DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity.

Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.

Fasted Exercise and Increased Dietary Protein Reduces Body Fat and Improves Strength in Jockeys.

The present study assessed the effects of a diet and exercise intervention in jockeys on body composition, metabolism, bone and mental health. 10 jockeys followed an individually prescribed 6-wk diet (Carbohydrate=2.5-3.5 g/kg, Protein=2.5 g/kg, Fat=1.0 g/kg). Body mass (59.2±4.6 vs. 57.6±4.5 kg), fat mass (7.5±3.5 vs. 6.2±2.6) and body fat (13.1±5.9 vs. 11.5±4.9%) all decreased (P<0.05) from pre to post-intervention whilst lean mass (47.1±5.3 vs. 47.0±5.5 kg) was maintained (P=0.80). RMR (1703±329 vs. 1975±313 kcal.d(-1)), VO2max (3.8±0.8 vs. 4.1±0.7 L/min(- 1)) chest strength (65±11 vs. 71±13 kg), leg strength (160±28 vs. 175±29 kg) and jumping height (40±6 vs. 48±5 cm) significantly increased (P<0.05). Bone health (DXA) did not change (P>0.05) at hip (-1.04±1.29 vs. - 0.76±0.71) or lumbar sites (-1.32±0.76 vs. - 1.31±0.77). Psychometrics (GHQ-12 and EAT-26) remained unchanged (10.3±4.3 vs. 8.9±3.8 and 14.8±9.6 vs. 11.0±5.6, P>0.05, respectively). This approach represents a marked difference from jockeys' habitual weight-making that largely involves dehydration and food deprivation.

Lifelong training preserves some redox-regulated adaptive responses after an acute exercise stimulus in aged human skeletal muscle.

Several redox-regulated responses to an acute exercise bout fail in aged animal skeletal muscle, including the ability to upregulate the expression of antioxidant defense enzymes and heat shock proteins (HSPs). These findings are generally derived from studies on sedentary rodent models and thus may be related to reduced physical activity and/or intraspecies differences as opposed to aging per se. This study, therefore, aimed to determine the influence of age and training status on the expression of HSPs, antioxidant enzymes, and NO synthase isoenzymes in quiescent and exercised human skeletal muscle. Muscle biopsy samples were obtained from the vastus lateralis before and 3 days after an acute high-intensity-interval exercise bout in young trained, young untrained, old trained, and old untrained subjects. Levels of HSP72, PRX5, and eNOS were significantly higher in quiescent muscle of older compared with younger subjects, irrespective of training status. 3-NT levels were elevated in muscles of the old untrained but not the old trained state, suggesting that lifelong training may reduce age-related macromolecule damage. SOD1, CAT, and HSP27 levels were not significantly different between groups. HSP27 content was upregulated in all groups studied postexercise. HSP72 content was upregulated to a greater extent in muscle of trained compared with untrained subjects postexercise, irrespective of age. In contrast to every other group, old untrained subjects failed to upregulate CAT postexercise. Aging was associated with a failure to upregulate SOD2 and a downregulation of PRX5 in muscle postexercise, irrespective of training status. In conclusion, lifelong training is unable to fully prevent the progression toward a more stressed muscular state as evidenced by increased HSP72, PRX5, and eNOS protein levels in quiescent muscle. Moreover, lifelong training preserves some (e.g., CAT) but not all (e.g., SOD2, HSP72, PRX5) of the adaptive redox-regulated responses after an acute exercise bout. Collectively, these data support many but not all of the findings from previous animal studies and suggest parallel aging effects in humans and mice at rest and after exercise that are not modulated by training status in human skeletal muscle.

Assessment of vitamin D concentration in non-supplemented professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function.

The current study implemented a two-part design to (1) assess the vitamin D concentration of a large cohort of non-vitamin D supplemented UK-based athletes and 30 age-matched healthy non-athletes and (2) to examine the effects of 5000 IU · day(-1) vitamin D(3) supplementation for 8-weeks on musculoskeletal performance in a placebo controlled trial. Vitamin D concentration was determined as severely deficient if serum 25(OH)D < 12.5 nmol · l(-1), deficient 12.5-30 nmol · l(-1) and inadequate 30-50 nmol · l(-1). We demonstrate that 62% of the athletes (38/61) and 73% of the controls (22/30) exhibited serum total 25(OH)D < 50 nmol · l(-1). Additionally, vitamin D supplementation increased serum total 25(OH)D from baseline (mean ± SD = 29 ± 25 to 103 ± 25 nmol · l(-1), P = 0.0028), whereas the placebo showed no significant change (53 ± 29 to 74 ± 24 nmol · l(-1), P = 0.12). There was a significant increase in 10 m sprint times (P = 0.008) and vertical-jump (P = 0.008) in the vitamin D group whereas the placebo showed no change (P = 0.587 and P = 0.204 respectively). The current data supports previous findings that athletes living at Northerly latitudes (UK = 53° N) exhibit inadequate vitamin D concentrations (<50 nmol · l(-1)). Additionally the data suggests that inadequate vitamin D concentration is detrimental to musculoskeletal performance in athletes. Future studies using larger athletic groups are now warranted.

Vascular endothelial growth factor and basic fibroblast growth factor in children with cyanotic congenital heart disease.

OBJECTIVE: Vascular endothelial growth factor and basic fibroblast growth factor are potent stimulators of angiogenesis. Children with cyanotic congenital heart disease often experience the development of widespread formation of collateral blood vessels, which may represent a form of abnormal angiogenesis. We undertook the present study to determine whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor and basic fibroblast growth factor. METHODS: Serum was obtained from 22 children with cyanotic congenital heart disease and 19 children with acyanotic heart disease during cardiac catheterization. Samples were taken from the superior vena cava, inferior vena cava, and a systemic artery. Vascular endothelial growth factor and basic fibroblast growth factor levels were measured in the serum from each of these sites by enzyme-linked immunosorbent assay. RESULTS: Vascular endothelial growth factor was significantly elevated in the superior vena cava (P =.04) and systemic artery (P =.02) but not in the inferior vena cava (P =.2) of children with cyanotic congenital heart disease compared to children with acyanotic heart disease. The mean vascular endothelial growth factor level, determined by averaging the means of all 3 sites, was also significantly elevated (P =.03). Basic fibroblast growth factor was only significantly elevated in the systemic artery (P =.02). CONCLUSION: Children with cyanotic congenital heart disease have elevated systemic levels of vascular endothelial growth factor. These findings suggest that the widespread formation of collateral vessels in these children may be mediated by vascular endothelial growth factor.

Thermal luminescence sensor for ground-path contamination detection.

A standoff method of detecting liquids on terrestrial and synthetic landscapes is presented. The interstitial liquid layers are identified through their unique molecular vibration modes in the 7.14-14.29-microm middle infrared (fingerprint) region of liberated thermal luminescence. Several seconds of 2.45-GHz beam exposure at 1.5 W cm(-1) is sufficient for detecting polydimethyl siloxane lightly wetting the soil through its fundamental Si-CH3 and Si-O-Si stretching modes in the fingerprint region. A detection window of thermal opportunity opens as the surface attains maximum thermal gradient following irradiation by the microwave beam. The contaminant is revealed inside this window by means of a simple difference-spectrum measurement. Our goal is to reduce the time needed for optimum detection of the contaminant's thermal spectrum to a subsecond exposure from a limited intensity beam.

Differential absorption mueller matrix spectroscopy and the infrared detection of crystalline organics.

The complete 16-element Mueller matrices for backscattering from amino acids, sugars, and other enantiomorphic compounds pressed into wafer form were measured at infrared wavelengths. For each compound a pair of CO(2) laser lines was selected from the 9.1-11.6-mum region such that one line excited an absorption band in the compound, whereas the other did not. It was observed that at least some of the matrix elements differed significantly depending on which of the two wavelengths was used in the measurement. We propose that a neural network pattern recognition system can be trained to detect the presence of specific compounds based on multiwavelength backscatter Mueller matrix measurements.

Patient satisfaction and the elderly.

There is considerable current interest in patient satisfaction surveys; among other things they are often used to measure quality in health care. However, there are many unresolved issues concerning them, including how they might best be conducted. Some have challenged their raison d'-etre, arguing that they rely on unproven assumptions -1; Williams, Soc. Sci. Med. 38, 509, 1994]. In this paper we examine some of these assumptions in the light of a recent study of elderly patients' experience of the District Nursing Service. In doing so we argue that users' capacity, or willingness, to evaluate health care services cannot be taken for granted; that patients may have few if any expectations on which to base an evaluation of the care they receive; that the sense of dependency that patients have on service providers can impact on expressions of satisfaction and that, outside the acute sector in particular, we need to take into account the varied nature of the relationships that emerge between patient and service providers. We also argue that elderly patients cannot be treated as consumers unproblematically. While they may be seen as an extreme example, we argue, nevertheless, that many of the issues raised are relevant to much wider populations. This has general implications for research and we suggest that appropriately chosen qualitative methods can provide a useful starting point in studies which aim to establish how, to what extent and whether patients evaluate health services.

The meaning of parenthood and couples' reactions to male infertility.

This paper reports findings from a postal survey of 205 couples belonging to the National Association for the Childless who saw their infertility as due to the male partner. Two self-report scales used in previous studies were administered to measure personal and social identity needs as a basis for parenthood (the Meaning of Parenthood scale), and emotional distress and marital problems. Endorsement of items on the Meaning of Parenthood (MOP) scale showed only small mean gender differences for each item and a consistent item rank order for men and women. Factor analysis confirmed that the scale tapped dimensions pertaining to social and personal identity needs. For women, distress was associated with ratings on the MOP scale which emphasized the link between femininity and motherhood, while for men distress was associated with ratings which emphasized masculinity and fatherhood. Implications of the results for further research and counselling in relation to male infertility are discussed.

Patient satisfaction studies: methodology, management and consumer evaluation.

Discusses how consumer evaluation studies of health-care services might be undertaken to provide valid assessments of consumer opinions and priorities, amenable to subsequent, effective management action. To do so, provides an account of the history of patient satisfaction surveys, presents a detailed examination of key examples, and discusses the well-documented strengths and weaknesses of this approach. Draws attention to recent critiques of survey methods and growing interest in qualitative research focusing on the rationale that the latter provides more useful data for managers. Argues that the search for a "best" consumer evaluation method is misplaced since appropriate methods should be determined by research objectives which themselves may vary. Points to existing analyses of relevant research which offer sound methodological guidelines and concludes by offering explicit suggestions for the future conduct of consumer evaluation research.

Male infertility and donor insemination: couples' decisions, reactions and counselling needs.

This paper reports findings of a postal survey of 205 couples belonging to the National Association for the Childless, whose infertility had been attributed to the male partner. Spontaneous resolution was seldom reported, but 36 couples had become parents by donor insemination (DI) and 28 through adoption. Almost a third of respondents had managed to resolve their childlessness. Although reasons for rejecting DI or preferring other options were offered by 60 couples, 125 had taken active steps towards it. Most of the 80 couples who had been counselled had found this helpful. Regardless of counselling, of the 76 couples who had considered whether or not to tell their children of their mode of conception, 56 (74%) stated that they had no intention of doing so. Quantitative indices from two self-report scales confirm that male infertility is commonly a source of distress, especially for the female partner. However, the data also suggest that this is not necessarily associated with chronic marital discord. Couples who had already decided for or against DI reported less distress than others. The need for mutual support may well be enhanced until the couple's quest for a child has been either achieved or abandoned.