Wearable technology has brought in a rapid shift in the areas of healthcare and lifestyle management. The recent development and usage of wearable devices like smart watches has created significant impact in areas like fitness management, exercise tracking, sleep quality assessment and early diagnosis of diseases like asthma, sleep apnea etc. This thesis is dedicated to the development of wearable systems and algorithms to fulfill unmet needs in the area of cardiorespiratory monitoring.

First, a pneumotach based flow sensing technique has been developed and integrated into a face mask for respiratory profile tracking. Algorithms have been developed to convert the pressure profile into respiratory flow rate profile. Gyroscope-based correction is used to remove motion artifacts that arise from daily activities. By using Principal Component Analysis, the follow-up work established a unique respiratory signature for each subject based on the flow profile and lung parameters computed using the wearable mask system.

Next, wristwatch devices to track transcutaneous gases like oxygen (TcO2) and carbon dioxide (TcCO2), and oximetry (SpO2) have been developed. Two chemical sensing approaches have been explored. In the first approach, miniaturized low-cost commercial sensors have been integrated into the wristwatch for transcutaneous gas sensing. In the second approach, CMOS camera-based colorimetric sensors are integrated into the wristwatch, where a part of camera frame is used for photoplethysmography while the remaining part tracks the optical signal from colorimetric sensors.

Finally, the wireless connectivity using Bluetooth Low Energy (BLE) in wearable systems has been explored and a data transmission protocol between wearables and host for reliable transfer has been developed. To improve the transmission reliability, the host is designed to use queue-based re-request routine to notify the wearable device of the missing packets that should be re-transmitted. This approach avoids the issue of host dependent packet losses and ensures that all the necessary information is received.

The works in this thesis have provided technical solutions to address challenges in wearable technologies, ranging from chemical sensing, flow sensing, data analysis, to wireless data transmission. These works have demonstrated transformation of traditional bench-top medical equipment into non-invasive, unobtrusive, ergonomic & stand-alone healthcare devices.

Sedentary behavior and excessive weight gain have been proven to deteriorate many characteristics of muscle. Low muscular power and mass with excess fat mass are risk factors for a multitude of chronic conditions and functional disabilities. Resistance training (RT) has long been accepted as a rehabilitative method of maintaining or enhancing muscular performance and composition. There are various methods of determining lower extremity muscular power; however, isokinetic dynamometry has emerged as one of the most accurate and reliable methods in clinical and research settings. Likewise, various methods exist for determining muscle thickness; however, many of those methods are expensive and can expose individuals to radiation. Ultrasonography has emerged as an accurate and reliable alternative to measuring lower extremity muscle thickness. The objective of this study was to assess the effects of high-load/low-volume (HLLV) and low-load/high-volume (LLHV) RT on isokinetic knee extensor and flexor peak power in sedentary, RT naïve, overweight or obese men and women (Body Mass Index ≥ 25 kg/m2). Twenty-one subjects (n = 21) completed this study and were randomized into one of the following groups: control, a HLLV group that performed three sets of 5 repetitions for all exercises until volitional fatigue, and LLHV which performed three sets of 15 repetitions for all exercises until volitional fatigue. Subjects randomized to the RT groups performed full-body exercises routines on three non-consecutive days per week. Changes in isokinetic knee extensor and flexor peak power, quadriceps ultrasound muscle thickness, and right leg segment of dual-energy X-ray absorptiometry (DEXA) scans were measured before and after the 12-week RT intervention. There were no significant differences found in group, time or, group by time interactions for knee extensor and flexor peak power using isokinetic dynamometry. Other than a group interaction for vastus intermedius muscle thickness (P=0.008), no significant interactions or differences were observed for any of the other variables tested. Based on the results of this study, neither high- nor low-load RT resulted in significant differences between intervention groups in peak power of the knee extensors and flexor, muscle thickness changes of the vastus intermedius, and vastus lateralis and, in the right lower extremity segmented body composition measures using DEXA.

Obesity is highly prevalence in United States. Obesity can be seen as a positive energy balance, especially a positive fat balance. This may be due in part to how the human body uses energy sources. When a person overconsumes a meal that contains high amounts of both carbohydrate and fat, carbohydrate will stimulate its own oxidation and suppress fat oxidation. This can result in a positive fat balance, which could eventually lead to obesity. Also, it has been shown that after consuming a meal endothelial function is frequently impaired for several hours during the postprandial period. Long-term endothelial dysfunction is a major cause of different types of cardiovascular disease. Exercise has been shown to stimulate fat oxidation and, when performed the day before meal ingestion, precondition arteries by enhancing endothelial function in the basal state. However, the acute effect of exercise on postprandial period is unknown. The purpose of this study is to examine the effect of high intensity interval exercise (HIIE) on the substrate oxidation and endothelial function in the postprandial period after consumption of “meal” consisting of a sugar-sweetened beverage (SSB) and a candy bar (480 kcal; ~75% sugar). Five subjects (4 males, 1 female; age=25yr, BMI=25 kg/m2) completed two conditions in random order: 1) no exercise control; 2) high-intensity interval exercise on a cycle ergometer: alternating 1-min intervals at 90-95% HRmax separated by 1-min of active recovery at 50W, for a duration sufficient to expend ~480 kcal. Endothelial function was measured by flow-mediated dilation (FMD) at baseline, and at 1, 2 and 4 hours postprandial. Substrate oxidation was measured by indirect calorimetry during the entire first hour postprandial and then during the last 20 min of hours 2-5 postprandial. Absolute postprandial fat oxidation (g/5 hours) was higher in HIIE (exercise: 5.47 ± 9.97, control: -9.78 ± 3.80; p<0.011). Absolute postprandial carbohydrate oxidation (g/5 hours) was higher in control group (control: 27.79 ± 6.20, exercise: -1.48 ± 7.75; p<0.019). Therefore, these results show that HIIE results in greater fat oxidation during the postprandial period in comparison to a no-exercise control condition. For FMD, there was no significant difference between groups, and no group x time interaction. However, there was a significant time effect (p<0.046), with both groups demonstrating a reduction in FMD during the postprandial period. FMD in the control condition decreased from 12% to 7.5% during the first 2 hours postprandial, and from 11.4% to 7.3% in the HIIE condition. These results indicate that HIIE performed 1 hour prior to ingestion of a SSB and candy bar does not prevent postprandial endothelial dysfunction.

Cardiovascular disease has long been one of the leading causes of morbidity in the world and places a large burden on the health care system. Exercise has been shown to reduce the risk of developing cardiovascular disease and the risk factors associated with it. Much of the focus of research has been on aerobic exercise modalities and their effect on these risk factors, and less is known in regard to the effect of resistance training. One novel risk factor for cardiovascular disease is arterial stiffness, specifically aortic stiffness. Aortic stiffness can be measured by carotid-femoral pulse wave velocity (PWV) and central pressure characteristics such as central blood pressures and augmentation index. The objective of this study was to assess the effect that two different 12-week long resistance training interventions would have on these measurements in sedentary, overweight and obese men and women (BMI ≥ 25 kg/m2). Twenty-one subjects completed the study and were randomized into one of the following groups: control, a low repetition/high load (LRHL) group which performed 3 sets of 5 repetitions for all exercises, and a high repetition/low load (HRLL) group which performed 3 sets of 15 repetitions for all exercises. Those in the resistance training groups performed full-body exercise routines on 3 nonconsecutive days of the week. Changes in arterial stiffness, central blood pressures, and brachial blood pressures were measured before and after the 12-week intervention period. PWV showed significant group by time interaction (p= 0.024) but upon post hoc testing no significant differences were observed due to the control group confounding (control: 7.6 ± 0.8 vs. 7.1 ± 0.8, LRHL: 6.7 ± 0.5 vs. 6.9 ± 0.5, HRLL: 7.03 ± 0.67 vs. 6.59). No other significant interactions or differences were observed for any of the variables tested. Based on the results of this study a 12-week long resistance intervention training, neither high nor moderate-intensity resistance training, resulted in improvements in indices of vascular stiffness or central and peripheral blood pressures.

Estimates indicate that in the United States 1 in 8 women will develop breast cancer in their lifetime. Improved cancer screenings, early detection, and targeted treatments have increased breast cancer survival rates. However, breast cancer patients treated with chemotherapy are at an increased risk for cardiovascular disease, functional impairments, and loss of cardiorespiratory fitness. These negative outcomes have implications for early morbidity and mortality. The purpose of this thesis was to test the hypothesis that high-intensity exercise preconditioning (exercise commenced prior to initiating chemotherapy and continued throughout treatment cycles) preserves health-related outcomes in breast cancer patients treated with anthracycline-containing chemotherapy. Here, we present a subset of preliminary data from an ongoing trial (NCT02842658) that is focused on VO2peak and skeletal muscle outcomes from the first 10 participants that have enrolled in the trial. Breast cancer patients (N=10; 50 ± 11 y; 168 ± 4 cm; 92 ± 37 kg; 32.3 ± 12.3 kg/m2) scheduled to receive anthracycline-containing chemotherapy were randomly assigned to one of two interventions: 1) exercise preconditioning, (3 days per week of supervised exercise throughout treatment) or 2) standard of care (attention-control). Pre-testing occurred 1-2 week prior to chemotherapy. The interventions were initiated 1 week prior to chemotherapy and continued throughout anthracycline treatment. Post-testing occurred 3-7 days following the last anthracycline treatment. VO2peak (L/min) was reduced by 16% in the control group (P < 0.05), whereas VO2peak was preserved in the exercise preconditioning group. Trends for greater preservation and/or improvement in the exercise preconditioning group were also observed for lean body mass and peak heart rate. Hand grip strength was not changed in either group (P > 0.05). Both groups demonstrated an increase in ultrasound-derived echogenicity measures of the vastus lateralis (P < 0.05), indicating changes in the composition of the skeletal muscle during treatment. These preliminary data highlight that exercise preconditioning may serve as a strategy to preserve cardiorespiratory fitness and perhaps lean mass during anthracycline treatment of breast cancer. There remains a need for larger, definitive clinical trials to identify strategies to prevent the array of chemotherapy-induced toxicities that are observed in breast cancer patients treated with anthracyclines.

About 75% of men and 66.58% of women are considered overweight or obese (BMI ≥25). $117 billion dollars is spent each year in medical costs due to physical inactivity. Aerobic exercise has been well defined in its’ benefits to cardiovascular health; however, the effects of resistance training are still not well defined. The purpose of this preliminary analysis was to evaluate the vascular health effects (central and peripheral blood pressure and VO2 max) of two different types of resistance training programs: high load, low repetitions resistance training and low load, high repetitions resistance training. Fourteen participants aged 18-55 years (6 males, 8 females) were involved in this preliminary analysis. Data were collected before and after the 12-week long exercise program (36 training sessions) via pulse wave analysis and VO2peak testing. Multivariate regression analysis of training program effects, while adjusting for body mass index and time, did not result in significant training effects on central and peripheral diastolic blood pressure, nor VO2peak. A statistical trend was observed between the different training programs for systolic blood pressure, suggesting that subjects partaking in the high load, low repetitions program exhibited higher systolic blood pressures than the low load, high repetitions group. With a larger sample size, the difference in systolic blood pressure may increase between training program groups and indicate that greater loads with minimal repetitions may increase lead to clinically significant elevations in blood pressure. Further work is needed to uncover the relationship between different types of resistance training and blood pressure, especially if these lifting regimens are continued for longer lengths of time.

The purpose of this study was to investigate the effects of high intensity interval exercise (HIIE) on postprandial fat and carbohydrate oxidation after a high carbohydrate and fat meal in healthy adults. It was hypothesized that the HIIE would result in greater postprandial fat oxidation than the control condition. Three subjects, all non-obese (BMI<30) from the ages of 21-24, underwent a 3 visit protocol. The first visit was to establish a VO2 max (on a cycle ergometer) and the following two were randomized between a control and exercise condition. The exercise condition was comprised of one hour rest to provide baseline data, followed by a 1 minute on (90-95% HR max), one minute off high intensity interval protocol on a cycle ergometer. This was conducted until the same amount of kcal as the standard meal (490 kcal. 250 kcal snickers and 240 kcal sprite) was expended. After the exercise, the participant waited for one hour to minimize the effects of the excess post-exercise oxygen consumption (EPOC) period, and then consumed the meal. Once this was completed, VO2 was measured for the last 10 minutes of every 30 minutes for a full 5 hours postprandial. The same methodology was employed in the control condition except for the exercise protocol. Results showed a significantly greater fat oxidation in the HIIE condition, oxidizing 28 grams, 32 grams, and 27 grams of fat in each of the 3 subjects compared to 14, 16, and 17 grams in the control condition respectively. This supports the notion that HIIE results in greater postprandial fat oxidation compared to seated rest.

Walking interventions focused on increasing step counts are typically associated with salutary effects on glycemia, fasting insulin, insulin resistance and blood lipids which may be in turn associated with improvements in cardiorespiratory fitness (peak oxygen uptake – VO2peak) and vascular stiffness. We hypothesized that a novel 4-month, behavioral economics-based walking intervention would have favorable effects on glucose homeostasis and blood lipids and that these in turn would be related to VO2peak and vascular stiffness (carotid femoral pulse wave velocity – cfPWV).

We carried out secondary analyses on a subsample of sedentary, overweight/obese adults who participated in a 4-month, 2x2, randomized-controlled walking intervention examining the effects of goal setting (static v. adaptive goals) and rewards (immediate v. delayed) on steps/day (N=96). Fasting blood samples (n=58) were collected from participants before and after the intervention. Premenopausal females were in the follicular phase of their menstrual cycles. Lipid and glucose levels were measured using an automated chemistry analyzer, while insulin was measured using radio-immunoassay. Homeostatic model of insulin resistance (HOMA-IR) was calculated using the following formula (HOMA-IR=glucose x insulin / 405). We examined associations [partial correlations (adjusted for age)] between changes in blood biomarkers and VO2peak and cfPWV, irrespective of group, and we used linear mixed models to examine between-group differences in levels of and change in biomarker outcomes.

Groups did not differ in overall levels of, or degree of change in, biomarker outcomes (all p>0.05). Mean changes, irrespective of group, in biomarkers were as follows: glucose Δ= 0.74± 4.5mg/dl; insulin Δ= 0.09 ± 4.1 µU/ml; total cholesterol Δ= 0.24 ± 20.6 mg/dl; HDL-C Δ= 0.27 ± 5.1 mg/dl; LDL-C Δ= 1.3 ± 19.9 mg/dl; triglycerides Δ= 1.7 ± 27.2 mg/dl; HOMA-IR Δ = -.0548 ± 1.05). We found no significant associations between change in biomarker levels and change in VO2peak or change in cfPWV (all correlation coefficients < 0.15; p > 0.05).

A 4-month, behavioral economics-based mHealth intervention focused on increasing steps/day did not bring about favorable changes on markers of glycemia, insulin resistance and blood lipids.

The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.

Doxorubicin (DOX) is a cardiotoxic, anthracycline-based, anti-neoplastic agent that causes pathological cardiac remodeling due to altered protein expression associated with cardiotoxicity. DOX cardiotoxicity causes increased Akt phosphorylation, blunted AMPK phosphorylation and upregulated mTOR phosphorylation. Akt is activated by cellular stress and damage. AMPK is activated by increases in AMP and ADP concentrations and decreased ATP concentration. mTOR is active in cellular growth and remodeling. These proteins are cellular kinases with cascades that are influenced by one another. Exercise preconditioning may diminish the cardiotoxic effects on these proteins. Female, Ovariectomized Sprague-Dawley rats (N=33) were randomized to: Exercise+DOX (EX+DOX, n=9); Exercise+Vehicle (EX+VEH, n=8); Sedentary+DOX (SED+DOX, n=8); and Sedentary+Vehicle (SED+VEH, n=8) groups. DOX (4mg/kg) or VEH (saline) intraperitoneal injections were administered bi-weekly (cumulative dose of 12mg/kg). VEH animals received body weight matched volumes of saline based on dosing in animals receiving DOX. Exercise (EX) animals underwent high intensity (85-95% VO2 peak) interval training (HIIT) (4x4 min bouts) separated by low intensity (50-60% VO2max) intervals (2 min bouts) 5 days per week. Exercise began 1 week prior to the first injection and was continued throughout the study. Rats were euthanized 5 days after the last injection. Left ventricular tissue was isolated, processed into lysate and used for western blot analyses [2x2 ANOVA; (α=0.05)]. DOX induced significant phosphorylation of Akt and mTOR (p=0.035; p=0.032) only in SED+DOX rats, but unchanged in EX+DOX rats. No significant differences (p=0.374) in AMPK phosphorylation were observed between groups. Exercise Preconditioning prevents some DOX-induced changes in the cardiac mTOR signaling pathway implicated in pathological remodeling.