Digital Commons Network^™

Effects Of Gaba On Inflammation And Intestinal Barrier Disruption, Tyrel W. Long

EWU Masters Thesis Collection

Gut dysbiosis and intestinal barrier disruption have been linked to multiple sclerosis (MS). Our previous works show that experimental autoimmune encephalomyelitis (EAE) induction modifies the gut's microbiota composition, reducing frequencies of gamma-aminobutyric acid (GABA)-producing bacteria. GABA levels are reduced in the brains and circulation of MS patients. We engineered Lactococcus lactis with extra copies of gadB (glutamic acid decarboxylase) and gadC (glutamate/GABA antiporter) to increase GABA levels produced by the bacterium (GAD-L. lactis). EAE studies showed that the treatment with GAD-L. lactis and not with a L. lactis control expressing an empty plasmid (P-L. lactis) reduced the severity of the …

The Significance Of Cell-Surface Α2,3-Linked Sialic Acid In Osteoclasts, Christopher S. Harding

EWU Masters Thesis Collection

Osteoclasts are giant, multinucleated cells that, alongside osteoblasts, are central to maintaining physiologically healthy bone. The functions of osteoclasts and osteoblasts-degrading and depositing bone matrix, respectively-are paired in healthy bone tissue, thereby yielding no net bone loss or deposition. When these functions become imbalanced, it results in net bone loss or gain, depending on which cell type is being outcompeted. Osteoporosis is one of the most common pathologies stemming from such an imbalance, and predominantly affects postmenopausal women, as the ablation of circulating estrogen-a pro-death signal for osteoclasts-causes a prolongation of osteoclast lifespan and consequent lengthening of their resorptive activity. …

Healing Sanctuary, Kammy Downs

Master's Theses or Doctor of Nursing Practice

The natural world has hidden wisdom and resources that are disregarded as we misuse our responsibility to care for them. The benefits of being in tune with nature have been traded for a culture that manipulates nature on the altar of expediency, waste, and unquenchable desire. Healing Sanctuary presents a duality. My work speaks about the relationship between the seen and unseen, represented by ten larger-than-life drawings of medicinal herbal plants that have had a profound physical healing effect on me. At the same time, plants, roots, and seeds create visceral metaphors for mental health. Our accomplishments, outlook on life, …

The Effect Of Young Blood Anti-Aging Treatment On Protein Markers Of Age And Huntington Disease, Sujena H. Koilpillai

Honors Undergraduate Theses

Huntington disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine tract within the huntingtin (HTT) protein, forming mutant HTT (mtHTT). HD patients suffer from psychiatric, behavioral, cognitive, and motor abnormalities, with death typically occurring 15-20 years after symptom onset. Currently, there are no treatments able to slow disease progression or delay onset. HD is a disease of aging. Despite the mtHTT protein being produced throughout life, symptoms do not typically appear until adulthood. Furthermore, many cellular effects of normal aging are also seen in HD, including altered intercellular communication and loss of proteostasis. Recently, our lab found …

Regulation Of The Protease Activity For The Mitochondrial Omi/Htra2, Simon Larson

Honors Undergraduate Theses

Human High Temperature requirement A2 (HtrA2) also known as Omi, is a serine protease located in the mitochondria with an important function in both cell survival and death. My results show the proteolytic activity of Omi/HtrA2 varies under different conditions. I characterized the optimal condition for Omi/HtrA2 protease activity using an in vitro assay system. Additionally, I identified a new allosteric regulation of Omi/HtrA2 through interaction with a specific substrate, the MUL1 protein. MUL1 is a multifunctional E3 ubiquitin ligase anchored in the outer mitochondrial membrane with domains both inside mitochondria and in the cytoplasm. The data shown here strongly …

Essential Factors For A Healthy Microbiome: A Scoping Review, Patricia Grace-Farfaglia, Heather Frazier, Maura D. Iversen

Health Science Faculty Publications

Recent discoveries of the purpose and potential of microbial interactions with humans have broad implications for our understanding of metabolism, immunity, the host–microbe genetic interactions. Bioavailability and bioaccessibility of phytonutrients in foods not only enrich microbial diversity in the lower human gastrointestinal tract (GIT) but also direct the functioning of the metagenome of the microbiota. Thus, healthy choices must include foods that contain nutrients that satisfy both the needs of humans and their microbes. Physical activity interventions at a moderate level of intensity have shown positive effects on metabolism and the microbiome, while intense training (>70% VO₂max) …

Presentation Characteristics And Clinical Outcome Of Patients With Giant Cell Arteritis Followed By A Single Center, Mert Öztaş, Hami̇t Özgül, Emi̇re Seyahi̇, Serdal Uğurlu

Turkish Journal of Medical Sciences

Background/aim: Giant cell arteritis (GCA) is a large vessel vasculitis that may cause significant morbidity in the elderly population. We aimed to evaluate presentation characteristics, treatment, and outcome in a cohort of patients with GCA diagnosed and followed in a single center. Materials and methods: A retrospective chart review revealed 84 (41 M/43 F) registered patients diagnosed with GCA between 1990 and 2020. Clinical features at presentation and follow-up, radiographical imaging, temporal artery biopsy (TAB), and laboratory findings were retrieved from digital medical records or hard-copy patient files. Of these, 33 patients- follow-up period was less than 12 months; hence, …

Pd-L1 And Ebv Lmp1 Expressions In Classic Hodgkin Lymphomas And Its Correlation With Clinicopathological Parameters And Prognosis, Süleyman Özdemi̇r, Özlem Ton, Fevzi̇ye Kabukcuoğlu

Turkish Journal of Medical Sciences

Background/aim: Programmed death pathway leads to T cell anergy. Wide range of malignancies take advantage of this pathway by programmed death-ligand 1 (PD-L1) expression either on neoplastic cells or on the nonneoplastic cells of tumour microenvironment. New therapeutic approaches have been directed against this pathway. We studied PD-L1 expression on both neoplastic Hodgkin and Reed-Sternberg (HRS) cells and cells of tumour microenvironment in classic Hodgkin lymphoma (CHL) patients and compared it with Ebstein-Barr virus (EBV) positivity, clinical data, and survival rates. Materials and methods: Lymph node excision materials of 56 CHL patients diagnosed between 2007 and 2017 were included in …

A Combination Of Q-Tof Lc/Ms And Lc-Ms/Ms Based Metabolomics In Pediatric-Onset Multiple Sclerosis Demonstrates Potential Biomarkers For Unclassified Patients, İsmai̇l Solmaz, Ozan Kaplan, Mustafa Çelebi̇er, İnci̇lay Lay, Fatma Banu Anlar

Turkish Journal of Medical Sciences

Background/aim: Metabolomics has the potential to provide putative biomarkers and insights into the pathophysiology and diagnosis of pediatric multiple sclerosis (pMS), which is an inflammatory demyelinating disorder of the central nervous system with a broad spectrum of clinical manifestations. In this study, we aimed to investigate serum metabolomics in pMS to help elucidate the pathophysiology of MS. Materials and methods: An untargeted approach was applied using the quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS) method to study plasma metabolites in patients with pMS (n = 33), patients with unclassified central nervous system demyelinating diseases (n = 6), and age-matched healthy …

The Role Of Pericytes On The Efficacy Of Bevacizumab In Colorectal Cancer, Merve Besler, Fatma Sena Dost, Fi̇li̇z Çay Şenler, Bi̇lge Ayça Kirmizi, Berna Savaş, Hakan Akbulut

Turkish Journal of Medical Sciences

Background/aim: Pericytes are mesenchymal cells surrounding capillary vessels and are known to play an essential role in tumor angiogenesis. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface proteoglycan and its release from pericytes and vascular smooth muscle cells is very important in tumor angiogenesis. Bevacizumab, which is a monoclonal antibody frequently used in the treatment of metastatic colorectal cancer, binds to the ligand of vascular endothelial growth factor A (VEGFA) and inhibits tumor angiogenesis. However, no reliable biomarker for predicting patients that will show a good response to this therapy has been established yet. In this study, we aimed …

The Survival Outcomes And Prognostic Factors Of Hepatocellular Carcinoma Among Type 2 Diabetes Patients: A Two-Centre Retrospective Cohort Study, Noor Atika Azit, Shahnorbanun Sahran, Voon Meng Leow, Manisekar K. Subramaniam, Suryati Mokhtar, Azmawati Mohammed Nawi

Turkish Journal of Medical Sciences

Background/aim: To determine the survival outcomes and prognostic factors associated with hepatocellular carcinoma (HCC) survival in type 2 diabetes (T2D) patients. Materials and methods: This was a retrospective cohort study involving two hepatobiliary centres from January 1, 2012, to June 30, 2018. Medical records were analysed for sociodemographic, clinical characteristics, laboratory testing, and HCC treatment information. Survival outcomes were examined using the Kaplan?Meier and log-rank test. Prognostic factors were determined using multivariate Cox regression. Results: A total of 212 patients were included in the study. The median survival time was 22 months. The 1-, 3-, and 5-year survival rates were …

Low Handgrip Strength Is Associated With Diabetic Foot Disease In Geriatric Patients With Type 2 Diabetes, Eren İmre, Neşe Koçakgöl, Erdi̇ İmre

Turkish Journal of Medical Sciences

Background/aim: This study aims to reveal the prevalence of low handgrip strength in older patients with type 2 diabetes who have diabetic foot disease and to assess the association of handgrip strength with diabetic foot disease in older patients with type 2 diabetes. Materials and methods: Eighty-nine geriatric patients with diabetic foot ulcers and 69 patients without diabetic foot ulcers who presented to the endocrinology outpatient clinic between August 2020 and November 2021 were included in the study. The exclusion criteria were the usage of steroids, stroke-induced quadriplegia, myopathy, disability, hemodialysis treatment, type 1 diabetes, patients under 65 years of …

Mammalian Target Of Rapamycin Cell Signaling Pathway In Phosphatase And Tensin Homolog Induced Kinase 1 Knockout Rat Model Of Familial Parkinson's Disease, Martha Helena Mortell

Theses and Dissertations--Medical Sciences

More than 10 million people are living with Parkinson’s disease (PD), one million of which are people in the United States. PD is the second most common age-related neurodegenerative disorder, after Alzheimer’s disease, and is characterized by the accumulation of a-synuclein aggregates and the degeneration of dopaminergic neurons. The loss of endogenous dopamine in PD brain accounts for the motor decline presented clinically in PD patients. Etiological factors of PD include oxidative damage and inflammation, although the detailed mechanisms remain unknown. Risk factors for PD include gender, age, environmental factors, and gene mutations.

The current thesis research employed phosphatase and …

Apoe Genotype And Sex Modulate Ketogenic Diet Enhancements To Metabolism And Gut Microbiome In Young Mice, Andrew T. Yackzan

Theses and Dissertations--Medical Sciences

The apolipoprotein ε (APOE) allele in humans has been associated with risk for development of Alzheimer’s disease (AD). There are predominately three variations of the allele – ε2 (E2), ε3 (E3), and ε4 (E4) – with E4 contributing the greatest risk of AD development. Recent research has unveiled evidence of neurometabolic and neurovascular deficits in E4 carriers present decades before the onset of dementia; it is believed these chronic defects play a major role in the development of AD, thus making them a potential target for preventative intervention. The purpose of this study was to examine the effect of a …

Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia, along with Alzheimer’s disease (AD), and often manifests as a comorbidity of AD. Elevated plasma homocysteine, known as hyperhomocysteinemia (HHcy), is a risk factor for VCID; however, the mechanism underlying the connection between HHcy and development of VCID pathology remains elusive. Understanding this mechanism would reveal novel therapeutic targets with the potential to be disease modifying, which are a critical need for a disease that lacks any approved treatment. Previous studies from our lab have strongly associated neuroinflammation and blood brain barrier (BBB) dysregulation …

Establishment And Verification Of A Sars Cov2 Antibody Detection Assay Comparing Venous And Mitra Samples, Stephen C. Mayer

Theses and Dissertations--Medical Sciences

During the COVID-19 pandemic in 2020, the need for highly-specific, wide-spread, and rapid serological testing surged. In this study, we showed very strong positive correlation between venous blood collection and Mitra home sampling kits for the detection of anti- spike IgGs using an in-house ELISA protocol (based on a protocol from Mt. Sinai). This study demonstrates the utility of using at-home, patient-centric testing to enhance the sero-surveillance methods currently in place for viral tracking and monitoring.

Art Education In Medical Education: Benefits And Challenges, Sara K. Brown

Theses and Dissertations--Art and Visual Studies

Humanity is synergistic with art and medicine. Likewise, art education can be impactful throughout medical education. Art as a tool to develop the next generation of healthcare differs from the clinical goals of creative art therapies. Over the prior decade, many medical schools now provide curricular offerings in the arts and humanities. Less is known about the application in postgraduate medical settings. The focus of this thesis is to review the pairing of artist-educators with postgraduate medical training programs.

One such program is ArtsCAFE (Arts Connect Around Food and Enrichment), an intercollegiate project fusing experienced arts educators with medical educators …

A Study Of The Analysis Of Hemp-Derived Oil Products: Development Of A Method For The Analysis Of Phytocannabinoids In Medicinal Products, Erin Johnson

Theses and Dissertations--Pharmacology and Nutritional Sciences

Human interactions with cannabis have a history spanning millennia as a source of fiber, food, and medicine. The plant came across Asia, Europe, and Africa with the movements of people and travelers eventually coming to the Americas with European explorers. In colonizing North America, cannabis fiber was key to the production of canvas and ropes for ships. Although fiber was the driver for cannabis production in the United States, medicinal uses were prevalent and propelled the eventual regulations. The Pure Food and Drug Act of 1906 mandated accurate labeling on drugs such as cannabis followed by the Marihuana Tax Act …

Modeling The Effects Of Adverse Childhood Experiences Using A Mouse Model Of Neglect: Mechanisms Of Adiposity Expansion In Females, Jacqueline Leachman

Theses and Dissertations--Pharmacology and Nutritional Sciences

Adverse childhood experiences (ACEs) are an independent risk factor for chronic disease, including obesity and metabolic syndrome. We have previously shown that a mouse model of early life stress, maternal separation and early weaning (MSEW), exacerbates high-fat diet (HF)-induced obesity only in adult female mice. In agreement, the analysis of several cohorts of participants exposed to ACEs have shown that women are more susceptible to develop obesity than men. Therefore, the aim of this study was to investigate the link between early life stress and obesity in pre-clinical and clinical settings. Male and female MSEW mice fed 1 week a …

Nutritional Status In Critical Care Of Covid-19 Patients, Dolph Lewis Davis Iii

Theses and Dissertations--Nutrition and Food Systems

Critical care nutrition is a poorly researched, and such a sudden pandemic event requiring manipulation of nutritional status via propofol-induced sedation for mechanical ventilation is potentially impactful on patient outcomes. This paper seeks to provide context to the impact of critical care protocols on the nutritional status of obese patients suffering from COVID-19.

How Exercise Affects The Musculoskeletal System In The Biological Sexes: A Literature Review, Lauren Connolly

Honors Program Theses

Exercise has countless benefits for the human body. Physical activity increases overall health and reduces the risk of developing many chronic diseases. While the entire body is impacted by exercise, the musculoskeletal system is perhaps targeted most directly. Muscle contraction is required to complete any form of exercise, which helps build muscle mass and consequently strengthens bones. The physiology of musculoskeletal growth after exercise is the same for all individuals. However, the magnitude of this growth is not the same for men and women. Men have a profound ability to gain muscle mass that most women are not capable of …

The Application Of The Skin Virome For Human Identification, Ema H. Graham, Jennifer Clarke, Samodha Fernando, Joshua Herr, Michael Adamowicz

Nebraska Center for Virology: Faculty Publications

The use of skin virome offers a unique approach for human identification purposes in instances where a viable and statistically relevant human DNA profile is unavailable. The skin virome may act as an alternative DNA profile and/or an additional form of probative genetic material. To date, no study has attempted to investigate the human virome over a time series across various physical locations of the body to identify its diagnostic potential as a tool for human identification. For this study, we set out to evaluate the stability, diversity, and individualization of the human skin virome. An additional goal was to …

Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to …

Treatment Of Hypothyroidism: Desiccated Thyroid Extract, Aimee Fong

Capstone Showcase

The treatment of hypothyroidism with Levothyroxine (T4) has been well studied and FDA approved. However, many patients continue to have signs and symptoms of hypothyroidism while on Levothyroxine treatment despite reaching appropriate thyroid levels. An additional thyroid treatment known as desiccated thyroid extract (DTE) is made from dried pig thyroid glands and is advertised as a “natural” alternative to Levothyroxine. Despite lack of FDA approval and studies surrounding DTE, clinicians have prescribed DTE to patients, many of whom reported relief of their symptoms. The following poster highlights the approach to the treatment of hypothyroidism with Levothyroxine and DTE and outlines …

The Safety Of Covid-19 Vaccines In Pregnancy, Lauren Zacharias

Capstone Showcase

SARS-CoV-2 has caused over 800,000 deaths in the United States since it was first detected here in 2020. Despite there being 3 available COVID-19 vaccines in the US, and recommendations by the CDC and countless other public health agencies that any potential risks are outweighed by the benefit of the vaccines, only 31% of pregnant women in the US are vaccinated against COVID-19 due to unfounded claims by an anti-vaccination movement that COVID mRNA vaccines cause infertility. This presentation explores where these claims originated, why they are untrue, the risks of COVID-19 infections in pregnancy, and the potential benefits of …

Plasmonic-Based Biosensor For The Early Diagnosis Of Prostate Cancer, Thakshila Liyanage, Bayan Alharbi, Linh Quan, Aurora Esquela-Kerscher, Gymama Slaughter

Bioelectrics Publications

A tapered optical fiber (TOF) plasmonic biosensor was fabricated and used for the sensitive detection of a panel of microRNAs (miRNAs) in human serum obtained from noncancer and prostate cancer (PCa) patients. Oncogenic and tumor suppressor miRNAs let7a, let-7c, miR-200b, miR-141, and miR-21 were tested as predictive cancer biomarkers since multianalyte detection minimizes false-positive and false-negative rates and establishes a strong foundation for early PCa diagnosis. The biosensing platform integrates metallic gold triangular nanoprisms (AuTNPs) laminated on the TOF to excite surface plasmon waves in the supporting metallic layer and enhance the evanescent mode of the fiber surface. …

The Role Of The Bone Marrow Microenvironment In Flt3-Itd Acute Myeloid Leukemia Stem Cell Resistance To Flt3 Inhibition, Nicholas R. Anderson

All ETDs from UAB

Acute myeloid leukemia (AML) is an aggressive, complex hematological malignancy. AML cases with constitutively-activating internal tandem duplications in the Flt3 receptor (Flt3-ITD) represent a distinct subtype of disease with poor prognosis, but unique opportunities for targeted therapy. Flt3-specific tyrosine kinase inhibitors (TKI) have entered clinical practice due to their ability to induce remissions in a large proportion of Flt3-mutant AML patients, but their long-term efficacy remains limited due to the persistence of leukemia stem cells (LSC) in the bone marrow (BM). Herein, we outline the importance of the bone marrow microenvironment (BMM) in harboring LSC through AML development and drug …

Defining Genetic Underpinnings Of Cellular Diversity And Vulnerability In The Context Of Parkinson's Disease, Stephanie M. Boas

All ETDs from UAB

of ALL survivors are at risk for reduced functional outcomes, and these outcomes may be more strongly related to executive functioning than neighborhood-specific variables or IEP support. Long-term goals include translating findings into practice to remediate adaptive or academic difficulties in ALL survivors.

Gabra5 Plays A Sexually Dimorphic Role In Pomc Neuron Activity And Glucose Balance, Zhou Pei, Yang He, Jonathan C Bean, Yongjie Yang, Hailan Liu, Meng Yu, Kaifan Yu, Ilirjana Hyseni, Xing Cai, Hesong Liu, Na Qu, Longlong Tu, Kristine M Conde, Mengjie Wang, Yongxiang Li, Na Yin, Nan Zhang, Junying Han, Camille Hs Potts, Nikolas A Scarcelli, Zili Yan, Pingwen Xu, Qi Wu, Yanlin He, Yong Xu, Chunmei Wang

Children’s Nutrition Research Center Staff Publications

Pro-opiomelanocortin (POMC) neurons are important for the regulation of body weight and glucose balance. The inhibitory tone to POMC neurons is mediated primarily by the GABA receptors. However, the detailed mechanisms and functions of GABA receptors are not well understood. The α5 subunit of GABAA receptor, Gabra5, is reported to regulate feeding, and we found that Gabra5 is highly expressed in POMC neurons. To explore the function of Gabra5 in POMC neurons, we knocked down Gabra5 specifically from mature hypothalamic POMC neurons using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 strategy. This POMC-specific knock-down of Gabra5 did not affect …

Tissue-Specific Mechanisms Of Bile Acid Homeostasis And Activation Of Fxr-Fgf19 Signaling In Preterm And Term Neonatal Pigs, Caitlin Vonderohe, Greg Guthrie, Barbara Stoll, Shaji Chacko, Harry Dawson, Douglas G Burrin

Children’s Nutrition Research Center Staff Publications

The tissue-specific molecular mechanisms involved in perinatal liver and intestinal farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling are poorly defined. Our aim was to establish how gestational age and feeding status affect bile acid synthesis pathway, bile acid pool size, ileal response to bile acid stimulation, genes involved in bile acid-FXR-FGF19 signaling and plasma FGF19 in neonatal pigs. Term (n = 23) and preterm (n = 33) pigs were born via cesarean section at 100% and 90% gestation, respectively. Plasma FGF19, hepatic bile acid and oxysterol profiles, and FXR target gene expression were assessed in pigs …