Thesis (M.S.)--Boston University

The aim of this thesis was to determine the synergistic effect of milk and exercise to: promote fat loss while maintaining protein balance and muscle; improve cardiovascular fitness and strength; and to evaluate the short-term adaptations of the inflammatory system and metabolic risk factors in overweight adolescents (boys ages 11-15 years, girls ages 9 to 13 years). A 7-day dietary intervention with 1-h intense exercise was used with randomization to milk (MILK: n=26, 8 male, 18 female) or carbohydrate beverage (CONT; n=29, 12 male, 17 female) post exercise. Both groups received a diet based on their resting energy expenditure. To determine whole body protein balance (WBPB), participants consumed 15N-glycine. Subjects performed a maximal cycling test to determine changes in power and 1-repetition maximum testing to determine changes in strength. Blood was taken to evaluate glucose and insulin; tumour necrosis factor-alpha (TNF-α), interleukin-6 and c-reactive protein ; and blood pressure was measured pre and post intervention. Although body weights did not change, the MILK group maintained more muscle (-0.2 ± 0.6 vs. -0.7 ± 0.8 kg, p<0.01) and had a greater loss in body fat (-0.4 ± 1 vs. 0.5 ± 1.0 %, p<0.006). The changes in body composition were supported by a greater WBPB after training in the MILK group (1.64 ± 1.1 vs. 0.84 ± 0.6, p<0.001). Power increased only in the MILK group with an increase of 0.13 watts/kg (p<0.05) with an increase in V02max that approached significance (p=0.06). Improvements in strength and the blood risk factors were not different between the groups. There was a greater decline in mean arterial pressure in the MILK group (-3 ± 6 mmHg vs. 2 ± 7 mmHg, p< 0.04). The exercise intervention led to an increase in TNF-α in both groups (0.3 ± 0.7 pg/ml vs. 0.5 ± 0.7 pg/ml, p<0.001). These data support the consumption of milk after exercise in the early stages of pediatric obesity treatment. / Thesis / Doctor of Philosophy (PhD) / The aim of this thesis was to determine if milk and exercise work together to: promote body fat loss while maintaining protein balance and muscle in overweight adolescents; increase fitness and strength; and assess changes in inflammatory markers and disease risk factors. A 7-day diet with 1-hour exercise sessions was performed with milk or a carbohydrate drink. Protein balance was measured by a urine marker. Pre and post the following measures were used: cycling test for power; weight lifting test for strength; blood for disease markers; and blood pressure. After the week, the milk group were in a more positive protein balance, maintained more muscle, had a greater loss in body fat, greater increase in power and lower blood pressure compared to the carbohydrate group. Some of the inflammatory markers increased in both groups. Exercise combined with the nutrients from milk can have a positive effect on adolescent health.

The purpose of this study was to investigate the neuropsychological outcomes of pediatric subjects undergoing temporal lobe surgery, and then compare the outcomes between subjects in the iMRI and the standard operating suites. This study involved 77 children ages one to 21 years (M = 11.98) at time of surgery for intractable epilepsy. Forty-seven returned for repeat neuropsychological assessment. At baseline, subjects with early onset of epilepsy (≤ 7 years) scored worse on a measure of attention (p = .02), FSIQ (p < .01), perceptual reasoning (p < .01), and processing speed (p = .06). At one-year follow-up, interactions were observed for the response style domain of the attention measure (p = .03), FSIQ (p = .06) and working memory (p = .08). Follow-up at one year, for the group as a whole, revealed decline in verbal memory (p = .04) and reading comprehension (p = .02); and improvement for word reading (p = .05). No significant differences were observed between the iMRI and standard operating suite. Though, hemisphere, duration of epilepsy, preoperative seizure frequency, lesional disease, seizure type, presence of epileptogenic focus, and number of lobes involved accounted for variance in neuropsychological outcomes. These results provide further support for that certain preoperative individual, disease, and therapeutic variables are predictive of neurocognitive outcome following surgery for temporal lobe epilepsy. Additionally, the results demonstrated that surgery may also impact attention.

Thesis (M.S.)--Boston University

Mild traumatic brain injury (mTBI), or concussion, results from sudden acceleration or deceleration of the brain and subsequent complex tissue propagation of shock waves that disrupt structure and function. Concussions can cause many symptoms including headache, dizziness, and difficulty concentrating. These can be detrimental to children, a ecting their participation in school, sport, and social activities. Therefore, return to school (RTS) and return to activity (RTA) protocols have been developed to help safely return children to these activities without risking further injury. The goal of this study was to develop machine learning (ML) algorithms to predict RTA and RTS stages, that can easily be incorporated into a smartphone application (APP). Ideally this would assist children in tracking and determining their RTA and RTS progression leading them to a safe and timely return. Support vector machine classi er (SVC) and random forest (RF) algorithms were developed to predict RTA/RTS stages. Both were modeled on previously acquired data, and on newly acquired data, and results were compared. Models were trained and tested using accelerometry and symptom data from pediatric concussion patients. A sliding window technique and feature extraction were performed on raw acceleration data to extract suitable features, which were combined with yes/no symptom recordings as ML inputs. The dataset consisted of 67 participants aged 10 to 18, 42 female and 25 male, with a total of 844408 samples. The best results for RTS prediction showed average accuracy of 83% for RF and 66% for SVC. For RTA predictions, the best results had average accuracy of 60% for RF and 58% for SVC. For new data, RTS predictions showed an accuracy of 45% for RF and 41% for SVC. RTA predictions had an accuracy of 35% for RF and 30% for SVC. RF models had superior performance on all data. These results show that predicting RTA/RTS is possible with ML. However, improvements to these models can be made by training on more data prior to APP implementation. More data is needed, as recruitment during this study was limited due to Covid-19 restrictions. / Thesis / Master of Applied Science (MASc) / Concussions are recorded in approximately 300,000 athletes annually and are estimated to a ect up to 3.8 million individuals per year in the United States alone. Understanding when its safe to return to normal routine after an injury is important but challenging. Therefore, a series of stages have been developed to lead children through a safe and timely return to sport and activity after concussion. The goal of this study was to develop machine learning (ML) algorithms which predict these return stages using symptom recordings and gross body movement data. Algorithms could be incorporated into a smartphone application (APP) to provide accessible return guidelines for children with concussions. Algorithms were created and model performance was tested using symptom and body movement data collected from children after a concussive injury. The results of this study show that it is possible to predict return to school and return to activity stages with ML, and with improvements, can be used to facilitate return from injury

Natural Killer (NK) cells are recruited into circulation in response to physiological stress such as exercise. In adults, NK deployment and receptor expression are proportional to exercise intensity, and the cytotoxic CD56dim NK subset is preferentially deployed compared to immunoregulatory CD56bright subset. We know much less about the NK response to different exercise stimuli in children; however, pre-pubertal children are less responsive to acute exercise and recover faster than post-pubertal children and adults. The aims of this study were to (1) investigate the effects of exercise intensity and structure on NK recruitment and receptor expression, (2) compare the response among pre-pubertal and post-pubertal children, and (3) assess if factors such as fitness and physical activity were correlated with the magnitude of NK cell response. Healthy, recreationally active, pre- and post-pubertal boys and girls were recruited from the Hamilton community (N=11; 5 pre-pubertal, 6 post-pubertal). At the initial study visit, participants completed an aerobic fitness test to determine V̇O2peak and ventilatory threshold. At the subsequent visits, participants performed one of four cycling structures in a randomized, counterbalanced order, including: high-intensity continuous (HI-CONT), high-intensity intermittent (HI-INT), moderate-intensity continuous (MI-CONT), or moderate-intensity intermittent (MI-INT) exercise. Blood was collected pre-, post-exercise, 30- and 60-minutes into recovery. NK cells, CD56dim, and CD56bright NKs, activating (NKG2D and DNAM1) and inhibitory receptors (NKG2A and KIR2DL2/DL3) were quantified via flow cytometry. Participants were also outfitted with an accelerometer to measure physical activity. Three-way mixed ANOVA were used to examine effects of time, exercise and puberty on NK parameters, with Tukey’s HSD post hoc where appropriate. Pre-pubertal children showed no significant increase in the NK concentration in response to any of the exercise stimuli. Post-pubertal children, increased their NK cell concentration PRE to POST in all exercise stimuli except MI-CONT. Greater increases in NK concentration were seen POST HI-INT (124723 +/- 91596 cells/mL) and MI-INT (109644 +/- 84664 cells/mL), compared to HI-CONT (19931 +/- 1492 cells/mL) and MI-CONT (17082 +/- 9516 cells/mL), respectively (p < 0.001). Only increases in the expression of NKG2A were observed during REC1 (63.6 +/- 13.7 %), and REC2 (64.2 +/- 12.8 %) compared to PRE (57.9 +/- 13.4%) (p < 0.01). However, the density of NKG2D, NKG2A and DNAM1 were all significantly increased at REC2 compared to PRE. Fitness (R2= - 0.742) but not moderate-to-vigorous physical activity (R2= 0.098) or sedentary time (R2= 0.621) were significantly negatively associated with the magnitude of NK cell response. We demonstrated that an acute bout of intermittent cycling (5 min of exercise) leads to greater NK recruitment and a more immunoregulatory NK environment than continuous cycling in post-pubertal children. Contrarily, we showed that pre-pubertal children are not responsive to acute exercise of 30-minutes or shorter. Across our cohort, exercise also upregulated the density of expression of both activating and inhibitory receptors. Future research should examine if the NK cell response to acute exercise is maintained with repeated exercise exposures or exercise training. / Thesis / Master of Science (MSc) / This study looked at how exercise can be used to change the behavior of Natural Killer cells. These are cells that are part of the immune system and help protect people from viruses and cancer cells by quickly detecting cells that don’t belong in our bodies. They can also produce messenger chemicals to make other protective cells in the body aware of invaders. In this study children came into the lab and completed a different cycling exercise every time. In total, they completed four cycling exercises that included: 1) very hard cycling for 30 minutes; 2) very hard cycling in intervals, with 15 seconds of pedalling as hard and as fast as possible followed by a 1 minute rest, and repeating this for a total of 20 times; 3) comfortable cycling for 30 minutes; and 4) comfortable cycling in intervals. During each visit blood was collected from participants in order to count the number of natural killer cells there were before and after exercise as well as 30- and 60-minutes after the participants stopped cycling. Our study showed that in younger kids (8 to 10 years old), exercise doesn’t change how many natural killer cells are in the blood. However, in teens (14 to 18 years old) we showed that pedaling in intervals increased the number of natural killer cells in the blood more than riding a bicycle for 30 minutes straight. Our research helps us understand how exercise can be used to make our immune system stronger.

Conceptualizing mental health difficulties among a pediatric oncology population from a traumatic stress perspective is gaining speed. Research has shown support for the development of posttraumatic stress reactions among chronically ill children and their family members. Despite this evidence, the majority of intervention studies have not incorporated key trauma-informed intervention components that have proven to be effective in symptom reduction for trauma-exposed children. Examining key aspects of both the child trauma and pediatric psychology fields have enabled researchers to meld their strengths into one comprehensive approach. This revised perspective has clinical implications for the development of prevention and intervention techniques that are more likely to yield superior outcomes. Yet, an evidence-based, trauma-informed intervention for youth has not yet been empirically examined among a pediatric oncology population. Thus, the purpose of this study was to examine the efficacy of TF-CBT intervention program for children/adolescents diagnosed with cancer and their parents. Methods: This was a prospective longitudinal study that utilized a single-subject, non-concurrent multiple baseline design to assess the efficacy of TF-CBT intervention. A sample of five youth (ages 9 to 15) and seven parents enrolled in the study; three youth and five parents completed their participation in the study. Manualized treatment consisted of six sessions lasting approximately two hours per session (including child and parent) that targeted psychoeducation, relaxation training, affective identification and expression skills, cognitive processes, coping strategies, trauma processing, and family processes. Examined constructs, including posttraumatic stress symptomatology, depression, quality of life, parenting stress, coping utilization, coping efficacy, somatization, internalizing, and externalizing symptoms, were assessed by child self-report, parent report, and parent self-report at enrollment (baseline), post-treatment, and one-, and three-month follow-up. Results: Simulation Modeling Analysis (SMA) revealed a statistically significant reduction, from baseline to intervention, for one parent's PTSS (R = -0.711, p = .027) and another parent's PTSS reduction approached significance (R = -0.747, p = .055). Comparatively, no significant reduction was found for child PTSS. One child showed a significant improvement in coping efficacy (R = 0.619, p = .048) as a function of the intervention, and an additional two child participants approached significance (R = 0.618, p = .055; R = 0.689, p = .094). Visual inspection of the data did reveal noteworthy reductions for some study participants in both domain specific (i.e., PTSS) and broader psychological outcomes (e.g., quality of life, somatization, internalizing and externalizing symptoms, etc.). Conclusions: These results provide some support for a trauma-informed CBT intervention for pediatric oncology patients in remission and their parents. / Ph. D.

To examine the pediatric dentists’ perspective on level of care to children 0-3 years old by general dentists, an electronic survey was sent out to 5185 AAPD members and 769 responded (response rate: 14.8%). Forty-six percent agreed with a general dentist providing a dental home to children 0-3 years old. Only 24% agreed that general dentists could perform complex restorative and behavior management procedures for 0-3 years old. Younger respondents, pediatric dentists who practice in rural areas or teaching pediatric dentistry, and those who perceived adequate exposure during dental school were more likely to agree on general dentists proving a dental home (p values ranged from <0.0001 to 0.022). This study finding can help guide what level of care general dentists may provide and when a referral to a pediatric dentist is recommended and the appropriate competency level of entry-level general dentists to care for 0-3 years old.

Now in its Second Edition, this text focuses exclusively on the management of hospitalized pediatric patients from admission to discharge. It is an excellent resource for residency programs, hospitalist fellowships, and continuing education for physicians whose practice includes the management of hospitalized newborns and children. Because pediatric hospital care is provided by a wide variety of healthcare professionals and in many different hospital settings, this text provides a framework for unified management and effective and efficient care. This edition includes new sections on emergency medicine and psychiatric hospitalization and expanded coverage of management of children with complex and chronic conditions.

Purpose: Compare the efficacy of two benzodiazepines (diazepam or midazolam) in combination with meperidine and hydroxyzine for pediatric dental sedation. Methods: A randomized, double blind observation study of behaviors and outcomes related to two sedation groups. Frankl and Houpt behavior scores were recorded at three time points: injection time, initiation of treatment and at the end of treatment. Postoperative phone call surveys were conducted within eight hours of discharge to assess sleep, activity, and behavior. Results: A total of 40 sedation subjects were included in the study, of which 20 were treated with diazepam triple Combination (Di+M+H) and 20 with midazolam triple regime (Mi+M+H). Treatment was successful for 45% of cases with midazolam and 70% with diazepam (P value=.20). Houpt sleep scores were significantly higher for diazepam than midazolam at injection (P-value=.0043) and during treatment (P-value=.0152). Although Frankl scores, Houpt move and Houpt cry scores tended to favor diazepam, none were statistically significantly different. More abnormal behavior was reported with midazolam, though not statistically significant (35% vs 6%, P-value=.0854). Postoperative sleep time was longer for midazolam, but not significantly different (median sleep time: 61 vs 45 minutes, P-value=.2071). Conclusion: The diazepam, meperidine, hydroxyzine triple combination sedation regimen shows promising results as a successful alternative to midazolam triple combination. Longer postoperative monitoring may be required with diazepam, but this study has shown postoperative sleep times to be less than previously reported. Larger sample size is needed to determine if the current trend will be maintained.