Matching Items (96)
Description
The emergence of invasive non-Typhoidal Salmonella (iNTS) infections belonging to sequence type (ST) 313 are associated with severe bacteremia and high mortality in sub-Saharan Africa. Distinct features of ST313 strains include resistance to multiple antibiotics, extensive genomic degradation, and atypical clinical diagnosis including bloodstream infections, respiratory symptoms, and fever. Herein, I report the use of dynamic bioreactor technology to profile the impact of physiological fluid shear levels on the pathogenesis-related responses of ST313 pathovar, 5579. I show that culture of 5579 under these conditions induces profoundly different pathogenesis-related phenotypes than those normally observed when cultures are grown conventionally. Surprisingly, in response to physiological fluid shear, 5579 exhibited positive swimming motility, which was unexpected, since this strain was initially thought to be non-motile. Moreover, fluid shear altered the resistance of 5579 to acid, oxidative and bile stress, as well as its ability to colonize human colonic epithelial cells. This work leverages from and advances studies over the past 16 years in the Nickerson lab, which are at the forefront of bacterial mechanosensation and further demonstrates that bacterial pathogens are “hardwired” to respond to the force of fluid shear in ways that are not observed during conventional culture, and stresses the importance of mimicking the dynamic physical force microenvironment when studying host-pathogen interactions. The results from this study lay the foundation for future work to determine the underlying mechanisms operative in 5579 that are responsible for these phenotypic observations.
ContributorsCastro, Christian (Author) / Nickerson, Cheryl A. (Thesis advisor) / Ott, C. Mark (Committee member) / Roland, Kenneth (Committee member) / Barrila, Jennifer (Committee member) / Arizona State University (Publisher)
Created2016
Description
Invasive salmonellosis caused by Salmonella enterica serovar Typhimurium ST313 is a major health crisis in sub-Saharan Africa, with multidrug resistance and atypical clinical presentation challenging current treatment regimens and resulting in high mortality. Moreover, the increased risk of spreading ST313 pathovars worldwide is of major concern, given global public transportation networks and increased populations of immunocompromised individuals (as a result of HIV infection, drug use, cancer therapy, aging, etc). While it is unclear as to how Salmonella ST313 strains cause invasive disease in humans, it is intriguing that the genomic profile of some of these pathovars indicates key differences between classic Typhimurium (broad host range), but similarities to human-specific typhoidal Salmonella Typhi and Paratyphi. In an effort to advance fundamental understanding of the pathogenesis mechanisms of ST313 in humans, I report characterization of the molecular genetic, phenotypic and virulence profiles of D23580 (a representative ST313 strain). Preliminary studies to characterize D23580 virulence, baseline stress responses, and biochemical profiles, and in vitro infection profiles in human surrogate 3-D tissue culture models were done using conventional bacterial culture conditions; while subsequent studies integrated a range of incrementally increasing fluid shear levels relevant to those naturally encountered by D23580 in the infected host to understand the impact of biomechanical forces in altering these characteristics. In response to culture of D23580 under these conditions, distinct differences in transcriptional biosignatures, pathogenesis-related stress responses, in vitro infection profiles and in vivo virulence in mice were observed as compared to those of classic Salmonella pathovars tested.
Collectively, this work represents the first characterization of in vivo virulence and in vitro pathogenesis properties of D23580, the latter using advanced human surrogate models that mimic key aspects of the parental tissue. Results from these studies highlight the importance of studying infectious diseases using an integrated approach that combines actions of biological and physical networks that mimic the host-pathogen microenvironment and regulate pathogen responses.
Collectively, this work represents the first characterization of in vivo virulence and in vitro pathogenesis properties of D23580, the latter using advanced human surrogate models that mimic key aspects of the parental tissue. Results from these studies highlight the importance of studying infectious diseases using an integrated approach that combines actions of biological and physical networks that mimic the host-pathogen microenvironment and regulate pathogen responses.
ContributorsYang, Jiseon (Author) / Nickerson, Cheryl A. (Thesis advisor) / Chang, Yung (Committee member) / Stout, Valerie (Committee member) / Ott, C Mark (Committee member) / Roland, Kenneth (Committee member) / Barrila, Jennifer (Committee member) / Arizona State University (Publisher)
Created2015
Description
Pitchers are a vital part of the game of baseball and may account for up to two-thirds of the variance in win percentage. As they rise through the ranks of competition, physical skill set becomes less of a factor when compared to mentality. Pitchers are the “first line of defense” for keeping opponents from having an opportunity to score, as well as for holding onto their own team’s lead. Baseball pitchers not only face pressure to perform, but also experience stress from factors such as low pay, adjusting to higher levels of competition, and internal team competition for a limited number of spots. Athletes are often resistant to seeking aid from sport psychologists and often turn to unfavorable means to cope (i.e. drugs/alcohol, excessive exercise) with stress instead. Meditation has been shown to have beneficial effects on psychological factors associated with performance including emotional regulation, anxiety, confidence, focus, and mindfulness. Mobile applications have become a popular means of delivering mindfulness. The purpose of this study was to determine the feasibility and preliminary effectiveness of delivering a mindful meditation intervention using a mobile meditation application to improve psychological factors associated with performance (i.e. emotional regulation, anxiety (somatic and cognitive), confidence, focus, mindfulness) to minor league baseball pitchers. Pitchers in instructional league (Phase one) and off season (Phase two) were asked to meditate daily for 10-minutes each day for three weeks (Phase one) and eight weeks (Phase two). Pitchers were asked to complete self-report questionnaires and satisfaction surveys at pre- and post-intervention. Pitchers in phase one reported enjoying meditation, had improvements in self-confidence and sport confidence, and reported moderate decreases in cognitive anxiety and concentration disruption. Pitchers in phase two also enjoyed meditating (94.7%) and had improvements in self-confidence and moderate decreases in somatic anxiety. Low adherence due to timing (off-season) of intervention may have been a contributing factor to fewer outcomes. Future research should explore the feasibility and effectiveness of implementing meditation during the baseball season.
ContributorsDowling, Tiffany (Author) / Huberty, Jennifer (Thesis advisor) / Ransdell, Lynda (Committee member) / Buman, Matthew (Committee member) / Michel, Jesse (Committee member) / Arizona State University (Publisher)
Created2018
Description
Myeloproliferative neoplasm (MPN) patients suffer from fatigue and a reduced overall quality of life, both of which are not resolved with current pharmacologic therapy. The purpose of this study was to examine the effects of a 12-week online-streamed yoga intervention on fatigue and QoL in MPN patients as compared to a wait-list control group as well as to determine the feasibility of remotely collecting blood and saliva samples in a national sample. MPN patients were asked to complete 60 min/week of online yoga for 12 weeks. MPN fatigue and QoL were assessed online with single-item questions taken from the MPN SAF (fatigue and QoL) and NIH PROMIS (QoL) at baseline, week 7, and week 12. The practicality of the blood and saliva measures were defined as >70% completion rate at both baseline and week 12. Fidelity of the intervention (i.e., weekly yoga participation) was assessed via both self-report (i.e., daily log) and objective measurement (i.e., Clicky). Of the 62 MPN patients that enrolled in the study, 48 completed the intervention with 27 participating in the yoga group and 21 participating in the wait-list control group. Weekly yoga participation averaged ~41 min/week as measured objectively, whereas self-report yoga participation averaged ~56 min/week. The blood draw was determined to be practical with a 92.6% completion rate at baseline and a 70.4% completion rate at week 12. There were no significant differences from baseline to week 12 in MPN SAF fatigue (ES=0.18; p=0.724) or MPN SAF QoL (ES=-0.53; p=0.19), however, NIH PROMIS QoL was significantly improved from baseline to week 12 (ES=0.7; p=0.031) when compared to the control group. This study builds upon the findings from a prior feasibility study in demonstrating the feasibility of online yoga as well as its preliminary effects of improving total symptom burden, fatigue, pain, depression, anxiety, and sleep disturbance in MPN patients. Given the effects of yoga demonstrated both in the feasibility study and the current pilot study, a future randomized controlled trial with a larger sample size is warranted in order to further investigate the effectiveness of online yoga for MPN patient symptom burden and QoL.
ContributorsEckert, Ryan (Author) / Huberty, Jennifer (Thesis advisor) / Mesa, Ruben (Committee member) / Gowin, Krisstina (Committee member) / Dueck, Amylou (Committee member) / Kosiorek, Heidi (Committee member) / Larkey, Linda (Committee member) / Arizona State University (Publisher)
Created2017
Description
In sub-Saharan Africa, an invasive form of nontyphoidal Salmonella (iNTS) belonging to sequence type (ST)313 has emerged as a major public health concern causing widespread bacteremia and mortality in children with malaria and adults with HIV. Clinically, ST313 pathovars are characterized by the absence of gastroenteritis, which is commonly found in “classical” nontyphoidal Salmonella (NTS), along with multidrug resistance, pseudogene formation, and chromosome degradation. There is an urgent need to understand the biological and physical factors that regulate the disease causing properties of ST313 strains. Previous studies from our lab using dynamic Rotating Wall Vessel (RWV) bioreactor technology and “classical” NTS strain χ3339 showed that physiological fluid shear regulates gene expression, stress responses and virulence in unexpected ways that are not observed using conventional shake and static flask conditions, and in a very different manner as compared to ST313 strain D23580. Leveraging from these findings, the current study was the first to report the effect of fluid shear on the pathogenesis-related stress responses of S. Typhimurium ST313 strain A130, which evolved earlier than D23580 within the ST313 clade. A130 displayed enhanced resistance to acid, oxidative and bile stresses when cultured in the high fluid shear (HFS) control condition relative to the low fluid shear (LFS) condition in stationary phase using Lennox Broth (LB) as the culture medium. The greatest magnitude of the survival benefit conferred by high fluid shear was observed in response to oxidative and acid stresses. No differences were observed for thermal and osmotic stresses. Based on previous findings from our laboratory, we also assessed how the addition of phosphate or magnesium ions to the culture medium altered the acid or oxidative stress responses of A130 grown in the RWV. Addition of either
phosphate or magnesium to the culture medium abrogated the fluid shear-related differences observed for A130 in LB medium for the acid or oxidative stress responses, respectively. Collectively, these findings indicate that like other Salmonella strains assessed thus far by our team, A130 responds to differences in physiological fluid shear, and that ion concentrations can modulate those responses.
phosphate or magnesium to the culture medium abrogated the fluid shear-related differences observed for A130 in LB medium for the acid or oxidative stress responses, respectively. Collectively, these findings indicate that like other Salmonella strains assessed thus far by our team, A130 responds to differences in physiological fluid shear, and that ion concentrations can modulate those responses.
ContributorsGutierrez-Jensen, Ami Dave (Author) / Nickerson, Cheryl A. (Thesis advisor) / Barrila, Jennifer (Thesis advisor) / Ott, C. M. (Committee member) / Roland, Kenneth (Committee member) / Arizona State University (Publisher)
Created2017
Description
Physical activity, sedentary behaviors, and sleep are often associated with cardiometabolic biomarkers commonly found in metabolic syndrome. These relationships are well studied, and yet there are still questions on how each activity may affect cardiometabolic biomarkers. The objective of this study was to examine data from the BeWell24 studies to evaluate the relationship between objectively measured physical activity and sedentary behaviors and cardiometabolic biomarkers in middle age adults, while also determining if sleep quality and duration mediates this relationship. A group of inactive participants (N = 29, age = 52.1 ± 8.1 years, 38% female) with increased risk for cardiometabolic disease were recruited to participate in BeWell24, a trial testing the impact of a lifestyle-based, multicomponent smartphone application targeting sleep, sedentary, and more active behaviors. During baseline, interim (4 weeks), and posttest visits (8 weeks), biomarker measurements were collected for weight (kg), waist circumference (cm), glucose (mg/dl), insulin (uU/ml), lipids (mg/dl), diastolic and systolic blood pressures (mm Hg), and C reactive protein (mg/L). Participants wore validated wrist and thigh sensors for one week intervals at each time point to measure sedentary behavior, physical activity, and sleep outcomes. Long bouts of sitting time (>30 min) significantly affected triglycerides (beta = .15 (±.07), p<.03); however, no significant mediation effects for sleep quality or duration were present. No other direct effects were observed between physical activity measurements and cardiometabolic biomarkers. The findings of this study suggest that reductions in long bouts of sitting time may support reductions in triglycerides, yet these effects were not mediated by sleep-related improvements.
ContributorsLanich, Boyd (Author) / Buman, Matthew (Thesis advisor) / Ainsworth, Barbara (Committee member) / Huberty, Jennifer (Committee member) / Arizona State University (Publisher)
Created2017
Description
Introduction: Less than half of U.S. adults meet the aerobic physical activity guidelines to exercise at least 150 minutes a week. An individual's decision to be physically active is influenced by their perceptions of physical activity. To address perceptions, interventions need to be implemented where adults spend one third of their day; the workplace. A number of physical activity interventions have been conducted and few have been successful at improving physical activity; therefore, there is a need to explore novel approaches to improve physical activity in the worksite. The purpose of this pilot study was to examine the impact of a seven-day gratitude intervention on perceptions of physical activity and happiness in the workplace. Methods: Full-time employees at two worksites participated in a seven-day online journaling study. Participants were randomized into the intervention (gratitude) or control group and were assessed for perceptions of physical activity and happiness at baseline, immediate post-test (day 7) and one-week follow-up (day 14). Results: Results of this study indicate that the seven-day gratitude intervention may not significantly improve perceptions of physical activity or increase happiness. Future research should consider assessing the individual's readiness for change at baseline, increasing the length of the intervention, testing participant level of gratitude at baseline and employing a larger sample size.
ContributorsRowedder, Lacey (Author) / Huberty, Jennifer (Thesis advisor) / Chisum, Jack (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2014
Description
Understanding how microorganisms adapt and respond to the microgravity environment of spaceflight is important for the function and integrity of onboard life support systems, astronaut health and mission success. Microbial contamination of spacecraft Environmental Life Support Systems (ECLSS), including the potable water system, are well documented and have caused major disruption to spaceflight missions. The potable water system on the International Space Station (ISS) uses recycled wastewater purified by multiple processes so it is safe for astronaut consumption and personal hygiene. However, despite stringent antimicrobial treatments, multiple bacterial species and biofilms have been recovered from this potable water system. This finding raises concern for crew health risks, vehicle operations and ECLSS system integrity during exploration missions. These concerns are further heightened given that 1) potential pathogens have been isolated from the ISS potable water system, 2) the immune response of astronauts is blunted during spaceflight, 3) spaceflight induces unexpected alterations in microbial responses, including growth and biofilm formation, antimicrobial resistance, stress responses, and virulence, and 4) different microbial phenotypes are often observed between reductionistic pure cultures as compared to more complex multispecies co-cultures, the latter of which are more representative of natural environmental conditions. To advance the understanding of the impact of microgravity on microbial responses that could negatively impact spacecraft ECLSS systems and crew health, this study characterized a range of phenotypic profiles in both pure and co-cultures of bacterial isolates collected from the ISS potable water system between 2009 and 2014. Microbial responses profiled included population dynamics, resistance to silver, biofilm formation, and in vitro colonization of intestinal epithelial cells. Growth characteristics and antibiotic sensitivities for bacterial strains were evaluated to develop selective and/or differential media that allow for isolation of a pure culture from co-cultures, which was critical for the success of this study. Bacterial co-culture experiments were performed using dynamic Rotating Wall Vessel (RWV) bioreactors under spaceflight analogue (Low Shear Modeled Microgravity/LSMMG) and control conditions. These experiments indicated changes in fluid shear have minimal impact on strain recovery. The antimicrobial efficacy of silver on both sessile co-cultures, grown on 316L stainless steel coupons, and planktonic co-cultures showed that silver did not uniformly reduce the recovery of all strains; however, it had a stronger antimicrobial effect on biofilm cultures than planktonic cultures. The impact of silver on the ability of RWV cultured planktonic and biofilm bacterial co-cultures to colonize human intestinal epithelial cells showed that, those strains which were impacted by silver treatment, often increased adherence to the monolayer. Results from these studies provide insight into the dynamics of polymicrobial community interactions, biofilm formation and survival mechanisms of ISS potable water isolates, with potential application for future design of ECLSS systems for sustainable human space exploration.
ContributorsKing, Olivia G (Author) / Nickerson, Cheryl (Thesis advisor) / Barrila, Jennifer (Committee member) / Ott, C (Committee member) / Yang, Jiseon (Committee member) / Arizona State University (Publisher)
Created2019
Description
Background: Unmanaged stress is a major contributing factor to the development of disease in both men and women. Middle-aged adults (40-64) have some of the highest stress of all age groups and the use of meditation may provide relief for conditions such as stress. A smartphone application (app) may help limit the magnitude of the perceived challenges of meditation. The purpose of this study is to determine the feasibility of a consumer-based meditation app (i.e., Calm) to reduce stress in middle-aged adults who self-report elevated stress. The preliminary effects of Calm on stress and health outcomes related to stress were explored as well as the preliminary effects of Calm on mindfulness and coping behaviors for stress were explored.
Methods: Adults were recruited to a 4-week app-based health and well-being study. Participants were randomized into either a mindfulness meditation (i.e. Calm) group or a health education (POD) control group. Participants were asked to participate at least 10 minutes per day. Assessments were conducted for stress, anxiety, depression, mindfulness, physical activity, eating habits, and coping behaviors at pre- and post-intervention and voluntary phone interviews were held post-intervention. App usage data were collected subjectively through weekly participation logs and through objective app usage data provided by Calm.
Results: Eighty-three participants were enrolled into the study and 60 completed the intervention and were analyzed. Feasibility and demand benchmarks were met with 96% of participants satisfied with the intervention and 93% found it enjoyable, appropriate, and useful. There was a 70% adherence (minutes/week) to the meditation intervention. Recruitment of men into the intervention group was 38.1% and retention of men was 81.3%. Significant changes were not observed in stress, anxiety, depression, or mindfulness, physical activity, eating habits, and coping behaviors.
Conclusion: The findings of this study support the feasibility of a 4-week, mobile app-based mindfulness meditation intervention (i.e. Calm) in middle-aged adults. These finding do not demonstrate preliminary efficacy of Calm to reduce stress, anxiety, and depression or improvement of mindfulness, physical activity, eating habits, or coping behaviors among middle-aged adults who report elevated stress. These results can be applied for improved design of future studies.
Methods: Adults were recruited to a 4-week app-based health and well-being study. Participants were randomized into either a mindfulness meditation (i.e. Calm) group or a health education (POD) control group. Participants were asked to participate at least 10 minutes per day. Assessments were conducted for stress, anxiety, depression, mindfulness, physical activity, eating habits, and coping behaviors at pre- and post-intervention and voluntary phone interviews were held post-intervention. App usage data were collected subjectively through weekly participation logs and through objective app usage data provided by Calm.
Results: Eighty-three participants were enrolled into the study and 60 completed the intervention and were analyzed. Feasibility and demand benchmarks were met with 96% of participants satisfied with the intervention and 93% found it enjoyable, appropriate, and useful. There was a 70% adherence (minutes/week) to the meditation intervention. Recruitment of men into the intervention group was 38.1% and retention of men was 81.3%. Significant changes were not observed in stress, anxiety, depression, or mindfulness, physical activity, eating habits, and coping behaviors.
Conclusion: The findings of this study support the feasibility of a 4-week, mobile app-based mindfulness meditation intervention (i.e. Calm) in middle-aged adults. These finding do not demonstrate preliminary efficacy of Calm to reduce stress, anxiety, and depression or improvement of mindfulness, physical activity, eating habits, or coping behaviors among middle-aged adults who report elevated stress. These results can be applied for improved design of future studies.
ContributorsLaird, Breanne Michelle (Author) / Huberty, Jennifer (Thesis advisor) / O'Rourke, Holly (Committee member) / Larkey, Linda (Committee member) / Arizona State University (Publisher)
Created2020
Description
The discovery that mechanical forces regulate microbial virulence, stress responses and gene expression was made using log phase cultures of Salmonella Typhimurium (S. Typhimurium) grown under low fluid shear (LFS) conditions relevant to those encountered in the intestine. However, there has been limited characterization of LFS on other growth phases. To advance the growth-phase dependent understanding of the effect of LFS on S. Typhimurium pathogenicity, this dissertation characterized the effect of LFS on the transcriptomic and phenotypic responses in both stationary and lag phase cultures. In response to LFS, stationary phase cultures exhibited alterations in gene expression associated with metabolism, transport, secretion and stress responses (acid, bile salts, oxidative, and thermal stressors), motility, and colonization of intestinal epithelium (adherence, invasion and intracellular survival). Many of these characteristics are known to be regulated by the stationary phase general stress response regulator, RNA polymerase sigma factor S (RpoS), when S. Typhimurium is grown under conventional conditions. Surprisingly, the stationary phase phenotypic LFS stress response to acid and bile salts, colonization of human intestinal epithelial cells, and swimming motility was not dependent on RpoS. Lag phase cultures exhibited intriguing differences in their LFS regulated transcriptomic and phenotypic profiles as compared to stationary phase cultures, including LFS-dependent regulation of gene expression, adherence to intestinal epithelial cells, and high thermal stress. Furthermore, the addition of cell-free conditioned supernatants derived from either stationary phase LFS or Control cultures modulated the gene expression of lag phase cultures in a manner that differed from either growth phase, however, these supernatants did not modulate the phenotypic responses of lag phase cultures. Collectively, these results demonstrated that S. Typhimurium can sense and respond to LFS as early as lag phase, albeit in a limited fashion, and that the lag phase transcriptomic and phenotypic responses differ from those in stationary phase, which hold important implications for the lifecycle of this pathogen during the infection process.
ContributorsFranco, Karla Paola (Author) / Nikerson, Cheryl A (Thesis advisor) / Bean, Heather D (Committee member) / Stout, Valerie (Committee member) / Ott, C Mark (Committee member) / Barrila, Jennifer (Committee member) / Arizona State University (Publisher)
Created2020