• Value orientation and activity interests in two cultural groups

      Jih, Guey-Fang; Department of Occupational Therapy (1987-04)
      A study of value· orientation in Ufe goals and activity interests was conducted to explore how culture influences thes_e two variables. The relationship between value· orientation and activity interests was also investigated to explore the theoretical framework of human occupation. The human occupation model borrowed the general system theory and assumed that t Man as an open system, interacted with the environment through a process of input, throughput , output and feedback. The environment is physical, social and cultural phenomena. Output information results in purposeful occupation or human occupation. A descriptive survey was designed using two questionnaires to measure the value orientation and activity interests in two cultural g~oups, American occupational therapy students at the Medical College of Georgia, Augusta, GA, U. S. A. and Chinese occupational therapy students at the National Taiwan University, Taipei, Taiwan,· R. 0. C .. The questionnaires were translated into Chinese for the Chinese subjects. The California Life Goals Evaluation Schedules was administered to measure the value orientation in life goals. It included 150 statements categorized into 10 categories: esteem, profit, power, fame, leadership, security, social service, interesting experiences, self expression and independence. Matsutsuyu's Neuropsychiatric Institution Interest Checklist was used to measure activity interests which were categorized with the assistance of occupational therapy faculty at the Medical College of Georgia. The 80 activity items were categorized as active, passive, cooperative, competitive, creative, structured, solitary and group activities. A total.of 35 questionnaires was sent out for the Chinese subjects. All of them were returned , but one of them was not completed. A total of 50 questionnaires was distributed for the American subjects. Thirty·questionnaires were returned, 20 of them were completed. ·Data were analyzed using "STATGRAPHICS" computer package. The statistical tests utilized were_ Student's t-test and Pearson product moment Correlations. Findings indicated that the value orientation in these two groups had .statistically significant differences in fame, power, leadership, security, interesting experiences, and independence. But, there were no significant differences in the activity interests except-in the category of structured activities. A further finding was that the American group in this study tended to prefer passive, cooperative, creative and group activities. The Chinese group tended to prefer passive, and cooperative activities and had no significant preferences in creative versus structured and solitary versus group activities. Considering the correlation of value and activity interests in each cultural group, the results showed that there existed some correlations of value and activity interests. These findings did not supp·ort all the hypotheses, but did provide clues of relationship in value and activity interests.
    • A Variable Prenatal Stress Paradigm as a Valid Drug Discovery Platform for Cognitive Deficits Associated with Neuropsychiatric Disorders

      Wilson, Christina Ann; Department of Pharmacology and Toxicology (2012-10)
      Cognitive dysfunction is now recognized to be central to the functional disability of several neuropsychiatric disorders. However, treatment options for the management of cognitive symptoms are limited and the development of novel therapeutics has been made difficult by the lack of appropriate animal models. It has been suggested that variable prenatal stress (PNS) in rodents might be an etiologically appropriate model for some components of schizophrenia. Thus, the overall goal of this dissertation project was to conduct a comprehensive behavioral study of the model to assess face validity, and to make a preliminary assessment of its construct and predictive validity. Our results indicate that exposure to PNS results in elevated corticosterone levels following exposure to acute stress, increased aggressive behaviors, as well as increased locomotor activity and stereotypic behaviors. Further, PNS rats had altered innate fear responses to predator odor as well as impaired fear extinction. Additionally, PNS in rats was associated with impairments of sustained attention, inhibitory response control, and recognition memory all of which could be attenuated by the norepinephrine reuptake inhibitor, atomoxetine. Collectivity, these data support the premise that PNS in rodents is a valid model system for studying some behavioral components of neuropsychiatric disorders as well as their treatment.
    • Variables That Affect Adaptation In Post-Mastectomy Women

      Pritzker, Joanie K; School of Nursing (1982-05)
    • Vascular dysfunction in pulmonary hypertension: Role of protein kinase G-1a nitration

      Aggarwal, Saurbh; Vascular Biology Center (2011-06)
      Pulmonary hypertension is a common and debilitating complication of pulmonary, cardiac, and extrathoracic pathologies. The development of pulmonary hypertension is associated with elevated pulmonary arterial pressure (PAP), and increased vascular remodeling. Pulmonary vascular tone is regulated through the activation of protein kinase G-la (PKG-la), which is the isoform predominantly found in the lungs, via a complex signaling pathway that involves nitric oxide (NO), natriuretic peptides (NP), and cyclic guanosine monophosphate (cGMP). Vascular injury secondary to increased reactive oxygen (ROS) and nitrogen species (RNS) in pulmonary hypertension disrupts these regulatory mechanisms, potentiating the development of vascular dysfunction. However, the molecular mechanisms underlying this dysfunction are not completely understood and were the focus of this study.
    • Venous Contraction to Endothelin-1 in Congestive Hearth Failure

      Reddy, Vikram; Department of Cellular Biology and Anatomy (2003-04)
      Endothelin-1 (ET-1) is produced by endothelial cells and can stimulate either the ETa or the ETB receptors. The role o f ET-1 and the identity of the endothelin receptors involved in mediating tone in the mesenteric small veins of the Golden Syrian hamster are not known. ET-1 induces venoconstriction, thereby increasing the preload to the heart in congestive heart failure. However, mechanisms mediating contraction to ET-1 in the mesenteric small veins of the cardiomyopathic hamsters in the early and late stages of CHF are not known. Therefore, mechanisms mediating ET-1 induced contraction were determined in the mesenteric small veins o f the Golden Syrian and cardiomyopathic hamsters in the early and late stages of CHF. Baseline intraluminal diameter of small veins was measured before and after treatment with either ETa or ETB receptor antagonists. ET-1 induced contraction was higher in the early stage o f CHF, while it was decreased in the late stage of CHF. Blockade of the ETA receptor decreased ET-1 induced contraction in the mesenteric small veins from the control and cardiomyopathic hamsters in both the early and late stage o f CHF. ETB receptor blockade decreased the ET-1 induced contraction in the control and cardiomyopathic hamsters in the early, but not late, stage o f CHF. Therefore, ET-1 induced contraction in the mesenteric small veins is mediated by the ETa receptors alone in the late stage of CHF, while both the ETa and ETB receptors mediate vasoconstriction in the controls and in the early stage o f CHF. Stimulation of ET-1 receptors is associated with an increase in calcium levels within the vascular smooth muscle cells. It is not known whether the increase in reactivity to ET-1 in the early stage o f CHF or the decrease in reactivity to ET-1 in the late stage of CHF is due to problems with mobilization o f the intracellular calcium levels within the vascular smooth muscle cell. Following ET-1, calcium levels within the vascular smooth muscle cell were increased to a larger extent in the early stage o f CHF, than in the late stage of CHF, in agreement with the vascular reactivity data. Calcium levels were also measured before and after treatment with either ETa or ETb receptor antagonists. Blockade o f the ETa receptor inhibited the ET-1 induced increase in calcium levels in the mesenteric small veins from the control and cardiomyopathic hamsters in both the early and late stage of CHF. However, ETB receptor blockade inhibited the ET-1 induced increase in calcium levels in only the control and cardiomyopathic hamsters in the early stage o f CHF. These results indicate the absence of a functional responses mediated by the ETb receptor in the late stage of CHF. Studies have shown that NO can modulate the contraction to ET-1 in the vasculature. Baseline intraluminal diameter o f small veins were measured before and after treatment with N-nitro-L-arginine (LNA), a specific inhibitor o f nitric oxide synthase. LNA decreased the contraction to ET-1 in the early stage o f CHF, but increased contraction to ET-1 in the late stage of CHF. This indicates that NOS mediates a vasodilatory effect that counteracts contraction to ET-1 in the late stage, but contributes to the vasoconstrictor effect of ET-1 in the late stage o f CHF. NOS activity was measured to identify the NOS isoforms contributing to the modulation o f ET-1 induced vascular reactivity. Total NOS activity was significantly increased in the cytosolic fraction of small veins from hamsters in the late stage o f CHF and in the particulate fraction in hamsters in the early stage of CHF. In the late stage, the increase in NOS activity was inhibitable by 1400W, an iNOS selective inhibitor, suggesting that an increase in iNOS decreases the contraction to ET-1. In summary, in the early stage of CHF, there is an increase in the vascular reactivity to ET-1 associated with an increase in intracellular calcium levels and partially mediated by NOS. This may increase preload and impair myocardial function in CHF. There is an absence o f ETb receptor-mediated responses in the late stage of CHF, associated with very high plasma ET-1 levels and impaired intracellular calcium signaling. NOS activity is significantly enhanced in the mesenteric small veins from the cardiomyopathic hamsters in the late phase of CHF, and this increase in NOS activity is at least partially dependent on iNOS and may contribute to impaired venous contraction to ET-1 in cardiomyopathic hamsters. This may serve as a compensatory mechanism to decrease the preload to the failing heart.
    • Vitamin D Moderators and Supplementation Outcomes

      Havens, Robyn Lynn; Department of Physiological and Technological Nursing (1/25/2018)
      Abstract Robyn L. Havens Vitamin D Moderators and Supplementation Outcomes (Under the direction of Dr. Elizabeth NeSmith) Vitamin D insufficiency is a global health concern affecting approximately 1 billion people, including about one third of the American population. Vitamin D insufficiency promotes the development of chronic diseases. The people most at risk for developing chronic diseases from vitamin D insufficiency are those individuals in the vulnerable populations who experience poor health outcomes. Currently, researchers and clinicians disagree as to the recommended daily allowance and therapeutic range supporting sufficient serum vitamin D concentrations. To provide data to resolve this disagreement, the objectives of this secondary analysis were to determine if age, sex, and body mass index were moderators of serum vitamin D concentration and if varying dosages of vitamin D supplementation affected serum interleukin-6 concentrations. The data records of 60 healthy male and female African American participants were examined who were aged 13-45 years, categorized as overweight or obese, and exhibited a baseline serum vitamin D concentration ≤ 50 nmol/L. The participants were randomized into four treatment groups for the original study: 1) a control group that received a placebo; (2) a group that received monthly supervised doses of 18,000 IU (equivalent to 600 IU/day); (3) a group that received monthly supervised doses of 60,000 IU (equivalent to 2,000 IU/day); and (4) a group that received monthly supervised doses of 120,000 IU (equivalent to 4,000 IU/day). After 16 weeks of vitamin D supplementation, the only statistically significant interaction found was with sex as a moderating variable despite the small sample size of men. No other significant interactions were found, including no interaction with vitamin D supplementation and interleukin-6. Despite lacking statistical significance, the data results suggested that the 2,000 or 4,000 IU/day dosages of vitamin D supplementation was needed for the overweight/obese African American participants to achieve a sufficient serum vitamin D concentration > 50 nmol/L as recommended in the 2011 Institute of Medicine report. These results also suggest that the overweight/obese, African American adolescents and adults needed much more vitamin D supplementation than the 600 IU/day recommended by National Institute of Health researchers. Lastly, the findings suggest that the national clinical guidelines published by the Endocrine Society may warrant revision to at least 2,000 IU/day to be effective for individuals in vulnerable populations. Future research is needed to further elucidate the role vitamin D plays in maintaining overall good health and the benefits of vitamin D supplementation. Keywords: vitamin D, vitamin D insufficiency, vitamin D supplementation, age, sex, body mass index, interleukin-6, vulnerable populations conceptual model
    • The VL region of IgG GAR and its role in anti-flavin specificity

      Kiefer, Charles R; Department of Cell and Molecular Biology (1981-05)
    • w do baccalaureate degree nurses differ from diploma and associate degree nurses in ethical decision-making?

      King, Rebecca B.; School of Nursing (1987-04)
      The purpose of this ex post facto study was to test the hypothesis that baccalaureate degree nurses would make more ethical decisions at a higher moral reasoning level than diploma ·,. or associate degree nurses. A convenience sample of 86 registered nurses voluntarily participated in the study. The Judgement About Nursing Decisions (JAND) instrument, developed by Dr. Shake' Ketefian, was used to measure ethical judgements and decision-making. A demographic survey accompanied the JAND test. Results of the one-way analysis of variance test revealed no significant difference in the mean JAND scores of the baccalaureate degree, diploma and associate degree nurses. These findings resulted in the rejection of the study hypothesis. Results of the seven factor analysis revealed that one factor out of seven pupported that baccalaureate degree nurses make more ethical decisions ·at a higher· moral reasoning level than diploma or associate degree nurses. The findings of this investigation indicate the need to further study what factors play an active role in moral reasoning and ethical decision-making. The findings also support the need to revise and develop valid and reliable tools to measure moral reasoning and ethical behavior.
    • You Really Are Too Kind: Implications Regarding Friendly Submissiveness in Trainee Therapists

      Cain, Lylli; Department of Psychological Sciences; Augusta University (4/20/2018)
      To facilitate patient growth, therapists must immerse themselves in the patient’s world while also being able to see what is needed for change. This process requires finding a delicate balance between supporting and pushing patients. Therapists in training are additionally tasked with incorporating supervisors’ suggestions with their own views on what is needed to help their patients. Beginning therapists with tendencies to be overly accommodating may struggle to reconcile these competing demands. Thus, the aim of the present work is to explore how trainee friendly submissiveness (FS) interfaces with psychotherapy. Prior to training, clinical graduate trainee (n = 35) FS was assessed using the Inventory of Interpersonal Problems-32. Process and outcome data were then collected from each therapist’s first training case. Specifically, each trainee was assigned an undergraduate student volunteer with whom they had four non-manualized therapy sessions over the academic semester. After the third session, patients and trainees completed questionnaires assessing session impact and the working alliance, and two expert raters coded third session videotapes for techniques. Following termination, patients rated the overall helpfulness of the therapy. Trainee FS was significantly negatively associated with patient-rated depth, alliance, and overall helpfulness with moderate effects. Findings from a mediation analysis further suggested that trainees with high FS struggled to focus the therapy in a way that felt productive to patients. Implications for clinical training are discussed.
    • β-adrenergic receptor/β-arrestin-mediated microRNA maturation regulatory network: A new player in cardioprotective signaling

      Teoh, Jian Peng; Department of Biochemistry and Molecular Biology / Cancer Center (1/25/2018)
      Chronic treatment with the β-blocker carvedilol (Carv) has been shown to reduce established maladaptive left ventricle (LV) hypertrophy and to improve LV function in experimental heart failure. However, the detailed mechanisms by which carvedilol improves LV failure are poorly understood. We previously showed that carvedilol is a β-arrestin-biased β1-adrenergic receptor ligand, which activates cellular pathways through β-arrestins in the heart independent of G protein-mediated second messenger signaling, a concept known as biased signaling. Here, we sought to (i) identify the effects of Carv on LV gene expression on a genome-wide basis and (ii) investigate whether Carv could regulate novel miR expression/biogenesis, thereby providing a novel mechanism for its cardioprotective effects. Gene expression profiling analysis revealed that subsets of genes are differentially expressed after Carv treatment. Further analysis categorized these genes into pathways involved in tight junction, cardiac response to malaria, viral myocarditis, glycosaminoglycan biosynthesis, and arrhythmogenic right ventricular cardiomyopathy (ARVC). Genes encoding proteins in the tight junction, malaria, and viral myocarditis pathways were upregulated in the LV by Carv, while genes encoding proteins in the glycosaminoglycan biosynthesis and ARVC pathways were downregulated by Carv. In addition, our findings also revealed that Carv indeed upregulates 3 mature miRs, but not their pre-miRs and pri-miRs, in a β-arrestin1/2-dependent manner. Interestingly, Carv-mediated activation of miR-466g or miR-532-5p, and miR-674 is dependent on β2AR and β1AR, respectively. Mechanistically, β-arrestins regulate maturation of 3 newly identified βAR/β-arrestin-responsive miRs (β-miRs) by associating with the Dicer complex as well as two RNA binding proteins (hnRNPK and dyskerin) on three pre-miRs. Cardiac cell approaches uncover that β-miRs act as gatekeepers of cardiac cell function by repressing deleterious targets. Our findings indicate a novel role for βAR-mediated β-arrestin signaling activated by Carv in miR maturation, which may be linked to its protective mechanism. Altogether, our findings indicate that (i) the gene expression changes may reflect the molecular mechanisms that underlie the functional benefits of Carv therapy and (ii) the novel role for βAR-mediated β-arrestin signaling activated by Carv in miR maturation, which may be linked to its protective mechanism.
    • Βeta-Arrestin1 and G Protein-Coupled Receptor Kinase5 Regulate Cancer Progression

      Kim, Jae II; Department of Neuroscience and Regenerative Medicine (2010-12)
      Cancer is a leading cause of death worldwide, accounting for nearly seven million deaths per year. Available clinical data establish a protective effect of COX-2 inhibition on human cancer progression, but the appearance of unwanted side effects remains a major hurdle for the general application of COX-2 inhibitors as effective cancer therapeutics. Major COX-2 effectors are prostaglandins and we explored the idea that PGE2 promotes mitogenic signals that could be exploited for targeted therapy of cancer. PGE2 signals through EP1, EP2, EP3, and EP4 that belong to the superfamily of GPCR that have been demonstrated to signal through G proteins and βArrestins. In the first part of this thesis project we determined the role of βArrestins in PGE2-regulated cancer cell migration. We report that the COX-2 effector PGE2 signals selectively via EP4 to enhance A549 lung cancer cell migration. We further find that this mode of signaling requires the presence of βArrestin1 and tyrosine kinase c-Src activity. Hence, this study provides preclinical-based rationale for the selective targeting of EP4 to inhibit PGE2-induced lung cancer cell migration. In the second part of this thesis project we determined the role of G protein-coupled receptor kinase 5 (GRK5) in cancer cell proliferation and tumor growth. Recent studies have implicated distinct GRK roles in the regulation of non-GPCR substrates, some of which have well-defined roles in cancer progression such as tumor suppressor p53. Here we report that GRK5 is required for prostate cancer cell cycle progression, cell proliferation, and prostate tumor growth. We identified HDAC4 as a novel GRK5 substrate, whose gene and protein expression is regulated by its kinase activity. In addition, we found that serine 246 residue of HDAC4 is phosphorylated by GRK5, a site known to regulate HDAC4 activity and subcellular localization. GRK5 can also phosphorylate an HDAC4 fragment (419-670 amino acid residues) that also contains two important regulatory serine phosphorylation sites. As many studies have shown HDAC4 involvement in cancer, our findings may provide a possible mechanism of HDAC4 regulation by GRK5.