Mountain Scholar :: Browsing by Author "Hickey, Matthew, committee member"

Browsing by Author "Hickey, Matthew, committee member"

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Open Access
A case study of a wheat-free diet on autoimmune disease progression
(Colorado State University. Libraries, 2014) Connor, Trevor, author; Cordain, Loren, advisor; Hickey, Matthew, committee member; Ryan, Elizabeth, committee member; Schenkel, Alan, committee member
Background and Aims: Autoimmune disease encompasses a broad range of over 80 conditions for which only three have an identified environmental trigger. Gliadin is the trigger in celiac disease, a condition that has been linked to other autoimmune conditions including Crohn's disease and type I diabetes (T1D). The purpose of this study was to investigate case studies of autoimmune patients who employed a wheat-free or Paleo-style diet (WFP) to manage their conditions. Methods: A descriptive case study was performed that utilized questionnaires administered online and medical records from autoimmune disease patients who had consumed a WFP diet. Results: Fifty-seven patients were evaluated in the study (mean age 37.3 yrs., SD 10.1), including 23 males and 34 females, 24 of whom provided medical records. Thirty of the 57 volunteers demonstrated signs of disease improvement while consuming a WFP. The rates varied across conditions with eight of eight Crohn's disease patients experiencing remission, while three of four T1D patients exhibited signs of improvement. Five of 15 patients with ankylosing spondylitis, rheumatoid arthritis, or undifferentiated and multiple connective tissue disorders worsened while on the diet. Conclusions: Patients with single organ autoimmune diseases previously linked to increased intestinal permeability showed the greatest improvement after consuming a WFP. The results of these case studies warrant further controlled research examining the effects of wheat consumption on Crohn's disease and T1D.
Open Access
A one-week controlled diet and exercise intervention significantly improves insulin sensitivity without changes in plasma adiponectin concentrations in young non-Hispanic white and Mexican American adults
(Colorado State University. Libraries, 2010) Botero, Maria Fernanda, author; Melby, Chris, advisor; Allen, Kenneth, committee member; Hickey, Matthew, committee member
Background: Hypoadiponectinemia (low levels of adiponectin in blood) has been linked to insulin resistance and type 2 diabetes (T2D). In the USA, the prevalence of these latter two conditions is higher in Mexican Americans (MA) when compared to Non-Hispanic Whites (NHW). Variations in plasma adiponectin concentrations may partially contribute to differences in insulin resistance and T2D prevalence rates between adults of these two ethnic groups. Also, plasma adiponectin concentrations in MA and NHW adults may respond differently to a diet and exercise intervention. Objectives: 1. To determine whether or not pre-intervention fasting plasma adiponectin concentrations differ between sedentary, non-obese MA and NHW adults; 2. To determine if a combined one-week exercise and diet intervention (controlled low-saturated fat, low-sugar, high-fiber diet) improves both plasma adiponectin concentrations and insulin sensitivity in both NHW and MA adults; 3. To determine if changes in insulin sensitivity are associated with changes in circulating adiponectin concentrations. Methods: During the pre-study phase, volunteers underwent all initial screening tests. Eligible participants [n= 37; (20 NHW; 9 males, 11 females and 17 MA; 4 males, 13 females aged 18-40 years), fasting blood glucose < 126 mg/dl, blood pressure < 140/90 mm Hg, BMI < 30 kg/m2] continued with a 7-day baseline period, in which they were asked to maintain their regular food intake and their usual low level of exercise. A 3-hour intra-venous glucose tolerance test (IVGTT) for the measurement of insulin sensitivity was performed at the end of this period, as well as measurement of fasting plasma adiponectin. The intervention phase started immediately the day after and ended 7 days later. Subjects consumed a diet that was rich in vegetables, fruits, dietary fiber, and lean proteins and low in saturated fat and refined carbohydrates. Study investigators prepared all foods which were provided to participants. Subjects also exercised on a stationary cycle ergometer for 6 out of the 7 days of the intervention (40-45min/session at 65%V02 max). At the end of the intervention, 16-17 hours after the last exercise bout, plasma adiponectin was again measured and another IVGTT was performed. Dependent variables were analyzed using a 2 X 2 repeated measures ANOVA. Results: Insulin action, determined by the 3-h insulin area under the curve (IAUC) in response to glucose infusion, improved significantly (p<0.05) in response to the intervention (IAUC µU*min/L pre, post: MA = 2297, 1635; NHW = 1794, 1210). At baseline, plasma adiponectin levels were not significantly different between NHW and MA adults (NHW= 11.42 mµ/ml, MA= 11.17 mµ/ml) and there were no significant changes in adiponectin in response to the intervention in either group. Conclusion: A one-week diet and exercise intervention significantly improved insulin action in both MA and NHW adults, but changes in circulating adiponectin were not observed. Thus, the improvement in insulin sensitivity in response to a short-term diet/exercise intervention was disassociated from any changes in circulating adiponectin.
Open Access
A single session of moderate exercise, without energy deficit, may reduce svcam-1 concentrations in young, sedentary females
(Colorado State University. Libraries, 2010) Krause, Molly Annamarie, author; Melby, Christopher, advisor; Hickey, Matthew, committee member; Nelson, Tracy, committee member
Purpose: Cardiovascular disease remains the number one cause of death within the United States and globally [1, 2]. Postprandial lipemia and vascular adhesion molecules are becoming more widely recognized as biomedical makers associated with increased risk of developing CVD [3-5]. It has been well established that moderate exercise can improve some aspects of postprandial metabolism such as decreased triglycerides and improved insulin sensitivity [6]. However, there is limited data regarding the effect of prior moderate exercise on attenuating postprandial response specific to adhesion molecules [7, 8]. The purpose of this study was to determine the effects of a single bout of acute exercise, with energy replacement, on plasma soluble vascular adhesion molecule-1 (sVCAM-1), a marker of endothelial dysfunction, measured during fasting and in response to a high-fat, high-carbohydrate meal in young, non-obese, sedentary females. Methods: Eight, non-obese (x body mass index=24.6 kg/m2), habitually sedentary females (x age= 19.6 y) participated in this study. Following preliminary testing, each subject completed two trials in random order: 1) Exercise (Ex) 2) Non-exercise (Non-Ex). Each trial took place over 2 days. On the evening of day 1, subjects either rested (Non-Ex) or completed a cycle ergometer exercise bout at 65% peak heart rate, eliciting net exercise energy expenditure of ~285kcalories. On the morning of day 2 of each trial a fasting venous blood sample was drawn for measurement of sVCAM-1, followed by the consumption of a high-fat, high-sugar meal by each participant. Postprandial venous blood samples were then taken over at 2, 4, and 6 hours following meal ingestion for measurement plasma sVCAM-1 concentrations. Results: There was no significant treatment by time interaction on sVCAM-1 concentrations, nor was there a significant main effect of time. There was a significant condition effect on circulating soluble VCAM-1 concentrations such that concentrations were lower before and following the high-fat, high-sugar meal challenge for the EX compare to the NonEx condition. Conclusions: Results from the current study suggest that a single session of moderate exercise, without an energy deficit, may reduce sVCAM-1 concentrations in young, sedentary females. However, this finding must be viewed with caution owing to possible issues with thesVCAM-1 measurements, and the assay repeated prior to drawing any conclusions about the effect of acute exercise on circulating sVCAM-1 concentrations measured the morning after exercise.
Open Access
A sophisticated logic of enhancement: a disability-sensitive, welfare-maximizing stance in philosophy of medicine and procreative ethics
(Colorado State University. Libraries, 2024) Law, David Benjamin, author; Gorin, Moti, advisor; McShane, Katie, committee member; Hickey, Matthew, committee member
Julain Savulescu and Guy Kahane have developed a compelling yet controversial set of arguments that provide a theoretical and action-guiding grounding for the fields of medicine and procreative ethics. In medicine, they argue that medicine should do much more than merely treat patients; instead, it should "enhance" them to enjoy the greatest possible welfare. They argue that enhancement is justified by the same moral principles that justify treating patients in a medical setting. Similarly, in procreative ethics, they contend that when pre-natal selection is available, a similar welfare-maximizing principle should inform what children we should bring into existence. They argue that the "most advantaged child" among those that could be selected ought to be selected. There is something deeply compelling about these arguments but also deeply concerning; we should, of course, want the greatest welfare for ourselves, others, and our children, but we should also worry that accomplishing these ends via medicine and procreative selection may be using inappropriate means, relay implicit prejudices, or even constitute a kind of eugenics. In this thesis, I interrogate Savulescu and Kahane's arguments for the logic of enhancement and argue that a compelling and largely cohesive view emerges that has significant implications for the philosophy of medicine and procreative ethics. The view is, however, imperfect. Several adjustments and compromises must be made to make the view fully cohesive and to accommodate the highly compelling arguments made by disability rights theorists. In suggesting these adjustments and compromises, I ultimately defend the logic of enhancement from its most potent objections and contend that it is a highly illuminating view for ethical and theoretical work in the philosophy of medicine and procreative ethics.
Open Access
Acute beet juice ingestion improves estimates of insulin sensitivity in obese adults
(Colorado State University. Libraries, 2014) Beals, Joseph William, author; Bell, Christopher, advisor; Hickey, Matthew, committee member; Gentile, Christopher, committee member
Poor glucose regulation is strongly associated with low nitric oxide (NO) bioavailability; a characteristic that may be improved with stimulation of NO generating pathways. For example, endothelial nitric oxide synthase null mice demonstrate improved glucose metabolism following sodium nitrate ingestion. Dietary nitrates are sequentially reduced in the oral and gastric cavities to NO, a process that is attenuated by rinsing with an antibacterial mouthwash. We hypothesized that acute dietary nitrate consumption will improve glucose tolerance. 9 sedentary, healthy, obese adults (2 male; body mass index: 33.7 ± 4.0 kg/m2: age: 45±7 years; mean ± SE) were studied. Using a randomized crossover design, four oral glucose tolerance tests were performed (equal carbohydrate load). To assess the influence of dietary nitrate, subjects consumed either 500mL of beet juice + 25g glucose, or 500mL of water + 75g glucose, with and without prior antibacterial mouthwash use. Beet juice was selected because it is rich in nitrate. Venous blood samples were collected for the determination of glucose and insulin concentrations. Neither the circulating glucose nor insulin responses were influenced by beet juice and/or mouthwash (P>0.05). However, the Matsuda Index, an estimate of insulin sensitivity, was greater for beet juice compared with beet juice preceded by mouthwash (104.6 ± 11.7 vs. 83.5 ± 11.1; P<0.05). These preliminary data suggest that acute dietary nitrate ingestion may promote insulin sensitivity in obese adults.
Open Access
An exploration of varying attentional focus strategies on the exercise experience
(Colorado State University. Libraries, 2023) Oselinsky, Katrina, author; Graham, Daniel, advisor; Cleary, Anne, committee member; Thomas, Micheal, committee member; Hickey, Matthew, committee member
Background: Research indicates attentional focus (AF) has a significant impact on the overall exercise experience, however, little is known regarding how AF manipulations via the use of distracting technology exerts a beneficial influence on the exercise experience. Additionally, the effect of varying AF strategies on the exercise experience may vary based on individual characteristics and/or familiarity with the exercise task. Purpose: The goal of Study 1 was to determine if distinct exerciser profiles could be created from a sample of group fitness participants. The goal of Study 2 was to determine if AF mediates the relationship between immersive virtual reality (VR) technology and ratings of perceived exertion (RPE)/enjoyment during an exercise session. Methods: In Study 1, a sample of group fitness participants (n=31) completed one traditional cycling class in which only audio cues were presented (AUD) and one video-enhanced immersive cycling class (IMM) in which a combination of music and video images was presented. After each cycling session, participants complete a brief survey that asked them to rate their perceived exertion, AF, and enjoyment of the exercise sessions. In Study 2, additional study volunteers (n=84) were randomly assigned to complete either an audio-only cycling class or an immersive VR-enhanced cycling class in which a combination of music and video images was presented. After cessation of the exercise session, participants completed a brief survey regarding their experiences in which they reported their recalled, in-task AF, RPE, and level of exercise enjoyment. Results: Study 1 leveraged Latent profile analysis (LPA) which indicated three, distinct classes could be drawn from the sample of 31 group fitness participants. These classes were classified as Low Heart Rate (HR) Dissociator, High HR Dissociator, and Associator. Results of Study 2 indicated AF did not act as a mediator relating immersive technology with RPE and exercise enjoyment (n=84). Additionally in Study 2, experimental condition did not have a significant influence on AF, RPE, or enjoyment directly, however, post-hoc, exploratory analyses revealed that average heart rate and time spent working in a moderate to vigorous heart rate zone (i.e., time spent at 70% or greater of age calculated heart rate maximum) were significantly greater in the immersive video enhanced condition than the audio only. Conclusions: Study 1 expands on the extant literature by elucidating the different attentional focus techniques used by different groups of exercisers and the varying response patterns of these sub-groups on commonly assessed exercise experience variables. Study 1 demonstrates the need for a deeper exploration of how individual characteristics differentially impact the exercise experience and how emerging analytical techniques can be employed to create more targeted interventions. Study 2 suggests that although AF was not a mediator relating immersive technology to RPE and exercise enjoyment, this technology does seem to exert a beneficial influence on the exercise experience as evidenced by the increased work rate found in this study. The results of Study 2 suggest future research should seek to identify other causal mechanisms that explain how immersive technology exerts its beneficial influence on the exercise experience.
Open Access
Combining curcumin and alpha-lipoic acid to treat cardiometabolic syndrome
(Colorado State University. Libraries, 2015) Binns, Scott Edward, author; Bell, Christopher, advisor; Ryan, Elizabeth, committee member; Hickey, Matthew, committee member
INTRODUCTION: Obesity is associated with increased risk of developing cardiometabolic disease characterized by decreased insulin sensitivity, positive energy balance, and cardiovascular disease. Separately, the dietary compounds curcumin (CUR) and alpha lipoic acid (ALA) increase energy expenditure and insulin sensitivity. However the efficacy of combined CUR and ALA supplementation to improve characteristics of cardiometabolic health in overweight humans has never been evaluated. METHODS: 11 overweight and sedentary adults were randomly assigned to a placebo (n=5; age: 44 ± 8 years; body mass index: 31.9 ± 2.1 kg/m²; VO₂peak: 26.8 ± 4.1 ml/kg/min; (mean ± SE)) or CUR+ALA (n=6; age: 38 ± 7 years; body mass index: 32.2 ± 1.2 kg/m²; VO₂peak: 24.9 ± 3.7 ml/kg/min) 12-week intervention. Measurements of resting metabolic rate (RMR) and thermic effect of feeding (TEF) via indirect calorimetry, and insulin sensitivity via the hyperinsulinemic euglycemic clamp technique were assessed in a pre/post treatment manner. Additionally, resting blood pressure, and body composition via dual energy x-ray absorptiometry (DEXA) were measured. RESULTS: 12-weeks of CUR+ALA supplementation did not change RMR (1467 ± 89.9 to 1539 ± 94.4 kcal/day; P=0.239) or TEF AUC (P=0.51). Additionally, no change in glucose infusion rate occurred as a result of supplementation (12.8 ± 2.1 to 12.4 ± 1.2 mg/FFM kg/min; P=0.690). Resting systolic blood pressure was unaffected in the CUR+ALA group (116 ± 3.2 to 123.8 ± 25.4 mmHg; P=0.31). Body fat percentage did not change with CUR+ALA supplementation (43.8 ± 2.2 to 41.6 ± 1.9 body fat percent; P=0.162), however, body fat percentage decreased in all subjects regardless of treatment (P=0.002). DISCUSSION: These preliminary data do not support the use of CUR+ALA to improve metabolic and cardiovascular health in overweight adults.
Open Access
Considering risk, responsibility, and reward: the experiences of women of color in science speaking truth to power
(Colorado State University. Libraries, 2023) Moreira, Stephanie "Mo", author; Basile, Vincent, advisor; Archibeque-Engle, Shannon, committee member; Diaz, Hermen, committee member; Hickey, Matthew, committee member
The purpose of this study was to understand the risks, responsibility, and rewards women of color in the sciences navigate and negotiate when choosing to speak truth to power. The theoretical lenses that guided this work included Critical Race Theory, Critical Feminist Theory, Harding's strong objectivity, and Foucault's analysis of parrhesia (speaking truth to power). Employing the counternarrative, participants were provided an opportunity to reflect on their intentions, motivations, and behaviors when choosing to be outspoken about oppression in their personal and professional settings. The research questions for this study were: (1) What motivating factors guide women of color in the sciences to choose to speak truth to power? (2) How do women of color in the sciences envision the future of science culture? If speaking truth to power is a game, as Foucault suggests, the study identified five rules that served as a social contract for women of color in science. The emerging rules include: (1) stay true to oneself, (2) avoid ruining it for other women of color, (3) live to die another day, (4) if you must leave, go out on your own terms, and (5) share the map with others. Manipulating relationships and creating boundaries served as strategies that women of color in science uniquely operationalize to achieve their goals.
Open Access
David Hume's theory of justice: an examination of the possibility of an instinctual concept of property and natural virtue of justice
(Colorado State University. Libraries, 2015) Maimone, Charles L., author; Rollin, Bernard, advisor; Archie, Andre, committee member; Hickey, Matthew, committee member
In this work I argue that David Hume's classification of the virtue of justice as artificial is mistaken, and propose that the possibility of the existence of a natural virtue of justice should be taken seriously within Hume's moral framework. In the first chapter of this work, I present Hume's moral theory, with a focus on Hume's distinction between natural and artificial virtues. In the second chapter, I argue that Hume's certainty concerning the classification of justice as an artificial virtue is mistaken, and offer a positive account of the possibility of a natural origin, and ultimately a natural virtue of justice. In the third chapter I will entertain possible objections Hume might offer to my argumentation, and offer responses accordingly.
Open Access
Effects of obesity on the energetics of gradient walking
(Colorado State University. Libraries, 2012) Reynolds, Michelle, author; Browning, Raymond, advisor; Hickey, Matthew, committee member; Greene, David, committee member
Walking is a popular and convenient form of physical activity and can play an important role in the treatment and prevention of obesity. During level walking, obese adults are reported to have a greater net metabolic rate (W/kg) but a similar metabolic cost (J/kg/m) compared to non-obese adults. Individuals routinely walk up or down grades, but the metabolic response to gradient walking in obese individuals is not well understood. PURPOSE: To quantify metabolic rate and metabolic cost during level and gradient walking in obese and non-obese adults. A secondary purpose was to determine metabolic prediction equations' ability to estimate energy expenditure in obese adults. METHODS: Thirty-two obese (18 female, mass = 103.2 (15.8) kg, BMI = 35.0 (4.5) kg/m2, mean (SD)) and nineteen non-obese (10 female, mass = 64.9 (10.6) kg, BMI = 21.6 (2.0) kg/m2) volunteers participated in this study. We measured oxygen consumption while subjects stood and walked on a dual-belt force measuring treadmill at eleven speed/grade combinations ranging from 0.50 m/s to 1.75 m/s and -3° to 9°. We calculated gross and net (gross-stand) metabolic rate and metabolic cost for each condition. A two-factor repeated measures ANOVA determined how group (obese vs. non-obese) and speed/grade affected metabolic rate/cost. Bland-Altman plots and linear regression was used to determine the accuracy of prediction equations compared to measured oxygen consumption. RESULTS: Net metabolic rate increased with walking speed and grade, ranging from 1.91 (0.06) W/kg at 1.25 m/s, -3° to 5.91 (0.13) W/kg at 1.50 m/s, 3°, (mean (SE)). Obese individuals walked with a smaller gross metabolic rate (p<0.001), net metabolic rate (p=0.013), gross metabolic cost (p<0.001) and net metabolic cost (p=0.006) compared to non-obese adults. Body fat percentage, VO2 peak, and step width did not explain the variance in metabolic rate. Positive joint work was related to net metabolic rate during level walking, but not during uphill walking. ACSM and Pandolf prediction equations did not accurately predict metabolic rate/energy expenditure at all speed/grade combinations. Thus, we developed a new prediction equation for obese adults that is more accurate in predicting the energetics of walking. CONCLUSIONS: The smaller metabolic rate in obese adults suggests these individuals have better economy when walking on level or uphill/downhill grades. The mechanism by which economy is improved in obese adults has yet to be discovered.
Open Access
Ethical realism and the Darwinian Dilemma
(Colorado State University. Libraries, 2012) Rabinowitz, Aaron, author; Tropman, Elizabeth, advisor; MacKenzie, Matthew, committee member; Hickey, Matthew, committee member
In this thesis, I will examine a recent objection against ethical realism put forth by Sharon Street, a prominent advocate of ethical constructivism. Street's Darwinian Dilemma argues that ethical realism is incompatible with evolutionary psychology and that attempts to reconcile the two theories will result in the unacceptable epistemic conclusion that humans lack ethical knowledge. Street believes that the Darwinian Dilemma provides a strong reason for abandoning ethical realism in favor of ethical constructivism. It is my contention that the ethical realist can successfully defend herself against Street's objection. I will consider several possible responses that are available to the ethical realist for defusing the Darwinian Dilemma, including my preferred response which I believe has largely been neglected in the literature. I will argue that these responses provide the ethical realist with a functional defense against Street's challenge, and that ethical realism therefore remains superior to ethical constructivism.
Open Access
Evaluating the impact of a novel immersive simulation on affect, rate of perceived exertion, and attention during a group cycling class
(Colorado State University. Libraries, 2022) Oselinsky, Katrina, author; Graham, Daniel, advisor; Cleary, Anne, committee member; Tompkins, Sara, committee member; Hickey, Matthew, committee member
Background: Emerging evidence within the exercise psychology literature has highlighted the importance of positive affective responses to physical activity (PA) for both PA adoption and maintenance. A potential avenue to increase positive affective responses to PA is through attentional focus. Purpose: The goal of this study was to examine the impact of a novel immersive technology on participants attentional focus, ratings of perceived exertion (RPE), affect, and enjoyment during a group cycling class. Methods: Participants were asked to take one traditional group cycling class with audio cues only (AUD) and one video enhanced immersive cycling class (IMM). Heart rate (HR) data was gathered throughout each class. At the conclusion of each session, participants completed a brief survey asking them to report their RPE, attentional focus, and affect during the cycling class. Results: Participants on average reported lower RPEs and higher enjoyment in the IMM class compared to the AUD class. Although attention was not significantly different between classes, when instructor was held constant, participants reported significantly more dissociative attentional focus during the IMM class than the AUD class. Finally, HR did not differ significantly between classes. Conclusions: To combat the rising rates of physical inactivity researchers must strive to make the PA experience more enjoyable. This study supports the use of a novel immersive technology to lower RPE and increase enjoyment without compromising actual exertion.
Open Access
Functional analysis of SMYD2 and SMYD3 lysine methyltransferases
(Colorado State University. Libraries, 2016) Edwards, Melissa Ashley, author; Brown, Mark, advisor; Tucker, Haley, committee member; Partin, Kathryn, committee member; Hickey, Matthew, committee member
The proteins SMYD2 and SMYD3 are two of five members of a unique family of lysine methyltransferases defined by a catalytic SET domain that is split into two segments by a MYND protein interaction domain, followed by a cysteine-rich post-SET domain. The SMYD family members have been shown to be essential for cellular development, cell cycle progression, and when dysregulated, tumorigenesis. SMYD1 has been widely studied as a pivotal component of cardiac and skeletal muscle development. Although their three dimensional structures have been solved, less is known about functional consequences of SMYD2 and SMYD3. Aberrant overexpression of SMYDs 2 and 3 have been implicated in numerous malignancies, and both have been studied as potential therapeutic targets. The overriding aim of our research is to obtain a more thorough understanding of SMYD2 and SMYD3 function. In Chapters 1 and 2, we outline essential background regarding the SMYD family and the methods used in our studies. In Chapter 3, we address the consequences of the interaction of SMYD3 with the nuclear chaperone, HSP90. Each have been independently implicated as proto-oncogenes in several human malignancies. Loss of SMYD3-HSP90 interaction leads to SMYD3 mislocalization within the nucleus, thereby severing its association with chromatin. This results in reduction of SMYD3-mediated cell proliferation and, consequentially, impairment of SMYD3’s oncogenic activity. We suggest a novel approach for blocking HSP90-driven malignancy which may have reduced toxicity over current HSP90 inhibitors. In Chapter 4, we turn our attention to SMYD2 and its putative role in hematopoietic carcinogenesis. In order to study the effect of SMYD2 in tumor initiation, we employed transforming oncogenes to study the consequences of SMYD2 loss in three hematopoietic models: B-Acute Lymphocytic Leukemia (B-ALL), Chronic Myeloid Leukemia (CML), and Mixed Lineage Leukemia (MLL). Loss of SMYD2 in CML and MLL, but not in B-ALL, models led to cell cycle block following by widespread apoptosis and cell death. Tumorigenicity, as assessed in vitro by colony formation and in vivo by NOD/SCID transformation, was dependent upon SMYD2. Gene expression analyses indicated that, as previously determined in multiple studies, impairment included reduction in the level of the p53 tumor suppressor. Collectively, these studies establish SMYD2 as a putative proto-oncogene in CML and MLL. In Chapter 5, we report our efforts to extend the above findings to the living organism. SMYD2 was conditionally deleted via cre/Lox methodology from the germline of C57BL.6 mice exclusively in hematopoietic progenitors. SMYD2-deficient mice were born healthy and achieved normal lifespans. However, consistent with our findings of Chapter 4, we observed significant blocks in the progression of fetal and bone marrow hematopoietic stem cells to both B lymphocyte and myeloid lineages. While these blocks led to an overall reduction of mature peripheral B cells, SMYD2-deficient mice maintained a relatively normal immune response. These studies further support a model in which SMYD2 is required for normal hematopoiesis transformation.
Open Access
Impact of timing of milk intake on nitrogen balance in hypocaloric exercising older individuals
(Colorado State University. Libraries, 2011) Heusinger, Daniel, author; Miller, Benjamin, advisor; Melby, Christopher, advisor; Hamilton, Karyn, committee member; Melanson, Ed, committee member; Hickey, Matthew, committee member
We have previously shown that in older adults, consumption of protein immediately after aerobic exercise, rather than earlier in the day, enhances nitrogen balance when energy balance is maintained. Since some older individuals consume lower calorie diets, it is important to know if these benefits also occur during hypocaloric feeding. The purpose of the study was to investigate if consumption of protein immediately after aerobic exercise rather than earlier in the day can improve nitrogen balance in older individuals consuming a hypocaloric diet. In a randomized crossover design, healthy sedentary male (n=2; age=67.0±1.0 years; BMI=27.4±0.3 kg/m²) and female (n=8; age=63.0±1.8 years; BMI=22.3±0.6 kg/m²) subjects completed two separate 3-day exercise and nutrition interventions. Exercise (60 minutes of stationary cycling at 55% of VO2max) was performed daily. Diets were hypocaloric (-15% daily intake), with a protein+carbohydrate (PRO+CHO) or carbohydrate only (CHO) drink consumed in the morning and the opposite drink consumed after exercise. Both diets (15% protein, 30% fat, and 55% carbohydrate) were isonitrogenous and isocaloric with only the timing of the drinks differing. A 24-hour stay in a metabolic chamber confirmed negative energy balance, while 24-hour urine collections determined nitrogen balance. The 3-day mean nitrogen balance was not significantly greater in the PRO+CHO trial (0.097±0.526g N) trial than the CHO trial (-0.070 ±0.520g N) (p=0.280). Thus, older individuals in negative energy balance do not maintain a significantly more positive nitrogen balance by consuming protein after aerobic exercise as opposed to earlier in the day. These results differ from our previous work and indicate that energy balance is an important determinant of the anabolic effect of protein feeding.
Open Access
Impact of timing of protein intake on nitrogen balance in exercising older individuals on a hypercaloric diet
(Colorado State University. Libraries, 2011) Minor, Brian, author; Miller, Benjamin, advisor; Hamilton, Karyn, committee member; Melanson, Ed, committee member; Hickey, Matthew, committee member; Melby, Christopher, committee member
We have previously shown that in older adults, consumption of protein in the form of chocolate milk immediately after exercise enhances nitrogen balance (NBAL) when energy balance is maintained. Since it is known that hypercaloric diets increase nitrogen (N) retention, it is important to know if the timing of protein intake after aerobic exercise provides further increases in N retention compared to the consumption of carbohydrate only post exercise. PURPOSE: To investigate if consumption of protein and carbohydrate (PRO + CHO) immediately after exercise as opposed to earlier in the day can improve NBAL in older individuals consuming a hypercaloric diet. METHODS: In a randomized cross-over design, subjects completed two separate 3-day exercise and nutrition interventions. Exercise (60 minutes of stationary cycling at 55% of VO2max) was performed daily at 4:30 PM. Diets were hypercaloric (calculated at +15% daily intake), with a PRO+CHO or carbohydrate only (CHO) drink consumed at 10 am and the opposite drink consumed after exercise (5:30 PM). Both diets (1.2 g protein/kg bodyweight, 30% fat, and balance as carbohydrate) were isonitrogenous and isocaloric with only the timing of the drinks differing. A 24 hour stay in a metabolic chamber confirmed positive energy balance while 24-hour urine collections determined NBAL. RESULTS: The 3-day mean NBAL was not significantly different (p=.0881) (n=6) between the CHO trial (.970 ± .517 g N) and the PRO + CHO trial (1.659 ± .430 g N) although a trend toward increased NBAL with PRO+CHO was apparent. The mean energy balance was not significantly different (p=.2906) between the CHO trial (+13.09 ± 1.94%) and the PRO + CHO trial (+ 14.28 ± 1.75%). Further analyses comparing the positive energy balance cohort to previously completed negative, and even energy balance cohorts distinguished the role of energy balance and timing of nutrition effects. CONCLUSION: Older individuals in positive energy balance do not maintain a significantly more positive NBAL balance by consuming protein after aerobic exercise as opposed to earlier in the day although energy balance does change the effect of protein timing on NBAL.
Open Access
Liposomal encapsulated alpha-lipoic acid, benfotiamine and curcumin prevent overfeeding mediated increases in waist circumference
(Colorado State University. Libraries, 2017) Grimm, Nathan Carlisle, author; Bell, Christopher, advisor; Dooley, Gregory, committee member; Hickey, Matthew, committee member
INTRODUCTION: To determine if liposomal (L) encapsulated alpha-lipoic acid (0.5g), benfotiamine (0.5g) and curcumin (2.0g) (ABC) would prevent the unfavorable metabolic consequences of sedentary high-fat overfeeding in healthy young adults. METHODS: 29 young (18-30 years), healthy, physically active men and women were randomly assigned to ingest placebo (n=9), ABC (n=10), or L-ABC (n=10) twice daily for 28 days. Between days 22 and 28 all participants abstained from their normal regular exercise and consumed a high calorie, high fat diet. RESULTS: On Day 29, circulating alpha lipoic acid was greater (p<0.01) in L-ABC (412±73 ng/mL) compared with ABC (154±33 ng/mL). During the sedentary high fat overfeeding, dietary intake was not different (p>0.60) between groups (~3,400 kcal/day; ~50% from fat). Sedentary high fat overfeeding increased (p<0.05) waist circumference in the placebo (+2.7±2.7 cm) and ABC (+3.3±2.0) groups but not the L-ABC group (+0.7±2.7). The magnitudes of increase (p<0.05) in body mass (1.7±0.3 kg), fat mass (0.7±0.2 kg), and blood pressure (3±1 mmHg) and decrease (p<0.05) in insulin sensitivity (Matsuda Index: -2.9±0.9) after overfeeding were not different between groups (all p>0.50). DISCUSSION: Liposomal encapsulated alpha-lipoic acid, benfotiamine and curcumin: 1) promoted alpha-lipoic acid bioavailability; and, 2) prevented sedentary high-fat overfeeding mediated increases in waist circumference in usually active healthy young adults. These data may have important public health implications for periods of inactive overconsumption such as during seasonal celebrations.
Open Access
Obesity accelerates mammary carcinogenesis in a rat model of polygenic obesity susceptibility
(Colorado State University. Libraries, 2015) Matthews, Shawna Beth, author; Thompson, Henry J., advisor; Henry, Charles, committee member; Hickey, Matthew, committee member; Melby, Christopher, committee member
Given the ongoing obesity epidemic, in which more women in the US are overweight or obese than are lean, the impact of obesity on the development of breast cancer is an important public health concern. Obese women with breast cancer generally have larger tumors and poorer prognosis than lean women with breast cancer. In an effort to deconstruct the biological mechanisms that link obesity and breast cancer, we have developed a novel rat model with high relevance to the polygenic development of obesity and breast cancer in humans. These rats have differing susceptibility to obesity when fed a diet of similar macronutrient composition as that consumed by the average American woman. Diet susceptible (DS) rats rapidly accumulate excess body fat and display metabolic perturbations, including resistance to insulin and leptin, which normally provide "stop eating" anorexigenic cues. In contrast, diet resistant (DR) rats remain lean despite being fed the same diet. Findings from experiments conducted in our novel rat model have provided several critical pieces of information. When DR and DS rats were treated with a chemical carcinogen, DS rats displayed markedly accelerated mammary cancer formation compared to DR rats, including higher cancer incidence, multiplicity, and tumor burden, in conjunction with reduced cancer latency. The larger tumor mass in DS rats was found to be attributable to higher growth rates in DS vs. DR tumors, due to a combination of accelerated cell cycle progression and reduced apoptotic efficiency. Importantly, DS rats tended to develop more tumors that were negative for sex hormone receptor expression, a subtype of breast cancer with high rates of breast cancer mortality. This observation was corroborated by an endocrine ablation experiment, i.e., bilateral ovariectomy. Removal of the ovaries puts a strong selection pressure on expansion of cell populations that can grow in the absence of high circulating levels of sex hormones. In addition to removal of the primary source of circulating sex hormones, several experiments failed to provide evidence in support of peripheral production of estrogen by adipose tissue. In spite of the lack of estrogen at the host systemic and local (mammary gland) level, ovariectomized DS rats displayed elevated cancer multiplicity and sum tumor weight compared to ovariectomized DR rats, indicating that obesity in DS rats promotes the growth of cancer cells in an estrogen-independent manner. Clinically, chronic inflammation in adipose tissue as a consequence of obesity has been shown to create a permissive environment for the development of breast cancer. While DS rats display evidence of heightened fat storage in the form of adipocyte hypertrophy, there was no evidence of inflammation accompanying this hypertrophy in the rat mammary gland in the current studies. Thus, peripheral production of estrogen by fat tissue and chronic inflammation in fat tissue—two of the mainstream mechanisms proposed to link excess fat and breast cancer—do not appear to be obligatory biological processes for the effect of obesity on the increased cancer response in DS rats in our model. These findings suggest that our novel rat model represents a preclinical tool that facilitates investigation of mechanisms beyond those currently considered to link obesity to carcinogenesis of the breast. Breast cancer is a highly heterogeneous disease, and the integrated rat model reported herein is a tool that complements monogenic models of obesity and breast cancer in an effort to deconstruct the complex problem of breast cancer in clinical subpopulations whose disease is not explained via traditional mechanisms.
Embargo
Personal and contextual influences on Saudi parents' willingness and tolerance for children's risky play
(Colorado State University. Libraries, 2024) Alarawi, Rana M., author; Bundy, Anita, advisor; Lane, Shelly, committee member; Hepburn, Susan, committee member; Hickey, Matthew, committee member
Objective: The purpose of this dissertation was to examine personal and environmental factors that influence Saudi parents' willingness to promote, and tolerance of, risk taking in children's play. In this dissertation, I tested a conceptual model that explains the transactions among multiple constructs: factors affecting parental risk willingness, coping efficacy, perceptions of child, and risk tolerance. I also introduced a new tool, the Factors Affecting Tolerance for Risk in Play Scale (FAC-TRiPS) to assess personal, social and cultural factors affecting parental tolerance for risk in play. Lastly, I examined variations between Saudi mothers and fathers in relation to their willingness to allow and tolerate risk in play. Importance: Risky play is defined as "thrilling and exciting forms of physical play that involve uncertainty and a risk of physical injury" (Sandseter, 2010, p.22). Benefits of children's participation in "risky play" are broadly recognized (Barker et al., 2014; Brussoni, Olsen, et al., 2012; Gray et al., 2015; Sandseter, 2007; Sandseter & Kennair, 2011). However, most related research originates in Western countries; none focuses on outdoor play in Eastern countries, including Saudi Arabia. Further, while the literature identifies varying perspectives on risky play among parents, there is limited understanding of parental, social, and cultural contexts shaping and influencing Saudi parents' tolerance of risk in play. Participants: The sample included 90 Saudi parents with children ages 7 to 10 years who were able to read and speak English. Parents of this age group are expected to accept risky play. Method: This cross-sectional, quantitative dissertation encompassed three studies. In the first study, I used moderation analysis to test a conceptual model examining the relationship among factors contributing to parents' willingness to allow risky play and their risk tolerance. I also investigated the moderating effects of parental coping self-efficacy and parents' perceptions of their children's coping ability on the relationships among factors contributing to parents' willingness to allow risky play and their risk tolerance. In the second study, I utilized Rasch analysis to explore evidence for construct validity and internal reliability of data gathered with the FAC-TRiPS. In the third study, I examined gender variations in Saudi parents' willingness to promote, and tolerance for, risk taking in children's play by answering two research questions: (1) Do Saudi mothers and fathers differ systematically on FAC-TRiPS items? and (2) How does the inclusion of gender influence the relationship among factors affecting parental perceptions of tolerance for children's risky play? Results: Findings of the first study showed that play factors contributing to parents' willingness to allow risk (e.g., fear of injury and fear of negative judgment) were negatively correlated with risk tolerance. Additionally, parents' coping self-efficacy significantly moderated the relationships among play factors contributing to parents' willingness to allow risk and their tolerance for encouraging children to engage in risk taking. That is, parents with high self-efficacy were more inclined to perceive less stress in such situations and were more apt to allow their children to engage in risky play. However, parental perceptions of their children's coping ability did not have a moderating effect on the interaction between factors contributing to parents' willingness to allow risky play, and their tolerance for, risky play. In the second study, preliminary analysis suggested that the FAC-TRiPS yielded valid and reliable data measuring factors influencing parents' risk tolerance. Because the instrument in its early stages of development, further research with a larger sample is needed to refine items and enhance the instrument's functionality and precision. In the third study, although parent gender did not significantly predict risk tolerance, Saudi mothers and fathers exhibited systematic differences on three FAC-TRiPS items. Mothers reported more fears surrounding potential negative judgment and repercussions from an authority while fathers were more influenced of Media reports. Within the context of other factors, gender appeared to play a complex and indirect role in determining parents' risk tolerance. Conclusion: This research serves as a useful foundation for understanding the impact of context on parents' willingness to promote children's participation in risky play. Key themes across the three studies indicate that risk tolerance is likely influenced by a multitude of factors including personal, psychological, and cultural factors. This research represents the first to study a sample from Saudi Arabia, contributing an Eastern perspective to the existing body of research on risky play. Nevertheless, its findings invite further exploration into gender, societal, and cultural influences on how parents perceive and approach their children's participation in risky play environments. Additionally, further validation of the FAC-TRiPS and the Risk Tolerance model is needed. Findings of this research lend further support to the critical role of environmental facilitators and barriers on functioning as well as raise a need for creating a culture in which the duty of care is balanced with the dignity of risk in order to enable children of all abilities to participate in playful and age-appropriate risk-taking opportunities.
Open Access
Pharmacokinetic investigation of commercially available edible marijuana products in humans: potential influence of body composition and influence on glucose control
(Colorado State University. Libraries, 2021) Ewell, Taylor, author; Bell, Christopher, advisor; Hickey, Matthew, committee member; Hamilton, Karyn, committee member; Weir, Tiffany, committee member
Our investigation of five commercially available edible marijuana products containing 10mg of delta-9-tetrahydrocannabinol (THC) aimed to describe the pharmacokinetics of these products, investigate the potential influence of body composition on THC bioavailability, and, based on epidemiological research completed in the last decade, determine if acute marijuana ingestion influences glucose tolerance when compared to a THC-free gummy. We studied seven regular marijuana users. We utilized a single-blind randomized controlled crossover study design in which participants self-administered edible marijuana or a THC-free gummy. Thirty minutes following marijuana ingestion a standard oral glucose tolerance test was initiated via consumption of a 75g glucose drink. There was, at minimum, a four-day washout period between trials. Average time to peak plasma THC concentration ranged from 35 to 90 minutes, and average peak THC concentrations ranged from 3.2 to 5.5 ng/ml. Significant differences between products were identified twenty- and thirty-minutes post-ingestion. Several measures of body composition had significant correlations with plasma THC, although none of these correlations persisted across all products. There were no differences in indices of glycemic control between marijuana products or the THC-free gummy. Following acute edible marijuana ingestion in habitual users, significant differences in THC pharmacokinetics existed between similar products, possibly due to body composition, although glucose control was not impacted. In summary, these data may inform recreational users to the proper dose for marijuana ingestion to achieve the desired outcome and to avoid overdose.
Open Access
Physical activity: improving assessment tools and behavior in children
(Colorado State University. Libraries, 2014) Schaefer, Christine A., author; Browning, Ray, advisor; Hickey, Matthew, committee member; Nelson, Tracy, committee member; Graham, Dan, committee member
Adequate physical activity (PA) is a critical component of chronic disease prevention and a healthy lifestyle. Unfortunately, studies suggest that US children do not meet the recommended 60 minutes of PA per day. However, recent advances in measurement techniques are enabling researchers to gather more detailed objective PA data, allowing for an improved understanding of children's PA accumulation and patterns. This information will enable researchers and policy makers to better design and evaluate interventions aimed at increasing PA, ultimately reducing the prevalence of chronic disease. These ongoing advances in objective PA monitoring devices call for studies to test and refine the methods by which PA data are processed and interpreted. Specifically, although these novel PA devices and methods (e.g., accelerometers and activity intensity classification methodologies) are being calibrated and validated using laboratory protocols, their accuracy in estimating children's free-living PA has not been well-established. Additionally, given the well-established sporadic nature of children's activity, it is critical to measure activity during very short time intervals (i.e., 1-2 second bouts), requiring devices that can record and store acceleration data at a relatively high-resolution (e.g. 30-100 Hz). Importantly, though many intervention studies have been conducted with the goal of increasing daily PA, none have used high frequency acceleration data to examine the accumulation of PA in a free-living setting, nor to evaluate the effectiveness of these PA interventions. However, the need to do so is widely recognized among the PA monitoring community. Therefore, the following dissertation describes a series of experiments with the overall aim of improving PA measurement tools and behaviors in children. In the first study (Chapter 2), we attempt to establish cutpoints to distinguish between sedentary, light, moderate and vigorous activity using a novel wrist-mounted accelerometry device. We also examine the effects of various bout lengths (periods of consecutive seconds of activity above the moderate threshold) on the estimated MVPA accumulation. Moderately accurate cutpoints resulted (~70-75% accuracy). We also found very high estimates of daily MVPA (>300 minutes). Because of the high estimates of daily MVPA as well as the relative difficulty in distinguishing between light and moderate activity by the confusion matrix, we began to further investigate the effects of the specific processing methodologies we used. This led us to the second study (Chapter 3), whereby we attempted to investigate the ability of three different processing methodologies to accurately detect MVPA. In this study, we applied three different processing methodologies (band pass filtered: BPEN, unfiltered: ENMO, and low pass filtered: LPENMO) to three separate independent samples of children: a calibration sample, a direct observation (classroom/recess) sample, and a multi-day, free-living sample. Results from this study suggested that BPEN is likely overestimating MVPA. ENMO and LPENMO both appeared to accurately detect MVPA compared to direct observation data (~85%). Because of these relatively good accuracies, and because low pass filtering is considered a best practice in signal processing, we elected to move forward with the low pass filtering methodology. Once we had established a methodology that we felt accurately detected MVPA, we were able to process and analyze data from the IPLAY (Intervention of PhysicaL Activity in Youth) study. IPLAY is a large-scale, school-based intervention aimed at increasing activity through either curriculum intervention (SPARK), environmental intervention (renovated playgrounds), or the combination of the two (see Chapter 4 for a more detailed description of the intervention). Results revealed no differences in lunch recess, school day or full day MVPA between the groups. In addition, relatively high estimates of daily MVPA resulted (~140 minutes), as well as a lack of effect of BMI z-score on MVPA accumulation. The combination of these studies adds a significant contribution to the literature around PA in children. Specifically, the investigation into processing methodologies demonstrates how critical this step is in being able to interpret acceleration data. It also provides a framework for other investigators to process acceleration data, with the goal of producing comparable results. The evaluation of the IPLAY study suggests the need for additional opportunities for children to be active during the day. The high estimates of daily MVPA suggest the need to further investigate how/when activity is being accumulated. Finally, an investigation into whether the PA guidelines ought to be re-established given novel methodologies for quantifying PA is warranted.