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Articles 1 - 30 of 77
Full-Text Articles in Medicine and Health Sciences
Interim Monitoring Efficacy, Safety And Futility In Phase Iii Clinical Trials, Qing Li
Interim Monitoring Efficacy, Safety And Futility In Phase Iii Clinical Trials, Qing Li
All ETDs from UAB
Phase III trials often have both efficacy and safety outcomes. Sometimes the safety outcomes are closely associated with the efficacy outcomes. We sought to find a statistical method to treat both efficacy and safety outcomes as bivariate primary outcomes and set up stopping rules at interim stages based on the following criteria: (1) greater safety; (2) greater efficacy; (3) futility. We first examined the internal pilot design to adjust sample size for clinical trials with a bivariate response (efficacy and safety). Three nuisance parameters (two variances and correlation) need to be considered when doing sample size recalculation for the internal …
Enzymatic And Proteomic Analysis Of Spinal Cord In A G93a Als Mouse Model, Page Jones
Enzymatic And Proteomic Analysis Of Spinal Cord In A G93a Als Mouse Model, Page Jones
All ETDs from UAB
Mutations to copper,zinc superoxide dismutase (Cu,Zn SOD or SOD1) are the only known causes of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized primarily by death of spinal motor neurons. While the molecular mechanisms responsible for motor neuron death in this disease remain to be elucidated, recent studies implicate mitochondrial dysfunction as a key factor in the pathogenesis of ALS. In support of this, we observed ALS-dependent alterations in key functions including creatine kinase activity and ATP levels, which could be linked to changes in the mitochondrial proteome. Importantly, extensive research efforts have failed to develop a treatment that significantly …
The Au-Rich Element Mrna Decay-Promoting Activity Of Brf1 Is Regulated By Mitogen-Activated Protein Kinase Activated Protein Kinase 2, Sushmit Maitra
The Au-Rich Element Mrna Decay-Promoting Activity Of Brf1 Is Regulated By Mitogen-Activated Protein Kinase Activated Protein Kinase 2, Sushmit Maitra
All ETDs from UAB
Regulated mRNA decay is a highly important process for the tight control of gene expression. Inherently unstable mRNAs contain AU-rich elements (AREs) in the 3’ untranslated regions that direct rapid mRNA decay by interaction with decay-promoting ARE-binding proteins (ARE-BPs). The decay of ARE-containing mRNAs is regulated by signaling pathways, which are believed to directly target ARE-BPs. Here, we show that BRF1 involved in ARE-mediated mRNA decay (AMD) is phosphorylated by MAPK-activated protein kinase 2, MK2. In vitro kinase assays using different BRF1 fragments suggest that MK2 phosphorylates BRF1 at four distinct sites, S54, S92, S203, and an unidentified site at …
Role Of Variant Sialylation In Regulating Tumor Cell Behavior, Faheem M. Shaikh
Role Of Variant Sialylation In Regulating Tumor Cell Behavior, Faheem M. Shaikh
All ETDs from UAB
Many different tumors have been documented to have elevated levels of the enzyme ST6Gal I, a Golgi glycosyltransferase that adds α2-6 sialic acids to glycoproteins. Concurrently, upregulated ST6Gal I is associated with metastasis and poor patient prognosis. We initially showed that HD3 colonocytes made to express oncogenic-ras, a common mutation in colon carcinoma, have increased expression of ST6Gal I and elevated α2-6 sialylated integrins. Having established that ras regulates ST6Gal I expression in colon epithelial cells, we found that colonocytes carrying hyper α2-6 sialylated β1 integrins exhibit increased adhesion to and migration toward collagen I. Further, we found that β1 …
Wavelet-Based Regression And Classification For Longitudinal Diffusion Tensor Imaging Data, William R. Prucka
Wavelet-Based Regression And Classification For Longitudinal Diffusion Tensor Imaging Data, William R. Prucka
All ETDs from UAB
Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique capable of in vivo characterization of the spatial and angular dependence of free water diffusion in tissue. By studying intra- and extra-cellular water mobility, inference can be made about the surrounding medium. The non-uniform angular dependence of diffusion, known as anisotropy, is evident in fibrous tissues, which exhibit greater diffusion parallel versus perpendicular to the fiber orientation. DTI’s sensitivity to anisotropy makes it an effective tool for measuring the integrity of fibrous myelinated white matter tracts in the brain. For demyelinating diseases such as multiple sclerosis (MS), DTI has …
Randomized Controlled Trial Of Low Cost Interventions To Reduce Childhood Immunization Dropouts In Pakistan, Hussain Raza Usman
Randomized Controlled Trial Of Low Cost Interventions To Reduce Childhood Immunization Dropouts In Pakistan, Hussain Raza Usman
All ETDs from UAB
Childhood immunization coverage in Pakistan remains sub-optimal despite universal and free of cost availability of vaccines. Structural impediments to progress may include the immunization card that is hard to read and interpret. A randomized controlled trial was conducted to assess the effect of redesigned immunization card and center-based education to mothers on immunization completion at rural immunization centers in Karachi, Pakistan. Other objectives were to identify the predictors of immunization completion and to identify factors associated with delay at first dose of diphtheria-tetanuspertussis (DTP1). Mother-child units were enrolled from six immunization centers at DTP1 and randomized to four study groups: …
The Effect Of Malaria And Intestinal Helminth Coinfection On Birth Outcomes In Ghana, Nelly J. Yatich
The Effect Of Malaria And Intestinal Helminth Coinfection On Birth Outcomes In Ghana, Nelly J. Yatich
All ETDs from UAB
Several studies have reported the relationship between malaria during pregnancy and adverse pregnancy outcomes including maternal anemia, low birthweight, as well as preterm delivery and small for gestational age infants. Some studies have also demonstrated the linkage between helminth infection and maternal anemia. Few studies have assessed the occurrence of coinfection of these infections in pregnancy and its effects on maternal anemia and birth outcomes. The objective of this dissertation was to assess the effect of malaria and intestinal helminth coinfection on birth outcomes in Ghana. A cross-sectional study of 785 women presenting for delivery in two hospitals in Kumasi, …
Occupational Stressors, Job Satisfaction, And Back Pain In Firefighters, Mantana Damrongsak
Occupational Stressors, Job Satisfaction, And Back Pain In Firefighters, Mantana Damrongsak
All ETDs from UAB
Occupational back pain is a significant health and safety problem in many industrialized countries for persons who are required to perform work-related forceful movement and lifting. Firefighters, an occupational group at high risk for back injury, perform many job tasks under hazardous work conditions. One-third of firefighters retire due to job-related health and safety problems and 49.4% of this group retire as a result of back pain, the leading cause of early retirements in firefighters. Most studies have examined factors influencing back problems among other workers, especially nurses and hospital workers, but few studies have investigated factors that influence back …
Growth Hormone Signaling And Action In Osteoblasts, Douglas J. Digirolamo
Growth Hormone Signaling And Action In Osteoblasts, Douglas J. Digirolamo
All ETDs from UAB
Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exert profound growth promoting actions during pre- and post-natal skeletal development. GH and IGF- 1 appear to cause these anabolic actions by influencing a variety of effects on osteoblast proliferation, differentiation, and survival. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including bone, the individual contributions of these two molecules to anabolic responses in bone remains poorly defined. In this dissertation research, I sought to distinguish the direct and indirect (IGF-1 dependent) GH actions on osteoblasts. In the first section of this thesis, I …
Determinants Of Growth Hormone Receptor Downregulation, Luqin Deng
Determinants Of Growth Hormone Receptor Downregulation, Luqin Deng
All ETDs from UAB
Growth hormone (GH), a 22 kD polypeptide primarily produced in the anterior pituitary gland, is a key regulator of postnatal growth and affects carbohydrate, protein and lipid metabolism. Growth hormone receptor (GHR) is a single membrane-spanning type Ⅰ glycoprotein of the cytokine receptor family and is initially synthesized as a precursor and undergoes carbohydrate processing during transport through the Golgi. It has no intrinsic kinase activity. One molecule of GH binding to predimerized GHR on the cell surface induces the receptor conformational change activating the cytoplasmic domainassociated tyrosine kinase, Janus Kinase 2 (JAK2), which phosphorylates GHR, followed by the activation …
Using Rna Interference To Study The Function Of The Tethering Protein P115 In Er-Golgi Traffic, Robert Grabski
Using Rna Interference To Study The Function Of The Tethering Protein P115 In Er-Golgi Traffic, Robert Grabski
All ETDs from UAB
Metazoan cells are characterized with elaborate network of intracellular membranous compartments. These membranes allow the cell to spatially separate antagonistic processes and environments, and maintain sequential order of reactions necessary for maturation and secretion of biosynthetic cargo. The core transport machinery consists of coat proteins, tethering factors, SNAREs and small Ras-like GTPases. We have explored the function of the tethering factor p115 in organellogenesis and in secretory traffic. The p115-depleted system was utilized to explore structurefunction relationships within p115. Here, we analyzed the architecture of the Golgi after RNAi induced depletion of p115. We show that in p115 depleted cells …
Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton
Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton
All ETDs from UAB
seeking behavior following chronic drug use lasts for many months or even years. Short-term withdrawal experiments have suggested that the neuroadaptations thought to underlie learning and memory may also contribute to addictive behavior. However, there is little information about the physiological mechanisms that participate in craving and relapse following long-term withdrawal. Here I show in hippocampal slices from rats treated with nicotine for 1 week that there is a change in the excitability of CA1 pyramidal cells that persists for up to 9 months following the cessation of drug treatment. The expression of this enhanced excitability is dependent on different …
Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini
Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini
All ETDs from UAB
Novel combinatorial strategies need to be explored to achieve tumor eradication. In this regard, viral vector based gene therapy and nanotechnology offer unique possibilities for cancer therapy. As an example, multifunctional adenoviral (Ad) vectors capable of targeting, imaging, and successful cancer gene therapy have been advanced into multiple clinical trials. Similarly, novel multifunctional gold nanoparticles (AuNPs) have been utilized for drug delivery, targeting, imaging, and hyperthermia tumor therapy. Therefore, to accrue the benefits of both gene therapy and nanotechnology for cancer therapy, we proposed to combine Ad vectors and AuNPs in a single multifunctional nanodevice. Towards this goal, herein, we …
Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu
Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu
All ETDs from UAB
The hematological disorder sickle cell disease (SCD) is a prevalent human genetic disease. It causes severe tissue damage that can result in strokes, splenic infarction, kidney failure, liver and lung disorders, painful crises, and other complications. Although palliative therapies and allogenic stem cell transplantation therapies have been developed for this disorder, there is still no optimal treatment and SCD patients continue to suffer significant morbidity. Recently, several powerful technologies have been developed that increase the possibility for developing therapeutic treatments for SCD. Previously, our lab group demonstrated that SCD can be corrected in our humanized mouse model by transduction of …
The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran
The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran
All ETDs from UAB
The development of molecular imaging technologies has allowed biomedical researchers to study the process of cancer metastasis in animal models of disease. Bioluminescence imaging has been a crucial tool for non-invasive monitoring of tumor growth, dissemination, and response to therapies. In this report, we have applied bioluminescence imaging to evaluate the efficacy of Death Receptor 5 agonist therapy for the treatment of breast cancer metastasis, predominately to the skeleton, in an athymic nude mouse model. Initially, we determined that bioluminescence imaging was the most ideal technology for studying secondary bone lesions in vivo when compared to both x-ray Computed Tomography …
The Role Of Ddx3 In Regulating Apoptosis, P53 And Snail, Mianen Sun
The Role Of Ddx3 In Regulating Apoptosis, P53 And Snail, Mianen Sun
All ETDs from UAB
Cancer is a common disease that causes high rates of lethality. Resistance to cancer therapy is one major obstacle for producing an effective cancer treatment. Clarifying mechanisms of cancer development, such as resistance to apoptosis and metastasis, can provide important information for developing effective cancer treatment strategies. In the present study, DDX3 was demonstrated to have effects on both responses to cancer treatment and cancer development. DDX3 together with glycogen synthase kinase-3 (GSK-3) was found to impede death receptor-induced apoptosis, which is important because death receptors are activated by some cancer treatments. Additionally, DDX3 was shown to regulate two proteins …
Characterization Of Suds3 As A Brms1 Family Member In Breast Cancer, Alexandra C. Silveira
Characterization Of Suds3 As A Brms1 Family Member In Breast Cancer, Alexandra C. Silveira
All ETDs from UAB
BRMS1 and SUDS3 belong to a protein family characterized by the Sds3-like domain. These proteins are core members of SIN3-HDAC chromatin remodeling complexes and thus, regulate transcription. BRMS1 decreases the expression of various metastasis-promoting proteins. This regulation contributes to BRMS1-mediated metastasis suppression through the inhibition of motility and by sensitizing cells to anoikis, as well as through other unidentified mechanisms related to growth at a secondary site. Although BRMS1 and SUDS3 share high sequence similarity and are found in the same complexes, studies have yet to address whether these similarities result in overlapping functions. Additionally, it is unclear how BRMS1 …
Partner Referral Among Patients With Sexually Transmitted Diseases In Dhaka, Bangladesh, Nazmul Alam
Partner Referral Among Patients With Sexually Transmitted Diseases In Dhaka, Bangladesh, Nazmul Alam
All ETDs from UAB
This dissertation puts together three closely related articles on partner referral for sexually transmitted diseases (STD). The first paper sought to understand feasibility and acceptability of partner referral for STD in less developed countries using a systematic literature review. The results summarized from 39 articles indicate that partner referral outcome was more common for spousal partners than for causal partners. Client's reported barriers included stigma and fear of abuse while infrastructural barriers included limited resources are important. Client centered counseling was found to be effective in increasing partner referral in Africa. The second paper aimed to determine if intention of …
Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett
Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett
All ETDs from UAB
Sortases are transpeptidases that covalently link surface proteins to the stempeptide on the cell wall peptidoglycan of Gram-positive bacteria. This work endeavored to characterize the various sortase enzymes and their effect on the virulence of Streptococcus pneumoniae. The genome of S. pneumoniae may encode up to four sortase enzymes. We found that 38 of 54 strains of serotype 6B clonal complex 14 (CC14) carry the genes for the secondary sortases srtB, srtC, and srtD. The presence of these sortases did not seem to influence the ability of strains within CC14 to infect the nasopharynx, lungs, or blood of strains within …
Structural And Functional Properties Of Human Αa-Crystallin, Jose Mauro Chaves
Structural And Functional Properties Of Human Αa-Crystallin, Jose Mauro Chaves
All ETDs from UAB
The three specific aims of the project were: (1) compare effects of deamidation alone (i.e., αA-N101D, αA-N123D, αA-N101/123D), truncation alone (αA-NT mutant [deletion of residue no. 1-63], or αA-CT mutant [deletion of residue no. 140-173]), or both truncation plus deamidation on structural and functional properties of human lens αA-crystallin; (2) identify components of complexes in the water soluble-high molecular weight (WS-HMW) proteins of normal aging and cataractous human lenses; and (3) determine interactions among WT-αA, αA-NT and αA-CT crystallin species with filensin and phakinin (beaded filament proteins) in vitro. The comparative structural and functional differences between αA-deamidated and/or truncated mutants …
Microbial Biofilm Attachment To Caenorhabditis Elegans, Kevin Drace
Microbial Biofilm Attachment To Caenorhabditis Elegans, Kevin Drace
All ETDs from UAB
The closely related bacterial species Xenorhabdus nematophila, Yersinia pestis and Y. pseudotuberculosis make biofilms capable of adhering to the head of the model nematode Caenorhabditis elegans. Y. pestis uses biofilms to block the digestive tract of its vector, the flea, in order to enhance its efficiency of transmission. I investigated the role of biofilms in X. nematophila and found that, like its Yersinia sp. counterparts, production of biofilm requires a four-gene operon: hmsHFRS. X. nematophila is an insect pathogen and an obligate symbiont of the nematode Steinernema carpocapsae. However, an X. nematophila hmsH mutant that failed to make biofilms on …
Human Papillomavirus: Segregation And Replication, Luan D. Dao
Human Papillomavirus: Segregation And Replication, Luan D. Dao
All ETDs from UAB
Human papillomavirus are small DNA tumor viruses. The viral genome is a small circular double stranded DNA that replicates autonomously as an extrachromosomal plasmid. Occasionally infections by the high risk HPV viruses can lead to DNA integration and progression to cancer. How the HPV DNA is maintained and becomes established in the dividing host cells is not well understood. Additionally, as a double-stranded DNA virus it is likely that double-stranded DNA breaks in the viral genome, either from replication or random damage, will trigger a DNA repair response from the host cell. Such responses have been alternatively reported to be …
Success Rates Of Temporary Anchorage Devices Placed In An Orthodontic Clinic, Alex C. Schreiber
Success Rates Of Temporary Anchorage Devices Placed In An Orthodontic Clinic, Alex C. Schreiber
All ETDs from UAB
In recent years, the use of a variety of temporary placed implants to attain absolute anchorage has been described in the orthodontic literature. The use of temporary implants, fixed to bone, overcomes some of the limitations of traditional anchorage and their reliance on patient compliance. The purpose of this study was to evaluate factors relating to the successful placement of miniscrew temporary anchorage devices in an orthodontic clinic. The orthodontic records of patients who had miniscrews placed during their treatment at the University of Alabama at Birmingham School of Dentistry Postgraduate Orthodontic Clinic were selected. After application of the inclusion …
Perception Of Motion-In-Depth: Induced Motion Effects On Monocular And Binocular Cues, John Eric Gampher
Perception Of Motion-In-Depth: Induced Motion Effects On Monocular And Binocular Cues, John Eric Gampher
All ETDs from UAB
Three cues are available to the visual system to determine motion: image displacement across the retina (retinal slip), eye movements, and configuration changes within a scene (Becklen and Wallach, 1985). Any one may lead to the false perception of motion. Induced motion is the illusory movement of one object (or objects) as a result of other movement in the visual field. A wide variety of displays have been used to study induced motion, leading to apparently different classes of induced motion. Current theories of induced motion can be categorized based on local motion, global motion, eye movement suppression, and cognitive …
Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee
Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee
All ETDs from UAB
Retinol dehydrogenase 12 (RDH12) is a member of the microsomal short-chain dehydrogenase/reductase superfamily of proteins that is highly expressed in photorecep-tor cells. Mutations in RDH12 are associated with severe early-onset autosomal recessive retinal dystrophy, leading to legal blindness. Disease-associated RDH12 variants exhibit lower protein levels when expressed in eukaryotic cells. However, the physiological role of RDH12 remains unclear. As established previously, RDH12 recognizes both retinoids and lipid peroxidation products (medium-chain aldehydes) as substrates and exhibits the highest catalytic efficiency for all-trans-retinaldehyde. As the main goal of this dissertation, we characterized the catalytic properties of RDH12 and its naturally occurring mutants …
Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams
Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams
All ETDs from UAB
Insulin secretory defects within pancreatic beta-cells (β-cells) of islets of Langerhans play a role in the pathogenesis of diabetes mellitus. Furthermore, it is also well established that ATP and zinc are co-secreted with insulin in response to elevated extracellular glucose. Despite this knowledge, the physiological roles of extracellular secreted ATP and zinc within islets are ill-defined. We hypothesized that secreted ATP and zinc are autocrine purinergic signaling molecules that activate P2X purinergic receptor (P2XR) channels expressed by β-cells to enhance glucose-stimulated insulin secretion (GSIS). To test this postulate, ELISA, luciferin/luciferase-based bioluminescence and zinquin-based fluorescence assays were utilized to examine insulin, …
A Comparative Study Of Extraction Treatment Efficiency Using Conventional Edgewise Brackets And Self-Ligating Brackets, Stan C. Cox Jr
A Comparative Study Of Extraction Treatment Efficiency Using Conventional Edgewise Brackets And Self-Ligating Brackets, Stan C. Cox Jr
All ETDs from UAB
The purpose of the present study was to assess treatment efficiency of one selfligating bracket system (In-Ovation, GAC International, Bohemia, NY) compared to a conventional ligating bracket system (Ovation, GAC International, Bohemia, NY) in extraction cases used in the same practice. Treatment duration, number of appointments, and number of arch wires used per patient were compared within one private orthodontic practice. The total sample size was 155 patients, 83 consecutively finished with conventionally-ligated Ovation brackets and 72 consecutively finished with In-Ovation self-ligating brackets. After applying the exclusion criteria, there were 68 patients in the self-ligated (SL) group and 79 patients …
Potential Iatrogenic Effects On Enamel Treated With A Light Cured Flouride Releasing Filled Resin, Henry G. Griggs Jr
Potential Iatrogenic Effects On Enamel Treated With A Light Cured Flouride Releasing Filled Resin, Henry G. Griggs Jr
All ETDs from UAB
White spot lesions have long been a problem in fixed appliance orthodontic treatment. Various methods of prevention have been used in the past, most requiring patient compliance. The use of non-compliant orthodontic sealants to form a barrier on the facial surface of the tooth has been attempted in the past with limited success due mainly to the inability of composite resins to fully polymerize. Pro Seal(Reliance Orthodontic Products, Inc, Itasca, IL) is new product which claims to fully polymerize and provide protection from white spot lesions during orthodontic treatment. In vitro studies support this claim. The side effects of acid …
The Physical And Mental Health Of Spouse Caregivers In Dementia: Finding Meaning As A Mediator Of Burden, Susan M. Mclennon
The Physical And Mental Health Of Spouse Caregivers In Dementia: Finding Meaning As A Mediator Of Burden, Susan M. Mclennon
All ETDs from UAB
The purpose of this study was to examine the effect of caregiver burden on the physical and mental health of caregivers of spouses with dementia and to determine if finding meaning through caregiving mediated the relationship between burden and health. This was a cross-sectional, correlational study in a convenience sample of 84 community-residing spouse caregivers of adults with dementia recruited from North- Central Florida. Measures included the Zarit Burden Interview, the Finding Meaning through Caregiving Scale, and the Medical Outcomes Short Form-36, version 2. Data analyses consisted of descriptive, correlational, and standard multiple regression statistical methods. The sample consisted of …
Mapks Regulate Nuclear Import Of Human Papillomavirus Type 11 Replicative Helicase E1, Jei-Hwa Yu
Mapks Regulate Nuclear Import Of Human Papillomavirus Type 11 Replicative Helicase E1, Jei-Hwa Yu
All ETDs from UAB
Papillomaviruses (PV) are prevalent pathogens that infect human or animal squamous epithelia. Its genome is a double strand circular DNA of approximately 7.9 kb. It contains origin of replication (ori) and encodes early viral proteins for viral DNA amplication, and late capsid proteins for packaging viron. The viral DNA replicates as extrachromosomal nuclear plasmid in the host cell. Infections by low risk virus, such as HPV-6 and -11, can result in benign papillomas, condylomata, and low grade squamous intraepithelial dysplasias (SIL), whereas infection by high risk virus, such as HPV-16 and -18, can progress to high grade SIL, carcinoma in …