Matching Items (27)

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Government Subsidization, Public Assistance, and the Socioeconomics of Type-Two Diabetes

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Type-two diabetes represents a pathological state of insulin resistance due to systemic, complex interactions between numerous identified and linked metabolic genes. According to current medical literature, the genetic predisposition to

Type-two diabetes represents a pathological state of insulin resistance due to systemic, complex interactions between numerous identified and linked metabolic genes. According to current medical literature, the genetic predisposition to type-two diabetes, coupled with environmental risk-factors, such as poverty and poor dietary habits, further exacerbate the risk of developing the disease. My research investigated the hypothesis that government poverty programs are associated with the surge in type-two diabetes among people of low socioeconomic status. My research suggests that government subsidies for the Commodity Supplemental Food Program, Women Infants and Children, Supplemental Nutrition Assistance Program, National School Lunch Program, and corn production influence individual dietary choices that lead to consumption of excessive amounts of refined sugars and fats and a surge in the prevalence of obesity, known risk-factors for developing type-two diabetes. These policies and programs may directly or indirectly promote and incentivize diets with excessive refined sugars and fats. As such, current programs paradoxically contradict current medical literature and direct individual choices that have increased the known risk-factors for developing type-two diabetes. Future efforts should reassess poverty and agricultural subsidy programs in relation to medical recommendations for diabetes prevention. The enormous societal and economic burden associated with type-two diabetes calls for further research to assess the efficacy of current public policy and the allocation of government funds.

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  • 2017-05

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Early Life Stress: An Increased Risk of Schizophrenia through Activation of the Complement Component Pathway

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Schizophrenia is a debilitating psychiatric disorder with poorly understood genetic and environmental factors. An allelic variant of complement component 4 (C4), a protein first identified in innate immune response

Schizophrenia is a debilitating psychiatric disorder with poorly understood genetic and environmental factors. An allelic variant of complement component 4 (C4), a protein first identified in innate immune response is strongly associated with schizophrenia. In the brain, activity of C4 leads to dendritic pruning, a process that may be causal in disease progression. Environmental factors, such as early life exposure to significant stressors also associate with increased risk of schizophrenia in later life. My hypothesis is that these factors do not act independently, but rather in tandem to influence disease etiology.
This hypothesis is supported by previous studies demonstrating that stress-induced elevation of glucocorticoids increases the transcription of C4. I propose that activated glucocorticoid receptors directly increase C4 protein expression as a transcription factor activator. Additionally, I propose that activated glucocorticoid receptors inhibit the expression of the transcription factor nuclear factor-light-chain-enhancer of activated B cells (NF-κB), thereby leading to decreased expression of the C4 inhibitor CUB and Sushi multiple domains 1 (CSMD1).
Glucocorticoid receptors and C4 are richly expressed in the hippocampus, a region critical in memory consolidation, spatial, and declarative memory. I propose that stress-induced upregulation of C4 activity in the hippocampus promotes excessive synaptic pruning, contributing to specific deficits and hippocampal shrinkage seen in schizophrenia. Stress exposure during fetal development and adolescence likely acts through the proposed mechanisms to increase hippocampal C4 activity and subsequent schizophrenia risk. These mechanisms may reveal novel interactions between environmental and genetic risk factors in the etiology of schizophrenia through complement activation.

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  • 2017-05

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Chronic Variable Stress Effects on Anxiety and Expression of Organic Cation Transporter 3

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Monoamine neurotransmitters (e.g., serotonin, norepinephrine, and dopamine) are powerful modulators of mood and cognitive function in health and disease. We have been investigating the modulation of monoamine clearance in select

Monoamine neurotransmitters (e.g., serotonin, norepinephrine, and dopamine) are powerful modulators of mood and cognitive function in health and disease. We have been investigating the modulation of monoamine clearance in select brain regions via organic cation transporters (OCTs), a family of nonselective monoamine transporters. OCTs are thought to complement the actions of selective monoamine transporters in the brain by helping to clear monoamines from the extracellular space; thus, assisting to terminate the monoamine signal. Of particular interest, stress hormones (corticosterone; CORT) inhibit OCT3-mediated transport of monoamine, to putatively lead to prolonged monoamine signaling. It has been demonstrated that stress levels of CORT block OCT3 transport in the rat hypothalamus, an effect that likely underlies the rapid, stress-induced increase in local monoamines. We examined the effect of chronic variable stress (CVS) on the development of mood disorders and OCT3 expression in limbic and hypothalamic regions of the rat brain. Animals subjected to CVS (14-days with random stressor exposure two times/day) showed reduced body weight gain, indicating that CVS was perceived as stressful. However, behavioral tests of anxiety and depressive-like behaviors in rats showed no group differences. Although there were no behavioral effects of stress, molecular analysis revealed that there were stress-related changes in OCT3 protein expression. In situ hybridization data confirmed that OCT3 mRNA is expressed in the hippocampus, amygdala, and hypothalamus. Analysis of Western blot data by two-way ANOVA revealed a significant treatment effect on OCT3 protein levels, with a significant decrease in OCT3 protein in the amygdala and hippocampus in CVS rats, compared to controls. These data suggest an important role for CORT sensitive OCT3 in the reduction of monoamine clearance during stress.

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  • 2016-05

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A Mechanistic Model of Art Therapy

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The goal of my study is to test the overarching hypothesis that art therapy is effective because it targets emotional dysregulation that often accompanies significant health stressors. By reducing the

The goal of my study is to test the overarching hypothesis that art therapy is effective because it targets emotional dysregulation that often accompanies significant health stressors. By reducing the salience of illness-related stressors, art therapy may improve overall mood and recovery, particularly in patients with cancer. After consulting the primary literature and review papers to develop psychological and neural mechanisms at work in art therapy, I created a hypothetical experimental procedure to test these hypotheses to explain why art therapy is helpful to patients with chronic illness. Studies found that art therapy stimulates activity of multiple brain regions involved in memory retrieval and the arousal of emotions. I hypothesize that patients with chronic illness have a reduced capacity for emotion regulation, or difficulty recognizing, expressing or altering illness-related emotions (Gross & Barrett, 2011). Further I hypothesize that art therapy improves mood and therapeutic outcomes by acting on the emotion-processing regions of the limbic system, and thereby facilitating the healthy expression of emotion, emotional processing, and reappraisal. More mechanistically, I propose art therapy reduces the perception or salience of stressors by reducing amygdala activity leading to decreased activation of the hypothalamic-pituitary-adrenal (HPA) axis. The art therapy literature and my hypothesis about its mechanisms of action became the basis of my proposed study. To assess the effectiveness of art therapy in alleviating symptoms of chronic disease, I am specifically targeting patients with cancer who exhibit a lack of emotional regulation. Saliva is collected 3 times a week on the day of intervention: morning after waking, afternoon, and evening. Stress levels are tested using one-hour art therapy sessions over the course of 3 months. The Perceived Stress Scale (PSS) assesses an individual's perceived stress and feelings in past and present situations, for the control and intervention group. To measure improvement in overall mood, 10 one-hour art sessions are performed on patients over 10 weeks. A one-hour discussion analyzing the participants' artwork follows each art session. The Spielberger State-Trait Anxiety Inventory (STAI) assesses overall mood for the intervention and control groups. I created rationale and predictions based on the intended results of each experiment.

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  • 2018-05

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Developmental Changes in Vascular Density of the Hypothalamic Paraventricular Nucleus Following Prenatal Exposure to Dexamethasone

Description

The goal of the studies described in this thesis was to determine the changes in vascular density in the paraventricular nucleus (PVN) of the hypothalamus following prenatal exposure to the

The goal of the studies described in this thesis was to determine the changes in vascular density in the paraventricular nucleus (PVN) of the hypothalamus following prenatal exposure to the synthetic glucocorticoid hormone, dexamethasone (DEX). DEX is a synthetic glucocorticoid used clinically in women at risk for preterm delivery or in preterm infants to promote proper pulmonary development in high-risk neonates. Prenatal exposure to glucocorticoids such as DEX may change the development of important brain regulatory centers such as the PVN, resulting in increased risk for diseases in adulthood.
Previous studies have demonstrated that the hypothalamus regulates neuroendocrine and autonomic function and behavior. Within the hypothalamus, the paraventricular nucleus (PVN) is an integratory node that contains neurons associated with the control of neuroendocrine and autonomic responses. The PVN also has one of the highest density of blood vessels within the brain. Alterations of normal PVN angiogenesis by dexamethasone could potentially result in long-term modifications of brain and endocrine functions.
Timed-pregnant Sprague Dawley female rats received DEX on gestational days 18-21 and the resulting progeny were sacrificed at Postnatal Day (PND) 0, 4, 14, and 21. A tomato lectin, Lycopersicon Esculentum labeled with DyLight594 was used to stain blood vessels in the PVN and scanning confocal microscopy was used to analyze the experimental brains for PVN blood vessel density
Analysis of data using a 3-way analysis of variance (ANOVA) with age, sex and treatment as main factors, showed a significant age effect in vascular density. Analysis of female data by 2-way ANOVA demonstrated a significant effect of age, but no treatment or interaction effects. Post-hoc analysis shows significant differences at PND 2, 4, 14, and 21 compared to PND0. A Student‘s t-test of a planned comparison on PND2 showed a significant reduction by DEX treatment (p < 0.05). Analysis of data from females, using 2-way ANOVA demonstrated a significant effect of age, but no treatment or interaction effects. Post-hoc analysis shows significant differences at PND 2, 4, 14, and 21 compared to PND0. A planned comparison at PND 2 using Student’s t-test indicated a significant reduction by dex treatment.
The results of these studies demonstrate that there is significant postnatal angiogenic programming and that the vascular density of the PVN is altered by prenatal dexamethasone administration at PND2. The time-course shows developmental fluctuations in vessel density that may prove to be physiologically significant for normal brain function and developmental programming of brain and behavior.

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Date Created
  • 2014-05

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Dosage effects of highly selective D2 antagonist SV293 on drug-seeking behavior and locomotor activity

Description

Within the field of psychopharmacology, there has been difficultly with studying the functional effects of dopamine at the D2 receptor apart from other dopamine receptors due to the lack of

Within the field of psychopharmacology, there has been difficultly with studying the functional effects of dopamine at the D2 receptor apart from other dopamine receptors due to the lack of drugs that are selective for the D2 receptor. The purpose of this study was to observe the motivational and locomotor effects of using three varying doses (1.0, 3.0, and 5.6 mg/kg) of a new, highly selective D2 antagonist, SV293. These doses were tested across five different conditions that explore the effects of controls, SV293 by itself, and in combination with cocaine. These tests are designed to separately assess the effects of the antagonist between drug-seeking behaviors and locomotor activity. The cue tests showed that SV293 reduced drug-seeking and increased response latency at the high dose, suggesting a decrease in motivational effects of cocaine-related cues. SV293 alone also reduced drug-seeking and increased response latency at the high dose, suggesting a decrease in motivation for cocaine. Cocaine in combination with SV293 did not produce any significant effects on drug-seeking behavior, suggesting that SV293 did not alter the motivational effects of cocaine itself. Spontaneous locomotor activity tests with SV293 alone showed no reduction in locomotor activity; however, the addition of cocaine showed a significant decrease in locomotor activity at the high dose of SV293. Overall, the 5.6 mg/kg dose of SV293 decreases drug-seeking behavior elicited by cocaine-related cues and environmental stimuli, as well as cocaine-induced locomotor activity. This selective D2 antagonism could ultimately help elucidate the mechanisms of other dopamine receptors with particular emphasis on their involvement with drug addiction. Key words: cocaine, SV293, D2, antagonists, dopamine

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  • 2014-05

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Localization of the Organic Cation Transporters (OCT) and the Quantification of Organic Cation Transport and Serotonergic Gene Transcription in the Rat Brain

Description

The organic cation transporter 3 (OCT3) is a polyspecific monoamine transporter
found in the human and rat brain. In Rats, OCT3 is the only known monoamine transporter inhibited by physiological

The organic cation transporter 3 (OCT3) is a polyspecific monoamine transporter
found in the human and rat brain. In Rats, OCT3 is the only known monoamine transporter inhibited by physiological concentrations of corticosteroids. We hypothesized that CORT- mediated inhibition of OCT3 blocks the clearance of serotonin (5-HT) leading to an increase 5-HT receptor-mediated signaling. In experiment 1, due to conflicting reports on the location of OCT3 mRNA in the rat brain, in situ hybridization was performed on brain tissue sections. RNA was extracted from rat brain tissue, reverse transcribed into cDNA, and then polymerase chain reaction (PCR) was performed to generate riboprobe templates. The riboprobe templates were then used for in vitro transcription of digoxigenin (DIG)-labeled riboprobes complementary to OCT3. In experiment 2, 12 rats from an identical cohort were exposed to a chronic restraint stress paradigm (two hours/day for seven days, STRESS group), while the other 12 remained in their home cages (CTRL group). Twenty-four hours after the last stressor, all animals were euthanized and their brains immediately removed and frozen. Bilateral tissue punches were collected from 300μm coronal sections from the CA1 region of the dorsal hippocampus, basolateral amygdala (BLA), and dorsomedial hypothalamus (DMH). The relative OCT2, OCT3, and 5HT2a mRNA levels from each tissue punch were determined via quantitative real-time polymerase chain reaction (qPCR). The results of experiment 1 confirmed the presence of OCT3 mRNA in the CA1, amygdala, and the DMH. The results of experiment 2 show that chronic restraint stress did not alter gene expression for 5-HT2A, OCT2, and OCT3. These data may help reveal new information involving OCT3’s role in the hippocampus, amygdala and DMH in regards to localization and mRNA expression levels after exposure to a stressor.

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Date Created
  • 2013-05

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Fos Expression in Response to Nicotine and Social Reward in Adolescent Male Rats

Description

Previous findings from our lab have demonstrated that nicotine and social reward have synergistic effects when experienced together versus when experienced separately. The purpose of this experiment is to understand

Previous findings from our lab have demonstrated that nicotine and social reward have synergistic effects when experienced together versus when experienced separately. The purpose of this experiment is to understand the neural mechanisms underlying this synergistic effect by quantifying Fos protein, a marker for neural activation, in various brain regions. We utilized the conditioning place preference (CPP) model to assess reward. Four groups of adolescent male rats (n=120) were given either nicotine (Nic) (0.1 mg/kg/mL) or saline (Sal) and were placed in the CPP apparatus either with a social partner (Soc) or alone (Iso). Thus, groups were: 1.)Sal+Iso, 2).Sal+Soc, 3).Nic+Iso, 4).Nic+Soc. Brains of some the rats (n=40) were collected for Fos staining 90 minutes after the last conditioning session to obtain Fos data in response to direct exposure to the stimuli. The following regions were analyzed for Fos expression: central amygdala (CeA), medial amygdala (MeA), basolateral amygdala (BLA), nucleus accumbens core (NAcCore), and nucleus accumbens shell (NAcShell). Place preference changes occurred in socially-conditioned groups reflecting social reward and in nicotine-conditioned groups reflecting nicotine reward. As expected, the Sal+Iso control group failed to display a preference change. Fos data revealed a significant increase in Fos expression in the CeA, MeA, NAcCore and NAcShell for socially-conditioned animals and a significant decrease in the NAcCore for nicotine-conditioned groups. Experiencing both social and nicotine rewards together appeared to produce greater activation in the BLA. However, there was an increase in Fos expression in the negative control group relative to Nic+Iso group. The results of CPP suggest that social, nicotine and their combination are rewarding. The combination of the nicotine and social reward could have been more rewarding than social and nicotine separately, but the test was not sensitive to reward magnitude. The increase in Fos expression in the negative control group in the BLA could be due to isolation stress. Overall, these results suggest that these brain regions had greater activation to social reward.

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Date Created
  • 2013-05

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Ambassador Handbook

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Arizona State University and Banner Thunderbird Hospital have partnered to provide pre-med students with an internship at a local emergency department. Students entering into this program will have access to

Arizona State University and Banner Thunderbird Hospital have partnered to provide pre-med students with an internship at a local emergency department. Students entering into this program will have access to each patient's vital signs, medical imaging, lab tests, and medications. This access presents students with an opportunity to learn about a variety of tools used in the assessment and treatment of emergency room patients. In order to enhance the amount of knowledge students take away from the program, I created a handbook summarizing a variety of diagnostic tests and medications. The first section of the handbook (assessment) is spilt up into the three following categories: vital signs, medical imaging, and lab tests. The second section (treatment) consists of one category, medications. Each section was written with emphasis on basic physiology, and is intended to provide pre-med students with a foundation for building further medical knowledge. Although this handbook was tailored to the information students are most likely to encounter working in Banner Thunderbird Hospital's emergency department, it is still appropriate for any student interested in learning about emergency medicine.

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  • 2018-05

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The Proteomic Profile of Chronic Stress and Recovery in the Hippocampus

Description

The stress response facilitates our ability to deal effectively with threatening situations, but exposure to severe or chronic stressors can lead to undesirable neural, physiological, and behavioral outcomes. Chronic stress

The stress response facilitates our ability to deal effectively with threatening situations, but exposure to severe or chronic stressors can lead to undesirable neural, physiological, and behavioral outcomes. Chronic stress is associated with structural changes in the rat hippocampus, with corresponding deficits in learning and memory. Recent studies have uncovered an inherent neuroplasticity that allows the hippocampus to recover from these stress-induced neural changes. Underlying mechanisms likely involve several different cellular and molecular pathways. In order to gain a more comprehensive understanding of these pathways, we investigated differences in protein expression throughout the timeline of chronic stress and recovery. Male Sprague-Dawley rats were randomly assigned to chronic restraint stress for 6hr/d/10d or 6hr/d/21d, stress for 6hr/d/21d followed by a recovery period of no stress for 10 or 21 days, or a control group. The proteome from the hippocampus of these rats was sequenced using liquid chromatography tandem mass spectrometry (LC-MS/MS) and analyzed. We hypothesized that chronic stress alters interneuronal signaling in the hippocampus by enhancing or attenuating the expression of proteins responsible for synaptic plasticity (functional) and neuronal structure (morphology). So far we have found that structural proteins, such as alpha-internexin, homer protein homolog 3, neurofilament light, and vimentin were significantly altered by chronic stress and recovery. In contrast, proteins necessary for or associated with myelination such as 2',3'-cyclic-nucleotide 3'-phosphodiesterase, myelin-associated glycoprotein, myelin basic protein S, and myelin proteolipid protein were significantly downregulated by chronic stress. Collectively, these results will provide a resource for further investigations into the mechanisms of the brain's recovery from chronic stress.

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Date Created
  • 2016-05