Matching Items (10)
Filtering by

Clear all filters

151797-Thumbnail Image.png
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

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
171573-Thumbnail Image.png
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

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
190821-Thumbnail Image.png
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)

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
187723-Thumbnail Image.png
Description
Tools designed to help match people with behaviors they identify as likely to lead to a successful behavioral outcome remain under-researched. This study assessed the effect of a participant-driven behavior-matching intervention on 1) the adoption of a new behavior related to fruit and vegetable (F&V) consumption, 2) study attrition, and

Tools designed to help match people with behaviors they identify as likely to lead to a successful behavioral outcome remain under-researched. This study assessed the effect of a participant-driven behavior-matching intervention on 1) the adoption of a new behavior related to fruit and vegetable (F&V) consumption, 2) study attrition, and 3) changes in F&V consumption. In this two-arm randomized controlled trial, 64 adults who did not meet standard F&V recommendations were allocated to an intervention (n=33) or control group (n=31). Participants in the intervention group ranked 20 F&V-related behaviors according to their perceived likelihood of engagement in the behavior and their perception of the behavior’s efficacy in increasing F&V consumption. Participants in the intervention group were subsequently shown the list of 20 behaviors in order of their provided rankings, with the highest-ranked behaviors at the top, and were asked to choose a behavior they would like to perform daily for 4 weeks. The control group chose from a random-order list of the same 20 behaviors to adopt daily for 4 weeks. During the study period, text messages were sent to all participants 90 minutes before their reported bedtime to collect Yes/No data reflecting successful behavior engagement each day. The binary repeated-measures data collected from the text messages was analyzed using mixed-effects logistic regression, differences in attrition were assessed using log-rank analysis, and change scores in F&V consumption were compared between the two groups using the Man-Whitney U test. P<0.05 indicated significance. The rate of successful behavior adoption did not differ significantly between the two groups (b=0.09, 95%CI= -0.81, 0.98, p=0.85). The log rank test results indicated that there was no significant difference in attrition between the two groups (χ2=2.68, df=1, p=0.10). F&V consumption increased significantly over the 4 weeks in the total sample (Z=-5.86, p<0.001), but no differences in F&V change scores were identified between the control and intervention groups (Z=-0.21, p=0.84). The behavior-matching tool assessed in this study did not significantly improve behavior adoption, study attrition, or F&V intake over 4 weeks.
ContributorsCosgrove, Kelly Sarah (Author) / Wharton, Christopher (Thesis advisor) / Adams, Marc (Committee member) / DesRoches, Tyler (Committee member) / Grebitus, Carola (Committee member) / Johnston, Carol (Committee member) / Arizona State University (Publisher)
Created2023
157086-Thumbnail Image.png
Description
Background In the United States (US), first-year university students typically live on campus and purchase a meal plan. In general, meal plans allow the student a set number of meals per week or semester, or unlimited meals. Understanding how students’ use their meal plan, and barriers and facilitators to meal

Background In the United States (US), first-year university students typically live on campus and purchase a meal plan. In general, meal plans allow the student a set number of meals per week or semester, or unlimited meals. Understanding how students’ use their meal plan, and barriers and facilitators to meal plan use, may help decrease nutrition-related issues.

Methods First-year students’ meal plan and residence information was provided by a large, public, southwestern university for the 2015-2016 academic year. A subset of students (n=619) self-reported their food security status. Logistic generalized estimating equations (GEEs) were used to determine if meal plan purchase and use were associated with food insecurity. Linear GEEs were used to examine several potential reasons for lower meal plan use. Logistic and Linear GEEs were used to determine similarities in meal plan purchase and use for a total of 599 roommate pairs (n=1186 students), and 557 floormates.

Results Students did not use all of the meals available to them; 7% of students did not use their meal plan for an entire month. After controlling for socioeconomic factors, compared to students on unlimited meal plans, students on the cheapest meal plan were more likely to report food insecurity (OR=2.2, 95% CI=1.2, 4.1). In Fall, 26% of students on unlimited meal plans reported food insecurity. Students on the 180 meals/semester meal plan who used fewer meals were more likely to report food insecurity (OR=0.9, 95% CI=0.8, 1.0); after gender stratification this was only evident for males. Students’ meal plan use was lower if the student worked a job (β=-1.3, 95% CI=-2.3, -0.3) and higher when their roommate used their meal plan frequently (β=0.09, 99% CI=0.04, 0.14). Roommates on the same meal plan (OR=1.56, 99% CI=1.28, 1.89) were more likely to use their meals together.

Discussion This study suggests that determining why students are not using their meal plan may be key to minimizing the prevalence of food insecurity on college campuses, and that strategic roommate assignments may result in students’ using their meal plan more frequently. Students’ meal plan information provides objective insights into students’ university transition.
Contributorsvan Woerden, Irene (Author) / Bruening, Meg (Thesis advisor) / Hruschka, Daniel (Committee member) / Schaefer, David (Committee member) / Vega-Lopez, Sonia (Committee member) / Adams, Marc (Committee member) / Arizona State University (Publisher)
Created2019
154702-Thumbnail Image.png
Description
Despite the safe and effective use of attenuated vaccines for over fifty years, measles virus (MV) remains an insidious threat to global health. Problematically, infants less than one year of age, who are the most prone to severe infection and death by measles, cannot be immunized using current MV vaccines.

Despite the safe and effective use of attenuated vaccines for over fifty years, measles virus (MV) remains an insidious threat to global health. Problematically, infants less than one year of age, who are the most prone to severe infection and death by measles, cannot be immunized using current MV vaccines. For this dissertation, I generated and performed preclinical evaluation of two novel MV vaccine candidates. Based on data from clinical trials that showed increasing the dosage of current MV vaccines improved antibody responses in six-month-old recipients, I hypothesized that increasing the relevant antigenic stimulus of a standard titer dose would allow safe and effective immunization at a younger age. I generated two modified MVs with increased expression of the hemagglutinin (H) protein, the most important viral antigen for inducing protective neutralizing immunity, in the background of a current vaccine-equivalent. One virus, MVvac2-H2, expressed higher levels of full-length H, resulting in a three-fold increase in H incorporation into virions, while the second, MVvac2-Hsol, expressed and secreted truncated, soluble H protein to its extracellular environment. The alteration to the virion envelope of MVvac2-H2 conferred upon that virus a measurable resistance to in vitro neutralization. In initial screening in adult mouse models of vaccination, both modified MVs proved more immunogenic than their parental strain in outbred mice, while MVvac2-H2 additionally proved more immunogenic in the gold standard MV-susceptible mouse model. Remarkably, MVvac2-H2 better induced protective immunity in the presence of low levels of artificially introduced passive immunity that mimic the passive maternal immunity that currently limits vaccination of young infants, and that strongly inhibited responses to the current vaccine-equivalent. Finally, I developed a more physiological infant-like mouse model for MV vaccine testing, in which MV-susceptible dams vaccinated with the current vaccine-equivalent transfer passive immunity to their pups. This model will allow additional preclinical evaluation of the performance of MVvac2-H2 in pups of immune dams. Altogether, in this dissertation I identify a promising candidate, MVvac2-H2, for a next generation measles vaccine.
ContributorsJulik, Emily (Author) / Reyes del Valle, Jorge (Thesis advisor) / Chang, Yung (Committee member) / Blattman, Joseph (Committee member) / Hogue, Brenda (Committee member) / Nickerson, Cheryl (Committee member) / Arizona State University (Publisher)
Created2016
152496-Thumbnail Image.png
Description
Background: Childhood obesity is one of the most serious public health concerns in the United States and has been associated with low levels of physical activity. Schools are ideal physical activity promotion sites but school physical activity opportunities have decreased due the increased focus on academic performance. Before-school programs provide

Background: Childhood obesity is one of the most serious public health concerns in the United States and has been associated with low levels of physical activity. Schools are ideal physical activity promotion sites but school physical activity opportunities have decreased due the increased focus on academic performance. Before-school programs provide a good opportunity for children to engage in physical activity as well as improve their readiness to learn. Purpose: The purpose of this study was to examine the effect of a before-school running/walking club on children's physical activity and on-task behavior. Methods: Participants were third and fourth grade children from two schools in the Southwestern United States who participated in a before-school running/walking club that met two times each week. The study employed a two-phase experimental design with an initial baseline phase and an alternating treatments phase. Physical activity was monitored using pedometers and on-task behavior was assessed through systematic observation. Data analysis included visual analysis, descriptive statistics, as well as multilevel modeling. Results: Children accumulated substantial amounts of physical activity within the before-school program (School A: 1731 steps, 10:02 MVPA minutes; School B: 1502 steps, 8:30 MVPA minutes) and, on average, did not compensate by decreasing their physical activity during the rest of the school day. Further, on-task behavior was significantly higher on days the children attended the before-school program than on days they did not (School A=15.78%, pseudo-R2=.34 [strong effect]; School B=14.26%, pseudo-R2=.22 [moderate effect]). Discussion: Results provide evidence for the positive impact of before-school programs on children's physical activity and on-task behavior. Such programs do not take time away from academics and may be an attractive option for schools.
ContributorsStylianou, Michalis (Author) / Kulinna, Pamela H. (Thesis advisor) / Van Der Mars, Hans (Committee member) / Amazeen, Eric (Committee member) / Adams, Marc (Committee member) / Mahar, Matthew T. (Committee member) / Arizona State University (Publisher)
Created2014
152558-Thumbnail Image.png
Description
Sustaining a fall can be hazardous for those with low bone mass. Interventions exist to reduce fall-risk, but may not retain long-term interest. "Exergaming" has become popular in older adults as a therapy, but no research has been done on its preventative ability in non-clinical populations. The purpose was to

Sustaining a fall can be hazardous for those with low bone mass. Interventions exist to reduce fall-risk, but may not retain long-term interest. "Exergaming" has become popular in older adults as a therapy, but no research has been done on its preventative ability in non-clinical populations. The purpose was to determine the impact of 12-weeks of interactive play with the Wii Fit® on balance, muscular fitness, and bone health in peri- menopausal women. METHODS: 24 peri-menopausal-women were randomized into study groups. Balance was assessed using the Berg/FICSIT-4 and a force plate. Muscular strength was measured using the isokinetic dynamometer at 60°/180°/240°/sec and endurance was assessed using 50 repetitions at 240°/sec. Bone health was tracked using dual-energy x-ray absorptiometry (DXA) for the hip/lumbar spine and qualitative ultrasound (QUS) of the heel. Serum osteocalcin was assessed by enzyme immunoassay. Physical activity was quantified using the Women's Health Initiative Physical Activity Questionnaire and dietary patterns were measured using the Nurses' Health Food Frequency Questionnaire. All measures were repeated at weeks 6 and 12, except for the DXA, which was completed pre-post. RESULTS: There were no significant differences in diet and PA between groups. Wii Fit® training did not improve scores on the Berg/FICSIT-4, but improved center of pressure on the force plate for Tandem Step, Eyes Closed (p-values: 0.001-0.051). There were no significant improvements for muscular fitness at any of the angular velocities. DXA BMD of the left femoral neck improved in the intervention group (+1.15%) and decreased in the control (-1.13%), but no other sites had significant changes. Osteocalcin indicated no differences in bone turnover between groups at baseline, but the intervention group showed increased bone turnover between weeks 6 and 12. CONCLUSIONS: Findings indicate that WiiFit® training may improve balance by preserving center of pressure. QUS, DXA and osteocalcin data confirm that those in the intervention group were experiencing more bone turnover and bone formation than the control group. In summary, twelve weeks of strength /balance training with the Wii Fit® shows promise as a preventative intervention to reduce fall and fracture risk in non-clinical middle aged women who are at risk.
ContributorsWherry, Sarah Jo (Author) / Swan, Pamela D (Thesis advisor) / Adams, Marc (Committee member) / Der Ananian, Cheryl (Committee member) / Sweazea, Karen (Committee member) / Vaughan, Linda (Committee member) / Arizona State University (Publisher)
Created2014
155895-Thumbnail Image.png
Description
Chronic diseases are the leading causes of death in the United States. Dietary behaviors influence the risk of developing multiple chronic diseases. The U.S. population consumes too few fruits and vegetables and too much sugar sweetened beverages (SSB) and fast food. The Social Ecological Model (SEM) was created as a

Chronic diseases are the leading causes of death in the United States. Dietary behaviors influence the risk of developing multiple chronic diseases. The U.S. population consumes too few fruits and vegetables and too much sugar sweetened beverages (SSB) and fast food. The Social Ecological Model (SEM) was created as a framework for health promotion interventions. The SEM organizes factors that can influence health into five layers: intrapersonal factors, interpersonal processes, institutional/organizational factors, community factors, and public policy. Each layer can influence dietary behaviors and other layers.

This work aims to understand how the community layer, represented by the food environment, moderates the association of two other layers and dietary behaviors: the interpersonal layer, represented by receiving health care provider’s (HCP) advice to lose weight, and the policy layer, represented by participation in the Supplemental Nutrition Assistance Program (SNAP), and a policy change within the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

Participant data were obtained from a household telephone survey of 2,211 adults in four cities in New Jersey from two cross-sectional panels in 2009-10 and 2014. Community food data were purchased and classified according to previously established protocol. Interaction and stratified analyses determined the differences in the association between HCP advice, SNAP participation, and time (for WIC participants) and eating behaviors by the food environment.

Interaction and stratified analyses revealed that HCP advice was associated with a decrease in SSB consumption when participants lived near a small grocery store, or far from a supermarket, limited service restaurant (LSR), or convenience store. SNAP participation was associated with a higher SSB consumption when respondents lived close to a small grocery store, supermarket, and LSR. There were no differences in fruit and vegetable consumption between two time points among WIC participants, or by food outlet.

The food environment, part of the community layer of SEM, moderated the relationship between the interpersonal layer and dietary behaviors and the policy layer and dietary behaviors. The association between HCP advice and dietary behaviors and SNAP participation and dietary behaviors were both influenced by the food environment in which participants lived.
ContributorsLorts, Cori Elizabeth (Author) / Ohri-Vachaspati, Punam (Thesis advisor) / Adams, Marc (Committee member) / Hooker, Steven (Committee member) / Roberto, Anthony (Committee member) / Tasevska, Natasha (Committee member) / Arizona State University (Publisher)
Created2017
157983-Thumbnail Image.png
Description
Background: Exercise is Medicine (EIM) is a health promotion strategy for addressing physical inactivity in healthcare. However, it is unknown how to successfully implement the processes.

Purpose: The purpose of this study was to understand how implementing EIM influenced provider behaviors in a university-based healthcare system, using a process evaluation.

Methods:

Background: Exercise is Medicine (EIM) is a health promotion strategy for addressing physical inactivity in healthcare. However, it is unknown how to successfully implement the processes.

Purpose: The purpose of this study was to understand how implementing EIM influenced provider behaviors in a university-based healthcare system, using a process evaluation.

Methods: A multiple baseline, time series design was used. Providers were allocated to three groups. Group 1 (n=11) was exposed to an electronic medical record (EMR) systems change, EIM-related resources, and EIM training session. Group 2 (n=5) received the EMR change and resources but no training. Group 3 (n=6) was only exposed to the systems change. The study was conducted across three phases. Outcomes included asking about patient physical activity (PA) as a vital sign (PAVS), prescribing PA (ExRx), and providing PA resources or referrals. Patient surveys and EMR data were examined. Time series analysis, chi-square, and logistic regression were used.

Results: Patient survey data revealed the systems change increased patient reports of being asked about PA, χ2(4) = 95.47, p < .001 for all groups. There was a significant effect of training and resource dissemination on patients receiving PA advice, χ2(4) = 36.25, p < .001. Patients receiving PA advice was greater during phase 2 (OR = 4.7, 95% CI = 2.0-11.0) and phase 3 (OR = 2.9, 95% CI = 1.2-7.4). Increases were also observed in EMR data for PAVS, χ2(2) = 29.27, p <. 001 during implementation for all groups. Increases in PA advice χ2(2) = 140.90, p < .001 occurred among trained providers only. No statistically significant change was observed for ExRx, PA resources or PA referrals. However, visual analysis showed an upwards trend among trained providers.

Conclusions: An EMR systems change is effective for increasing the collection of the PAVS. Training and resources may influence provider behavior but training alone increased provider documentation. The low levels of documented outcomes for PA advice, ExRx, resources, or referrals may be due to the limitations of the EMR system. This approach was effective for examining the EIM Solution and scaled-up, longer trials may yield more robust results.
ContributorsBirchfield, Natasha R (Author) / Der Ananian, Cheryl (Thesis advisor) / Krasnow, Aaron (Committee member) / Doebbeling, Bradley (Committee member) / Adams, Marc (Committee member) / Swan, Pamela (Committee member) / Arizona State University (Publisher)
Created2019