Medical Sciences Commons^™

Physiological And Pharmacological Roles Of Melatonin In The Pathophysiologicalcomponents Of Cellular Injury After Ischemic Stroke, Ertuğrul Kiliç, Berrak Çağlayan, Mustafa Caglar Beker

Turkish Journal of Medical Sciences

Apart from its metabolic or physiological functions, melatonin has a potent cytoprotective activity in the physiological and pathological conditions. It is synthetized by the pineal gland and released into the blood circulation but particularly cerebrospinal fluid in a circadian manner. It can also easily diffuse through cellular membranes due its small size and lipophilic structure. Its cytoprotective activity has been linked to its potent free radical scavenger activity with the desirable characteristics of a clinically- reliable antioxidant. Melatonin detoxifies oxygen and nitrogen-based free radicals and oxidizing agents, including the highly toxic hydroxyl-and peroxynitrite radicals, initiating cellular damage. However, the cytoprotective …

Graft-Versus-Cancereffect And Innovative Approaches In Thetreatment Of Refractorysolid Tumors, Uğur Şahi̇n, Taner Demi̇rer

Turkish Journal of Medical Sciences

Background/aim: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been used for the treatment of various refractory solid tumors during the last two decades. After the demonstration of graft-versus-leukemia (GvL) effect in a leukemic murine model following allo-HSCT from other strains of mice, graft-versus-tumor (GvT) effect in a solid tumor after allo-HSCT has also been reported in a murine model in 1984. Several trials have reported the presence of a GvT effect in patients with various refractory solid tumors, including renal, ovarian and colon cancers, as well as soft tissue sarcomas [1]. The growing data on haploidentical transplants also indicate GvT …

Bmp And Tgfß Use And Release In Bone Regeneration, Zeynep Bal, Junichi Kushioka, Joe Kodama, Takashi Kaito, Hideki Yoshikawa, Petek Korkusuz, Feza Korkusuz

Turkish Journal of Medical Sciences

A fracture that does not unite in nine months is defined as nonunion. Nonunion is common in fragmented fractures and large bone defects where vascularization is impaired. The distal third of the tibia, the scaphoid bone or the talus fractures are furthermore prone to nonunion. Open fractures and spinal fusion cases also need special monitoring for healing. Bone tissue regeneration can be attained by autografts, allografts, xenografts and synthetic materials, however their limited availability and the increased surgical time as well as the donor site morbidity of autograft use, and lower probability of success, increased costs and disease transmission and …

Adjustable Bone Plate: State Of Art, Gazi̇ Huri̇

Turkish Journal of Medical Sciences

Background/aim: The success of treatment of bone fracture and defects are based on a proper contact and compression between the bone fracture fragments. Intraoperative manipulations such as bone compression or distractions are generally done in order to achieve this. However, none of the bone plates currently in routine use allow these manipulations after fixation to the bone, requiring refixation and repeated drilling, and screwing operations. Based on this shortcoming, we designed a novel adjustable bone plate (ABP) system which allows bone shortening and lengthening even after fixation to the bone surface. The aim of the paper is to clarify the …

Hippocampal Cholinergic Function And Exploratory Behavior Throughout Development In A Genetic Mouse Model Of Alzheimer’S Disease, Ashley Andrea Blackwell

Graduate Research Theses & Dissertations

Dementia of the Alzheimer’s type is the most common form of dementia, affecting millions of people worldwide. Specific genetic mutations increase Alzheimer’s disease-related neuropathology and cognitive impairments. Deficits are observed in spatial orientation throughout the progression of Alzheimer’s disease, including wandering behavior or becoming lost in a familiar environment. Dementia of the Alzheimer’s type patients also exhibit disruptions in radial optic flow, which underlies self-movement cue processing. Currently, no treatments exist for Alzheimer’s disease. Genetic mouse models of Alzheimer’s disease have been developed to investigate the disease onset and progression and, further, to evaluate potential therapies and behavioral assessments. As …

Understanding The Host Immune Response Against Pseudomonas Aeruginosa To Develop Novel Therapeutics And Vaccines, Emel Sen Kilic

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium that causes a broad range of acute and chronic infections. The high adaptability and emergence of multidrug-resistant strains of this bacterium pose a significant threat to human health. Particularly, pneumonia caused by this pathogen is associated with high morbidity and mortality in immunocompromised patients. To prevent these infections, we aimed to develop novel vaccine strategies by characterizing the host immune response against P. aeruginosa. During respiratory infections, P. aeruginosa first contacts with epithelial cells along the respiratory tract. Using RNA-sequencing, we were able to characterize transcriptional changes of the epithelial cells in …

Will Pitch Velocity Remain Consistent Throughout A Competitive Baseball Season Following Blood Flow Restriction: An Observational Study, Mackenzie Marie Evans

Graduate Theses, Dissertations, and Problem Reports (ETD)

Context: Blood flow restriction (BFR) has previously been used in a rehabilitation setting to decrease the external load applied to post-surgical patients and those with chronic debilitating conditions. BFR in a performance context has been explored minimally, particularly as it applies to baseball pitching over time. Objective: The purpose of this study was to retrospectively investigate the trend in throwing velocity of fastballs with BFR implementation over one competitive season. Design: This study was a retrospective longitudinal design on pitching velocity of fastballs throughout a competitive season. Setting: The data collection and analysis was completed at …

Faculty Publications 2019, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 841 publications.

Clincial Translational Science Research Of The Functional Role Of Large Conductance Potassium Channels In Selective Destruction Of Triple Negative Breast Cancer Cells, Gina Sizemore

Graduate Theses, Dissertations, and Problem Reports (ETD)

ABSTRACT

The preliminary background that puts this research into context is threefold; it is the aggressive nature of triple negative breast cancer (TNBC), the complexity surrounding its pathology, and the significant lack of targeted treatment for this disease. To clarify the focus of my research, I have concentrated on identifying a targeted treatment for TNBC. In the process, I have identified cycles of reciprocity between treatment, clinical diagnosis, staging, and pathology that will be addressed in smaller papers. However, the weight of this work is in the discovery of a novel target for triple negative breast cancer. The value of …

Pulmonary Immune Responses To Respirable Elongate Mineral Particles Of Asbestiform And Non-Asbestiform Morphologies, Timur Khaliullin

Graduate Theses, Dissertations, and Problem Reports (ETD)

Inhalation exposure to asbestiform elongate mineral particles (EMPs) may cause pulmonary fibrosis, lung and pleural cancer. At the same time, epidemiological evidence for non-asbestiform EMP pathogenicity is scarce, with little if any risk of cancer, but consistent findings of pneumoconiosis and increased mortality. Globally, conditions caused by asbestos exposures contribute most to the occupational cancer burden and are responsible for the increasing mortality for occupational respiratory diseases. Immunological components of the fiber-induced lesions are extremely understudied, partly due to the lack of comparable test articles. In this study I utilized respirable preparations of asbestiform and non-asbestiform riebeckite and tremolite to …

Obese Zucker Rats As A Reverse Translational Model Of Human Left Ventricular Hypertrophy, Mackenzie Shelby Newman

Graduate Theses, Dissertations, and Problem Reports (ETD)

Heart failure is a lifelong disability that for over half of those affected leads to mortality within five years after initial diagnosis. Left ventricular hypertrophy (LVH) is one of the most reliable independent predictors of heart failure. Pathological LVH is irreversible, but early diagnosis is often missed due to its asymptomatic nature. Obese Zucker rats (OZR), which develop obesity due to dysfunctional leptin signaling, naturally exhibit a LVH that mimics the obese human condition. Animal models are necessary because human donor tissue is scarce. The central hypothesis is that genes and proteins that are differentially expressed during development of LVH, …

Words Have A Weight: Language As A Source Of Inner Grounding And Flexibility In Abstract Concepts, Guy Dove, Laura Barca, Luca Tummolini, Anna M. Borghi

Faculty and Staff Scholarship

The role played by language in our cognitive lives is a topic at the centre of contemporary debates in cognitive (neuro)science. In this paper we illustrate and compare two theories that offer embodied explanations of this role: the WAT (Words As social Tools) and the LENS (Language is an Embodied Neuroenhancement and Scaffold) theories. WAT and LENS differ from other current proposals because they connect the impact of the neurologically realized language system on our cognition to the ways in which language shapes our interaction with the physical and social environment. Examining these theories together, their tenets and supporting evidence, …

Investigating The Behavioral Effects Of Juvenile Stress In The Prairie Vole Model, Marigny C. Normann

Graduate Research Theses & Dissertations

Early life stress during the juvenile period, such as emotional neglect, interpersonal difficulties, or other forms of non-violent maltreatment can have consequences into adulthood. Specifically, the negative effects include increased risk of psychiatric or physical illnesses, social deficits, and maladaptive behavioral responses to stress. Since these effects have far-reaching implications that can negatively alter later behavior and physiology, the present study assessed the effects of early life social stress on later social and affective behaviors in a social rodent species – the prairie vole. The prairie vole displays behavioral, cardiovascular, and neuroendocrine responses to social stress similar to those of …

The Role Of Medial Septum Cholinergic Function In Processing Self-Movement Cues To Maintain Spatial Orientation, Jenna Rae Osterlund

Graduate Research Theses & Dissertations

Wandering is the most life-threatening and commonly reported symptom of Alzheimer’s Disease (AD), a neurodegenerative disorder characterized by an inability to maintain spatial orientation. The often deadly consequences of wandering are projected to rise in the coming decades due to the advancing aged population. These upcoming challenges necessitate a more comprehensive understanding of the neurobiology of spatial orientation in order to evaluate novel therapeutic techniques for symptoms such as wandering. The inability to maintain spatial orientation in AD may be due to the pathological degeneration of the hippocampal cholinergic system. This neurological system is conserved across species for its function …

A Framework For Heterologous Biosynthesis Of Natural Products In Mammalian Cells Via Polymer-Mediated Transfections, Logan Warriner

Theses and Dissertations--Chemical and Materials Engineering

With the promise to treat a multi-faceted list of serious inherited and acquired diseases, such as cancer, neurodegenerative and infectious diseases, and inherited genetic indications, gene therapy has continued to push the boundaries of traditional medicine since its earliest implementation. While much progress has been made, clinical success has largely remained elusive. Immunogenicity, difficulty producing commercially relevant quantities, and having a limited genetic payload still limits the ability of viruses to act as directed delivery agents for genetic material. As such, researchers have turned to cationic synthetic materials as a means of delivering nucleic acids, which can circumvent the immune …

Brain Development: Why The Young Sleep Longer, Budhaditya Chowdhury, Orie T. Shafer

Advanced Science Research Center

From absorbing new languages to mastering musical instruments, young children are wired to learn in ways that adults are not (Johnson and Newport, 1989). This ability coincides with periods of intense brain plasticity during which neurons can easily remodel their connections (Hubel and Wiesel, 1970). Many children are also scandalously good sleepers, typically getting several more hours of sleep per night than their parents (Jenni and Carskadon, 2007). As sleep deprivation has negative effects on learning and memory, learning like a child likely requires sleeping like one (Diekelmann and Born, 2010). Yet, how the ability to sleep for longer is …

Circuit Development In The Master Clock Network Of Mammals, Vania Carmonia-Alcocer, Kayla Rohr, Deborah A.M. Joye, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Daily rhythms are generated by the circadian timekeeping system, which is orchestrated by the master circadian clock in the suprachiasmatic nucleus (SCN) of mammals. Circadian timekeeping is endogenous and does not require exposure to external cues during development. Nevertheless, the circadian system is not fully formed at birth in many mammalian species and it is important to understand how SCN development can affect the function of the circadian system in adulthood. The purpose of the current review is to discuss the ontogeny of cellular and circuit function in the SCN, with a focus on work performed in model rodent species …

Spatial Memory And Executive Functioning In The Goto-Kakizaki Rat Model Of Diabetes, Lorielle Dietze

Theses and Dissertations (Comprehensive)

Type 2 diabetes mellitus is a disease that adversely affects cognitive function in areas extending to memory and executive functioning. The Goto-Kakizaki (GK) rat provides a model of type 2 diabetes that can illustrate the mechanisms by which this disease works. The present study compared hyperglycaemic GK rats and age-matched Wistar rats in the Morris water maze to assess spatial memory, and in a perceptual attentional set-shifting task to assess putative prefrontal-dependent executive functioning. Results showed there was no difference in path length during training trials, however, GK and Wistar rats differed in the path length travelled in the target …

I Was Determined To Breastfeed, And I Always Found A Solution: Successful Experiences Of Exclusive Breastfeeding Among Chinese Mothers In Ireland, John Kearney, Qianling Zhou, Haoyue Chen, Katherine Younger, Tanya M. Cassidy

Articles

Background: The prevalence of exclusive breastfeeding for at least 4 months was previously found to be very low among Chinese immigrants in Ireland, at 5.8% (Zhou et al., Front Public Health 6:351, 2018). This study investigates the successful experiences of Chinese mothers living in Ireland who exclusively breastfeed for between four and 6 months.

Methods: Participants were recruited from the sample of the Ireland Chinese Mother Survey. Qualitative in-depth interviews were conducted with fourteen participants in their homes or public places.

Results: A content analysis revealed that various factors contributed to a successful experience of exclusive breastfeeding among the group …

Novel Mechanisms Of Nitric Oxide Activation In The Kidney, Randee Sedaka

All ETDs from UAB

Globally, adult sodium consumption has far exceeded daily intake recommendations, leading to one in ten cardiovascular deaths. Given the rise in hypertension prevalence, uncontrolled hypertension with antihypertensive medication use, and significant associations between high salt intake and high blood pressure, there is a need to better understand the mechanisms involved in hypertension. Nitric oxide synthase 1 (NOS1) is a well-established regulator of fluid and electrolyte balance in the renal collecting duct (CD) with highest activity in the inner medulla (IM). We previously reported that high salt (HS) intake stimulates CD endothelin B receptor (ETBR)/NOS1-dependent generation of NO, thereby inhibiting the …

Diurnal Dysfunction In Control Of Sodium Excretion In Diet-Induced Obesity, Reham Soliman

All ETDs from UAB

The renal endothelin system plays a key role in sodium excretion, particularly under high salt (HS) diet. HS stimulates renal endothelin-1 (ET-1), which binds and activates the endothelin receptor B (ETB) to excrete the excess salt. Loss of ETB receptor is linked to the development of hypertension under HS. Central clock genes are important in maintaining rhythmic patterns of sodium excretion and ET-1 is identified as a target for clock genes, including Period and Bmal1. ET-1 excretion follows a diurnal rhythm along with sodium excretion. Sexual dimorphism is evident in the diurnal regulation of endothelin-mediated natriuresis and its downstream targets. …

Mitochondrial Priming Of Tumor Initiating Cells Involves Repression Of Mitochondrial Fission Activity Towards Redox Regulation Of The Cell Cycle Regulator Cyclin E, Brian Spurlock

All ETDs from UAB

Mitochondrial dynamics primarily refers to the opposing fission or fusion events between individual mitochondria, which maintains steady-state mitochondrial morphology in cells. Fission and fusion activities maintain the energetics of normal and neoplastic stem cells. We developed the novel approach mito-SinCe2 to study the bidirectional relationship between mitochondrial dynamics and energetics. Application of this method led to the hypothesis that mitochondria-dependent ovarian tumor initiating cells interconvert between 3 states with distinct mitochondrial energetics/dynamics relationships. Cells in one state, characterized by high mitochondrial ROS and low fission activity, appear to be primed for self-renewal by mitochondria. We call these cells mitochondria-primed stem …

Exploring The Roles Of Long Non-Coding Rnas In Glioblastoma Tumor Recurrence And Therapy Resistance, Christian Tyler Stackhouse

All ETDs from UAB

ABSTRACT Glioblastoma (GBM) is the most common and devastating primary CNS brain tumor with a median survival time of around 14 months. Most patients succumb to re-current disease which is often more malignant than the primary tumor and is frequently therapy resistant. There have not been significant advances in the treatment of GBM despite decades of research. This is partly due to the lack of accurate preclinical models and of the focus on primary rather than recurrent tumors. We created a 350 gene custom GBM-specific panel which contains 16 molecular signatures including molecular sub-typing signatures. We have demonstrated concordance of …

Role Of Endogenous Tau In Lewy-Like Pathology, Lindsay Stoyka

All ETDs from UAB

Lewy Body Diseases (LBDs) are a group of disorders characterized by intracellular inclusions of misfolded alpha-synuclein (α-synuclein). Of these, Parkinson’s Disease (PD) is the most common neurodegenerative movement disorder, and Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative dementia. PD is characterized clinically by bradykinesia, resting tremor, rigidity, and postural instability. In addition, up to 80% of patients eventually develop dementia, termed Parkinson’s Disease Dementia (PDD). DLB is characterized by onset of dementia before or concurrently with parkinsonism. Currently, no disease-modifying therapies exist for either of these diseases. Lewy pathology is found in regions important for cognition …

Toxin Secretion By Mycobacterium Tuberculosis, Uday Tak

All ETDs from UAB

Mycobacterium tuberculosis (Mtb) is a highly infectious airborne bacterial pathogen, and the causative agent of human tuberculosis. Mtb infects approximately one-third of the human population, and is responsible for more deaths than any other infectious disease in the history of mankind. Mtb is an intracellular pathogen and primarily infects myeloid cells, such as macrophages in the human lung. In macrophages, Mtb establishes a replication niche within membrane-bound vacuoles named phagosomes, while subverting immunity. The intracellular survival of Mtb depends on manipulation of host cellular processes through secreted effector proteins. Ultimately, this intracellular vacuole is ruptured by the type VII secretion …

Understanding The Impact Of Diet And Obesity On Anti-Tumor Immunity And Therapeutic Efficacy In Kidney Cancer, Rachael Miller Orlandella

All ETDs from UAB

Obesity is regarded as a major risk factor for developing renal cell carcinoma (RCC). Advanced-stage RCC exhibits chemotherapeutic resistance, but is responsive to immunotherapies such as the immune checkpoint inhibitor anti-programmed cell death-1 (anti-PD-1). Despite some clinical successes, response rates remain low for anti-PD-1 monotherapy (20-30%). Preclinical evaluations of immunotherapeutic strategies typically use lean mice and do not account for patient comorbidities. This may explain the underwhelming success rates following clinical translation of new cancer treatments. Recent studies found that obesity was associated with favorable outcomes and responses to immunotherapy in melanoma. However, the effects of obesity on anti-tumor immunity …

Disease Specific Dysregulation Of Stat1 And Stat5 Activation In Mature Cd4+ And Cd8+ T Cells Influences Enhanced Kinetic Responses And Inflammation In Patients With Treatment-Naïve Relapsing Remitting Multiple Sclerosis (Rrms), Brandon Jay Pope

All ETDs from UAB

Autoimmunity is propagated through the lack of effective mechanisms of central and peripheral tolerance. In relapsing remitting multiple sclerosis (RRMS), dysregulated adaptive immune cells have been shown to contribute to disease morbidity through the influence of immune-modulating cytokines in the peripheral blood. Interleukin-2 (IL-2) is a cytokine with several key functions in regulating homeostatic mechanisms within the human immune system. Interferon gamma (IFNγ) is a type II interferon that is needed for an effective response to intracellular bacteria infection through the actions of Th1 cells. IL-2 and IFNγ signaling occurs primarily through signal transducer and activator of transcription (STAT) activation. …

Novel Hiv Adaptation Strategy Against Host Cd8 T Cell Immunity, Kai Qin

All ETDs from UAB

Since the 1980s, HIV infection has caused millions of death and tremendous economic losses worldwide. Despite great scientific advances, the only effective therapy to date, antiretroviral therapy (ART), merely delays disease progression yet cannot eradicate viral infection. Therefore, an effective HIV vaccine that can prevent the acquisition of infection would be a desirable alternative. The critical role of CD8 T-cell immunity in HIV infection has been well documented and therefore not surprisingly a great deal of effort has been focused on developing an effective CD8 T-cell based HIV vaccine. However, by far, such CD8 T-cell based HIV vaccine trials have …

Investigating The Roles Of The Renal Primary Cilium Through The Use Of Intravital Imaging, Dustin Zachary Revell

All ETDs from UAB

Primary cilia are small microtubule based appendages present on nearly every cell type in the mammalian body, and are highly conserved from organisms as simple as algae to humans. Cilia function as complex signaling centers integrating a variety of pathways and play critical roles throughout development and in maintaining homeostasis. Mutations to ciliary proteins in humans result in a wide array of diseases termed ciliopathies, which have a broad range of symptoms affecting nearly every organ in the body. Renal primary cilia are present on the apical side of tubular epithelium, where they project into the lumen and are thought …

Noninvasive Neuromodulation Using A Benchtop Approach To Mri-Guided Focused Ultrasound Blood Brain Barrier Opening, Megan Rich

All ETDs from UAB

Fundamental neuroscience research has provided a deeper understanding of the genes, molecules and cellular circuitry involved in neurological disorders, however translating discovery into clinical application remains a major challenge. This bench to bedside gap is in part due to the discrepancy in techniques used in the laboratory vs. the clinic for targeting the mechanisms that underlie disease. Ideally this discrepancy would be resolved not only by implementing novel clinical techniques to provide more precise targeting of disease foci, but also by using the same techniques in the clinic that are used at the lab bench to provide a direct bench …