The muscle metabolome differs between healthy and frail older adults

Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy older and frail older subjects to determine the effect of age and frailty on the metabolic signature of skeletal muscle tissue. In addition, the effects of prolonged whole-body resistance-type exercise training on the muscle metabolome of older subjects were examined. The baseline metabolome was measured in muscle biopsies collected from 30 young, 66 healthy older subjects and 43 frail older subjects. Follow-up samples from frail older (24 samples) and healthy older subjects (38 samples) were collected after 6 months of prolonged resistance-type exercise training. Young subjects were included as a reference If thisgroup. Primary differences in skeletal muscle metabolite levels between young and healthy older subjects were related to mitochondrial function, muscle fiber type, and tissue turnover. Similar differences were observed when comparing frail older subjects with healthy older subjects at baseline. Prolonged resistance-type exercise training resulted in an adaptive response of amino acid metabolism, especially reflected in branched chain amino acids and genes related to tissue remodeling. The effect of exercise training on branched-chain amino acid-derived acylcarnitines in older subjects points to a downward shift in branched-chain amino acid catabolism upon training. We observed only modest correlations between muscle and plasma metabolite levels, which pleads against the use of plasma metabolites as a direct read-out of muscle metabolism and stresses the need for direct assessment of metabolites in muscle tissue biopsies

A comparison of sexual behaviour and attitudes of healthy adolescents in a Danish high school in 1982, 1996, and 2001

AIM: To assess changes in sexual behaviour among students at a high school in Denmark from 1982 to 2001. METHODS: An anonymous self-administered questionnaire was used to compare data from three identical cross-sectional surveys performed in 1982, 1996, and 2001. RESULTS: Girls: More girls reported their first sexual intercourse before their 16th birthday in 2001 (42%) than in 1996 (29%) In 1982 it was also 42% (Chi-square for trend: p = 0.003). Fewer girls with no regular partner used condoms for their personal protection in 2001 (2%) than in 1996 (9%) and 1982 (0%) (Chi-square for trend p = 0.016). The proportion of girls with no regular partner who considered protection from sexually transmitted disease important for their choice of contraception was 39% in 2001 compared with 71% in 1996 and only 10% in 1982 (Chi-square for trend: p < 0.0001). Boys: More boys reported sexual debut before their 16th birthday in 2001 (40%) than in 1996 (37%) and 1982 (24%) (Chi-square for trend: p = 0.023). For boys with no regular partner, condom was preferred for personal protection by 85% in 2001, 91% in 1996 and 61% in 1982 (Chi-square for trend p = 0.007). Protection against sexually transmitted infection declined, especially among boys with no regular partner, from 51% in 2001 to 72% in 1996 and 21% in 1982 Chi-square for trend: p < 0.0001). The tendency towards earlier sexual debut and less use of safe sex practices to protect against sexually transmitted infections (STI) was accompanied by a rise in the number of detected STIs during this period. CONCLUSIONS: The period from 1982 to 1996 during which sexual attitudes were directed toward safer sex seems to have given way to a reverse trend in the period from 1996 to 2001. These findings may have significant implications for health care authorities organising preventive strategies for healthy adolescents

Harmful lifestyles' clustering among sexually active in-school adolescents in Zambia

<p>Abstract</p> <p>Background</p> <p>HIV is a leading cause of morbidity and mortality in Zambia. Like many other African nations with high HIV burden, heterosexual intercourse is the commonest mode of HIV spread. The estimation of prevalence and factors associated with sexual intercourse among in-school adolescents has potential to inform public health interventions aimed at reducing the burden of sex-related diseases in Zambia.</p> <p>Methods</p> <p>We carried out secondary analysis of the Zambia Global School-Based Health Survey (GSHS) 2004; a cross sectional survey that aims to study health-related behaviors among in-school adolescents. We estimated frequencies of relevant socio-demographic variables. The associations between selected explanatory variables and self-reported history of sexual intercourse within the last 12 months were assessed using logistic regression analysis.</p> <p>Results</p> <p>Data from 2136 in-school adolescents who participated in the Zambia Global School-Based Health Survey of 2004 were available for analysis. Out of these respondents, 13.4% reported that they had sexual intercourse in the past 12 months prior to the survey; 16.4% and 9.7% among males and females respectively. In multivariable logistic regression analysis, with age less than 15 years as the referent the adjusted odds ratio (AOR) of having engaged in sexual intercourse in adolescents of age 15 years, and those aged 16 years or more were 1.06 (95% CI 1.03–1.10) and 1.74 (95% 1.70–1.79) respectively. Compared to adolescents who had no close friends, adolescents who had one close friend were more likely to have had sexual intercourse, AOR = 1.28 (95% CI 1.24–1.32). Compared to adolescents who were not supervised by their parents, adolescents who were rarely or sometimes supervised by their parents were likely to have had sexual intercourse, and adolescents who were most of the time/always supervised by their parents were less likely to have had sexual intercourse; AORs 1.26 (95% CI 1.23–1.26) and 0.92 (95% CI 0.90–0.95) respectively. Compared to adolescents who did not smoke dagga, adolescents who smoked dagga 1 or 2 times, and those who smoked dagga 3 or more times in their lifetime were 70% and 25% more likely to have had sexual intercourse, respectively. Adolescents who drank alcohol in 1 or 2 days, and those who took alcohol in 3 or more days in a month preceding the survey were 12% and 9% more likely to have had sexual intercourse, respectively, compared to adolescents who did not drink alcohol in the 30 days prior to the survey. Furthermore, adolescents who had been drunk 1 or 2 times, and who had been drunk 3 or more times in a life time were 14% and 13% more likely to have had sexual intercourse compared to those who have never been drunk in their lifetime.</p> <p>Conclusion</p> <p>We identified a constellation of potentially harmful behaviours among adolescents in Zambia. Public health interventions aimed at reducing prevalence of sexual intercourse may be designed and implemented in a broader sense having recognized that sexually active adolescents may also be exposed to other problem behaviours.</p

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome

TINS, Target Immobilized NMR Screening: An Efficient and Sensitive Method for Ligand Discovery

SummaryWe propose a ligand screening method, called TINS (target immobilized NMR screening), which reduces the amount of target required for the fragment-based approach to drug discovery. Binding is detected by comparing 1D NMR spectra of compound mixtures in the presence of a target immobilized on a solid support to a control sample. The method has been validated by the detection of a variety of ligands for protein and nucleic acid targets (KD from 60 to 5000 μM). The ligand binding capacity of a protein was undiminished after 2000 different compounds had been applied, indicating the potential to apply the assay for screening typical fragment libraries. TINS can be used in competition mode, allowing rapid characterization of the ligand binding site. TINS may allow screening of targets that are difficult to produce or that are insoluble, such as membrane proteins

Strong quasiconvexity, stability, and lower relative divergence in right-angled Artin groups

Let $\Gamma$ be a simplicial, finite, connected graph such that $\Gamma$ does not decompose as a nontrivial join. We prove that two notions of strong quasiconvexity and stability are equivalent in the right-angled Artin group $A_\Gamma$ (except for the case of finite index subgroups). We also characterize non-trivial strongly quasiconvex subgroups of infinite index in $A_\Gamma$ (i.e. non-trivial stable subgroups in $A_\Gamma$) by quadratic lower relative divergence. These results strengthen the work of Koberda-Mangahas-Taylor on characterizing purely loxodromic subgroups of right-angled Artin groups.Comment: This article has been subsumed by the preprint arXiv:1707.0558

Weight loss moderately affects the mixed meal challenge response of the plasma metabolome and transcriptome of peripheral blood mononuclear cells in abdominally obese subjects

Introduction: The response to dietary challenges has been proposed as a more accurate measure of metabolic health than static measurements performed in the fasted state. This has prompted many groups to explore the potential of dietary challenge tests for assessment of diet and lifestyle induced shifts in metabolic phenotype. Objectives: We examined whether the response to a mixed-meal challenge could provide a readout for a weight loss (WL)-induced phenotype shift in abdominally obese male subjects. The underlying assumption of a mixed meal challenge is that it triggers all aspects of phenotypic flexibility and provokes a more prolonged insulin response, possibly allowing for better differentiation between individuals. Methods: Abdominally obese men (n = 29, BMI = 30.3 ± 2.4 kg/m2) received a mixed-meal challenge prior to and after an 8-week WL or no-WL control intervention. Lean subjects (n = 15, BMI = 23.0 ± 2.0 kg/m2) only received the mixed meal challenge at baseline to have a benchmark for WL-induced phenotype shifts. Results: Levels of several plasma metabolites were significantly different between lean and abdominally obese at baseline as well as during postprandial metabolic responses. Genes related to oxidative phosphorylation in peripheral blood mononuclear cells (PBMCs) were expressed at higher levels in abdominally obese subjects as compared to lean subjects at fasting, which was partially reverted after WL. The impact of WL on the postprandial response was modest, both at the metabolic and gene expression level in PBMCs. Conclusion: We conclude that mixed-meal challenges are not necessarily superior to measurements in the fasted state to assess metabolic health. Furthermore, the mechanisms accounting for the observed differences between lean and abdominally obese in the fasted state are different from those underlying the dissimilarity observed during the postprandial response