<p>Obesity is a major public health problem globally and in the United States (U.S.). Amongst adults in the U.S., prevalence estimates of obesity reached 42.4% in 2017-2018 [1]. Obesity is both a contributor and outcome of chronic disease development including type 2 diabetes and metabolic syndrome [2,3]. Underlying modifiable risk factors for these chronic conditions include lifestyle habits such as dietary intake and physical activity. </p><p>Much of nutrition research investigating the relationship of dietary intake to health outcomes has taken a reductionist approach with a focus on single nutrients and food groups; however, the complexity of the overall diet with all its constituents is being increasingly recognized. Dietary patterns examine the quantities, frequencies, and combinations of food and beverages consumed allowing a more comprehensive investigation of the diet-health relationship [4], yet, the concept and creation of patterns have not considered elements beyond nutrients and food, such as time of eating, which could be an important aspect of dietary patterns. Moreover, most physical activity research has focused on the effect of intensity or counts of activity on health [5–8], while studies investigating daily physical activity patterns have focused on distinct time periods i.e., type of day (weekday vs. weekend) or seasonality [9,10]. Nevertheless, connecting these patterns to health outcomes through the integration of time across an entire day has received little attention.</p><p>Studies that have incorporated time to the concept of dietary patterns focus on behaviors such as breakfast skipping and late meal consumption and show associations with health [11–14]. For instance, compared to early lunch eaters, late lunch eaters lost less weight and had reduced glucose tolerance [15,16]. In contrast, studies that have investigated timing of exercise focused on early vs. evening exercise [17–19]. For example, exercise performed in the morning vs. evening has been associated with a greater reduction in weight and odds of obesity [17,18]. Furthermore, several studies have investigated links between timing of exercise relative to a single meal or over a single day with health [20–24] and revealed a potential benefit to modulating time of these behaviors on postprandial metabolic response. Together, these studies establish the importance of timing of these behaviors in terms of links to health; however, studies are limited by a focus on single time spans or blocks of time in a day. Consideration of the patterns of dietary intake and activity throughout a day, or “temporal dietary and physical activity patterns”, are a novel concept that may provide insight to the behavioral patterns related to health outcomes. Notably, one of the challenges in this work is utilizing methods that will characterize dietary and physical activity patterns as an exposure by integrating timing and other characteristics of these patterns in relation to health. </p> To our knowledge, there are no published reviews that have emphasized joint consideration of the time of eating and exercise, with a focus on the time of day of these events and association with health outcomes. Therefore, Chapter 1 focuses on summarizing current literature that has integrated both of these concepts by answering the question, how does the timing of exercise relative to eating throughout the day effect postprandial response in adults? Moreover, Chapters 2 and 3, include primary research in which a novel distance measure, based on dynamic time warping, is used to develop independent temporal dietary and physical activity patterns over a 24-hour period using data from the National Health and Nutrition Examination Survey and examine their association with short- and long-term health outcomes.

Obesity is an important global health factor due to associated comorbidities and its pervasive occurrence. In my thesis, I aimed to contribute to a better understanding of the mechanisms that underlie obesity development as well as its adverse consequences in the brain. Both studies analyzed subsets of the LIFE-Adult study, a deeply-phenotyped, cross-sectional cohort study based on the general population of Leipzig. In the first study, I investigated the association of compulsive eating, a specific type of obesity-associated eating behavior, body mass index (BMI) and gray matter structure. Compulsive eating behavior, was selectively associated with cortical thickness of the right lateral orbitofrontal cortex, a region important for impulse control. Higher BMI was related to widespread reductions of cortical thickness. Orbitofrontal cortex structure may therefore predict compulsive eating behavior, while higher BMI is associated with decreased cortical thickness even in young and middle-aged adults. In the second study, I focused on the link between BMI, functional brain networks and cognitive function in older adults. Here, higher BMI was related to reduced connectivity of the default mode network, a network of brain regions known as a biomarker of aging and dementia. This finding demonstrates that functional connectivity may be an biomarker allowing to detect obesity-associated brain changes at an early stage. Taken together, these findings support the view of obesity as a risk factor for brain health. Yet, more longitudinal studies are needed to confirm this and reveal the underlying mechanisms.:List of Abbreviations i Table of Figures ii 1. Introduction 1 1.1 Central regulation of food intake 1 1.2 Characteristics of addictive-like eating behavior 3 1.3 Obesity as a risk factor for brain damage and cognitive decline 5 1.4 Assessment of brain structure and function with magnetic resonance imaging 8 1.4.1 A very short introduction to MRI 8 1.4.2 Structural MRI: Measuring the size and shape of the brain 8 1.4.3 Resting state functional MRI: Investigating the intrinsic brain architecture 10 2. Published studies 12 2.1 Neuroanatomical correlates of food addiction symptoms and body mass index in the general population 12 2.2 Higher body mass index is associated with reduced posterior default mode connectivity in older adults 24 3. Summary 38 References 43 Appendix 54 Supplementary Information for “Neuroanatomical correlates of food addiction symptoms and body mass index in the general population” 54 Author contributions to the publication “Neuroanatomical correlates of food addiction and body mass index in the general population” 59 Author contributions to the publication “Higher body mass index is associated with reduced posterior default mode connectivity in older adults” 60 Declaration of Authenticity 61 Curriculum Vitae 62 List of publications 63 List of conference contributions 65 Acknowledgments 66

Ertapenem is an antibiotic commonly used to treat a broad spectrum of infections and is part of a broader class of antibiotics called carbapenems. Unlike other carbapenems, ertapenem has a longer half-life and thus only has to be administered once a day. Previously, a physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of ertapenem following a single one gram dose in normal height, normal weight males. Due to the absorption properties of ertapenem, the amount of fat in the body can influence how the drug binds, how quickly the drug passes through the body, and thus how effective the drug might be. Thus, we have revised the model so that it is applicable to males and females of differing body mass index (BMI). Simulations were performed to consider the distribution of the antibiotic in males and females with varying body mass indexes. These results could help to determine if there is a need for altered dosing regimens in the future.

Background In South Africa, hypertensive disorders of pregnancy are the leading cause of maternal mortality. More than 50% of anaesthesia-related deaths are attributed to complications of airway management. We compared the prevalence and risk factors for hypoxaemia (SpO2<90%) during induction of general anaesthesia in parturients with and without hypertensive disorders of pregnancy. We hypothesised that hypertensive disorders of pregnancy are associated with desaturation during tracheal intubation. Methods Data from 402 cases in a multicentre obstetric airway management registry were analysed. The prevalence of peri-induction hypoxaemia (SpO2<90%) was compared in patients with and without hypertensive disorders of pregnancy. Quantile regression of SpO2 nadir was performed to identify confounding variables associated with, and mediators of hypoxaemia.Results In the cohort of 402 cases, hypoxaemia occurred in 19% with and 9% without hypertension (estimated risk difference, 10%; 95% CI 2% to 17%; P=0.005). Quantile regression demonstrated a lower SpO2 nadir associated with hypertensive disorders of pregnancy as body mass index increased. Room-air oxygen saturation, Mallampati grade, and number of intubation attempts were associated with the relationship. Conclusions Clinically significant oxygen desaturation during airway management occurred twice as often in patients with hypertensive disorders of pregnancy, compounded by increasing body mass index. Intermediary factors in the pathway from hypertension to hypoxaemia were also identified.

While a single residential move is a common experience for many families with children, residential moves that occur in higher frequency may serve as disruptive events in a child’s life. The present study draws upon data from the Fragile Families and Child Wellbeing Study of children from birth to 15 years of age to examine associations between residential moves and five measures of health and cognition: emergency room utilization, body mass index, incidence of asthma attack or asthma episode, repeated school grades, and scores on the Peabody Picture Vocabulary Test. Age-dependent, cumulative, and differential associations by sex and race are explored. Finally, the present study examines potential moderation of these associations by neighborhood context of a child’s city of birth. Cumulative analyses from the present study suggest that residential mobility is significantly associated with increased emergency room utilization over time, decreased body mass index over time, and a higher likelihood of a experiencing a repeated grade over time, and an increase in PPVT score over time. Age-dependent analyses of all children suggest that mobility in early childhood is significantly associated with emergency room usage and body mass index outcomes, while moves later in life are associated with increased body mass index and higher odds of repeating a school grade. The study further reveals significant sex and racial differences in both age-dependent and cumulative analyses. Evidence for age-dependent and cumulative associations between mobility and odds of an asthma attack emerged only when sex differences were examined. Several racial differences were observed in analyses. Notably, mobility was not a significant predictor of emergency room utilization for Black children at any time point examined nor in longitudinal analyses. Finally, evidence of consistent moderation effects by a child’s birth city neighborhood context was not found; however, significant moderation effects by neighborhood context were found for associations between mobility and emergency room utilization at age 1, BMI at age 3 and BMI at age 5. A central aim of the present study is to contribute to the growing body of empirical research about housing mobility and correlates to developmental outcomes for children. Results from the present study’s analysis can help inform housing-centered strategies to mitigate adverse outcomes for children from families experiencing housing hardship.

We seek to observe the association between childhood obesity by different measures and adult obesity, metabolic syndrome (MetS), and diabetes. Thousand two hundred and nine subjects from “Beijing Blood Pressure Cohort Study” were followed 22.9 ± 0.5 years in average from childhood to adulthood. We defined childhood obesity using body mass index (BMI) or left subscapular skinfold (LSSF), and adult obesity as BMI ≥28 kg/m2. MetS was defined according to the joint statement of International Diabetes Federation and American Heart Association with modified waist circumference (≥90/85 cm for men/women). Diabetes was defined as fasting plasma glucose ≥7.0 mmol/L or blood glucose 2 h after oral glucose tolerance test ≥11.1 mmol/L or currently using blood glucose-lowering agents. Multiple linear and logistic regression models were used to assess the association. The incidence of adult obesity was 13.4, 60.0, 48.3, and 65.1 % for children without obesity, having obesity by BMI only, by LSSF only, and by both, respectively. Compared to children without obesity, children obese by LSSF only or by both had higher risk of diabetes. After controlling for adult obesity, childhood obesity predicted independently long-term risks of diabetes (odds ratio 2.8, 95 % confidence interval 1.2–6.3) or abdominal obesity (2.7, 1.6–4.7) other than MetS as a whole (1.2, 0.6–2.4). Childhood obesity predicts long-term risk of adult diabetes, and the effect is independent of adult obesity. LSSF is better than BMI in predicting adult diabetes.

Objective: To test the hypothesis that body mass index (BMI) is a factor associated with passing a voiding trial after midurethral sling procedures for stress urinary incontinence (SUI). Study Design: The medical records of 136 consecutive patients who underwent placement of either tension-free vaginal tape (TVT) or transobturator tape (TOT) for SUI during a 1-year period (September 1, 2007 to August 31, 2008) were retrospectively reviewed. Variables assessed were BMI, age, and passing or failing a postoperative urinary voiding trial. Patients with concomitant pelvic organ prolapse surgeries were not included in this analysis. Results: Sixty-seven patients underwent TVT, whereas 69 had TOT procedures. In the TVT group, 30 patients (42%) were unable to void immediately postoperatively compared with 11 patients (16%) in the TOT group (P = 0.0003). The mean (SD) age and BMI of patients who failed or passed voiding trials was 58.6 (12.0) years and 28.0 (4.9) kg/m2 or 53.5 (12.3) years and 29.8 (5.7) kg/m2, respectively. Of 38 patients who did not pass a voiding trial on the day of the procedure, 31 (82%) passed on postoperative day 1, and all patients had passed a voiding trial by postoperative day 11. The mean (SD) BMI for 7 patients who did not pass voiding trial by postoperative day 1 was 28.3 (5.2) kg/m2. Conclusions: Women with higher BMIs were more likely to pass voiding trials after midurethral sling procedures. Patients who had TOT placement had greater success passing a postprocedure voiding trial than did patients who had TVT placement.

OBJECTIVES: The effect of body mass index (BMI) was assessed on unplanned cesarean section (CS) rate and its indications among healthy, nulliparous women without other risk factors for CS. METHOD: A cross sectional study was performed on 1649 healthy, nulliparous women at term who were admitted in spontaneous labor and delivered at Boston Medical Center between Jan 1st 2008 and Dec 31st 2012. The demographics and outcomes were compared by using a logistic regression analyses. RESULT: There were no statistically significant differences in unplanned CS rates between the three BMI groups (19% in normal weight, 24% in overweight, and 21% in obese women, p=0.1). Compared with normal weight women the crude odds ratio for overweight women was 1.34 (95%CI 1.03-1.76) and for obese women 1.04 (95%CI 0.84-1.54). A multivariate logistic regression analysis was used to adjust for maternal age, birth weight, race and augmentation of labor. The adjusted ORs were 1.073 (95%CI 0.781-1.473) for obese and 1.291 (95%CI 0.978-1.705) for overweight women. Obese women had a higher rate of CS for non-reassuring fetal status (56%, p= 0.01) compared to overweight (46.5%) and normal weight women (37%). CONCLUSION: high maternal BMI per se does not appear to be an independent risk factor for unplanned CS in healthy nulliparous women presenting at term with a singleton pregnancy in spontaneous labor.

Overweight and obesity in patients with intellectual and developmental disabilities (IDD) are at epidemic levels in the United States. The problem identified for this DNP project is the incidence of overweight and obesity in IDD. The framework used involved the quality model for improvement. For this DNP project a new program called the Daily-Enhanced Physical Activities Program (DEPA) was developed to promote weight loss, reduce sedentary activities, and optimal body mass index (BMI) for IDD patients. Local experts consisting of two registered nurses, two physical therapists, and one direct support personnel working with IDD patients were recruited. Each expert reviewed the newly developed DEPA program using a 10 question, 4-point Likert type scale survey. Results of expert surveys showed expert agreement that daily physical activity is necessary for IDD patients to reduce the risk for other chronic disease related to sedentary lifestyle. Furthermore, all experts 'agreed' that a disability should not prevent a person from engaging in activity to enhance the quality of life. Finally, all experts indicated that the selected population would take advantage of the DEPA project. Social change occurs when IDD patients are engaged with a structured DEPA project to possibly reduce obesity, increase activity and improve BMI.

BACKGROUND: Metabolic syndrome, elevated blood pressure (BP), elevated cholesterol and type 2 diabetes mellitus are health conditions that increase cardiometabolic risk (CMR). Sleep, physical activity, diet, are modifiable risk factors for the prevention of cardiometabolic disorders. Dietary fiber which is associated with higher fruit and vegetable intakes is known to lower the effects of obesity-related health issues. Further, these foods have an abundance of beneficial vitamins and minerals as well as low energy density. There is controversial, however, regarding the effect of fruit juice intake on CMR, particularly due to its lower fiber content. The objectives of this research were to estimate the effect of intakes of whole fruit and fruit juice on CMR, including effects on Body Mass Index (BMI), overweight/obesity, hypertension/prehypertension, lipid, and blood glucose levels. METHODS: The National Heart, Lung, and Blood Institute’s National Growth and Health Study (NGHS) cohort of white and black girls ages 9-10 years at baseline participated in a 10-year longitudinal study. Cardiometabolic outcomes included repeated measures of adiposity (e.g., body mass index (BMI)), and blood pressure, as well as laboratory measures such as fasting glucose and lipid levels. Linear regression and logistic regression were used to assess the association of fruit intake and fruit juice intake on CMR, while adjusting for age, race, tv/video, total vegetables, lean meat, and % calories from fat. Statistical Analysis Software (SAS Institute 15.2) analysis of data was performed. Results were considered statistically significant when p-value was <0.05. RESULTS: For girls in NGHS, BMI at the end of adolescence (ages 17-20 years) averaged to 21.3 kg/m2 for those who ate ≥0.75 cups of fruit and 22.1 kg/m2 for girls who ate <0.25 cups fruit. Similarly, girls with higher fruit juice consumption (≥0.75 cup-equivalents of juice per day) had a statistically significantly lower BMI than those with the lowest juice intake (<0.25 cup-eq/day). For each additional cup of whole fruit consumed on average per day between the ages of 9-17 was associated with 0.18 kg/m2 lower BMI (p<0.0001), after adjusting for age, race, tv/video viewing, total vegetable, lean meat intake, and % calories from fat. Adolescent girls (17 years or older) who drank < 0.25 or 0.25 - < 0.5 cup equivalent fruit juice were 1.60 or 1.63 (respectively) times more likely to become overweight (p-value 0.0005). Neither fruit intake nor fruit juice was associated with elevated fasting glucose risk or with high LDL risk. Whole fruit consumption was associated with a beneficial effect on HDL-cholesterol. Those with low whole fruit intake had a 1.42-fold increased risk of low HDL. CONCLUSIONS: These results indicate that 100% fruit juice and whole fruit consumption are both associated with beneficial effects on BMI and blood pressure among adolescent girls, suggesting that these foods may aid in the prevention of obesity and hypertension in the early adult years. KEY WORDS: adolescents, adiposity, body mass index, blood pressure, cardiometabolic health, dietary fiber, dyslipidemia, juice, glucose, metabolic syndrome, obesity, fruit.