Analysis of sedentary behaviour levels and patterns in adults with Down syndrome.

BACKGROUND: Sedentary behaviour (SB) among adults with Down syndrome (DS) may differ based on personal or environmental factors. OBJECTIVE: Investigate differences in SB levels and patterns of adults with DS based on sex, age, and residence-type across weekdays and weekends. METHODS: Thirty-four adults with DS (15 men; 37 ± 12 years) underwent accelerometry-based measurements of sedentary time, bouts, and breaks for 7 days. We evaluated differences with 2 × 2 mixed-model (group-by-day) ANOVA. RESULTS: Younger (19-36 years) individuals had less sedentary time (p = .042), and shorter (p = .048) and fewer (p = .012) bouts than older (37-60 years) individuals. Group home residents had more bouts on weekends than adults living with parent/guardians (p = .015). CONCLUSIONS: Adults with DS spent half their waking hours in SB of short bouts. Age and residence may influence SB.

Physical activity and arterial stiffness: is body fat a mediator?

PURPOSE: Physical activity (PA) and body fat percentage (%BF) are independently associated with arterial stiffness, but it has not been explored if there is an associative pathway among these variables. This study examined whether %BF mediates the relationship between PA or sedentary behavior levels with arterial stiffness. METHODS: Fifty adults (1:1 men:women; age 28 ± 11 year) had carotid-femoral pulse wave velocity (CF-PWV) measured by applanation tonometry, %BF by bioelectrical impedance, and PA levels by accelerometry. Accelerometer data determined minutes per day spent in sedentary, light, moderate-to-vigorous physical activity (MVPA), and Total PA. RESULTS: Pearson correlation indicated statistically significant associations among age, %BF, CF-PWV, MVPA, and Total PA (r = 0.34-0.65, p < 0.05). Sedentary and light PA were not associated with CF-PWV. Mediation analysis indicated significant total effects of MVPA (ß = - 0.34, p = 0.044) and age (ß = 0.65, p < 0.001) on CF-PWV. %BF mediated the relationship between Total PA and CF-PWV due to indirect effect of Total PA on %BF (ß = - 0.34, p = 0.02) and %BF on CF-PWV (ß = 0.44, p = 0.002), and partially mediated the relationship between age and CF-PWV (ß = 0.54, p < 0.001). Total PA retained its significant effect on %BF (ß = - 0.28, p = 0.04) and the effect of %BF on CF-PWV remained significant (ß = 0.26, p = 0.03), despite age having a significant effect on both %BF (ß = 0.31, p = 0.023) and CF-PWV (ß = 0.54, p < 0.001). CONCLUSIONS: %BF mediated the relationship between Total PA and arterial stiffness, even after accounting for age. Engagement in more Total PA may help to reduce %BF, resulting in decreased arterial stiffness.

External validation of Cardiac disease, Hypertension, and Logarithmic Left anterior descending coronary artery radiation dose (CHyLL) for predicting major adverse cardiac events after lung cancer radiotherapy.

Background and purpose: Major adverse cardiac events(MACE) are prevalent in patients with locally advanced-non-small cell lung cancer(LA-NSCLC) following radiotherapy(RT). The CHyLL model, incorporating coronary heart disease(CHD),Hypertension(HTN),Logarithmic LADV15 was developed and internally-validated to predict MACE among LA-NSCLC patients. We sought to externally validate CHyLL to predict MACE in an independent LA-NSCLC cohort. Patients and methods: Patients with LA-NSCLC treated with RT were included. CHyLL score was calculated:5.51CHD + 1.28HTN + 1.48ln(LADV15 + 1)-1.36CHD*ln(LADV15 + 1). CHyLL performance in predicting MACE was assessed and compared to mean heart dose(MHD) using Cox-proportional hazard(PH) analyses and Harrel's concordance(C)-indices. MACE and overall survival(OS) among low-vs high-risk groups(CHyLL < 5 vs ≥ 5) were compared. Results: In the external validation cohort(N = 102), the median age was 71 years and 55% were females. Most(n = 74,73%), had clinical Stage III disease and 35(34%) underwent surgery. CHyLL demonstrated good MACE prediction with C-index of 0.73(95% Confidence Interval(CI):0.58-0.89), while MHD did not (C-index = 0.46 (95% CI:0.30-0.62)). Per CHyLL, 32(31%) and 70(69%) patients were considered low-and high-risk for MACE, respectively. CHyLL consistently identified lower MACE rates in the low-vs high-risk group(log-rank p = 0.108):0 vs 8%(12 months),5 vs 16%(24 months),5 vs 16%(36 months),and 5 vs 19%(48 months) post-RT. In the pooled internal and external validation cohort(N = 303), MACE rates in low-vs high-risk groups were statistically significantly different(log-rank p = 0.01):1 vs 6%(12 months),3 vs 12%(24 months),6 vs 19%(36 months),and 6 vs 21%(48 months). Conclusions: CHyLL was externally validated and superior to MHD in predicting MACE. CHyLL has the potential to identify high-risk patients who may benefit from cardio-oncology optimization and to estimate personalized LADV15 constraints based on cardiac risk factors and acceptable MACE thresholds.

Health Outcomes of Physical Activity Interventions in Adults With Down Syndrome: A Systematic Review.

This systematic review examined whether physical activity interventions improve health outcomes in adults with Down syndrome (DS). We searched PubMed, APA PsycInfo, SPORTDiscus, APA PsycARTICLES, and Psychology and Behavioral Sciences Collection using keywords related to DS and physical activity. We included 35 studies published in English since January 1, 1990. Modes of exercise training programs included aerobic exercise, strength training, combined aerobic and strength training, aquatic, sport and gaming, and aerobic and strength exercise interventions combined with health education. The evidence base indicates that aerobic and strength exercise training improve physical fitness variables including maximal oxygen uptake, maximal heart rate, upper and lower body strength, body weight, and body fat percentage. Sport and gaming interventions improve functional mobility, work task performance, and sport skill performance. We concluded that adults with DS can accrue health benefits from properly designed physical activity and exercise interventions.

Vascular hemodynamics and blood pressure differences between young and older women.

BACKGROUND: Cardiovascular disease is one of the main causes of death in the United States, and hypertension is a primary risk factor. Therefore, the primary causes of hypertension need to be identified so they may be addressed for treatment. The purpose of this study was to compare blood pressure with hemodynamic values and identify factors that may explain blood pressure differences between a cohort of healthy normotensive younger and older women. METHODS: Participants were 49 young (age: 33.8 ± 5.9) and 103 old (age: 65.8 ± 4) who were non-hypertensive, had no previous history of heart disease or type 2 diabetes, body mass index less than 30 kg/m2, normal electrocardiography response at rest and during exercise, nonsmokers, and no use of medications known to affect cardiovascular or metabolic function. Body composition measured by dual-energy X-ray absorptiometry. Hemodynamic values measured by non-invasive pulse wave velocity through radial artery tonometry. Markers of inflammation measured through blood sample analysis. RESULTS: Significant differences exist between young and old groups in %fat (P < 0.001), systolic blood pressure (SBP) (P = 0.001), large artery elasticity (P = 0.005), small artery elasticity (P < 0.001), systemic vascular resistance (P = 0.004), total vascular impedance (P < 0.001), estimated cardiac output (P < 0.001), and tumor necrosis factor-⍺ (TNF-⍺) (P < 0.001). Using ANCOVA the difference in SBP between age groups was no longer significant after adjusting for small artery elasticity (P < 0.001) and TNF-⍺ (P = 0.041). CONCLUSIONS: These data demonstrate that blood pressure and vascular hemodynamic measures differ significantly between young and old women independent of body composition. Furthermore, these differences may be explained by the inflammation marker TNF-⍺ and/or small artery elasticity.

Distribution of Lewis (FUT3)genotype and allele: frequencies in a biethnic United States population.

The objective of the study was to examine the prevalence and distribution of four major single nucleotide polymorphisms (SNPs) (T59G, T1067G, T202C, and C314T) of the Lewis ( FUT3)gene in a biethnic United States population. This population-based cross-sectional study was based on data from the Atherosclerosis Risk in Communities (ARIC) Study, which included 761 males and females aged 45-64 years, who had no known/detected clinical atherosclerotic disease (577 Caucasians, 184 African Americans). The main outcome measures were prevalence of the Lewis genotype and allele frequencies for four SNPs of the FUT3gene. The most common genotype was the "wild type" at all four nucleotide positions ( WWWW), which was found to be present in 46.9% of ARIC participants. At least one mutant allele was detected in 51.7% of Caucasians, and 56.7% of African Americans ( P=0.59). The frequencies of mutant alleles ranged from 6.3% to 18.4% at the four FUT3gene sites examined. The distribution of the Lewis genotype and allele frequencies differed significantly by ethnicity at sites 59, 202, and 314. The prevalence of the Lewis genotype suggesting a lack of alpha(1,3/1,4) fucosyltransferase activity was 11.6% in Caucasians and 9.9% in African Americans ( P=0.67). Four specific SNPs of the Lewis genotype are common in the population at large. However, these four SNPs seem to fail to explain the majority of Lewis-negative phenotype in African Americans, given that Lewis-negative genotype prevalence was about one-third of what was expected. Use of rapid DNA sequencing and simultaneous Lewis phenotype determination could avoid the problems associated with haplotype determination and Lewis genotype grouping. Further studies testing SNPs of the Lewisgene are warranted, in particular among African Americans.

Genetic background of Lewis negative blood group phenotype and its association with atherosclerotic disease in the NHLBI family heart study.

OBJECTIVES: To examine the prevalence of four mutations, T59G, T1067A, T202C and C314T, of the human alpha(1,3/1,4) fucosyltransferase 3 (FUT 3) gene amongst persons with Lewis negative and those with Lewis positive blood group phenotype. An additional objective was to explore the hypothesis that these mutations are associated with coronary heart disease and inflammatory reaction. DESIGN: A population-based cross-sectional study. SETTING: Analysis of samples and data from the National Heart Lung and Blood Institute Family Heart Study. SUBJECTS: All Lewis (a-b-) participants (n = 136) and a sample of Lewis positive participants (n = 136) of the Family Heart Study; all were of Caucasian ethnicity. MAIN OUTCOME MEASURES: The prevalence of examined mutations by Lewis phenotype. RESULTS: The examined mutations were common and strongly associated with the Lewis (a-b-) phenotype. Accordingly, 90-95% of Lewis (a-b-) individuals amongst Caucasians can be identified by screening for these four mutations. Exploratory analyses suggested that with the exception of T59G, all examined mutations were positively associated with prevalent coronary heart disease, although not statistically significantly, perhaps due to the small number of prevalent coronary heart disease cases. C-reactive protein tended to be higher amongst persons with a TC or CC genotype at position 202 (3.07 +/- 0.41 vs. 2.08 +/- 0.32 mg L-1, P = 0.06). CONCLUSIONS: Four specific mutations of fucosyltransferase 3 gene are responsible for the vast majority of Lewis (a-b-) phenotypes in Caucasians. These mutations are common in the population at large and may be associated with increased risk of coronary heart disease. Further studies using larger samples are warranted.

RFG (ARA70, ELE1) interacts with the human androgen receptor in a ligand-dependent fashion, but functions only weakly as a coactivator in cotransfection assays.

Abnormalities of the human androgen receptor (hAR) cause a range of clinical defects in male development. A large proportion of these mutations are single amino acid substitutions in the hormone-binding domain (HBD) that alter AR function by interfering with the capacity of the AR to bind androgen or to form stable hormone-receptor complexes. Prior studies have suggested that the formation of such stable, active hormone-receptor complexes is a crucial step in the modulation of genes by the AR. It is presumed that these hormone-receptor complexes interact with other proteins to participate in the formation of active transcription complexes at the initiation sites of androgen-responsive genes. Using a yeast two-hybrid screening method, we isolated a partial cDNA encoding the carboxy terminus of a protein that interacts with the hAR-HBD (amino acid residues 623-917) in a ligand-dependent fashion in a yeast two-hybrid assay. Sequence analysis of this clone revealed that it encoded a portion of a protein that had been previously characterized as RFG (RET Fused Gene). Using glutathione-S-transferase (GST) fusions of the hAR HBD and immunoprecipitation of the in vitro translated proteins, we have demonstrated that this interaction can be reproduced in vitro. To determine the capacity of this protein to modulate the activity of the AR in transfection assays, we expressed full-length RFG in the CV1 and DU145 cell lines, in combination with an AR expression vector and model androgen-responsive genes [mouse mammary tumor virus (MMTV) and PRE2-tk luciferase]. Our results demonstrate that RFG alters the induction of these reporter genes very weakly (no greater than 2-fold compared with transfections without the RFG expression plasmid). Thus, while our findings are in agreement with published reports which indicate that RFG interacts with AR-HBD in a ligand-dependent fashion, in our assays RFG does not exert major effects on the activity of the hAR in response to androgen or to other steroid hormones.

Effect of estrogen on the elongation rate and number of RNA chains being synthesized in uterine nucleoli.

Administration of estradiol (E2) to ovariectomized mature rats resulted in a time-dependent increased transcriptional activity of uterine nucleoli isolated from hormone-treated animals compared to uterine nucleoli isolated from control animals. Early (4 h) E2 stimulation of uterine nucleolar transcription, resulted from an increased rate of elongation of chain growth on preinitiated nucleolar RNA with no significant effect of E2 on the number of nucleolar RNA chains being synthesized. Longer (24 h) treatment of animals with hormone resulted in both significant increased numbers of uterine nucleolar RNA chains in the act of synthesis and increased rate of elongation of nucleolar RNA chain growth. Salt extraction (150 mM NaCl) of uterine nucleoli isolated from 4 h E2-treated animals decreased transcriptional activity to the level observed in nucleoli isolated from control animals. The loss in nucleolar transcriptional activity from salt extraction was due to decreased rate of elongation of nucleolar RNA synthesis with no significant effect on the number of RNA chains being synthesized. Salt extracts from nucleoli isolated from 4 h E2-treated animals, but not control animals, contained factor(s) capable of stimulating the rate of elongation of nucleoli isolated from control animals to elongation rates observed in unextracted nucleoli isolated from 4 h E2-treated animals. Synthesis and phosphorylation of a high molecular weight uterine nucleolar protein(s) was seen after 4 h of E2 treatment with the nucleolar phosphoprotein(s) salt extractable.

Acceptance of amniocentesis by low-income patients in an urban hospital.

A study was made of increased accessibility of genetic services to low-income obstetric patients in Atlanta, Georgia. The proportion of black patients averaged 83%. Of 522 patients counseled from August, 1976, through 1978, 157 were offered amniocentesis, and 95 (61%) elected the procedure. For most of the patients (120, or 76%) who were eligible for amniocentesis, age (greater than or equal to 35 years at delivery) was an indication; and of these, only six (5%) had any prior knowledge of genetic risk. During the same time interval, 188 patients over 35 years of age who initiated prenatal care too late for prenatal diagnosis were counseled in the hospital after delivery; 101 (54%) indicated that they would have accepted amniocentesis. The conclusion was that (1) genetic services are acceptable to this socioeconomic group, and (2) accessibility and publicity are needed to promote utilization in this population.