Medicine and Health Sciences Commons^™

Klf2/Klf4 Double Knock-Out Mouse Embryos Show Cranial Bleeding With Endothelial Disruption Of The Primary Head Vein, Benjamin Curtis

Theses and Dissertations

Krüppel-like factors (KLFs) are a family of 3 Cys2/His2 zinc finger transcription factors with a diverse set of roles in cellular differentiation, cell cycle regulation, tumor suppression, erythropoiesis, angiogenesis, and other processes. During embryonic development, KLF2 has a role in vessel maturation. Adult conditional KLF4 knockout mouse embryos have thickened arterial intima follow vascular injury. Breeding KLF2+/- and KLF4+/- mice resulted in the generation of KLF2/KLF4 double knockout (DKO) embryos. KLF2/KLF4 DKO embryos died by E10.5 with cranial bleeding. Using immunohistochemistry, embryo whole-mounts were examined for differences in gross vascularization between wild-type (WT), KLF2-/- and KLF2/KLF4 (DKO embryonic day 9.5 …

Assessing Economic And Hrql Burden Of Food Allergy And Anaphylaxis In The U.S., Dipen Patel

Theses and Dissertations

Background: Food allergy, an abnormal immunologic response to food protein, has an estimated prevalence of 6% in young children and 3.7% in adults in the U.S. The only proven therapy for food allergy is strict elimination of the offending allergens. As a result, caregivers and patients could experience constant anxiety and stress that affects their quality of life. Additionally, food allergy can lead to significant economic impact on the health care system, since severe reactions often lead to ED visits and hospitalizations. Objectives: The first major objective was to determine the economic burden of Food Allergy and Anaphylaxis (FAA) patients …

The Impact Of Adolescent Nicotine Exposure On Drug Dependence In Adulthood, Mai Alajaji

Theses and Dissertations

Nicotine is one of the first and most commonly abused drugs in adolescence. According to The Center for Disease Control, every day more than 6000 adolescents try their first cigarette and over 3000 of them become daily smokers. Smoking among adolescents is a strong predictor of future drug abuse and dependence in adulthood. A number of studies has suggests that adolescents pre-exposed to nicotine may suffer permanent disruption of the brain’s reward systems through changes in dopamine receptor function. We hypothesize that nicotine exposure during adolescence causes long lasting neurobiological alterations that increase the likelihood of cocaine use in adulthood. …

Investigation And Optimization Of A Solvent / Anti-Solvent Crystallization Process For The Production Of Inhalation Particles, Swati Agrawal

Theses and Dissertations

Dry powder inhalers (DPIs) are commonly used to deliver drugs to the lungs. The drug particles used in these DPIs should possess a number of key properties. These include an aerodynamic particle size < 5μm and particle crystallinity for long term formulation stability. The conventionally used micronization technique to produce inhalation particles offers limited opportunities to control and optimize the particle characteristics. It is also known to induce crystalline disorder in the particles leading to formulation instability. Hence, this research project investigates and optimizes a solvent/anti-solvent crystallization process capable of directly yielding inhalation particles using albuterol sulfate (AS) as a model drug. Further, the feasibility of the process to produce combination particles of AS and ipratropium bromide monohydrate (IB) in predictable proportions and in a size suitable for inhalation is also investigated. The solvent / anti-solvent systems employed were water / ethyl acetate (EA) and water / isopropanol (IPA). Investigation and optimization of the crystallization variables with the water / EA system revealed that particle crystallinity was significantly influenced by an interaction between the drug solution / anti-solvent ratio (Ra ratio), stirring speed and crystal maturation time. Inducing a temperature difference between the drug solution and anti-solvent (Tdrug solution > Tanti-solvent) resulted in smaller particles being formed at a positive temperature difference of 65°C. IPA was shown to be the optimum anti-solvent for producing AS particles (IPA-AS) in a size range suitable for inhalation. In vitro aerosol performance of these IPA-AS particles was found to be superior compared to the conventionally used micronized particles when aerosolized from the Novolizer®. The solvent / anti-solvent systems investigated and optimized …

Membrane-Bound Matrix Metalloproteinases Influence Reactive Synaptogenesis Following Traumatic Brain Injury, Kelly Warren

Theses and Dissertations

Traumatic brain injury (TBI) produces axonal damage and deafferentation, triggering injury-induced synaptogenesis, a process influenced by matrix metalloproteinases (MMP) and their substrates. Here we report results of studies examining the expression and potential role of two membrane-bound MMPs, membrane-type 5-MMP (MT5-MMP) and a disintegrin and metalloproteinase-10 (ADAM-10), along with their common synaptic substrate N-cadherin, during the period of reactive synaptogenesis. Protein and mRNA expression of MT5-MMP, ADAM-10 and N-cadherin were compared in two TBI models, one exhibiting adaptive plasticity (unilateral entorhinal cortex lesion; UEC) and the other maladaptive plasticity (fluid percussion injury + bilateral EC lesions; TBI+BEC), targeting 2, 7, …

The Relationship Among Maternal Infant Bonding, Spirituality, And Maternal Perception Of Childbirth Experience, Linda Bennington

Theses and Dissertations

The beginning of life is an intense experience for both mother and baby and sets the foundation for future interactions. Researchers have theorized that maternal infant bonding begins prenatally and continues on through the postnatal period. Mṻller (1996) examined that process to determine if prenatal bonding was related to postnatal bonding and discovered that there was only a modest correlation between the two. This led to speculation as to what variables, besides prenatal bonding, could influence postnatal bonding. Klaus & Kennell (1976) noted the detrimental effects of a lack of bonding in terms of abuse and attachment disorders and emphasized …

Insights Into The Catalytic Mechanism Of Retro-Aldol Cleavage Of Β-Hydroxy Amino Acids By Escherichia Coli L-Threonine Aldolase, Remsh Soumya Govinda

Theses and Dissertations

With over 140 vitamin B6 (Pyridoxal 5’-phosphate, PLP) dependent enzymes, serving vital roles in various transamination, decarboxylation, retro-aldol cleavage and synthesis pathways these enzymes constitute the most versatile catalytic systems in nature. Enzymes of this group have an inherent reaction as well as substrate specificity. A single co-factor namely, PLP is used by specific enzymes of this group to serve distinct roles during the catalytic reaction. An ordered evolutionary adaptation in these enzymes has led to specialization achieved by each enzyme for catalyzing specific reactions. L-Threonine aldolase (L-TA) is one such PLP- dependent enzyme that catalyzes the retro-aldol cleavage of …

The Effect Of Anticholinergic Burden On Functional Outcomes In Patients With Moderate To Severe Alzheimer’S Disease, Sheetal Dharia

Theses and Dissertations

Background: Alzheimer’s disease (AD) is the most common form of dementia and is characterized by a progressive loss of memory, judgment, and thinking in older adults. The current treatment is cholinesterase inhibitors, which increase acetylcholine at the synapse. Medications with anticholinergic (AC) activity are given for a variety reasons including for the treatment of comorbid conditions or side effects of cholinesterase inhibitors (ChEIs). These drugs inhibit acetylcholine in the brain. Studies have shown the detrimental outcomes of using AC medications with ChEIs in older adults. Moreover, older patients take more medications and have an increased risk of developing AC toxicity …

Role Of Pyridoxine 5'-Phosphate Oxidase In Metabolism And Transfer Of Pyridoxal 5'-Phosphate, Sayali Karve

Theses and Dissertations

Deficiency of vitamin B6 due to mutations in key B6 metabolizing enzymes is suspected to contribute to several pathologies. Vitamin B6 in its active form, pyridoxal 5’-phosphate (PLP) is a cofactor for over 140 known B6 requiring (or PLP-dependent) enzymes, that serve vital roles in many biochemical reactions. There are three primary vitamin B6 forms, pyridoxine (PN), pyridoxamine (PM) and pyridoxal (PL) which are phosphorylated to pyridoxine 5’-phosphate (PNP), pyridoxamine 5’-phosphate (PMP) and PLP respectively. Pyridoxal kinase (PLK) and pyridoxine 5’-phosphate oxidase (PNPO) are the key enzymes involved in both salvage and de novo pathways of PLP biosynthesis. Mutations in …

The Development And Use Of A Geographic Information System For Evaluating The Association Between Pesticide Exposure And Prostate Cancer, Kristen Wells

Theses and Dissertations

Abstract 1 – A Geographic Information System for Evaluating Residential Pesticide Exposure and Prostate Cancer Incidence Agricultural pesticide exposure is hypothesized to be a risk factor for prostate cancer, and such exposures are of particular concern for men living in farming communities where large-scale pesticide applications occur. Prostate cancer incidence data were obtained from the State Health Registry of Iowa for the years 1996 through 2006, and county and census tract level age-adjusted incidence rates were calculated. Historical crop-specific land use records and pesticide sales data for the state of Iowa during 1990 were integrated into a geographic information system …

Pyridoxal Kinase: Its Role In Vitamin B6 Metabolism, Jigarkumar Desai

Theses and Dissertations

Pyridoxal kinase (PL kinase) and pyridoxine 5’-phosphate oxidase (PNP oxidase) are the two vitamin B6 salvage enzymes involved in metabolism of the primary inactive vitamin B6 (pyridoxal, pyridoxine and pyridoxamine) into the active cofactor form, pyridoxal 5’-phosphate (PLP). PLP, arguably the most important vitamin, is required by numerous vitamin B6 (PLP-dependent) enzymes as a co-factor. These enzymes serve vital roles in the metabolism of glucose, lipids, amino acids, heme, DNA/RNA and many neurotransmitters. High levels of vitamin B6 are linked to neurotoxicity, due to the non-specific interactions of PLP with non-B6 proteins. This problem is controlled, in part, by maintaining …

The Transcriptional Regulation Of Hla-E By Interferon-Gamma In Tumor Cells, Quintesia Grant

Theses and Dissertations

The human Class Ib gene, HLA-E inhibits both Natural Killer Cells and a subset of CD8+ cytotoxic T lymphocytes by engaging the CD94/NKG2A inhibitory receptor. IFN-γ induces the expression of HLA-E as well as Class Ia molecules, which are required for the killing of target cells. Since HLA-E has negative effects on immune killing of target cells, we have sought to identify locus specific mechanisms of IFN-γ induction in order to identify molecular targets for selective activation of Class Ia genes, but not HLA-E. We have previously identified a unique upstream IFN-γ response region in the HLA-E promoter and showed …

The Mechanism Of Obesity In Rai1+/- Mice, Kristie Schmidt

Theses and Dissertations

Smith-Magenis syndrome (SMS) is a genetic disorder caused by a deletion or mutation of the retinoic acid induced 1 (RAI1) gene on chromosome 17p11.2 that results in haploinsufficiency. SMS patients with a deletion account for 90% of the cases, while the other 10% have a mutation in RAI1. The syndrome is characterized by cognitive impairment, craniofacial abnormalities, sleep disturbances, developmental delay, obesity, and behavioral phenotypes. SMS is thought to affect 1:25,000 live births, although due to similar infantile phenotypes with Down syndrome and Prader-Willi syndrome, SMS may be mis- or under-diagnosed. In a study of 54 children, it was shown …

Cell Death And Sustained Senescence Arrest In Colon Carcinoma And Melanoma Tumor Cells In Response To The Novel Microtubule Poison, Jg-03-14, Jonathan Biggers

Theses and Dissertations

Previous studies from this and other laboratories have shown that the novel microtubule poison, JG-03-14, which binds to the colchicine binding site of tubulin, has the capacity to promote both autophagy and apoptosis in breast tumor cells, as well as interfering with endothelial cell function and potentially disrupting tumor vasculature. The current work was designed to investigate the interaction between JG-03-14 and cell culture models of colon carcinoma and melanoma, specifically HCT116 human colon carcinoma cells and B16F10 murine melanoma cells. In both cases, JG-03-14 promoted death in the bulk of the treated population. FACS analysis, DAPI and TUNEL staining …

Frequency Response Of Synthetic Vocal Fold Models With Linear And Nonlinear Material Properties, Stephanie M. Shaw

Theses and Dissertations

Previous studies have shown the importance of cricothyroid muscle activation in altering fundamental frequency in the human voice. Other studies have investigated the non-linear properties of vocal fold tissue and the impact of this non-linearity on frequency response. Several physical models of the vocal folds have been made for research purposes. However, all have been isotropic in nature with linear stress-strain properties. The purpose of this study was to create a physical model with non-linear stress-strain properties to investigate the frequency response of the model as cricothyroid muscle activation was simulated (in other words, as the vocal folds were stretched …

Mild Traumatic Brain Injury: Are Emergency Department Providers Identifying Which Patients Are At Risk?, Barbara Kay Stuart

Theses and Dissertations

Objective: Identify patients with specific emergency department (ED) discharge diagnoses who later report symptoms associated with a mild traumatic brain injury (MTBI), compare frequency and severity of MTBI symptoms by discharge diagnoses, investigate the frequency of head injury education provided to ED patients with each diagnosis, and finally, to learn what type of changes have occurred in the lives of patients as a result of their injury.

Methods: Fifty-two ED patients, aged 18 to 28 who were at least two weeks post injury, spoke English and were discharged with a diagnosis of concussion/closed head injury (CHI), head laceration, motor vehicle …

Resistance Exercise And Vascular Function: Training And Obesity-Related Effects, Grayson Lipford

Theses and Dissertations

Endothelial dysfunction, or the inability of an artery to dilate sufficiently when subjected to excessive shear stress, serves both as a predictor of future cardiovascular events as well as an early indication of atherosclerosis. Several chronic disease states, including obesity, have been shown to alter endothelial function, which may be mediated through circulating pro- and anti-inflammatory adipokines. Still, the mechanisms by which obesity-related low-grade inflammation alters endothelial function are not fully elucidated. Acute and chronic endurance exercise training has previously been shown to be effective in improving endothelial function; however, chronic resistance exercise training is not universally regarded as beneficial …

The Prevalence Of Postpartum Depression In Hispanic Immigrant Women, Nissa Breann Lucero

Theses and Dissertations

Purpose: The purpose of this study was to determine the prevalence of postpartum depression among Hispanic immigrant women seeking healthcare services at a community health clinic.

Data Sources: Hispanic immigrant women were recruited. Out of 116 study participants, 96 women were in the final sample. Using the Beck PDSS-Spanish version, women were screened for symptoms of postpartum depression.

Conclusions: The prevalence rate of significant symptoms of PPD was 54.2% for the entire sample of 96 women. Nearly 66% of women who screened positive for symptoms of PPD scored above the listed cutoff score for suicidal thoughts. Women were divided into …

An Acoustic And Perceptual Investigation Of Contrastive Stress In Children, Anita Susan Dromey

Theses and Dissertations

Key aspects of prosody have been studied in adults for a number of years; however, less attention has been paid to the acoustic patterns of prosody in children. Thus, the purpose of the present study was to evaluate how a group of 20 pre-adolescent children use prosody to mark contrastive stress compared to a control group of adult speakers. It was of interest to investigate whether the children's use of prosody differed between boys and girls or the part of speech being emphasized. The prosodic patterns of contrastive stress were evaluated in terms of duration, fundamental frequency, and intensity change …

Factors Influencing A Military Blood Donor’S Intention To Donate: An Application Of The Theory Of Planned Behavior, Andrew Schnaubelt

Theses and Dissertations

In the United States, blood product availability is dependent entirely on donations from volunteer blood donors. Current trends in blood collection and utilization raise concerns about the ability to meet future demands for blood products. At a time of high demand and deferrals, the Armed Services Blood Program has been unable to meet its requirements for blood and consequently needs to purchase blood from civilian agencies to meet the dual demands of the military community at home, as well as those deployed around the world. This creates a need to better understand the military blood donor in an effort to …

Variability Of Syntactic Complexity In Persons With And Without Multiple Sclerosis, Kristin Diane Bjorkman

Theses and Dissertations

Several recent studies have suggested that persons with multiple sclerosis (MS) have diminished syntactic complexity. A greater variability in responses to a variety of tasks has also been noted for persons with MS. However, naturalistic data on syntactic complexity and the complexity's variability in persons with MS have not been examined. In the present study, 8 volunteers with MS (age 18-70 years) and 10 adults without MS participated in both a 15-minute conversational language sample and a sentence completion task in two different sessions. No significant differences were found between groups on any measure, and variability within the groups was …

Development Of Psychometrically Equivalent Speech Recognition Threshold Materials For Native Speakers Of Samoan, Jennifer Lane Newman

Theses and Dissertations

The speech recognition threshold (SRT) is an important measure, as it validates the pure-tone average (PTA), assists in the diagnosis and prognosis of hearing impairments, and aids in the identification of non-organic hearing impairments. Research has shown that in order for SRT testing to yield valid and reliable measures, testing needs to be performed in the patient's native language. There are currently no published materials for SRT testing in the Samoan language. As a result, audiologists are testing patients with English materials or other materials not of the patient's native language. Results produced from this manner of testing are confounded …

Accuracy Of English Speakers Administering Word Recognition Score Tests In Mandarin, Kaylene Barrett Polley

Theses and Dissertations

The purpose of this study was to examine the accuracy of English-speakers in determining the word recognition score of native Taiwan Mandarin-speakers. Digitally recorded Mandarin word lists were presented to 10 native Mandarin-speakers from Taiwan (five male, five female), from whom oral and written responses were collected. Oral responses were scored by 30 native English-speakers, 15 of which had no experience with Mandarin and 15 with two to three years of college-level Mandarin courses or equivalent knowledge of Mandarin. The judges who had experience with Mandarin were able to score the WRS tests with 97% accuracy (with scores ranging from …

Understanding The Perspective Of Adolescent Siblings Of Children With Down Syndrome Who Have Multiple Health Problems, Carol Ann Graff

Theses and Dissertations

The purpose of this qualitative descriptive study was to obtain information from adolescent siblings of children with Down syndrome (CWDS) regarding their perceptions of living with a child who has Down syndrome (DS). Twenty-three adolescents between 12 and 19 years of age who lived with a child who had DS and additional health problems including cardiac, endocrine, gastrointestinal, hematological, neurological, and behavioral conditions were interviewed individually. After examining the tape recorded interviews, major themes revealed both positive and negative aspects of living with a child with DS who has major health problems. However, overall the adolescents reflected more positive experiences …

Regional Heterogeneity And Diversity Of Astrocytes In Response To Hiv-1 Proteins And Morphine, Wen Chen

Theses and Dissertations

HIV-infected individuals who abuse opiates have been found to have a higher incidence and a faster progression of HIV encephalitis. Astrocytes, the major support cells in the CNS, are known to play a critical role in the HIV neuropathy. Although astrocytes tend not to be productively infected by the HIV-1 virus, dysregulation of their pro- and anti- inflammatory cytokines/chemokines secretion is usually neurotoxic. Glutamate transport in astrocytes is reported to be impaired as well, which result in extrasynaptic excitatory neurotransmitter accumulation and over stimulation of postsynaptic neurons. It is long known that astrocytes from different brain regions have diverse responses …

Children Adopted Internationally Examining Developmental Status At Arrival And Six Month Follow Up, Ann Mccormick

Theses and Dissertations

In the past 5 years, almost 100,000 children have been internationally adopted. Research suggests that many of these children have growth and developmental delays, but few large scale studies have been completed. In the current study data obtained from a restrospective chart review of 534 children followed in the International Adoption Clinic at Cincinnati Children’s Hospital Medical Center between 1999 and 2007 was analyzed. Prevalence of developmental delays and sensory processing issues initially and after 6 months in country, the relationship of delays/issues with previously identified risk factors, and the frequency of recommendations for early intervention (EI) and therapy services …

The Relationship Between Acoustic And Kinematic Measures Of Diphthong Production, Gwi-Ok Jang

Theses and Dissertations

The purpose of this study was to examine the correlation between acoustic and kinematic measures of diphthong production in 11 individuals with multiple sclerosis (MS) and 11 neurologically healthy control speakers. The participants produced four diphthongs: /ɔɪ/, /aʊ/, /aɪ/, /eɪ/. These sounds were spoken in a sentence context. Their speech audio signal was recorded with a microphone and their tongue movements were recorded with a magnetic tracking system. The first and second formants (F1 and F2) were computed with acoustic analysis software, and these signals were time-aligned with the vertical and anteroposterior magnet movement records. Pearson correlations between F1 and …

Normal Masking Level Difference Parameters For Use In The Clinical Evaluation Of Auditory Processing Disorders, Maria Noelle Burnham

Theses and Dissertations

Masking Level Difference (MLD) tests are an established component of auditory processing test batteries; however, normative data for these tests vary according to procedure. In this study, forty normal, native-English speaking adults between the ages of 18 and 26 were tested for MLD via a newly developed computer software program using both an adaptive procedure (MLDA) and a Bekesy procedure (MLDB). The results from the two procedures were analyzed for sex differences and compared with each other. For both the MLDA and MLDB, the results showed statistically significant sex differences in the masked thresholds used to obtain the MLD (NoSo …

The Prevalence Of Maxillary Altered Passive Eruption In A Dental School Population., Francisco Carlos

Theses and Dissertations

AIM: The aim of this investigation is to determine the prevalence of maxillary altered passive eruption in a dental school population. METHODS: 100 subjects were examined clinically and had models fabricated of their maxilla. Demographic, periodontal, cast measurements were recorded for each subject. Demographic variables recorded included age, gender, and ethnicity, history of orthodontic treatment, presence of incisal /occlusal wear, appearance of gingival excess, and presence of gingival asymmetry. Measurements made on cast included clinical crown length, clinical crown width, papillary height, and distance from the lateral gingival zenith to the gingival aesthetic line. Clinical crown width-to-length ratio was calculated. …

The Elan Event-Related Potential In Children 5 To 12 Years Of Age, Melissa Crandall

Theses and Dissertations

The examination of Event Related Potentials during language processing tasks provides valuable information of how the brain processes language over time. In the current study, the development of the early left anterior negativity (ELAN) was analyzed in young children. Previous research has described the ELAN as a negative waveform elicited during syntactic processing between 200 and 500 ms post linguistic stimuli. Thirty children from 5 to 12 years of age listened to sentences that were linguistically correct, syntactically incorrect, or semantically incorrect. Sentences were presented for right monaural, left monaural, and binaural ear conditions to determine possible differences related to …