient-Specific Periaortic Mechanics And Pulmonary Artery Hemodynamics Based On Phase-Contrast Magnetic Resonance Imaging Sequences., Johane H. Bracamonte

Theses and Dissertations

Inverse modeling in cardiovascular medicine is a collection of methodologies that can provide non-invasive patient-specific estimations of clinical risk factors using medical imaging as inputs. Its incorporation into clinical practice has the potential to improve diagnosis and treatment planning with low associated risks and costs.

Herein, three different phase contrast magnetic resonance imaging (MRI) modalities were implemented as input data, displacement encoding with stimulated echoes (DENSE MRI) applied, and time-resolved velocity encoding phase-contrast MRI, in 1D and 3D, applied to pulmonary artery (PA) hemodynamics.

A model to account for the effect of periaortic interactions due to static and dynamic structures …

Investigating The Role Of Nlrp3 Inflammasome In Chemotherapy-Induced Peripheral Neuropathy, Urszula O. Warncke

Theses and Dissertations

Paclitaxel and oxaliplatin are commonly used antineoplastic drugs that cause chemotherapy-induce peripheral neuropathy (CIPN) in up to 90% of patients. The sensory symptoms of CIPN include numbness, loss of proprioception, tingling, spontaneous burning, shooting or electric shock-like pain, mechanical and thermal allodynia, and cold hypersensitivity among others. Affected patients struggle with daily activities, have a low quality of life, and might stop cancer treatment. Unfortunately, there are no effective prophylactic or therapeutic treatments for these side effects. Many studies point to the involvement of inflammation as a major contributor of CIPN pathology. We investigated the effects of genetic (NLRP3 …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko

Theses and Dissertations

Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …

Anthracyclines Attenuate The Nrf1-Mediated Bounce-Back Response, Bader Albalawi

Theses and Dissertations

Proteasome inhibitors, such as carfilzomib, are FDA-approved to treat multiple myeloma and mantle cell lymphoma. Unfortunately, proteasome inhibitors have only produced clinically significant results in patients with hematologic cancers, despite their predicted pan-cancer utility, and even hematologic cancer types frequently show intrinsic and acquired resistance.

One proposed mechanism responsible for the proteasome inhibitors' shortcomings is the NRF1-mediated bounce-back response. Identification of drugs that can potentiate the action of proteasome inhibitors could overcome resistance in patients with hematologic cancers and expand proteasome inhibitors' use to treat solid tumors. Our previous studies have identified anthracyclines as potential compounds that interfere with the …

Crosstalk Between Hippo And Rb Tumour Suppressor Pathways In Ovarian Cancer, Fatmata Sesay

Theses and Dissertations

The cell cycle is a highly regulated process that ensures the timely and accurate division of cells. Events of the normal cell cycle fall under two categories - positive and negative regulatory mechanisms. The first category, positive regulatory machinery, includes active protein complexes of cyclins in association with their partnering cyclin-dependent kinases (cyclin/CDK), which mediate series of phosphorylation events that relay a cell cycle progression from one stage to the next. The second category, the negative regulatory mechanisms, include the checkpoint controls consisting of the retinoblastoma (RB) family of proteins, some of which can form a transcriptional repressor complex DREAM. …

Macronutrient Intake: A Multi-Sport Study Of Female Division I Collegiate Athletes, Ffion Price

Theses and Dissertations

Background: Macronutrients play a critical role within collegiate athletes’ performance and health, with carbohydrates providing most of the energy needs for most athletes. There is little research examining the macronutrient intake of healthy collegiate female athletes across sports. The aim of the present study was to compare macronutrient intakes of female collegiate athletes within different sports and compare their intakes to recommendations. Methods: An observational study was conducted to determine whether a sample of female collegiate athletes (n=26) consumed the IOC nutritional recommendations. Sports included within the study were soccer, basketball, volleyball, and cross-country. Athletes were asked to complete a …

Relationship Between Cognitive Performance, Physical Activity, And Socio-Demographic/ Individual Characteristics Among Aging Americans, Imtiaz Masfique Dowllah

Theses and Dissertations

Despite the attenuation of association following adjustments for covariates, participants who engaged in 3–6 hr/wk of vigorous- and > 1 hr/wk of moderate-intensity PA scored significantly higher in tests that assessed executive function and processing speed domains of cognition compared to inactive peers (η2 = 0.005 & 0.007 respectively, p < 0.05). Also, after adjustment, the effects of 1–3 hr/wk of vigorous-intensity PA became trivial for the delayed recall memory domain test scores (β = 0.33; 95% CI: –0.01, 0.67; η2 = 0.002; p = 0.56). There was no clear dose-response relationship between the cognitive test scores and weekly moderate-intensity PA. Interestingly, higher handgrip strength and higher late-life body-mass-index were associated with a higher performance across all cognitive domains. Observed associations provide evidence linking habitual PA with superior cognition health among older adults. Furthermore, increased muscle strength and higher late-life adiposity may …

Hipertensioni Arterial Dhe Njohuritë E Të Semurëve Në Lidhje Me Dietën Dhe Stilin E Jetesës, Kaltrina Rexhepi Rizani

Theses and Dissertations

Hipertensioni është një problem serioz me ndikim të rëndësishme për individët, familjet, komunitetin dhe shërbimet shëndetësore. Hipertensioni arterial përcaktohet rritja e presionit të gjakut përmbi vlerat që konsiderohen normale. Sipas kritereve të përcaktuara nga OBSH (Organizata botërore e shëndetit) vlerat normale të presionit arterial janë rreth 140 mmHg, ndërsa presioni diastolik duhet ti ketë vlerat rreth 90 mmHg. Dihet se presioni arterial nuk është konstant dhe në periudha të ndryshme gjatë ditës ndryshon nga vlerat më të larta gjatë sistolës në vlerat më të ulëta gjatë diastolës së zemrës. Qëllimi i këtij studimi është të kuptojmë se cilët janë faktorët …

Cilësia E Jetës Te Pacientët Me Diabet Tip 2, Arta Rama

Theses and Dissertations

Hyrja: Diabeti mellitus i tipit 2 (T2DM) është një problem global shëndetësor në zgjerim, i lidhur ngushtë me epideminë e mbipeshes. Individët me diabet mellitus tip 2 janë në rrezik të lartë për të dy ndërlikimet mikrovaskulare (përfshirë retinopatinë, nefropatinë dhe neuropatinë) dhe komplikimet makrovaskulare (të tilla si sëmundjet kardiovaskulare) për shkak të hiperglikemisë dhe përbërësve individualë të sindromës së rezistencës ndaj insulinës (metabolike).

Qëllimi: Ky punim ka për qëllim ngritjen e cilësisë së jetës te personat që vuajnë nga diabeti mellitus tip 2, pra përmirësimin e jetesës, këshillimin që të mirren me sporte të ndryshme, përfshirë këtu ecjen …

“Menaxhimi Infermieror I Pacientëve Me Kancer Të Gjirit”, Elmira Çovanaj

Theses and Dissertations

Hyrje- Duke pasur parasysh se kanceri i gjirit tregon një rritje të përditshme të rasteve dhe këto rritje flasin për një dyfishim të rasteve në dekadat e ardhshme, atëherë në punim jam fokusuar në funksionet e gjirit si dhe anatominë dhe fiziologjinë e tij. Poashtu kam përshkruar patologjitë e gjirit,ndryshimet që ndodhin tek gjinjtë,etiologjia e semundjes etj.Kam përmendur faktorët e rrezikut,faktorët e dyshimt,faktorët e ndryshueshëm,faktorët e pandryshueshëm si dhe faktorët gjenetik. Një ndër rolet kryesore në trajtimin e kancerit të gjirit e luan infermierja.Roli i saj është i pazëvendësushëm. Qëllimi i punimit- Qëllim kryesor kam pasur të tregoj faktorët e …

Satisfaksioni I Infermierëve Me Kushtet E Punës Në Kujdesin Parësor Në Lipjan, Leonard Buja

Theses and Dissertations

Hyrje: Kënaqësia e punës së infermierëve është një aspekt shumë i rëndësishëm dhe një pikë shqetësimi për cdo organizatë shëndetsore. Infermierët kanë vendet më të shumta të punës në këto institucione, dhe zëvendësimi i personelit është i kushtueshëm dhe konsumon shumë kohë. Në punën spitalore shumë kolegë infermierë janë të ekspozuar ndaj niveleve të ndryshme të kënaqësisë në punë, por cfarë i bën infermierët të jenë të kënaqur ose jo me profesionin e tyre, të cilin mund ta kenë zgjedhur edhe vetë. Qëllimi i punimit: Qëllimi i këtij punimi ishte vlerёsimi i kënaqshmërisë në punë i infermierëve me kushtet e …

Njohuritë Dhe Praktikat Për Kontraceptivët Tek Femrat, Nexhibe Rexhepi

Theses and Dissertations

Në rastin e hartimit të këtij hulumtimi shkencor jam përpjekur që nivelin teorik e sistematik të trajtimit të qështjeve të caktuara të ia përshtasë parimeve të caktuara pedagogjike. Gjithashtu jam përpjekur që temën ta trajtoj në detaje, qysh nga kohët e lashta prej kur ka filluar njohja e metodave kontraceptive, përdorimi i tyre dhe inovacionet e tyre si pasojë e nevojave njerëzore për mbrojtjen nga sëmundjet transmisive dhe rritjes së kontrollit në lindje.

Abortet e shpeshta, numri i madhë i Shtatëzanive të padëshiruara, Edukimi i ulët seksual në Shoqërinë tonë më kanë shtyer të hulumtoj më shumë rreth këtyre çështjeve …

Ndikimi I Mjedisit Në Sëmundjet Kronike Obstruktive Të Mushkërive Dhe Shëndeti, Fitore Salihi

Theses and Dissertations

Sëmundja kronike obstruktive e mushkërive (SKOM) është shkaku kryesor i sëmundshmërisë dhe vdekshmërisë në të gjithë botën. Zhvillimi dhe përkeqësimi i SKOM ndikohen nga faktorët e mjedisit. Pirja e duhanit e cigareve është një faktor kryesor i rrezikut për sëmundjen e SKOM, dhe pirja e duhanit në mjedis gjithashtu kontribuon në zhvillimin e tij. Ekspozimi në punë ndaj avullit, pluhurit, gazit dhe tymrave janë faktorë të tjerë të rëndësishëm të rrezikut për sëmundjen e sëmundjes SKOM. Ndotja e ajrit në natyrë rrit pranimet në spital të lidhura me SKOM dhe është një faktor i rëndësishëm për përkeqësimin e sëmundjes dhe …

Cilësia E Jetës Tek Pacientët Me Diabet Të Tipit 2 Në Regjionin E Gjilanit, Lindita Rexhepi Ramadani

Theses and Dissertations

Diabeti është një sëmundje kronike që kërkon kujdes të vazhdueshëm mjekësor dhe edukim të pacientit për vetë-menaxhimi për të parandaluar komplikimet akute dhe për të zvogëluar rrezikun e komplikimeve afatgjata. Kujdesi ndaj diabetit është kompleks dhe kërkon që të adresohen shumë çështje, përtej kontrollit glikemik. Qëllimi i këtij hulumtimi është matja e cilësisë së jetës së personave me diabet te tipit 2. Përmes të dhënave të mbledhura do të synohet të paraqitet një pasqyrë e cilësisë së jetës së personave me diabet të tipit 2. Në studimin e realizuar kanë marrë pjesë 50 pacientë me diabet të tipit 2, të …