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BackgroundCardiovascular 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.MethodsProspective, 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.ResultsMorquio A patients demonstrated significantly higher (P

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.

The purpose of this study was to compare the muscle-to-bone ratio (MBR) in National Collegiate Athletic Association Division I football players (collegiate football players [CFP]) to healthy, age-matched controls. In addition, we examined MBR in CFP by position. A total of 553 CFP and 261 controls had their total and regional lean mass (LM), fat mass (FM), and bone mineral content (BMC) determined by dual x-ray absorptiometry (DXA). College football players were categorized by positions defined as offensive linemen (OL), defensive linemen (DL), tight end, linebacker (LB), running back (RB), punter or kicker, quarterback (QB), defensive back (DB), and wide receiver (WR). There were significant differences between CFP and controls for total LM (80.1 ± 10.0 vs. 56.9 ± 7.8 kg), FM (22.2 ± 12.5 vs. 15.2 ± 7.1 kg), and BMC (4.3 ± 0.5 vs. 3.1 ± 0.5 kg). Although there were significant differences in body composition between CFP and controls, there was no significant differences in total MBR between CFP and controls (18.6 ± 1.4 vs. 18.8 ± 1.7). Regionally, CFP had significantly lower trunk MBR than controls (26.7 ± 2.7 vs. 28.7 ± 4.2), but no difference was seen in leg or arm MBR. Positional differences in CFP were noted as total MBR being significantly higher in DL (19.0 ± 1.4) than in DB (18.1 ± 1.3), WR (18.1 ± 1.3), and LB (18.2 ± 1.3). OL had a significantly higher total MBR (19.2 ± 1.3) than DB(18.1 ± 1.3), LB (18.2 ± 1.3), QB (18.1 ± 1.0), and WR (18.1 ± 1.3). In addition, RB had significantly higher total MBR (18.8 ± 1.3) than DB (18.1 ± 1.3) and WR (18.1 ± 1.3). This study may provide athletes and training staff with normative values when evaluating total and regional MBR with DXA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/m2, n = 6), to those who were overweight (BMI ≥ 25 kg/m2, 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. [ABSTRACT FROM AUTHOR]

BackgroundTo determine the prevalence and severity of bone deficits in a cohort of childhood cancer survivors (CCS) compared to a healthy sibling control group, and the modifiable factors associated with bone deficits in CCS.MethodsCross-sectional study of bone health in 319 CCS and 208 healthy sibling controls. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). Generalized estimating equations were used to compare measures between CCS and controls. Among CCS, multivariable logistic regression was used to evaluate odds ratios for BMD Z-score ≤ -1.ResultsAll subjects were younger than 18 years of age. Average time since treatment was 10.1 years (range 4.3 - 17.8 years). CCS were 3.3 times more likely to have whole body BMD Z-score ≤ -1 than controls (95% CI: 1.4-7.8; p = 0.007) and 1.7 times more likely to have lumbar spine BMD Z-score ≤ -1 than controls (95% CI: 1.0-2.7; p = 0.03). Among CCS, hypogonadism, lower lean body mass, higher daily television/computer screen time, lower physical activity, and higher inflammatory marker IL-6, increased the odds of having a BMD Z-score ≤ -1.ConclusionsCCS, less than 18 years of age, have bone deficits compared to a healthy control group. Sedentary lifestyle and inflammation may play a role in bone deficits in CCS. Counseling CCS and their caretakers on decreasing television/computer screen time and increasing activity may improve bone 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 [plus or minus] 2.5 years; body mass index = 24.5 [plus or minus] 3.9 kg/m.sup.2) 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 [plus or minus] 7.8%) was significantly less than HW (22.8 [plus or minus] 8.5%, p < 0.001), BIA (20.1 [plus or minus] 9.1%, p < 0.001), skinfolds (19.7 [plus or minus] 9.7%, p < 0.001), and girths (21.2 [plus or minus] 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%., Author(s): Michelle M. Harbin [sup.1] , Alexander Kasak [sup.1] , Joseph D. Ostrem [sup.2] , Donald R. Dengel [sup.1] Author Affiliations: (1) Laboratory of Integrative Human Physiology, School of Kinesiology, [...]