Cohort Of Healthy Adolescents Research Articles

Serum Myostatin is Associated With Central-to-Peripheral Arterial Stiffness Gradient in Healthy Adolescents: The MACISTE Study.

Myostatin is a protein compound, structurally related to the transforming growth factor-beta protein, which plays a pivotal role in regulating muscle growth and extracellular matrix production. It exerts both profibrotic and antihypertrophic effects on vascular smooth muscle cells. Aim of the study was to explore the potential association between serum myostatin levels (sMSTN) and carotid-femoral pulse wave velocity (cf-PWV), carotid-radial pulse wave velocity (cr-PWV), and their ratio (PWVr), in a cohort of healthy adolescents. A cohort of 128 healthy subjects (mean age 17 ± 2 years, 59% male) was randomly selected from participants to the MACISTE (Metabolic And Cardiovascular Investigation at School, TErni) study. sMSTN was assessed utilizing an enzyme-linked immunosorbent assay. PWVs were measured in the supine position using high-fidelity applanation tonometry. The mean cf-PWV was 5.1 ± 0.9 m/s, cr-PWV was 6.9 ± 0.9 m/s, and PWVr was 0.75 ± 0.12. PWVr exhibited a linear increase across increasing quartiles of sMSTN (0.71 ± 0.1, 0.74 ± 0.1, 0.7 ± 0.1, 0.77 ± 0.1, P for trend = 0.03), whereas the association between sMSTN and each single component of PWVr (cf-PWV, cr-PWV) did not attain statistical significance. Quartiles of sMSTN displayed a positive trend with serum HDL-cholesterol (P = 0.01) and a negative one with LDL-cholesterol (P = 0.01). In a multivariate linear model, the association between PWVr and sMSTN was independent of SBP values, age, sex, heart rate, BMI, HDL-cholesterol, and HOMA Index. In healthy adolescents, sMSTN showed independent associations with PWVr, a measure of central-to-peripheral arterial stiffness gradient. sMSTN may exert differential effects on the structural and functional properties of the arterial wall.

Self-reported childhood family adversity is linked to an attenuated gain of trust during adolescence

A longstanding proposal in developmental research is that childhood family experiences provide a template that shapes a capacity for trust-based social relationships. We leveraged longitudinal data from a cohort of healthy adolescents (n = 570, aged 14–25), which included decision-making and psychometric data, to characterise normative developmental trajectories of trust behaviour and inter-individual differences therein. Extending on previous cross-sectional findings from the same cohort, we show that a task-based measure of trust increases longitudinally from adolescence into young adulthood. Computational modelling suggests this is due to a decrease in social risk aversion. Self-reported family adversity attenuates this developmental gain in trust behaviour, and within our computational model, this relates to a higher ‘irritability’ parameter in those reporting greater adversity. Unconditional trust at measurement time point T1 predicts the longitudinal trajectory of self-reported peer relation quality, particularly so for those with higher family adversity, consistent with trust acting as a resilience factor.

Impact of COVID-19 Lockdown on Metabolic/Inflammatory Profile in Adolescents: Cellular Studies and Predictive Biomarkers.

The COVID-19 pandemic and its lockdown restrictions changed people's lifestyles with potential negative impact on health. This longitudinal study aimed to assess the COVID-19 lockdown influence on the adherence to the Mediterranean Diet (MD) pattern and its effects on the metabolic inflammatory profile in a cohort of healthy adolescents. We analyzed anthropometric measurements, body composition, and MD adherence along with serum metabolic and inflammatory profile in 77 healthy adolescents from Southern Italy before and after the COVID-19 pandemic lockdown. Additionally, we evaluated the biological properties of pre- and post-lockdown serum on human HepG2 and HuH-7 hepatic cells. We didn't observe any significant differences in anthropometric and body composition parameters as well as in MD adherence score in adolescents between pre- and post-lockdown COVID-19. Intriguingly, despite the metabolic profile of adolescents in post-lockdown was within the normal range, we evidenced increased levels of fasting glucose, triglycerides, Total Cholesterol and LDL along with a reduction in HDL, in post- compared to pre-lockdown adolescent serum. In addition, elevated levels of TNF-α, IL-1β and ferritin were found in post-lockdown adolescents when compared to their pre-lockdown counterparts. Consistent with biochemical parameters, were observed in HepG2 and HuH-7 cells treated with pooled serum from post- respect to pre-lockdown period enhanced lipid accumulation with altered mitochondrial functions and increased reactive oxygen species production. Receiver operator characteristic curve analysis identified Total C Cholesterol, LDL, HDL, TNF-α and ferritin as predictive serum markers for metabolic and inflammatory profiling after lockdown period. Our findings highlight that the COVID-19 lockdown, forcing sedentary behavior, had a negative impact on adolescents' metabolic and inflammatory profile which may result in long-term unhealth outcomes.

Left Ventricular Strain Analysis During Submaximal Semisupine Bicycle Exercise Stress Echocardiography in Childhood Cancer Survivors

Background Childhood cancer survivors (CCSs) show relevant cardiac morbidity and mortality throughout life. Early detection is key for optimal support of patients at risk. The aim of this study was to evaluate 2-dimensional speckle-tracking echocardiography strain analysis during semisupine exercise stress in CCSs for detection of subclinical left ventricular dysfunction after cancer treatment. Methods and Results Seventy-seven CCSs ≥1-year postchemotherapy were prospectively examined at rest, low, and submaximal stress level and compared with a cohort of healthy adolescents and young adults (n=50). Global longitudinal strain (GLS), short axis circumferential strain, and corresponding strain rates were analyzed using vendor-independent software. CCSs at median 7.8 years postchemotherapy showed comparable left ventricular GLS, circumferential strain, and strain rate values at all stress stages to healthy controls. Yet, prevalence of abnormal GLS (defined as <2 SD of controls reference) in CCSs was 1.3% at rest, 2.7% at low, and 8.6% at submaximal stress. In CCSs, relative change of circumferential strain from rest to submaximal stress was lower than in healthy controls, median 16.9 (interquartile range [IQR], 3.4; 28.8) % versus 23.3 (IQR, 11.3; 33.3) %, P=0.03, most apparent in the subgroups of CCSs after high-dose anthracycline treatment and cancer diagnosis before the age of 5 years. Conclusions In this prospective 2-dimensional speckle tracking echocardiography strain study, prevalence of abnormal left ventricular GLS increased with stress level reflecting impaired cardiac adaptation to exercise stress in some CCSs. However, relatively early after last chemotherapy, this did not result in significant differences of mean GLS-, circumferential strain-, and strain rate values between CCSs and controls at any stress level.

SERUM MYOSTATIN IS ASSOCIATED WITH PULSE WAVE VELOCITY RATIO IN HEALTHY ADOLESCENTS. THE MACISTE STUDY

Objective: Serum myostatin (sMSTN) is a proteic compound that regulates muscle growth and production of extracellular matrix. sMSTN also exerts profibrotic and antihypertrophic effects on smooth muscle cells and fibroblasts. Aortic-brachial pulse wave velocity ratio (PWVr) is a pressure-independent measure of arterial stiffness gradient between the aorta and peripheral muscular arteries, known to reflect early arterial ageing and to be associated with cardiovascular (CV) risk. We explored the association between sMSTN and arterial stiffness gradient, measured through the PWVr, in a cohort of healthy adolescents. Design and method: 128 healthy subjects (mean age 17 ± 2 years, 59% men) were randomly recruited among participants of the Metabolic And Cardiovascular Investigation at School, TErni (MACISTE) study, a cross-sectional survey conducted at the “Renato Donatelli” High School in Terni, Italy. sMSTN was measured through enzyme-linked immunosorbent assay. PWV was measured by applanation tonometry (SphygmoCor) along the carotid-femoral (cf-PWV, aortic) and the carotid-radial (cr-PWV, brachial) pathways and expressed as the ratio between cf-PWV and cr-PWV. Blood pressure (BP) was recorded at the same time of PWV measurement and expressed as systolic/diastolic BP percentiles (z-score) based on age, sex and height. Results: Mean BP was 126 ± 12/68 ± 8 mmHg (z-score 1.2 ± 0.9/0.3 ± 0.7). Mean Cf-PWV was 5.1 ± 0.9 m/s, cr-PWV was 6.9 ± 0.9 m/s. PWVr was 0.75 ± 0.12. PWVr increased linearly at increasing quartiles of sMSTN (0.71 ± 0.09, 0.74 ± 0.13, 0.75 ± 0.14, 0.78 ± 0.12, p for trend = 0.03, Figure 1). Subjects with PWVr above average had higher BMI (21.7 ± 2.6 Kg/m2 vs 20.8 ± 2.3 Kg/m2, p = 0.04) and SBP (1.39 ± 0.97 vs 0.97 ± 0.91, p = 0.01), whereas they did not differ in terms of age, sex, heart rate, measures of adiposity, and other CV risk factors. In a multivariate linear model, PWVr was independently predicted by SBP and sMSTN, both if expressed as continuous variable (beta = 0.21, p = 0.018) or in quartiles (beta = 0.26, p = 0.011). Conclusions: In a cohort of healthy Italian adolescents, sMSTN was positively and independently associated to increased PWVr, a measure of arterial stiffness gradient. Our preliminary results raise the hypothesis that sMSTN might differentially interfere with structural and functional components of the arterial wall, and ultimately might contribute to the accelerated arterial ageing in adolescents.

Mumps virus-specific immune response outcomes and sex-based differences in a cohort of healthy adolescents

Despite high levels of MMR-II usage in the US, mumps outbreaks continue to occur. Evidence suggests that mumps vaccine-induced humoral immunity wanes over time. Relatively few studies have examined cell-mediated immunity or reported on sex-based differences. To better understand sex-based differences in the immune response to mumps vaccine, we measured neutralizing antibody titers and mumps-specific cytokine/chemokine responses in a cohort of 748 adolescents and young adults after two doses of MMR vaccine. We observed significantly higher neutralizing antibody titers in females than in males (120.8 IU/mL, 98.7 IU/mL, p = 0.038) but significantly higher secretion levels of MIP-1α, MIP-1β, TNFα, IL-6, IFNγ, and IL-1β in males compared to females. These data demonstrate that sex influences mumps-specific humoral and cell-mediated immune response outcomes, a phenomenon that should be considered during efforts to improve vaccines and prevent future outbreaks.

Diminished insulin sensitivity is associated with altered brain activation to food cues and with risk for obesity – Implications for individuals born small for gestational age

While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents. Additionally, HOMA-IR and insulinemia were higher in participants with impaired food memory. SGA individuals had higher snack caloric density and greater chance for impaired food memory. There was also an interaction between the HOMA-IR and birth weight ratio influencing external eating behavior. We suggest that diminished insulin sensitivity correlates with activation in visual attention areas and inactivation in inhibitory control areas in healthy adolescents. Insulin resistance also associated with less consistency in implicit memory for a consumed meal, which may suggest lower ability to establish a dietary pattern, and can contribute to obesity. Differences in feeding behavior in SGA individuals were associated with insulin sensitivity and hippocampal alterations, suggesting that cognition and hormonal regulation are important components involved in their food intake modifications throughout life.

Cardiovascular health behaviors and associations of sex, age, and education in adolescents - Results from the EVA Tyrol study

Background and aimsIdeal cardiovascular health (CVH) behaviors in adolescents are defined by body mass index (BMI), diet, physical activity and smoking, and are directly associated with better health in later life. To further improve health prevention programs we investigated the prevalence of these behaviors in a cohort of healthy adolescents and focused on the associations with sex, age, and education. Methods and resultsThe Early Vascular Aging Tyrol study is a cross-sectional study assessing 14- to 19-year-old pupils and apprentices in Western Austria and South Tyrol. Between May 2015 and July 2018 2047 adolescents (43.6% males, mean age 16.4 years) with complete data for all 4 health behaviors were included. The prevalence of ideal body mass index (BMI) was 78.3%, of ideal physical activity 42.5%, of non-smoking 70.4% and of ideal diet 8.1%. Females showed a higher smoking prevalence and a lower physical activity, but better dietary habits than males. Older adolescents of both sexes had lower prevalence of ideal smoking and diet. Apprentices and pupils of vocational schools had a higher BMI and a less favorable diet compared to secondary academic school students. Smoking prevalence was highest in apprentices. Non-ideal BMI was independently associated with smoking. ConclusionIn our cohort, only a minority showed ideal CVH behaviors which were best in adolescents younger than 16 years. We observed significant differences between males and females and a clear impact of school education with apprentices being at risk for non-ideal CVH behaviors. Clinical trial registration numberNCT03929692, clinicaltrials.gov.

Characterization of MR Imaging-Visible Perivascular Spaces in the White Matter of Healthy Adolescents at 3T.

Perivascular spaces play a role in cerebral waste removal and neuroinflammation. Our aim was to provide data regarding the burden of MR imaging-visible perivascular spaces in white matter in healthy adolescents using an automated segmentation method and to establish relationships between common demographic characteristics and perivascular space burden. One hundred eighteen 12- to 21-year-old subjects underwent T1- and T2-weighted 3T MR imaging as part of the National Consortium on Alcohol and Neurodevelopment in Adolescence. Perivascular spaces were identified in WM on T2-weighted imaging using a local heterogeneity approach coupled with morphologic constraints, and their spatial distribution and geometric characteristics were assessed. MR imaging-visible perivascular spaces were identified in all subjects (range, 16-287). Males had a significantly higher number of perivascular spaces than females: males, mean, 98.4 ± 50.5, versus females, 70.7 ± 36.1, (P < .01). Perivascular space burden was bilaterally symmetric (r > 0.4, P < .01), and perivascular spaces were more common in the frontal and parietal lobes than in the temporal and occipital lobes (P < .01). Age and pubertal status were not significantly associated with perivascular space burden. Despite a wide range of burden, perivascular spaces are present in all healthy adolescents. Perivascular space burden is higher in adolescent males than in females, regardless of age and pubertal status. In this population, perivascular spaces are highly symmetric. Although widely reported as a feature of the aging brain, awareness of the presence of perivascular spaces in a cohort of healthy adolescents provides the foundation for further research regarding the role of these structural variants in health and disease.

Handgrip strength is associated with improved spirometry in adolescents.

IntroductionPulmonary rehabilitation, including aerobic exercise and strength training, improves function, such as spirometric indices, in lung disease. However, we found spirometry did not correlate with physical activity (PA) in healthy adolescents (Smith ERJ: 42(4), 2016). To address whether muscle strength did, we measured these adolescents’ handgrip strength and correlated it with spirometry.MethodsIn 1846 non-smoking, non-asthmatic Germans (age 15.2 years, 47% male), we modeled spirometric indices as functions of handgrip strength by linear regression in each sex, corrected for factors including age, height, and lean body mass.ResultsHandgrip averaged 35.4 (SD 7.3) kg in boys, 26.6 (4.2) in girls. Spirometric volumes and flows increased linearly with handgrip. In boys each kg handgrip was associated with about 28 mL greater FEV1 and FVC; 60 mL/sec faster PEF; and 38 mL/sec faster FEF2575. Effects were 10–30% smaller in girls (all p<0.0001) and stable when Z-scores for spirometry and grip were modeled, after further correction for environment and/or other exposures, and consistent across stages of puberty.ConclusionsGrip strength was associated with spirometry in a cohort of healthy adolescents whose PA was not. Thus, research into PA’s relationship with lung function should consider strength as well as total PA. Strength training may benefit healthy lungs; interventions are needed to prove causality.

OP.7C.01] CENTRAL-TO-PERIPHERAL DIASTOLIC BLOOD PRESSURE ATTENUATION IN HEALTHY ADOLESCENT AND THE EFFECTS OF HEART RATE. THE MACISTE STUDY

Objective: Heart rate (HR) is directly associated to central-to-peripheral pulse wave amplification. We aimed at evaluating the associations between heart rate and each BP component in a cohort of healthy adolescents. Design and method: 470 healthy adolescents (17 ± 1.4 years, 56% boys, brachial BP 123/67 ± 11/7 mmHg, HR 72 ± 12 bpm) were enrolled in the present study. Brachial BP was measured on 3 occasions by validated devices. Central BP was estimated by radial and brachial applanation tonometries, and calibrated to brachial MAP/DBP (SphygmoCor). Results: Brachial and central BP were 123/67 ± 11/7 mmHg and 105/69 ± 9/8 mmHg. SBPamp was 1.17 ± 0.04, PPamp was 1.57 ± 0.13, while DBP amplification was 0.97 ± 0.01 (DBP ’attenuation’). HR had a direct correlation with brachial and central DBP (r = 0.38 and r = 0.46, both p < 0.01) and central SBP (r = 0.09, p = 0.04), but not with peripheral SBP (p = 0.59), and a negative one with brachial and central PP (r = −0.24 and r = −0.37, both p < 0.01). HR had a positive association with PPamp (r = 0.38, p < 0.01), and a negative one with SBPamp (r = −0.14, p < 0.01) and DBPamp (r = −0.55, p < 0.01). The slope of BP change for each 10-bpm HR increase was steeper for central DBP (2.8 ± 0.3 mmHg), than for peripheral DBP (2.2 ± 0.3 mmHg, p for difference between regression coefficients < 0.01), and for central and brachial DBP than for central SBP (0.7 ± 0.3 mmHg, both p < 0.01). Conclusions: HR is associated with more pronounced changes in DBP than in SBP, and in central than peripheral DBP. Increasing HR may attenuate DBP from centre to periphery. The assumption that DBP is constant along the arterial tree may not be valid during dynamic conditions.

Impact of psychological health on peripheral endothelial function and the HPA-axis activity in healthy adolescents

Background and aimsThe development of adolescence psychological health over a 3-year period and its relationship to peripheral endothelial function and the hypothalamic-pituitary-adrenal (HPA)-axis activity were examined in a cohort of healthy adolescents in a longitudinal study. MethodsA total of 162 adolescents (94 females) participated in both baseline (mean age 14.5 ± 1 years) and three-year follow-up studies. Psychological health was evaluated by self-report using the Beck Youth Inventories of Emotional and Social Impairment and the psychosomatic problem scale. Peripheral endothelial function was assessed using a peripheral artery tonometry device. The HPA-axis activity measured as cortisol awakening response (CAR) was assessed only at follow-up by collecting two saliva samples, immediately after awakening and 15 min later. Physical activity, smoking and parental education were assessed by questionnaires. ResultsAdolescents reported increased depression and decreased anger over three years, while only females reported increased psychosomatic complaints. Reduced peripheral endothelial function was associated with high level of anger (β = −0.332, p = 0.018) and disruptive behaviour (β = −0.390, p = 0.006) over three years in males, but not in females, after adjusting for covariates. Blunted cortisol awakening response was associated with high level of anxiety (β = −0.235, p = 0.017), depression (β = −0.203, p = 0.038), anger (β = −0.185, p = 0.048), and low level of self-concept (β = 0.289, p = 0.002) after adjusting for covariates. ConclusionsHigh level of negative emotions during adolescence may have adverse effects on peripheral endothelial function and the regulation of the HPA-axis activity, while high level of self-concept might be protective.

Depot medroxyprogesterone acetate use is not associated with risk of incident sexually transmitted infections among adolescent women.

To determine whether depot medroxyprogesterone acetate (DMPA) use is associated with an increased risk of acquisition of sexually transmitted infections (STIs) in a cohort of healthy adolescents, for whom prospective evidence is sparse. Adolescent women aged 14-17 years (n = 342) were recruited from clinical sites in the United States between 1999 and 2005. They returned quarterly for interviews and STI testing. During alternating 3-month periods, participants also completed daily diaries of sexual behaviors and performed weekly vaginal self-obtained swabs to test for STIs. Data collected through 2009 (median follow-up length = 42.2 months) were analyzed. Univariable and multivariable tests of association between STI acquisition during the 3-month diary period and covariates were calculated, using nonlinear mixed-effect logistic regression models to control for repeated measurements. In multivariable analysis, there were no significant associations between DMPA use in the current or previous 3-month period and incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis. The number of total or unprotected sexual events during the diary period was not associated with the risk of STI. Older age was a protective factor for the development of Chlamydia trachomatis (odds ratio = .85; 95% confidence interval = .76-.96). The only factor significantly associated with an increased risk of contracting all three STIs was a greater number of sexual partners during the diary period (odds ratio, range = 1.91-2.62). In this U.S.-based cohort of adolescent women, we found no evidence that DMPA use was associated with increased STI risk. Efforts to curb STI transmission among adolescents should focus on education about the reduced number of sexual partners.

High levels of soluble intercellular adhesion molecule-1, insulin resistance and saturated fatty acids are associated with endothelial dysfunction in healthy adolescents

Objective Atherosclerosis begins and progresses during childhood and adolescence. Endothelial dysfunction is one of the earliest abnormalities that can be detected in the development of atherosclerosis. As the determinants of endothelial function in childhood are unknown, we investigated the influence of cardiovascular risk factors on endothelial function in a cohort of healthy adolescents. Methods A total of 257 adolescents (age: 14.5 ± 1.0 years, 138 girls) participated in this study. Endothelial function was measured as reactive hyperemic index (RHI) using a fingertip peripheral arterial tonometry device. Blood samples were collected for analysis of lipids, insulin, glucose, fatty acid composition of plasma phospholipids, and markers of inflammation and endothelial function. Results There was no gender difference in RHI. Boys had higher plasma level of vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin and monocyte chemoattractant protein-1, and lower level of insulin, total cholesterol, high-density lipoprotein–cholesterol (HDL), low-density lipoprotein–cholesterol (LDL), ApoA1, ApoB, and docosahexaenoic acid of plasma phospholipids than girls. There was no gender difference regarding triacylglycerol, triacylglycerol/HDL, LDL/HDL and ApoB/ApoA. The RHI was inversely associated with plasma ICAM-1 ( p = 0.0003), HOMA index for insulin resistance (HOMA-IR, p = 0.001) and saturated fatty acids of plasma phospholipids (SFA, p = 0.001). The associations remained significant after adjusting for age, height, BMI- z-score, sex, blood pressure, HDL and smoking. Conclusion In healthy adolescents impaired endothelial function is significantly associated with high level of soluble ICAM-1, HOMA-IR and SFA.