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- Genre: Doctoral Dissertation
Description
The health benefits of physical activity are widely accepted. Emerging research also indicates that sedentary behaviors can carry negative health consequences regardless of physical activity level. This dissertation explored four projects that examined measurement properties of physical activity and sedentary behavior monitors. Project one identified the oxygen costs of four other care activities in seventeen adults. Pushing a wheelchair and pushing a stroller were identified as moderate-intensity activities. Minutes spent engaged in these activities contribute towards meeting the 2008 Physical Activity Guidelines. Project two identified the oxygen costs of common cleaning activities in sixteen adults. Mopping a floor was identified as moderate-intensity physical activity, while cleaning a kitchen and cleaning a bathtub were identified as light-intensity physical activity. Minutes spent engaged in mopping a floor contributes towards meeting the 2008 Physical Activity Guidelines. Project three evaluated the differences in number of minutes spent in activity levels when utilizing different epoch lengths in accelerometry. A shorter epoch length (1-second, 5-seconds) accumulated significantly more minutes of sedentary behaviors than a longer epoch length (60-seconds). The longer epoch length also identified significantly more time engaged in light-intensity activities than the shorter epoch lengths. Future research needs to account for epoch length selection when conducting physical activity and sedentary behavior assessment. Project four investigated the accuracy of four activity monitors in assessing activities that were either sedentary behaviors or light-intensity physical activities. The ActiGraph GT3X+ assessed the activities least accurately, while the SenseWear Armband and ActivPAL assessed activities equally accurately. The monitor used to assess physical activity and sedentary behaviors may influence the accuracy of the measurement of a construct.
ContributorsMeckes, Nathanael (Author) / Ainsworth, Barbara E (Thesis advisor) / Belyea, Michael (Committee member) / Buman, Matthew (Committee member) / Gaesser, Glenn (Committee member) / Wharton, Christopher (Christopher Mack), 1977- (Committee member) / Arizona State University (Publisher)
Created2012
Description
The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
Description
Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D. Recent evidence suggests high-intensity interval training (HIT) may yield similar or superior benefits in a shorter amount of time compared to traditional continuous exercise training. The purpose of this study was to compare the effects of HIT to continuous (CONT) exercise training for the improvement of endothelial function, glucose control, and visceral adipose tissue. Seventeen obese men (N=9) and women (N=8) were randomized to eight weeks of either HIT (N=9, age=34 years, BMI=37.6 kg/m2) or CONT (N=8, age=34 years, BMI=34.6 kg/m2) exercise 3 days/week for 8 weeks. Endothelial function was assessed via flow-mediated dilation (FMD), glucose control was assessed via continuous glucose monitoring (CGM), and visceral adipose tissue and body composition was measured with an iDXA. Incremental exercise testing was performed at baseline, 4 weeks, and 8 weeks. There were no changes in weight, fat mass, or visceral adipose tissue measured by the iDXA, but there was a significant reduction in body fat that did not differ by group (46±6.3 to 45.4±6.6%, P=0.025). HIT led to a significantly greater improvement in FMD compared to CONT exercise (HIT: 5.1 to 9.0%; CONT: 5.0 to 2.6%, P=0.006). Average 24-hour glucose was not improved over the whole group and there were no group x time interactions for CGM data (HIT: 103.9 to 98.2 mg/dl; CONT: 99.9 to 100.2 mg/dl, P>0.05). When statistical analysis included only the subjects who started with an average glucose at baseline > 100 mg/dl, there was a significant improvement in glucose control overall, but no group x time interaction (107.8 to 94.2 mg/dl, P=0.027). Eight weeks of HIT led to superior improvements in endothelial function and similar improvements in glucose control in obese subjects at risk for T2D and CVD. HIT was shown to have comparable or superior health benefits in this obese sample with a 36% lower total exercise time commitment.
ContributorsSawyer, Brandon J (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Lee, Chong (Committee member) / Swan, Pamela (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2013
Description
Purpose: The purpose of this study was to examine the acute effects of two novel intermittent exercise prescriptions on glucose regulation and ambulatory blood pressure. Methods: Ten subjects (5 men and 5 women, ages 31.5 ± 5.42 yr, height 170.38 ± 9.69 cm and weight 88.59 ± 18.91 kg) participated in this four-treatment crossover trial. All subjects participated in four trials, each taking place over three days. On the evening of the first day, subjects were fitted with a continuous glucose monitor (CGM). On the second day, subjects were fitted with an ambulatory blood pressure monitor (ABP) and underwent one of the following four conditions in a randomized order: 1) 30-min: 30 minutes of continuous exercise at 60 - 70% VO2peak; 2) Mod 2-min: twenty-one 2-min bouts of walking at 3 mph performed once every 20 minutes; 3) HI 2-min: eight 2-min bouts of walking at maximal incline performed once every hour; 4) Control: a no exercise control condition. On the morning of the third day, the CGM and ABP devices were removed. All meals were standardized during the study visits. Linear mixed models were used to compare mean differences in glucose and blood pressure regulation between the four trials. Results: Glucose concentrations were significantly lower following the 30-min (91.1 ± 14.9 mg/dl), Mod 2-min (93.7 ± 19.8 mg/dl) and HI 2-min (96.1 ± 16.4 mg/dl) trials as compared to the Control (101.1 ± 20 mg/dl) (P < 0.001 for all three comparisons). The 30-min trial was superior to the Mod 2-min, which was superior to the HI 2-min trial in lowering blood glucose levels (P < 0.001 and P = 0.003 respectively). Only the 30-min trial was effective in lowering systolic ABP (124 ± 12 mmHg) as compared to the Control trial (127 ± 14 mmHg; P < 0.001) for up to 11 hours post exercise. Conclusion: Performing frequent short (i.e., 2 minutes) bouts of moderate or high intensity exercise may be a viable alternative to traditional continuous exercise in improving glucose regulation. However, 2-min bouts of exercise are not effective in reducing ambulatory blood pressure in healthy adults.
ContributorsBhammar, Dharini Mukeshkumar (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Buman, Matthew (Committee member) / Swan, Pamela (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2013
Description
Eccentric muscle action (ECC) occurs when the force exerted by a working muscle is less than that of an outside resistance. This is characterized by muscle lengthening, despite actin-myosin crossbridge formation. Research has indicated that muscles acting eccentrically are capable of producing more force when compared to muscles acting concentrically. Further, research has shown ECC muscle actions may have different fatigue patterns that CON actions. The purpose of this study was to determine if a) ECC bench press yields greater strength than concentric (CON) as measured by one-repetition maximum (1RM), b) there is a difference between the number of repetitions that can be completed concentrically and eccentrically under the same relative intensities of 1RM (90%, 80%, 70%, 60%), c) a prediction model may be able to predict ECC 1RM from CON 1RM or CON repetitions to fatigue. For this study, 30 healthy males (age = 24.63 + 5.6 years) were tested for 1RM in CON and ECC bench press, as well as the number of repetitions they were able to complete at various intensities of mode-specific 1RM. A mechanical hoist was affixed to a gantry crane and placed over a standard weightlifting bench. The hoist was connected to 45lb plates that were loaded on a standard barbell, which allowed for mechanical raising and lowering of the barbell. For CON repetitions, the weight was mechanically lowered to the chest and the participant pressed it up. For ECC repetitions, the weight was mechanically raised and the participant lowered it. Paired t-tests showed that ECC 1RM was significantly (p < 0.05) greater than CON 1RM (ECC =255.17 + 68.37lbs, CON = 205.83 + 58.43lbs). There was a significant difference (p < 0.05) between the number of repetitions completed at 90% 1RM (CON = 4.57 + 2.21 repetitions, ECC = 7.67 + 3.24 repetitions). There were no differences in repetitions completed at any other intensity 1RM. CON 1RM and the number of repetitions completed with two different absolute loads (130-150lbs and 155-175lbs) concentrically and eccentrically were valid predictors of ECC 1RM. These data indicate that ECC actions yield increased force capabilities than CON actions, there is no difference in the rate of the fatigue, and ECC 1RM may be predicted from various CON tests.
ContributorsKelly, Stephen B., Jr (Author) / Hooker, Steven (Thesis advisor) / Brown, Lee (Committee member) / Buman, Matthew (Committee member) / Gaesser, Glenn (Committee member) / Swan, Pamela (Committee member) / Arizona State University (Publisher)
Created2013
Description
Meditation app usage is associated with decreases in stress, anxiety, and depression symptoms. Many meditation app subscribers, however, quickly abandon or reduce their app usage. This dissertation presents three manuscripts which 1) determined the behavioral, demographic, and socioeconomic factors associated with the abandonment of a meditation app, Calm, during the COVID-19 pandemic, 2) determined which participant characteristics predicted meditation app usage in the first eight weeks after subscribing, and 3) determined if changes in stress, anxiety, and depressive symptoms from baseline to Week 8 predicted meditation app usage from Weeks 8-16. In Manuscript 1, a survey was distributed to Calm subscribers in March 2020 that assessed meditation app behavior and meditation habit strength, and demographic information. Cox proportional hazards regression models were estimated to assess time to app abandonment. In Manuscript 2, new Calm subscribers completed a baseline survey on participants’ demographic and baseline mental health information and app usage data were collected over 8 weeks. In Manuscript 3, new Calm subscribers completed a baseline and Week 8 survey on demographic and mental health information. App usage data were collected over 16 weeks. Regression models were used to assess app usage for Manuscripts 2 and 3. Findings from Manuscript 1 suggest meditating after an existing routine decreased risk of app abandonment for pre-pandemic subscribers and for pandemic subscribers. Additionally, meditating “whenever I can” decreased risk of abandonment among pandemic subscribers. No behavioral factors were significant predictors of app abandonment among the long-term subscribers. Findings from Manuscript 2 suggest men had more days of meditation than women. Mental health diagnosis increased average daily meditation minutes. Intrinsic motivation for meditation increased the likelihood of completing any meditation session, more days with meditation sessions, and more average daily meditation minutes. Findings from Manuscript 3 suggest improvements in stress increased average daily meditation minutes. Improvements in depressive symptoms decreased daily meditation minutes. Evidence from this three-manuscript dissertation suggests meditation cue, time of day, motivation, symptom changes, and demographic and socioeconomic variables may be used to predict meditation app usage.
ContributorsSullivan, Mariah (Author) / Stecher, Chad (Thesis advisor) / Huberty, Jennifer (Committee member) / Buman, Matthew (Committee member) / Larkey, Linda (Committee member) / Chung, Yunro (Committee member) / Arizona State University (Publisher)
Created2022
Description
Mycobacterial infections, as represented by leprosy and tuberculosis, have persisted as human pathogens for millennia. Their environmental counterparts, nontuberculous mycobacteria (NTM), are commodious infectious agents endowed with extensive innate and acquired antimicrobial resistance. The current drug development process selects for antibiotics with high specificity for definitive targets within bacterial metabolic and replication pathways. Because these compounds demonstrate limited efficacy against mycobacteria, novel antimycobacterial agents with unconventional mechanisms of action were identified. Two highly resistant NTMs, Mycobacterium abscessus (Mabs) a rapid-growing respiratory, skin, and soft tissue pathogen, and Mycobacterium ulcerans (MU), the causative agent of Buruli ulcer, were selected as targets. Compounds that indicated antimicrobial activity against other highly resistant pathogens were selected for initial screening. Antimicrobial peptides (AMPs) have demonstrated activity against a variety of bacterial pathogens, including mycobacterial species. Designed antimicrobial peptides (dAMPs), rationally-designed and synthetic contingents, combine iterative features of natural AMPs to achieve superior antimicrobial activity in resistant pathogens. Initial screening identified two dAMPs, RP554 and RP557, with bactericidal activity against Mabs. Clay-associated ions have previously demonstrated bactericidal activity against MU. Synthetic and customizable aluminosilicates have also demonstrated adsorption of bacterial cells and toxins. On this basis, two aluminosilicate materials, geopolymers (GP) and ion-exchange nanozeolites (IE-nZeos), were screened for antimicrobial activity against MU and its fast-growing relative, Mycobacterium marinum (Mmar). GPs demonstrated adsorption of MU cells and mycolactone, a secreted, lipophilic toxin, whereas Cu-nZeos and Ag-nZeos demonstrated antibacterial activity against MU and Mmar. Cumulatively, these results indicate that an integrative drug selection process may yield a new generation of antimycobacterial agents.
ContributorsDermody, Roslyn June (Author) / Haydel, Shelley E (Thesis advisor) / Bean, Heather (Committee member) / Nickerson, Cheryl (Committee member) / Stephanopoulos, Nicholas (Committee member) / Arizona State University (Publisher)
Created2022
Description
This dissertation research project developed as an urgent response to physical inactivity, which has resulted in increased rates of obesity, diabetes, and metabolic disease worldwide. Incorporating enough daily physical activity (PA) is challenging for most people. This research aims to modulate the brain's reward systems to increase motivation for PA and, thus, slow the rapid increase in sedentary lifestyles. Transcranial direct current stimulation (tDCS) involves brain neuromodulation by facilitating or inhibiting spontaneous neural activity. tDCS applied to the dorsolateral prefrontal cortex (DLPFC) increases dopamine release in the striatum, an area of the brain involved in the reward–motivation pathways. I propose that a repeated intervention, consisting of tDCS applied to the DLPFC followed by a short walking exercise stimulus, enhances motivation for PA and daily PA levels in healthy adults. Results showed that using tDCS followed by short-duration walking exercise may enhance daily PA levels in low-physically active participants but may not have similar effects on those with higher levels of daily PA. Moreover, there was a significant effect on increasing intrinsic motivation for PA in males, but there were no sex-related differences in PA. These effects were not observed during a 2-week follow-up period of the study after the intervention was discontinued. Further research is needed to confirm and continue exploring the effects of tDCS on motivation for PA in larger cohorts of sedentary populations. This novel research will lead to a cascade of new evidence-based technological applications that increase PA by employing approaches rooted in biology.
ContributorsRuiz Tejada, Anaissa (Author) / Katsanos, Christos (Thesis advisor) / Neisewander, Janet (Committee member) / Sadleir, Rosalind (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2023
Description
The relationship between sleep and physical activity is an area of growing scientific interest, particularly in the context of older adults. The importance of examining long sleep duration and its influence on physical activity in this demographic becomes increasingly relevant given rising healthcare costs. This dissertation aims to investigate this intricate relationship via secondary analysis by examining the effects of moderate time-in-bed (TIB) restriction (60 minutes per night)) on various intensities of physical activity (sedentary, light, moderate, vigorous, moderate-vigorous physical activity) in older adults classified as long sleepers and average duration sleepers. It was hypothesized that moderate TIB restriction would result in differential changes in physical activity levels across various intensities, with long sleepers exhibiting increased physical activity and average sleepers displaying decreased activity, potentially influenced by alterations in TST (total sleep time) and SE (sleep efficiency). Utilizing a randomized controlled trial design, this study examined the effect of treatment changes in objectively measures activity (waist actigraphy) and subjects physical activity levels as measured by the Godin Leisure-Time Exercise Questionnaire . Eligible participants were long sleepers (sleeping > 9 hours per night) and average sleepers (sleeping 7-9 hours per night). Both types of sleepers were either randomized to TIB restriction or asked to maintain their average sleep patterns. Mean TIB restriction compared with baseline was 39.5 minutes in average sleepers and 52.9 minutes in long sleepers randomized to TIB restriction . Contrary to the original hypothesis, no significant effect of TIB restriction was observed across all physical activity levels in either long sleepers or average sleepers. However, a notable association was found between increased sleep efficiency (+0.09% [SD = ± 4.64%]) and light physical activity (±31 minutes [SD = ± 104.81, R=0.445, P < 0.007]) in long sleepers undergoing TIB restriction. While this study presents several methodological limitations, including its nature as a secondary analysis and the less-than-intended achievement of TIB restriction, it adds a valuable layer to the existing body of research on sleep and physical activity in older adults. The findings suggest that moderate TIB restriction may not be sufficiently impactful to change behavior in physical activity levels, thus highlighting the need for more nuanced, targeted research in this domain.
ContributorsPerry, Christopher (Author) / Youngstedt, Shawn D (Thesis advisor) / Petrov, Megan (Committee member) / Swan, Pamela (Committee member) / Buman, Matthew (Committee member) / Ringenbach, Shannon (Committee member) / Arizona State University (Publisher)
Created2023
Description
Mycobacterium tuberculosis (Mtb), the etiological agent of the tuberculosis disease, is estimated to infect one-fourth of the human population and is responsible for 1.5 million deaths annually. The increased emergence of bacterial resistance to clinical interventions highlights the lack in development of novel antimicrobial therapeutics. Prototypical bacterial two-component systems (TCS) allow for sensing of extracellular stimuli and relay thereof to create a transcriptional response. The prrAB TCS is essential for viability in Mtb, presenting itself as an attractive novel drug target. In Mtb, PrrAB is involved in the adaptation to the intra-macrophage environment and recent work implicates PrrAB in the dosR-dependent hypoxia adaptation. This work defines a direct molecular and regulatory connection between Mtb PrrAB and the dosR-dependent hypoxia response. Using electrophoretic mobility shift assays combined with surface plasmon resonance, the Mtb dosR gene is established as a specific target of PrrA, corroborated by fluorescence reporter assays demonstrating a regulatory relationship. Considering the scarce understanding of prrAB essentiality in nontuberculous mycobacteria and the presence of multiple prrAB orthologs in Mycobacterium smegmatis and Mycobacterium abscessus, CRISPR interference was utilized to evaluate the essentiality of PrrAB beyond Mtb. prrAB was found to be inessential for viability in M. smegmatis yet required for in vitro growth. Conversely, M. abscessus prrAB repression led to enhanced in vitro growth. Diarylthiazole-48 (DAT-48) displayed decreased selectivity against M. abscessus but demonstrated enhanced intrinsic activity upon prrAB repression in M. abscessus. Lastly, to aid in the rapid determination of mycobacterial drug susceptibility and the detection of mycobacterial heteroresistance, the large volume scattering imaging (LVSim) platform was adapted for mycobacteria. Using LVSim, Mtb drug susceptibility was detected phenotypically within 6 hours, and clinically relevant mycobacterial heteroresistance was detected phenotypically within 10 generations. The data generated in these studies provide insight into the essential role of PrrAB in Mtb and its involvement in the dosR-dependent hypoxia adaptation, advance the understanding of mycobacterial PrrAB essentiality and PrrAB-associated mycobacterial growth dependency. These studies further establish molecular and mechanistic connection between PrrAB and DAT-48 in Mtb and M. abscessus and develop a rapid phenotypic drug susceptibility testing platform for mycobacteria.
ContributorsHaller, Yannik Alex (Author) / Haydel, Shelley E (Thesis advisor) / Bean, Heather (Committee member) / Nickerson, Cheryl (Committee member) / Plaisier, Christopher (Committee member) / Acharya, Abhinav (Committee member) / Arizona State University (Publisher)
Created2023