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Childhood cancer survivors who receive a hematopoietic cell transplantation (HCT) are at increased risk for follicle-stimulating hormone (FSH) abnormalities, which may have a substantial negative impact on vascular function. The purpose of this study was to examine the association of vascular function with FSH in HCT recipients, non-HCT recipients and healthy controls. The study included childhood cancer survivors who were HCT recipients (n=24) and non-HCT recipients (n=308), and a control group of healthy siblings (n=211) all aged between 9 and 18 years. Vascular measures of carotid artery structure and function (compliance and distensibility), brachial artery flow-mediated dilation and endothelial-independent dilation were measured using ultrasound imaging. A fasting blood sample was collected to measure hormone levels. FSH was significantly higher in HCT recipients compared with non-HCT recipients and healthy controls (P

OBJECTIVE: We sought to evaluate the effect of 52 weeks of exenatide extended release (XR) on maintenance of meal replacement therapy induced BMI reduction in adolescents with severe obesity. METHODS: In this randomized, double-blind, placebo-controlled trial, 100 participants aged 12

Purpose: Many adult survivors of childhood cancer are at high-risk of developing cardiovascular disease. Cancer therapy may cause damage to the vascular endothelium, thereby initiating atherosclero...

Obesity is a well-established risk factor for insulin resistance and type 2 diabetes mellitus, and body fat distribution has important implications for this metabolic risk. In this cross-sectional study, we used dual X-ray absorptiometry body composition data from 123 young adult participants with overweight or obesity, and correlated with 2 indices of insulin resistance calculated from oral glucose tolerance tests. Participants were 70% women, with mean (standard error) age 30.1 (0.6) yr, body mass index (BMI) 34.0 (0.6) kg/m(2), homeostatic model assessment of insulin resistance (HOMA-IR) of 2.1 (0.2), and Matsuda insulin sensitivity index (Matsuda ISI) of 5.8 (0.4). In women, the strongest correlations were observed with the android-to-gynoid ratio (r = 0.52, p < 0.001 for HOMA-IR; r = 0.46, p < 0.001 for Matsuda ISI), and these correlations remained significant after adjustment for BMI. For men, the strongest correlations were with android fat mass (r = 0.40, p = 0.01 for HOMA-IR; r = 0.37, p = 0.02 for Matsuda ISI). Visceral adipose tissue was correlated with HOMA-IR and Matsuda ISI in women, and only with Matsuda ISI in men. BMI correlated with HOMA- IR and with Matsuda ISI in both women and men. Regional adiposity determined by dual X-ray absorptiometry correlates with indices of insulin resistance in sedentary young adults with overweight and obesity.

Introduction: Endothelial activation represents one of the earliest signs of the atherosclerotic process. Microparticles (MPs) in plasma, particularly endothelial MPs (EMPs) are reproducible biomarkers of endothelial dysfunction with a simple blood draw. The goal of this study was to examine the association of obesity with MPs, EMPs (CD31+/CD41– and/or CD 144+/CD31–), and activated EMPs (CD106+). Hypothesis: We hypothesized that higher body mass index (BMI), body fat percent (BF%), and visceral adipose tissue (VAT) would be associated with higher levels of MPs, EMPs, and activated EMPs. Methods: This was a cross-sectional study of 280 children and adolescents ages 8-18 years old. Whole venous blood was collected and processed for platelet free-plasma (PFP) collection less than 3 hours after being drawn. PFP samples were prepared using serial centrifugations and then frozen as 100 μl aliquots at -80 ° C. MPs were measured using flow cytometry with size ranging from 0.3 to 1.0 μm. EMPs were defined as MP with CD31+/CD41– and/or CD 144+/CD31–. Active EMP was identified as EMP with CD 106+. BF% and VAT were measured using dual X-ray absorptiometry. Linear (total MPs and EMPs) and logistic (activated EMPs) regression models were used to examine the associations with adiposity group, BF%, and VAT, adjusting for Tanner stage, sex, and race. Results: The mean age of the cohort was 12.7 years, consisting of 147 females and BMI distribution: 112 normal-weight, 77 overweight/obesity, 91 severe obesity. Youth with overweight/obesity and severe obesity had higher numbers of total MPs (28,690 per μL PFP/g [-2,315, 59,695], p=0.07 and 52,744 per μL PFP/g [22,163, 83,324], p85 th percentile compared to youth with a BMI th percentile. In the entire cohort, BF% (odds ratio, 1.02 [1.00, 1.04], p=0.108) and VAT (odds ratio, 1.00 [1.00, 1.00], p=0.472) were not significantly associated with active EMPs. Conclusions: Higher levels of endothelial cell damage and activation were associated with obesity and excess adiposity in youth. The potential role of MPs and EMPs as useful biomarkers of cardiovascular disease risk merits further study.

Background Circulating endothelial cells (CECs) reflect early changes in endothelial health; however, the degree to which CEC number and activation is related to adiposity and cardiovascular risk factors in youth is not well described. Methods and Results Youth in this study (N=271; aged 8–20 years) were classified into normal weight (body mass index [BMI] percentage P >0.05). Youth with severe obesity had a higher degree of CEC activation compared with normal weight youth (8.3%; 95% CI, 1.1–15.6 [ P =0.024]). Higher CEC number was associated with greater body fat percentage (0.02 per percentage; 95% CI, 0.00–0.03 [ P =0.020]) and systolic blood pressure percentile (0.01 per percentage; 95% CI, 0.00–0.01 [ P =0.035]). Higher degree of CEC activation was associated with greater visceral adipose tissue (5.7% per kg; 95% CI, 0.4–10.9 [ P =0.034]) and non–high‐density lipoprotein cholesterol (0.11% per mg/dL; 95% CI, 0.01–0.21 [ P =0.039]). Conclusions Methods of CEC quantification are associated with adiposity and cardiometabolic risk factors and may potentially reflect accelerated atherosclerosis as early as childhood.

We sought to examine the relationship between upper-leg compartmental lean mass, muscle-specific strength, and explosive strength following anterior cruciate ligament reconstruction. Twleve adolescent female athletes with prior anterior cruciate ligament reconstruction were individually-matched by age (16.4±0.9 vs. 16.4±1.0 yrs.), body mass index (23.2±2.1 vs. 23.2±2.7 kg/m2), and sport to 12 female athlete controls. One total-body and 2 lateral-leg dual X-ray absorptiometry scans measured total/segmental body composition. Isokinetic dynamometry measured knee extensor/flexor peak torque. Squat jumps on force platforms measured bilateral peak vertical ground reaction force. Paired t-tests assessed lean mass, peak torque, and force between previously-injured athletes’ legs and between previously-injured and control athletes’ legs. Previously-injured athletes’ involved vs. non-involved leg demonstrated lower total (7.13±0.75 vs. 7.43±0.99 kg; p

The coronavirus disease 2019 (COVID-19) pandemic has forced primary/grade schools and university closings as well as forced the suspension of a number of medical and laboratory testing procedures. Exercise science laboratories whether in clinical, research or educational locations were also forced to pause testing procedures. As the COVID-19 pandemic begins to subside in some areas of the world, exercise science laboratories are contemplating how to create a safe environment to resume some laboratory testing activities. In this article, we present suggestions for how exercise science laboratories can open and create a safe environment for subjects, laboratory personnel and equipment upon reopening.

This study examined the effects of hematopoietic cell transplantation (HCT) and associated preparative regimens on vascular structure and function. Measures of carotid artery stiffness and brachial artery endothelial-dependent dilation were obtained in patients who had survived ≥ 2 years after HCT for hematologic malignancy and were diagnosed at ≤21 years. HCT survivors (n = 108) were examined: 66 received total body irradiation (TBI) alone or with a low-dose cranial radiation boost (TBI±LD-CRT), 19 received TBI plus high-dose cranial radiation (TBI+HD-CRT), and 23 received a chemotherapy-only preparative regimen (CHEMO). Siblings (n = 83) were invited to participate as control subjects. Although endothelial-dependent dilation did not differ between siblings and HCT survivors, carotid cross-sectional compliance, cross-sectional distensibility, diameter compliance, and diameter distensibility were greater in siblings than HCT survivors. Comparing the HCT preparative regimens, carotid cross-sectional compliance, cross-sectional distensibility, diameter compliance, diameter distensibility, and incremental elastic modulus were significantly lower in the TBI+HD-CRT group compared with siblings or with TBI±LD-CRT and CHEMO treatment groups. Cross-sectional distensibility and diameter compliance were significantly lower in the TBI±LD-CRT group compared with siblings. TBI±LD-CRT and CHEMO groups did not differ from each other in these vascular measures. HCT preparative regimens containing TBI+HD-CRT resulted in greater arterial decrements, indicating increased risk for cardiovascular disease.

Introduction: Apolipoproteins are key regulators of cholesterol transport and clearance with each apolipoprotein having a specific protective or atherogenic role. The relationship between subclinical cardiovascular risk and each of the apolipoproteins in the pediatric population is insufficiently described within the literature. Therefore, the purpose of this study was to examine the association of apolipoproteins with measures of vascular structure and function in pediatric population. Hypothesis: We hypothesized apolipoprotein AI, AII, and CII would demonstrate a positive association, and apolipoprotein B, B/AI ratio, CIII, CIII/CII ratio, and E a negative association with carotid intima-media thickness (cIMT) and carotid-radial pulse wave velocity (PWV). Methods: A cross-sectional study of 338 children and adolescents (160 males, 178 females) aged 8-21 years (mean age 13.0±2.8 years) with a range of adiposities from normal body weight to severe obesity (mean BMI 26.8±8.9 kg/m 2 ). Apolipoproteins (AI, AII, B, CII, CIII, and E) were measured via human apolipoprotein magnetic bead panel (Millipore, MA, USA). Ultrasound imaging of the carotid artery was used to measure cIMT. PWV, a measure of arterial stiffness, was assessed via applanation tonometry (SphygmoCor TM ). Total body fat percent (BF%) was measured using dual X-ray absorptiometry. Linear regression models were adjusted for Tanner stage, sex, and race with further adjustments for BF%. Data are presented as mean [95% CI] with Holms-adjusted p-values to account for multiple testing. All apolipoprotein ratios were scaled to 0.1 μg/mL. Methods: There were significant positive associations between PWV and apolipoproteins: AII (0.036 m/sec per 10 μg/mL [0.017, 0.056], p = 0.010), E (0.158 m/sec per 10 μg/mL [0.08, 0.235], p = 0.002), and CIII/CII ratio (0.033 [0.014, 0.052], p = 0.019). After adding BF% to the models, PWV remained positively associated with higher levels of apolipoproteins: AII (0.036 m/sec per 10 μg/mL [0.016, 0.055], p = 0.012), E (0.161 m/sec per 10 μg/mL [0.082, 0.239], p = 0.002), and CIII/CII ratio (0.033 [0.014, 0.052], p = 0.02). Before accounting for multiple testing, apolipoprotein CIII/CII ratio was positively associated with cIMT (0.001 [0, 0.003], p = 0.033), but failed to maintain significance after p-value correction. Otherwise, there were no significant associations between any apolipoprotein and cIMT in the presence or absence of BF%. Conclusions: These findings suggest higher levels of apolipoprotein AII, E, and CIII/CII ratio are associated with higher arterial stiffness (PWV) in pediatrics, both in the presence and absence of excess body fat. Apolipoproteins, specifically AII, E, and CIII/CII ratio, may exert their effects on vascular function (PWV) before altering vascular structure (cIMT), which is congruent with the chronological pathophysiology of atherosclerosis.

Background Cardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities. Methods Prospective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals and P-values. Results Morquio A patients demonstrated significantly higher (P P P = 0.003) than control subjects and other MPS patients. Aortic root dilatation was noted in 56% of the Morquio A cohort, which also had highly prevalent mitral (73%) and aortic (82%) valve thickening, though hemodynamically significant valve dysfunction was less frequent (9%). Conclusions Increased carotid elasticity in Morquio A patients is an unexpected contrast to the reduced elasticity observed in other MPS. These Morquio A cIMT findings corroborate MPS IVA arterial post-mortem reports and are consistent with cIMT of other MPS. Aortic root dilatation in Morquio A indicates arterial elastin dysfunction, but their carotid hyperelasticity indicates other vascular intima/media components, such as proteoglycans, may also influence artery function. Studying MPS I and IVA model systems may uniquely illuminate the function of glycosaminoglycan-bearing proteoglycans in arterial health.

Background: Despite the benefits of aerobic exercise on body composition, runners with high body mass index (BMI) remain understudied. We examined body composition differences between sedentary insulin-resistant [obese insulin-resistant sedentary (OS-IR)], sedentary insulin-sensitive [obese insulin-sensitive sedentary (OS-IS)], and trained [obese trained (OT)] individuals with high BMI (≥25 kg/m(2)). We hypothesized that after matching for high BMI, OT individuals would have less fat mass (absolute and relative) and greater lean mass than OS-IR or OS-IS individuals. Methods: This is a retrospective analysis of OS-IR, OS-IS, and OT participants selected for similar age, sex, and BMI. Activity was self-reported. OT participants exercised at least 30 min/day (predominantly running) for 3–5 days/week. OS-IS and OS-IR participants actively exercised

OBJECTIVE Children with congenital adrenal hyperplasia (CAH) are exposed to fluctuating cortisol and androgen levels. The effects these hormonal states have on bone mineral density (BMD) and body composition are not well studied. The study's objective was to compare BMD and body composition, including visceral adipose tissue (VAT) and Android:Gynoid (A:G) ratio, in children with CAH vs healthy age-matched, sex-matched and BMI-matched controls. DESIGN Total body BMD (TBMD) Z-scores were adjusted for height-for-age Z-scores (TBMDHAZ). Hydrocortisone dose (mg/m2/d) was averaged over the past year. Bone age Z-scores were used as a surrogate for long-term androgen exposure in cases. Statistical analyses comparing cases and controls accounted for matched groups using mixed linear models. PATIENTS Forty-two cases with CAH (average age 12.3 years [SE 3]; 17 males) and 101 controls underwent a dual-energy X-ray absorptiometry scan. RESULTS Children with CAH had lower TBMD (0.81 vs 1.27, P = .003) and TBMDHAZ Z-scores (-0.51 vs -0.01, P = .001) than controls. In CAH cases, TBMD and TBMDHAZ Z-scores were positively correlated with bone age Z-scores (r = .63, P

The accuracy of an infrared three-dimensional (3D) body scanner in determining body composition was compared against hydrostatic weighing (HW), bioelectrical impedance analysis (BIA), and anthropometry. A total of 265 adults (119 males; age = 22.1 ± 2.5 years; body mass index = 24.5 ± 3.9 kg/m2) had their body fat percent (BF%) estimated from 3D scanning, HW, BIA, skinfolds, and girths. A repeated measures analysis of variance (ANOVA) indicated significant differences among methods (p

Objective To evaluate cardiovascular and metabolic function in youths adopted internationally from orphanages/institutions (postinstitutionalized) who were height-stunted at adoption. Study design A total of 30 postinstitutionalized youths (age, 9-18 years; body mass index [BMI] percentile, 7.2-90.4) who were height-stunted at adoption were compared with age- and BMI percentile-matched youths (n = 90). Measurements included total body fat and visceral adipose tissue (dual radiograph absorptiometry), arterial stiffness (augmentation index and pulse wave velocity), cardiac autonomic function (heart rate variability), blood pressure, and fasting lipid, glucose, and insulin levels. Linear regression analyses were computed controlling for parent education, age, trunk tissue fat, height-for-age, sex, and race. Results Compared with controls of the same age, sex, and BMI, the postinstitutionalized children had higher systolic blood pressure (P = .018), augmentation index (P = .033), total cholesterol (P = .047), low-density lipoprotein cholesterol (P = .03), triglycerides (P = .048), insulin (P = .005), and HOMA-IR (P = .01) values. The postinstitutionalized children had a lower low-frequency to high-frequency ratio (P = .008), indicating lower sympathetic tone, as well as a lower total lean mass (P = .016), a lower gynoid lean mass (P = .039), and a higher proportion of trunk tissue fat (P = .017). The postinstitutionalized and control children did not differ in any other body composition measures. Conclusions Early life stress, as represented by height-stunted growth in institutional care, may be associated with early pathways to cardiovascular and metabolic risk in youths even after moving into well-resourced homes early in life and in the absence of increased adiposity. These findings suggest that postinstitutionalized youths with a history of height stunting may need to be closely monitored for emergent cardiometabolic risk factors.

INTRODUCTION Subclinical cardiovascular risks of secondhand smoke (SHS) exposure among children and adolescents remains insufficiently described. METHODS This was a cross-sectional study of 298 children and adolescents (48.0% male, body mass index: 27.0±8.9kg/m2), including 49 self-reported cases with SHS. Arterial elasticity and stiffness (distensibility, compliance, incremental elastic modulus [IEM]) were obtained via ultrasound imaging in the abdominal aorta, brachial, and carotid arteries. A one-way analysis of variance compared differences between groups, and multiple linear regression adjusted for covariates. RESULTS SHS was associated with lower abdominal aorta diameter distensibility (aDD) (13.4±3.6% vs. 16.0±5.2%, p=0.009), and abdominal aorta cross-sectional distensibility (aCSD) (28.8±8.3% vs. 35.1±12.2% p=0.009), as well as higher abdominal aorta IEM (aIEM) (1241±794mmHg vs. 935±388mmHg, p=0.001). After adjustment for covariates, aDD (p=0.047), aCSD (p=0.040), and aIEM (p=0.017) remained significant; this significance persisted with the additional adjustment of percent body fat. Measures of brachial and carotid compliance and distensibility were not associated with SHS. CONCLUSIONS SHS was associated with abdominal aorta stiffness; the majority of vascular measures within the brachial and carotid artery remained unaffected following adjustment for covariates, including hypertension and adiposity. SHS may predispose individuals to increased abdominal aorta stiffness, an artery previously reported to exhibit increased susceptibility to atherosclerosis.

OBJECTIVES: Although physical activity ameliorates the metabolic impact of high body mass index (BMI), runners with BMI≥25 kg/m(2) are relatively understudied.This study had two goals: 1) Identify differences in body composition, as measured by dual X-ray absorptiometry (DXA), between overweight (BMI≥25 kg/m(2)) runners (OWR) and normal weight (BMI

Background: Epidemiologic observations have raised hypotheses regarding increased potato consumption as a correlate of weight gain, adiposity and diabetes risk, while nut consumption has been associated with weight control and metabolic health Furthermore, human diets are complex with phytochemicals potentially impacting the digestion and absorption of macro-and micronutrients We asked whether increased daily consumption of potatoes influences energy balance relative to almonds Methods: A randomized, controlled trial (30-day) of adult humans (n=180) prescribed daily, calorie-matched (300 kcal/day, n=60 subjects/group) consumption of either 1) almonds, 2) white potato French fries, or 3) white potato French fries with spices selected for alpha-glucosidase inhibitory properties Subjects were measured at baseline and completion (30-days) for primary (body fat measured by dual-energy x-ray absorptiometry, DXA) and secondary outcomes (body weight and markers of carbohydrate metabolism and insulin resistance) Results: A total of n=180 subjects were randomized to treatment groups, with sex (67 78% female), age (mean±SD, 30 35±8 74 years), BMI (26 11±4 15 kg/m2) and weight (75 56±15 44 kg) at baseline There were n=12 dropouts and n=3 terminations due to COVID19 follow-up limitations Change (completion minus baseline) in total fat mass by DXA was not significantly different among groups (mean (95% CI);Almonds: 214 88g (-5 15,434 92);Potatoes: 18 55g (-207 40,244 51);Potatoes+Spice mix: 231 05g (-1 33,463 43);p=0 347), nor change in fasting glucose (p=0 413), insulin (p=0 301) or HbA1c (p=0 234) Change in body weight was significantly different among groups (p=0 013;Almonds: 0 46kg (0 09,0 84);Potatoes: -0 26kg (-0 65,0 13);Potatoes+Spice mix: 0 45kg (0 06,0 85) Conclusions: There was no significant difference in the primary outcome of body fat change with 30 days of consumption of potatoes versus almonds

Background: In adolescents with severe obesity, long-term weight loss maintenance using lifestyle therapy alone is hampered by numerous biological adaptations favoring weight regain such as increased appetite and sense of food palatability and decreased satiety and resting energy expenditure. Anti-obesity pharmacotherapy may have a role in mitigating some of these physiological adaptations, thereby enhancing weight loss maintenance. We conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide extended release (XR) on the maintenance of BMI reduction and improvements in cardiometabolic risk factors induced by short-term meal replacement therapy (MRT) among adolescents with severe obesity. Methods: One-hundred adolescents ages 12 to

Purpose During reactive hyperemia, the brachial artery in some individuals constricts prior to dilation. Our aim was to describe the frequency of high-flow-mediated constriction (H-FMC) in adults, and its relationship to body composition and biomarkers of cardiovascular and metabolic risk. Methods Two hundred forty-six adults (124 male, 122 female; 36 ± 7 years old) were assessed for H-FMC via sonographic imaging of the brachial artery. Blood pressure, glucose, insulin, lipids, and body composition assessed via dual energy X-ray absorptiometry were collected. H-FMC was characterized as a 10-second average of maximal postocclusion constriction. Independent t test was used to compare H-FMC versus non-H-FMC individuals. Results H-FMC was observed in approximately 69% of adult participants (54 obese, 57 overweight, and 59 normal weight). Total body mass (82.3 ± 17.5 versus 76.3 ± 16.3 kg, p = 0.012), fat mass (27.7 ± 11.5 versus 23.8 ± 10.5 kg, p = 0.012), body mass index (27.7 ± 4.9 versus 26.1 ± 5.0 kg/m2, p = 0.018), and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (2.41 ± 1.03 versus 2.09 ± 0.72, p = 0.007) were higher in H-FMC than in non-H-FMC individuals. Flow-mediated dilatation (FMD) (6.12 ± 3.48 versus 8.09 ± 3.02%, p

Objective: Skipping breakfast and consuming fast food are related to the risk of obesity and are common adolescent behaviors. The relationship between these behaviors and biomarkers related to diabetes and CVD is understudied in this population. Methods: Data are from a study of the etiologic factors related to obesity risk in adolescents. Breakfast and fast food consumption were assessed using a self-report survey. Anthropometrics, fasting lipids, glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed. Multivariate analyses were used to examine the relationship between dietary behaviors and selected biomarkers, controlling for calories consumed, body mass index (BMI), and demographic covariates. Results: 367 adolescents (11 to 18-years; mean 14.7 ± 1.8 years) were assessed at the University of Minnesota-Twin Cities from 2006–2008. Breakfast consumption was significantly associated with lower BMI, body fat, insulin, HOMA-IR, and metabolic syndrome (MetS) cluster score, while fast food consumption was associated with higher BMI, body fat, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, HOMA-IR, and MetS cluster score. Some gender differences were observed. Conclusion: Breakfast and fast food consumption appear to be related to important metabolic syndrome biomarkers for chronic disease in a sample of healthy adolescents. The importance of this finding needs to be validated by examining the stability of this pattern over time and to assess the pattern in other populations., Highlights • Risk factor clustering may create metabolic dysfunction. • Eating breakfast is related to decrease metabolic risk in adolescents. • Eating fast food is related to increased metabolic risk in adolescents.

Summary Hypercapnia has been utilized as a stimulus to elicit changes in cerebral blood flow (CBF). However, in many instances it has been delivered in a non-controlled method that is often difficult to reproduce. The purpose of this study was to examine the within- and between-visit reproducibility of blood oxygen level-dependent (BOLD) signal changes to an iso-oxic square wave alteration in end-tidal carbon dioxide partial pressure (PetCO2). Two 3-Tesla (3T) MRI scans were performed on the same visit, with two square wave alterations administered per scan. The protocol was repeated on a separate visit with minimum of 3 days between scanning sessions. PetCO2 was altered to stimulate changes in cerebral vascular reactivity (CVR), while PetO2 was held constant. Eleven subjects (six females; mean age 26·5 ± 5·7 years) completed the full testing protocol. Excellent within-visit square wave reproducibility (ICC > 0·75) was observed. Similarly, square waves were reproducible between scanning sessions (ICC > 0·7). This study demonstrates BOLD signal changes in response to alterations in PetCO2 are reproducible both within- and between-visit MRI scans.

Though individual differences in arterial carbon dioxide and oxygen levels inherently exist, the degree of their influence on cerebral vascular reactivity (CVR) is less clear. We examined the reproducibility of BOLD signal changes to an iso-oxic ramping P(et)CO(2) protocol. CVR changes were induced by altering P(et)CO(2) while holding P(et)O(2) constant using a computer-controlled sequential gas delivery (SGD) device. Two MRI scans, each including a linear change in P(et)CO(2), were performed using a 3-Tesla (3T) scanner. This ramp sequence consisted of 1 minute at 30 mmHg followed by 4 minute period during where P(et)CO(2) was linearly increased from 30 mmHg to 50 mmHg, 1 minute at 51 mmHg, and concluded with 4 minutes at baseline. The protocol was repeated at a separate visit with 3 days between visits (minimum). Intraclass correlation coefficients (ICC) and coefficients of variation (CV) were used to verify reproducibility. Eleven subjects (6 females; mean age 26.5 ± 5.7 years) completed the full testing protocol. Good reproducibility was observed for the within-visit ramp sequence (Visit 1: ICC = 0.82, CV = 6.5%; Visit 2: ICC = 0.74, CV = 6.4%). Similarly, ramp sequence were reproducible between-visits (Scan 1: ICC = 0.74, CV = 6.5%; Scan 2: ICC = 0.66, CV = 6.1%). Establishing reproducible methodologies for measuring BOLD signal changes in response to P(et)CO(2) alterations using a ramp protocol will allow researchers to study CVR functionality. Finally, adding a ramping protocol to CVR studies could provide information about changes in CVR over a broad range of P(et)CO(2).

BACKGROUND The relationship between pediatric severe obesity (SO) and central aortic blood pressure (BP) has yet to be established. METHODS We conducted a cross-sectional study of 348 youth (48.5% male, age 12.7 ± 0.1 years) with a wide range of body mass index (BMI) values: normal weight (NW; ≥5th and RESULTS After adjustment for covariates, no significant sex differences were observed for radial−aortic systolic blood pressure (SBP) (P = 0.39), carotid−aortic SBP (P = 0.99), radial−aortic diastolic blood pressure (DBP) (P = 0.44), and carotid−aortic DBP (P = 0.53). Compared to youth with NW, youth with SO exhibited higher radial−aortic SBP (SO vs. NW: 102 ± 1 mm Hg vs. 90 ± 1 mm Hg, P CONCLUSIONS In a cohort of youth with a wide range of adiposity levels, central aortic BP was elevated among individuals with SO and associated with BMI but not body fatness.

Intramyocellular lipid (IMCL) is generally associated with insulin resistance and lipotoxicity. However, the “athlete’s paradox” is well documented, where IMCL levels are similar between athletes and patients with type 2 diabetes despite discrepant levels of insulin sensitivity. Differences in muscle lipid metabolites between aerobically trained, lean, insulin-sensitive (LT) vs. sedentary, overweight/obese, insulin-resistant (OIR) individuals remain insufficiently characterized and may help to explain the “athlete’s paradox.” LT [n=14: 50% females, 28.5±1.6 years (Mean±SE)] and OIR [n=24: 79% females, 29.8±1.6 years] subjects each provided 2 muscle biopsies from the vastus lateralis (bilateral, 6 hours apart, ≥48 hours after last exercise, ≥8 fasting, overnight admission prior to biopsy) for mass spectrometry analysis. At a separate visit, insulin sensitivity was quantified by a hyperinsulinemic-euglycemic clamp (mg glucose/kg FFM/min). As the sequential biopsy results were not significantly different, the results were averaged for each subject. Compared with the OIR group, the LT group had lower BMI (22.3±0.5 vs. 36.2±1.2 kg/m2:p Disclosure L.S. Chow: Research Support; Self; Eli Lilly and Company, National Institute of Diabetes and Digestive and Kidney Diseases. D.G. Mashek: None. T. Bosch: None. A. Bantle: None. M. Petterson: None. D.R. Dengel: None. M.D. Jensen: Other Relationship; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S.

Ventilation/carbon dioxide production (VE/VCO2slope) is used clinically to determine cardiorespiratory fitness and morbidity in heart failure (HF). Previously, we demonstrated that lower lean leg mass is associated with high VE/VCO2slope during exercise in HF. In healthy individuals, we evaluated 1) whether VE/VCO2slope differed between lean and overweight women and 2) the relationship between lean leg mass and VE/VCO2slope in overweight sedentary (OWS), overweight trained (OWTR) and lean, trained (LTR) women. Methods Gas exchange and ventilation were collected during a treadmill peak oxygen uptake test (VO2peak) in 40 women [26 OWS (29 ± 7 yrs., mean ± SD), 7 OWTR (33 ± 5 yrs) and 7 LTR (26 ± 6 yrs)]. Body composition was measured by dual X-ray absorptiometry. Results VO2peak was highest in LTR (46.6 ± 8 ml/kg/min) compared with OWTR (38.1 ± 4.9 ml/kg/min) and OWS women (25.3 ± 4.8 ml/kg/min, p 0.05). Higher lean leg mass was associated with lower VE/VCO2slope in overweight women (OWS + OWTR: r = −0.55, p

OBJECTIVE: To evaluate the relationships of depression and anxiety symptoms with CVD risk factors and measures of vascular health in youth. Major Depressive Disorder and Bipolar Disorder are considered cardiovascular disease (CVD) risk factors in youth. STUDY DESIGN: Participants (n=202) were 8-18-year-olds from a cross-sectional study evaluating cardiovascular health across a wide range of BMI values (normal weight to severe obesity). CVD risk measurement included blood pressure, fasting lipids, glucose, insulin, carotid artery intima-media thickness, compliance and distensibility, brachial artery flow-mediated dilation, carotid-radial artery pulse wave velocity, body fat percentage, and a metabolic syndrome cluster score. Anxiety and depression symptoms were self-reported on the Screen for Child Anxiety Related Disorders and Center of Epidemiological Studies Depression Scale for Children. Two sets of adjustment variables were used in evaluation of differences between those with and without anxiety or depression symptomatology for the CVD risk factor and vascular outcomes. The first set included adjustment for Tanner stage, sex, and race; the second additionally adjusted for percent body fat. RESULTS: Anxiety was not significantly associated with CVD risk factors or vascular health in either model. Depression was associated with HDL cholesterol, triglycerides, and metabolic syndrome cluster score; these relationships were attenuated when accounting for percent body fat. CONCLUSIONS: When accounting for body fat, we found no clear relationship of self-reported depression or anxiety symptoms with CVD risk factors or vascular health in youth.

Background: Measures of carotid intima media thickness (cIMT) in adults are correlated with adiposity and the metabolic syndrome (MetS) and predict cardiovascular (CV) events. Relations in children are not as well studied. Our objective was to determine the relations of cIMT with body mass index (BMI) and CV risk score in children. Methods: The study included 291 children (158 M/133 F) 6–18 years of age (140 aged 6–11/151 aged 12–18) with measurements of height, weight, waist circumference; fasting lipids, glucose, insulin, and cIMT. A CV risk cluster score was developed from sum of the z-scores of the five MetS components (waist circumference, blood pressure, serum triglycerides, high-density lipoprotein cholesterol, and insulin). Partial Pearson correlation coefficients were adjusted for age, sex, and race. Results: There was no significant age difference in cIMT from 6 to 18 years of age. BMI and CV risk score were significantly correlated (P

To determine the associations of adiposity and insulin resistance with measures of vascular structure and function in children.A cross-sectional study included 252 children (age 15.1 ± 2.4 years; body mass index percentile 68.2 ± 26.5%; Tanner 2-5). Measurements of body fat percentage were obtained with dual-energy X-ray absorptiometry and visceral adipose tissue (VAT) with computed tomography. Insulin resistance was measured with hyperinsulinemic euglycemic clamp. Vascular measurements for endothelial function (brachial artery flow-mediated dilation [FMD]), vascular structure (carotid intima-media thickness [cIMT]), vascular stiffness (carotid incremental elastic modulus), and pulse wave velocity were analyzed by tertiles of adiposity and insulin resistance. Additional analyses with ANCOVA and linear regression were adjusted for Tanner, sex, race, and family relationship; FMD was also adjusted for baseline artery diameter.FMD was positively associated with high adiposity (body mass index, body fat percentage, and VAT) (P.01 all). Insulin resistance was not associated with FMD. cIMT was significantly, positively related to obesity, VAT, and insulin resistance (P.05 all). No differences in carotid incremental elastic modulus and pulse wave velocity were observed in relation to adiposity or insulin resistance.The findings suggest that adiposity is associated with higher FMD, and insulin resistance and VAT are associated with higher cIMT in children. Further research is needed to clarify the progression of these relations.

University of Minnesota M.S. thesis. May 2014. Major: Kinesiology. Advisor: Donald R. Dengel, Ph.D. 1 computer file (PDF); v, 43 pages.

Until recently cardiovascular disease is often thought of as a disease that manifests itself during middle age. Researchers and clinicians have begun to realize that the initial signs of cardiovascular disease begin early on in childhood with changes present in both vascular structure and function. This increased recognition has resulted in considerable effort to develop accurate and reliable methods to measure as well as track changes in vascular structure and function applicable to study this process in children and adolescents. Certain genetic abnormalities and chronic diseases, which present or emerge in childhood often result in meaningful changes to vascular structure and function, which aid in our understanding of the vascular disease process. In this review, we will discuss different methods of assessing vascular structure and function, the diseases in childhood associated with decrements and maladaptive changes in the vascular system, and whether modification of lifestyle (ie, weight loss, dietary and/or exercise changes) can affect vascular structure and function in children.

Objective: To determine visceral adipose tissue (VAT) volume (VATvol) by dual energy X-ray absorptiometry (DXA) in spinal cord injured (SCI) and able-bodied (AB) participants and to explore the relationships between VATvol and routine anthropometric measures. Methods: Sixty-three subjects with SCI and 126 healthy male AB controls were stratified as low risk [LR: waist circumference (WC)

Purpose When assessing vasomotor endothelial function by reactive hyperemia, the brachial artery, in some individuals, constricts immediately before beginning to dilate following cuff release. We call this response high-flow-mediated constriction (H-FMC). The aim of this study was to describe the rate of the H-FMC during reactive hyperemia in children and adolescents throughout a range of body mass index (BMI) values, and to investigate differences in flow-mediated dilation (FMD), cardiovascular, and anthropometric measures between subjects with and without H-FMC. Methods FMD was assessed in 136 children and adolescents (61 male, 75 female; 13 ± 3 years) by sonographic imaging of the brachial artery. H-FMC was characterized as the lowest point from the baseline brachial artery diameter immediately following reactive cuff release. Independent t tests were used to compare subjects with and without H-FMC. Results H-FMC was observed in 91 of the 136 participants (66.9%). No significant difference was found between H-FMC and non-H-FMC subjects for age (p = 0.602), gender (p = 0.767), height (p = 0.227), or weight (p = 0.171). BMI percentile was nonsignificantly higher (91.8 ± 14.9th versus 84.6 ± 22.8th percentile, p = 0.057) and FMD was significantly lower (5.43 ± 3.41% versus 8.05 ± 3.97%, p

Introduction: The relationship between different central BP measurements with hypertension status in youth is not well documented. We hypothesized that measures of central BP would be positively associated with hypertension status in youth independent of adiposity. Methods: We recruited 149 males and 160 females for this cross-sectional analysis (mean±SD: age = 12.8±2.7; BMI percentile (%) = 78.5±27.8). Body fat % was measured by dual energy X-ray absorptiometry (DXA) and brachial BP was measured using an automated cuff to calculate systolic BP (SBP) and diastolic BP (DBP). Determined by systolic percentile, there were 238 normotensive (th ), 29 pre-hypertensive (th - th ), and 42 hypertensive (th ) individuals enrolled. Central BP was determined using the SphygmoCor MM3 system to calculate carotid-aorta SBP (caSBP) carotid-aorta DBP (caDBP) radial-aorta SBP (raSBP) and radial-aorta DBP (raDBP). Central BP measures were compared across hypertension status groups using ANCOVA, with post-hoc Tukey HSD, adjusted for age, sex, and race. Pearson correlations (unadjusted) and multiple linear regression models, examining the relationship between central BP measures with brachial BP adjusted for age, sex, race, and height, were conducted with further adjustment for body fat % (shown as β±SE). Results: raSBP, caSBP, raDBP, and caDBP were significantly different between the normotensive and hypertensive groups (all p Conclusion: These data suggest that central BP, regardless of measurement site, is highly associated with brachial BP and hypertension status in youth independent of adiposity.

Purpose: When assessing vasomotor endothelial function of the brachial artery by reactive hyperemia, blood flow is stopped and creates a period of low-flow mediated constriction (L-FMC). Little is known about how this parameter influences flow-mediated vasodilation (FMD). The purpose of this study was to better understand this relationship and to determine the intra- and inter-day reproducibility of brachial L-FMC in healthy adults. Methods: Brachial L-FMC and FMD were measured on 26 healthy, young adults (13 males, 13 females; 24.6 ± 2.7 years). Each subject had two assessments conducted on two separate visits, separated by a minimum of seven days. Brachial artery pre-occlusion baseline diameter was imaged during rest and prior to cuff-occlusion. Continuous imaging of the artery was captured during the last 20 seconds of cuff-occlusion to 180 seconds post-cuff release. An L-FMC was considered present if the relative change from pre-occlusion baseline to L-FMC artery diameter was less than -0.1%. Peak FMD was measured as the greatest 10-second average in brachial artery diameter following occlusion compared to pre-occlusion baseline. Results: Overall, there was a strong, positive correlation between increased brachial L-FMC and blunted FMD (visit 1 test 1: r=0.758, p p p p Conclusion: The results of the present study suggest that the degree of vasoconstriction to low-flow conditions influences the subsequent maximal dilation during reactive hyperemia. However, L-FMC in young adults is variable as evidenced by the weak inter- and intra-day reproducibility of the measure. Further research is needed to study brachial L-FMC reproducibility among varying subject populations and the implications L-FMC has on the interpretation of FMD results.

Purpose: This study aimed to investigate the accuracy and reliability of a novel dual-energy x-ray absorptiometry (DXA) scanning method in the frontal plane for total, fat, and lean mass quantification of the anterior and posterior upper leg compartments. Methods: Twenty-one (11 females; X¯age = 20.3 ± 1.3 yr) college athletes were assessed for total and regional body composition using DXA. The segmentation of anterior/posterior thigh compartments was measured with participants lying on their right and left sides and the scanned leg elevated with two foam pads. Custom regions of interest (ROIs) were created manually with enCoreTM software for each scan using bony landmarks to quantify lean, fat, and total masses. Paired t-tests assessed this novel positioning method's accuracy against standard positioning. Intraclass correlation coefficients and coefficients of variation examined inter- and intrarater reliability for lateral scan measures of total, fat, and lean masses from manually created ROIs. Results: All mean ± SD differences between frontal and lateral DXA scans of right (R) and left (L) leg total mass (R: 8.42 ± 195.57 g; L: 19.47 ± 131.80 g), fat mass (R: 61.26 ± 215.66 g; L: −5.89 ± 239.97 g), and lean mass (R: −103.00 ± 302.54 g; L: −27.58 ± 288.14 g) were nonsignificant (P value range = 0.15–0.91). Intraclass correlation coefficients were high for all composition measures between and within raters, ranging from 0.983 to 0.999 and from 0.954 to 0.999, respectively, with low variation across measures (all coefficients of variation ≤ 5%). Conclusion: The results of this study suggest that DXA measures using lateral subject positioning and custom ROIs to assess upper leg total, fat, and lean masses are accurate and reliable compared with total-body frontal subject positioning. Future studies are needed to determine the clinical usefulness of lateral view measures regarding prevention or rehabilitation of sports- or age-related injury.

Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but cardiovascular disease causes mortality in a significant percentage of survivors. Markers must be developed to predict MPS cardiac risk and monitor efficacy of investigational therapies.MPS patients underwent carotid artery ultrasonography from which carotid intima-media thickness (cIMT) and three measures of arterial stiffness were calculated: carotid artery distensibility (cCSD), compliance (cCSC), and incremental elastic modulus (cIEM). MPS carotid measurements were compared to corresponding data from pediatric and adult healthy cohorts. 33 MPS patients (17 MPS I, 9 MPS II, 4 MPS IIIA, and 3 MPS VI; mean age 12.5 ± 4.7 years), 560 pediatric controls (age 13.1 ± 4.0 years), and 554 adult controls (age 39.2 ± 2.2 years) were studied. Age and sex-adjusted aggregate MPS cIMT (0.56 ± 0.05 mm) was significantly greater than both pediatric (+0.12 mm; 95% CI +0.10 to +0.14 mm) and adult (+0.10 mm; 95% CI +0.06 to +0.14 mm) control cohorts; similar findings were observed for all MPS subtypes. Mean MPS cIMT approximated the 80th percentile of the adult cohort cIMT. MPS patients also demonstrated significantly increased adjusted arterial stiffness measurements, evidenced by reduced cCSD, cCSC, and increased cIEM, compared to pediatric and adult control cohorts. Regardless of treatment, MPS patients demonstrate increased cIMT and arterial stiffness compared to healthy pediatric and adult controls. These data suggest that relatively young MPS patients demonstrate a “structural vascular age” of at least 40 years old.

Bosch, TA, Carbuhn, AF, Stanforth, PR, Oliver, JM, Keller, KA, and Dengel, DR. Body composition and bone mineral density of Division 1 collegiate football players: a consortium of college athlete research study. J Strength Cond Res 33(5): 1339-1346, 2019-The purpose of this study was to generate normative data for total and regional body composition in Division 1 collegiate football players using dual-energy x-ray absorptiometry (DXA) and examine positional differences in total and regional measurements. Data were used from the Consortium of College Athlete Research (C-CAR) group. Four hundred sixty-seven players were included in this study. Height, body mass, total and regional fat mass, lean mass, and bone mineral density were measured in each athlete in the preseason (June-August). Players were categorized by their offensive or defensive position for comparisons. Linemen tended to have the higher fat and lean mass measures (p ≤ 0.05 for all) compared with other positions. Positions that mirror each other (e.g. linemen) had similar body composition and body ratios. All positions were classified as overweight or obese based on body mass index (BMI) (>25 kg·m), yet other than offensive and defensive linemen, all positions had healthy percent body fat (13-20%) and low visceral fat mass (

Background Understanding the heritable contribution of vascular measures, from parent to offspring, may aid in risk stratification and atherosclerosis prevention efforts. We hypothesized that measures of vascular structure and function would be heritable in this cohort of parents and their adolescent offspring. Methods and Results High‐resolution ultrasound scans of the brachial and carotid arteries were obtained in parents (n=558) and their offspring (n=369). Lumen diameter and flow‐mediated dilation were measured in the brachial artery. Intima‐media thickness, lumen diameter, incremental elastic modulus, diameter distensibility, and cross‐sectional distensibility were measured, and carotid cross‐sectional compliance was measured in the carotid artery. Carotid–radial pulse wave velocity was obtained using SphygmoCor ® . Heritability analysis (h 2 , expressed as %) using Sequential Oligogenic Linkage Analysis Routines was performed on the entire cohort and adjusted for age, sex, race, body–mass index, smoking, and mean arterial pressure. Data are presented as mean± SE . Measures of brachial artery diameter (h 2 =25±9%, P =0.001), lumen diameter (h 2 =55±9%, P 2 =29±13%, P =0.014), diameter distensibility (h 2 =28±7%, P 2 =27±7%, P 2 =26±9%, P Conclusions These data show that the majority of noninvasive measures of vascular structure and function are heritable, suggesting that measurement of these subclinical risk factors in parents may be helpful in assessing childhood risk for future cardiovascular disease.

Objective The purpose of this study was to measure the linearity of visceral adipose tissue (VAT) accumulation with measures of total body adiposity to determine whether a threshold exists and to explore the association with cardiometabolic risk factors in adults. Methods Using a cross-sectional design, data were obtained from 723 adults (324 females) age 19-47 years. Body mass index ranged from 15 to 52 kg/m2. Segmented linear regression was used to identify sex-specific percent body fat thresholds at which VAT slope changes. Linear regression measured the association of VAT mass, total fat mass, and subcutaneous fat with cardiometabolic risk factors above and below each threshold. Results Adiposity thresholds were identified at 23.4% body fat in males and 38.3% body fat in females beyond which the slope of VAT per unit of percent body fat increased to strongly positive. Males and females above these adiposity thresholds had significant dyslipidemia (P

Background Childhood cancer survivors (CCS) are at high risk of developing treatment-related late effects, including cardiovascular disease and diabetes. Late effects can be exacerbated by low physical activity (PA) levels. Relationships between PA and cardiovascular risk factors during childhood have not been well described in CCS. Procedure PA and cardiovascular risk factors were measured cross-sectionally in 319 CCS and 208 sibling controls aged 9–18 years. Comparisons between CCS and controls and associations of outcomes with PA (dichotomized at 60 min/day or treated as continuous) were performed with linear regression. Results Among CCS, the high PA group had lower percent fat mass (24.4% vs. 29.8%, P