Indiana University-Purdue University Indianapolis (IUPUI) / Various methods exist to measure physical activity (PA). Subjective methods, such as diaries and surveys are relatively inexpensive ways of measuring one’s PA; how ever, they are riddled with measurement error and bias due to self-report. Wearable accelerometers offer a noninvasive and objective measure of subjects’ PA and are now widely used in observational and clinical studies. Accelerometers record high frequency data and produce an unlabeled time series at the sub-second level. An important activity to identify from such data is walking, since it is often the only form of exercise for certain populations. While much work has been done to advance the use of accelerometers in public health research, methodology is needed for quan tifying the physical characteristics of different types of PA from the raw signal. In my dissertation, I advance the accelerometry research methodology in a three-paper sequence. The first paper is a novel application of functional linear models to model the physical characteristics of walking. We emphasize the signal processing used to prepare the data for analyses, and we apply the methods to a motivating dataset collected in an elder population. The second paper addresses the classification of PA. We designed an experiment and collected the data with the purpose of extracting useful and interpretable features for differentiating among walking, descending stairs, and ascending stairs. We build subject-specific classification models utilizing a tree based classifier. We evaluate the effects of sensor location and tuning parameters on the classification rate of these models. The third paper addresses the classification of walking types at the population level. We propose a robust normalization of features extracted for each subject and compare the model classification results to evaluate the effect of feature normalization. In summary, this work provides a framework for better use of accelerometers in the study of physical activity. / 2 years

Indiana University-Purdue University Indianapolis (IUPUI) / Efforts to encourage the medical community to prescribe exercise for disease prevention and management have increased significantly in recent years. In patients with obstructive sleep apnea (OSA), it is encouraging that exercise has been shown to improve sleep efficiency, daytime sleepiness, and disease severity. However, in order to better understand the dose-response relationship between exercise and OSA-related outcomes, accurate and reliable methods for assessing physical activity habits are needed. Purpose: To determine the test-retest reliability and validity of two self-report physical activity questionnaires [Physical Activity Vital Sign (PAVS); International Physical Activity Questionnaire-Short Form (IPAQ-SF)] in an OSA population. Methods: 39 adults with moderate-to-severe OSA wore an accelerometer for seven consecutive days and completed the PAVS and IPAQ-SF (twice within 10 d), along with questionnaires on quality of life, sleepiness, and treatment adherence. Test-retest reliability was determined using intraclass correlation coefficients (ICC). Criterion and construct validity were determined using Pearson (r) and Spearman correlation coefficients (ρ), respectively. Results: PAVS and IPAQ-SF scores were reported as total min/wk of moderate-vigorous physical activity (MVPA). Test-retest reliability for MVPA was excellent for PAVS (ICC = 0.982) and good for IPAQ-SF (ICC = 0.766). MVPA assessed via accelerometry was strongly correlated with PAVS (r = 0.802) and moderately with IPAQ-SF (r = 0.569). Both PAVS and IPAQ-SF were significantly correlated with body mass index (BMI) (ρ = -0.273 and -0.268, respectively), but no other variables. Conclusions: The PAVS and IPAQ-SF are reliable and valid PA questionnaires and may be utilized as a tool for accurately assessing physical activity levels in OSA patients.

There is an increasing interest in how therapeutic drugs could alter the human gut microbiota composition and function. While some knowledge is accumulating on the antimicrobial impact of some psychotropics on isolated strains or the gut microbiota of animal models, information about other classes of psychotropics and representative species from the human gut is poorly investigated. The antimicrobial effect of psychotropic drugs is usually neglected as a confounding factor when investigating gut microbiome biomarkers, knowing that patients are generally put in long-term medication. The purpose of the present study was to investigate (in vitro and ex-vivo) the antimicrobial activity of some oral commonly prescribed psychotropics from different therapeutic classes on colonic microbiota diversity and metabolism and the potential capacity of probiotics to alleviate related dysbiosis. The findings of this study revealed an important in vitro inhibitory activity of psychotropic drugs, which were also expressed as drastic alterations in gut microbiota composition ex-vivo. Indeed, the relative abundances of Firmicutes and Actinobacteria were lowered while the Proteobacteria population was increased. Families of Lachnospiraceae, Lactobacillaceae, and Erysipelotrichaceae were also declined by psychotropics (aripiprazole) treatment. These microbial changes were translated into a decrease of the major SCFA (butyrate, acetate, and propionate) at the metabolic level. The addition of a probiotic combination (Lactobacillus rhamnosus and Bifidobacterium longum) concomitantly with a psychotropic (aripiprazole) had a protective effect by attenuating the decline of microbiota composition and increasing the concentrations of SCFA. These findings provide evidence that psychotropics, through their antimicrobial effect, have the potential to alter the human gut microbiota composition and metabolism, while probiotics can mitigate the related dysbiosis.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy Candidate: Michaela Teplanská Supervisor: PharmDr. Daniela Hulcová, Ph.D. Title of diploma thesis: Derivatives of Amaryllidaceae alkaloid vittatine as potential drugs Haemanthamine type Amaryllidaceae alkaloids are characterized by interesting biological activity. This group also includes alkaloid vittatine with antitumor, antibacterial, antifungal and antimalarial effects. Although vittatine does not inhibit cholinesterases, its derivatives have shown promising activity against butyrylcholinesterase, which is one of the targets of potential drugs in the treatment of Alzheimer's disease. Another series of semisynthetic vittatine derivatives was prepared in order to examine their biological activity. Reactions with acyl chlorides gave 11 aromatic esters. Identification of the prepared substances was performed by ESI HRMS, NMR and optical rotation measurements. The derivatives were tested for inhibitory activity against human cholinesterases. The results show that the substances were not active against acetylcholinesterase, but almost all of them inhibited butyrylcholinesterase. The most active was 3-O-(6-chloro-2- fluoro-3-methylbenzoyl)vittatine with an IC50 value 0.29 ± 0.03 μM. According to the calculated value...

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Abstract Human Immunodeficiency Virus (HIV), a chronic medical condition characterized by cycles of wellness and illness, has the potential to decrease the physical activity levels and functional independence of infected individuals. Although antiretroviral therapy has been credited with improving and maintaining the immune status of infected patients by increasing cluster of differention 4 (CD4) count and suppressing viral load, the short- and long-term side effects of antiretroviral medication and the possible negative impact of these side effects on physical well-being have not yet been fully investigated. Therefore, I assessed the relationship between CD4 count, habitual physical activity levels and functional independence in a group of HIV positive South African adults either taking or not taking antiretroviral medication. I also compared the aerobic capacity, muscle strength and physical activity levels (activity counts) of age-matched black HIV negative females and HIV positive females who were taking antiretroviral medication. For the first part of the study, a Lifestyle and Physical Activity Questionnaire was completed by 186 black* male and female HIV positive outpatients who were recruited from a Johannesburg based antiretroviral roll out site. Of these patients, 121 were on first line antiretroviral treatment (median time of seven months), and 65 patients were not taking any medication. The questionnaire, as well as recording HIV history and current CD4 count, assessed each patient’s ability to independently perform one or more tasks of daily living as well as his/her monthly occupational, household and recreational physical activity levels. From the subjects’ responses, a total metabolic equivalent (MET) score for one month was calculated. The second part of the study assessed the full blood counts, aerobic capacity (submaximal bicycle ergometer test), lower limb strength (isokinetic dynamometry), hand grip strength (hand dynamometer) and seven day physical activity counts (actigraphy) of ten HIV positive black females recruited from the same Johannesburg antiretroviral roll out site. All of these patients had been taking first line antiretroviral treatment for a median time period of seven months. Ten HIV negative age-matched black females acted as their controls. From the questionnaire, significant correlations were observed between CD4 count and length of time on antiretroviral medication (P < 0.0001; r = 0.45), and between CD4 count and total monthly physical activity level (P = 0.0067; r = 0.20). Patients who considered themselves functionally independent had a significantly higher CD4 count that those patients who required help from others (P = 0.0031). The second part of the study revealed no significant difference in aerobic capacity, lower limb muscle strength (peak torque), handgrip strength and seven day physical activity counts between the female HIV positive patients and HIV negative controls. My results show that the use of antiretroviral medication (median time of seven months) increases CD4 count which translates into an increased habitual physical activity level and greater sense of functional independence. I have also shown that HIV positive females who are taking antiretroviral medication have an aerobic capacity, leg strength, handgrip strength and physical activity count which is not statistically different to their HIV negative counterparts. In this sample, the side effects associated with the administration of antiretroviral medication did not negatively impact on physical well-being. However, more research needs to be conducted on the possible physical activity limiting side effects of longer term antiretroviral medication administration, which may limit habitual physical activity levels. * Footnote: Race does not refer to any biological attributes but rather to the compulsory classification of people into the Population Registration Act. Although the act has been amended, these categories are still powerful and commonly used by the South African Government and statistical services.

Background: As obesity continues to be a global epidemic, health professionals continue to search for effective intervention and prevention programs. As suggested early in the 20th century, sport participation creates an environment not only for one to be physically active at a particular moment, but also to cultivate and develop skills necessary to lead a physically active lifestyle across one’s lifespan. Further, sports can provide individuals with an ideal environment to cultivate the psychological constructs of resilience and self-efficacy, traits that can provide them with protective agents that support physical and mental health, thus promoting greater life satisfaction. Purpose: The purpose of this study was twofold: (1) to determine the impact of previous high school sport participation on college freshmen’s current levels of exercise self-efficacy, resilience, and psychological need satisfaction in exercise; and (2) to examine relationships between demographic variables and exercise self-efficacy, resilience, and psychological need satisfaction in exercise (PNSE). Methods: A cross-sectional, stratified random sampling technique was employed to collect responses from college freshmen across the country (n = 156) using a SurveyMonkey survey instrument. ANOVA and Kruskal-Wallis H tests were completed to examine differences, based on demographic and sports participation factors, on the constructs of exercise self-efficacy, resilience, and PNSE. Independent samples t tests were conducted with dichotomous demographic variables. Ordinary least squares (OLS) multiple linear regression modelling was completed to attempt to predict exercise self-efficacy, resilience, and PNSE scores for respondents based upon their demographic and sports participation variables. Results: The results of analyses indicated that both resilience and PNSE, but not self-efficacy, were associated with sports participation. High school GPA, total physical activity, having met moderate PA guidelines, and being a collegiate athlete were each associated with exercise self-efficacy. Furthermore, high school GPA, total physical activity, freshmen standing, and being a collegiate athlete were each associated with resilience. Lastly, total physical activity and moderate PA guidelines met were associated with PNSE. Conclusion: The findings of this study may support sports participation as a way to develop exercise self-efficacy, resilience, and PNSE. Collectively, these findings may support the development of a model for adolescent programming that could include the development of each of these constructs, the implications of which could positively affect both academic and athletic domains.

Demand for tea is increasingly driven by its reported antioxidative properties. To ascertain such efficacy, the antioxidative activity (AA) of freshly brewed commercially available full-leaf white, green, oolong, and black tea was determined using a dynamic method. Various amounts (w/v) of tea were brewed at different temperatures for a constant period of time. The AA was calculated based on the ability of the brew to quench hydroxyl-radicals as quantified by chemiluminescence detection. Black tea had the strongest radical scavenging ability followed by green tea. Their AA was far greater than those of the other two types of tea tested. This efficacy finally eroded on serial dilution to a tea concentration of 0.15625 X 10-4 g/mL. The significant data clearly substantiate the sound premise that tea, particularly black tea, is unique in its dramatic ability to counter the adverse onslaught of radicals that are known contributors to human morbidity and mortality.

PrnB is a heme-containing enzyme, which catalyzes the ring rearrangement reaction of 7-chlorotryptophan to produce 3-(3-Chloro-2-nitrophenyl)pyrrole. This thesis describes the initial isolation and characterization of PrnB, the second enzyme associated with the pyrrolnitrin biosynthetic pathway in Burkholderia ambifaria. Additionally, alternative peroxidase reactivity was used to study how amino-acids bind to the substrate binding pocket of PrnB. The peroxidase activity of PrnB was measured using three different peroxidase activity assays at various pH values. The peroxidase data was compared to similar studies with the classic peroxidase, Horseradish peroxidase (HRP). Generally, PrnB showed weak peroxidase reactivity. However this weak reactivity was an experimental handhold, where tryptophan and other substrate binding events can be explored using classic inhibition steady-state kinetics. The rate of 2-aminophenol oxidation by PrnB was used as a model assay to monitor how molecules such as L-tryptophan, L-alanine, indole, L-phenylalanine, and L-tyrosine interact with the PrnB active site.