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Fatty acid esters of hydroxy fatty acid (FAHFA) are anti-diabetic and anti-inflammatory lipokines. Recently FAHFAs were also found to predict cardiorespiratory fitness in a cross-sectional study of recreationally trained runners. Here we report the influences of body composition and gender on static FAHFA abundances in circulation. We compared the association between circulating FAHFA concentrations and body composition, determined by dual x-ray absorptiometry, in female recreational runners who were lean (BMI < 25 kg/m 2 , n = 6), to those who were overweight (BMI ≥ 25 kg/m 2 , n = 7). To characterize the effect of gender we also compared circulating FAHFAs in lean male recreational runners (n = 8) to recreationally trained lean female (n = 6) runner group. Circulating FAHFAs were increased in females in a manner that was modulated by specific adipose depot sizes, blood glucose, and lean body mass. As expected, circulating FAHFAs were diminished in the overweight group, but strikingly, within the lean cohort, increases in circulating FAHFAs were promoted by increased fat mass, relative to lean mass, while the overweight group showed a significantly attenuated relationship. These studies suggest multimodal regulation of circulating FAHFAs and raise hypotheses to test endogenous FAHFA dynamic sources and sinks in health and disease, which will be essential for therapeutic target development. Baseline circulating FAHFA concentrations could signal sub-clinical metabolic dysfunction in metabolically healthy obesity.

The association of post-adoption experiences of discrimination with depressive symptoms was examined in 93 previously institutionalized (PI) youth (84% transracially adopted). Additionally, we explored whether sleep quality statistically moderated this association. Notably, we examined these associations after covarying a measure of autonomic balance (high/low frequency ratio in heart rate variability) affected by early institutional deprivation and a known risk factor for depression. PI youth exhibited more depressive symptoms and experiences of discrimination than 95 comparison youth (non-adopted, NA) raised in their biological families in the United States. In the final regression model, there was a significant interaction between sleep quality and discrimination, such that at higher levels of sleep quality, the association between discrimination and depression symptoms was non-significant. Despite being cross-sectional, the results suggest that the risk of depression in PI youth involves post-adoption experiences that appear unrelated to the impacts of early deprivation on neurobiological processes associated with depression risk. It may be crucial to examine methods of improving sleep quality and socializing PI youth to cope with discrimination as protection against discrimination and microaggressions.

The purpose of this study was to determine the effect of circulating microvesicles isolated from chronic electronic (e‐)cigarette users on cultured human umbilical vein endothelial cell (HUVEC) expression of nuclear factor‐κB (NF‐κB), cellular cytokine release, phosphorylation of endothelial nitric oxide synthase (eNOS) and NO production. The HUVECs were treated with microvesicles isolated via flow cytometry from nine non‐tobacco users (five male and four female; 22 ± 2 years of age) and 10 e‐cigarette users (six male and four female; 22 ± 2 years of age). Microvesicles from e‐cigarette users induced significantly greater release of interleukin‐6 (183.4 ± 23.6 vs. 150.6 ± 15.4 pg/mL; P = 0.002) and interleukin‐8 (160.0 ± 31.6 vs. 129.4 ± 11.2 pg/mL; P = 0.01), in addition to expression of p‐NF‐κB p65 (Ser536) (18.8 ± 3.4 vs. 15.6 ± 1.5 a.u.; P = 0.02) from HUVECs compared with microvesicles from non‐tobacco users. Nuclear factor‐κB p65 was not significantly different between microvesicles from the non‐tobacco users and from the e‐cigarette users (87.6 ± 8.7 vs. 90.4 ± 24.6 a.u.; P = 0.701). Neither total eNOS (71.4 ± 21.8 vs. 80.4 ± 24.5 a.u.; P = 0.413) nor p‐eNOS (Thr495) (229.2 ± 26.5 vs. 222.1 ± 22.7 a.u.; P = 0.542) was significantly different between microvesicle‐treated HUVECs from non‐tobacco users and e‐cigarette users. However, p‐eNOS (Ser1177) (28.9 ± 6.2 vs. 45.8 ± 9.0 a.u.; P < 0.001) expression was significantly lower from e‐cigarette users compared with non‐tobacco users. Nitric oxide production was significantly lower (8.2 ± 0.6 vs. 9.7 ± 0.9 μmol/L; P = 0.001) in HUVECs treated with microvesicles from e‐cigarette users compared with microvesicles from non‐tobacco users. This study demonstrated increased NF‐κB activation and inflammatory cytokine production, in addition to diminished eNOS activity and NO production resulting from e‐cigarette use. Highlights What is the central question of this study? Circulating microvesicles contribute to cardiovascular health and disease via their effects on the vascular endothelium. The impact of electronic (e‐)cigarette use on circulating microvesicle phenotype is not well understood. What is the main finding and its importance? Circulating microvesicles from e‐cigarette users increase endothelial cell inflammation and impair endothelial nitric oxide production. Endothelial inflammation and diminished nitric oxide bioavailability are central factors underlying endothelial dysfunction and, in turn, cardiovascular disease risk. Deleterious changes in the functional phenotype of circulating microvesicles might contribute to the reported adverse effects of e‐cigarette use on cardiovascular health.

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 < 0.001). Multivariate ANOVA indicated a significant main effect of sex and method (p < 0.001), with a non-significant interaction (p = 0.101). Bonferroni post-hoc comparisons identified that BF% from 3D scanning (18.1 ± 7.8%) was significantly less than HW (22.8 ± 8.5%, p < 0.001), BIA (20.1 ± 9.1%, p < 0.001), skinfolds (19.7 ± 9.7%, p < 0.001), and girths (21.2 ± 10.4%, p < 0.001). The 3D scanner decreased in precision with increasing adiposity, potentially resulting from inconsistences in the 3D scanner’s analysis algorithm. A correction factor within the algorithm is required before infrared 3D scanning can be considered valid in measuring BF%.

Noncommunicable diseases (NCDs) have become the primary health concern for most countries around the world. Currently, more than 36 million people worldwide die from NCDs each year, accounting for 63% of annual global deaths; most are preventable. The global financial burden of NCDs is staggering, with an estimated 2010 global cost of $6.3 trillion (US dollars) that is projected to increase to $13 trillion by 2030. A number of NCDs share one or more common predisposing risk factors, all related to lifestyle to some degree: (1) cigarette smoking, (2) hypertension, (3) hyperglycemia, (4) dyslipidemia, (5) obesity, (6) physical inactivity, and (7) poor nutrition. In large part, prevention, control, or even reversal of the aforementioned modifiable risk factors are realized through leading a healthy lifestyle (HL). The challenge is how to initiate the global change, not toward increasing documentation of the scope of the problem but toward true action—creating, implementing, and sustaining HL initiatives that will result in positive, measurable changes in the previously defined poor health metrics. To achieve this task, a paradigm shift in how we approach NCD prevention and treatment is required. The goal of this American Heart Association/European Society of Cardiology/European Association for Cardiovascular Prevention and Rehabilitation/American College of Preventive Medicine policy statement is to define key stakeholders and highlight their connectivity with respect to HL initiatives. This policy encourages integrated action by all stakeholders to create the needed paradigm shift and achieve broad adoption of HL behaviors on a global scale.

Objective: Relationships between gonadotropins, sex hormones, and vascular structure and function in adolescents of varying weight statuses have not been fully investigated. In the present study, we examined associations among these in female and male adolescents with normal weight or obesity. Methods: We performed a cross-sectional analysis of adolescents (n = 58; 12–<18 years) grouped according to BMI percentile (BMI%) into normal weight (5th–<85th BMI%; n = 25) and obesity (≥95th BMI%; n = 33) categories. Fasting blood samples were collected to measure follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol. Vascular function was measured via ultrasonography for measures of carotid artery diameter compliance (cDC), incremental elastic modulus (cIEM), and brachial artery flow mediated dilation (FMD). Results: Females with obesity had a significantly (p = 0.009) greater mean FMD compared with those with normal weight. FSH, LH, testosterone, and estradiol did not differ between normal weight and obesity groups in either sex. After adjusting for age and multiple comparisons, higher testosterone was associated with decreased cDC (R2 = 0.189; p = 0.018) and increased cIEM (R2 = 0.346; p = 0.002) across all females. In all males, higher estradiol was associated with decreased cDC (R2 = 0.404; p = 0.006) and increased cIEM (R2 = 0.411; p = 0.003). Conclusion: We found that testosterone and estradiol were associated with vascular measures in female and male adolescents, respectively. Future studies are needed to confirm these relationships in larger cohorts and among those with BMIs in the overweight (85th–<95th BMI%) and severe obesity (BMI ≥120% of the 95th percentile and/or ≥35 kg/m2) categories.

BackgroundSubclinical cardiovascular risks of secondhand smoke (SHS) exposure among children and adolescents remains insufficiently described.MethodsThis was a cross-sectional study of 298 children and adolescents (48.0% male, body mass index: 27.0 ± 8.9 kg/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.ResultsSHS 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 ± 794 vs. 935 ± 388 mmHg, 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.ConclusionsSHS 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.

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  < 0.001) adjusted carotid intima-media thickness (cIMT), mean (SD) of 0.56 mm (0.03) compared to control subjects, 0.44 mm (0.04). The Morquio A cohort had significantly greater adjusted carotid elasticity (carotid cross-sectional compliance + 43%, P  < 0.001; carotid incremental elastic modulus − 33%, 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: Chemotherapy and radiation accelerate aging of multiple systems, including the immune and musculoskeletal systems. Resistance training may mitigate some of the late physiologic effects of cancer therapy. Methods: We developed a community-based pilot study of resistance training for long-term cancer survivors meeting criteria for pre-frailty or frailty (N = 8; 6 allogeneic hematopoietic cell transplant, 1 autologous hematopoietic transplant, 1 breast cancer survivor) and their caregivers (N = 8 healthy controls) consisting of a baseline assessment, 10 weeks of personalized resistance training at least once weekly as a group and as many additional times on an individual basis as their schedule allowed, and an end-of-study assessment to measure change in strength and body composition. Blood samples were collected at the start of the study and after the 10-week training program to assess changes in peripheral blood mononuclear cell DNA methylation patterns, gene expression measured by RNA sequencing, and stool microbiome analysis using metagenomics. The median number of resistance training sessions was 25 sessions. Results: Cancer survivors and controls both more than doubled their squat and press volume after 10 weeks. At baseline, cancer survivors exhibited a pro-inflammatory transcriptomic and epigenetic profile with elevated interferon signaling and reduced naïve T cell signatures compared to healthy controls, consistent with immune senescence. After 10 weeks of resistance training, these differences normalized, suggesting that exercise exerted anti-inflammatory and immune-restorative effects in cancer survivors at both gene expression and methylation levels. Ten fecal microbial pathways that were lower in relative abundance in patients compared with controls at baseline were no longer significantly different post-exercise. Conclusions: Our data suggest that in addition to beneficial changes in body composition, resistance training may exert an immune restorative effect in cancer survivors.

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.