524 research outputs found

    Empowering youth sport environments: Implications for daily moderate-to-vigorous physical activity and adiposity

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    AbstractBackgroundEvidence suggests involvement in youth sport does not guarantee daily guidelines for moderate-to-vigorous physical activity (MVPA) are met, and participation may not mitigate the risks associated with physical inactivity. The need to promote higher habitual MVPA engagement amongst children active in the youth sport context has therefore been underlined. Framed by self-determination theory, the aim of the present study was to examine the implications of the motivational climate created in youth sport, for children's daily engagement in MVPA and associated adiposity. Specifically, we sought to test a motivational sequence in which children's perceptions of an empowering coach-created motivational climate were related to autonomous and controlled motivation, which in turn predicted sport-related enjoyment. Finally, enjoyment is assumed to predict accelerometer assessed daily MVPA and, following this, adiposity.MethodsMale and female youth sport participants aged 9–16 years (n = 112) completed multi-section questionnaires assessing their perceptions of the motivational climate created in youth sport (i.e., autonomy supportive, task involving, socially supportive), autonomous and controlled motivation, and sport-related enjoyment. Daily MVPA engagement was determined via 7 days of accelerometry. Percent body fat (BF%) was estimated using bio-electrical impedance analysis.ResultsPath analysis revealed perceptions of an empowering motivational climate positively predicted players' autonomous motivation, and in turn, sport-related enjoyment. Enjoyment was also significantly negatively related to players' BF%, via a positive association with daily MVPA.ConclusionFostering more empowering youth sport environments may hold implications for the prevention of excess adiposity, through encouraging higher habitual MVPA engagement. Findings may inform the optimal design of youth sport settings for MVPA promotion, and contribute towards associated healthy weight maintenance amongst youth active in this context. Longitudinal and intervention studies are required to confirm these results

    Bifidobacterium breve with α-Linolenic Acid and Linoleic Acid Alters Fatty Acid Metabolism in the Maternal Separation Model of Irritable Bowel Syndrome

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    peer-reviewedThe aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (109 microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.This work was supported by the Science Foundation of Ireland – funded Centre for Science, Engineering and Technology, the Alimentary Pharmabiotic Centre

    The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing

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    Kinetoplastid parasites—trypanosomes and leishmanias—infect millions of humans and cause economically devastating diseases of livestock, and the few existing drugs have serious deficiencies. Benzoxaborole-based compounds are very promising potential novel anti-trypanosomal therapies, with candidates already in human and animal clinical trials. We investigated the mechanism of action of several benzoxaboroles, including AN7973, an early candidate for veterinary trypanosomosis. In all kinetoplastids, transcription is polycistronic. Individual mRNA 5'-ends are created by trans splicing of a short leader sequence, with coupled polyadenylation of the preceding mRNA. Treatment of Trypanosoma brucei with AN7973 inhibited trans splicing within 1h, as judged by loss of the Y-structure splicing intermediate, reduced levels of mRNA, and accumulation of peri-nuclear granules. Methylation of the spliced leader precursor RNA was not affected, but more prolonged AN7973 treatment caused an increase in S-adenosyl methionine and methylated lysine. Together, the results indicate that mRNA processing is a primary target of AN7973. Polyadenylation is required for kinetoplastid trans splicing, and the EC50 for AN7973 in T. brucei was increased three-fold by over-expression of the T. brucei cleavage and polyadenylation factor CPSF3, identifying CPSF3 as a potential molecular target. Molecular modeling results suggested that inhibition of CPSF3 by AN7973 is feasible. Our results thus chemically validate mRNA processing as a viable drug target in trypanosomes. Several other benzoxaboroles showed metabolomic and splicing effects that were similar to those of AN7973, identifying splicing inhibition as a common mode of action and suggesting that it might be linked to subsequent changes in methylated metabolites. Granule formation, splicing inhibition and resistance after CPSF3 expression did not, however, always correlate and prolonged selection of trypanosomes in AN7973 resulted in only 1.5-fold resistance. It is therefore possible that the modes of action of oxaboroles that target trypanosome mRNA processing might extend beyond CPSF3 inhibition

    Microstructural abnormalities in white and gray matter in obese adolescents with and without type 2 diabetes

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    Aims/hypotheses In adults, type 2 diabetes and obesity have been associated with structural brain changes, even in the absence of dementia. Some evidence suggested similar changes in adolescents with type 2 diabetes but comparisons with a non-obese control group have been lacking. The aim of the current study was to examine differences in microstructure of gray and white matter between adolescents with type 2 diabetes, obese adolescents and healthy weight adolescents. Methods Magnetic resonance imaging data were collected from 15 adolescents with type 2 diabetes, 21 obese adolescents and 22 healthy weight controls. Volumetric differences in the gray matter between the three groups were examined using voxel based morphology, while tract based spatial statistics was used to examine differences in the microstructure of the white matter. Results Adolescents with type 2 diabetes and obese adolescents had reduced gray matter volume in the right hippocampus, left putamen and caudate, bilateral amygdala and left thalamus compared to healthy weight controls. Type 2 diabetes was also associated with significant regional changes in fractional anisotropy within the corpus callosum, fornix, left inferior fronto-occipital fasciculus, left uncinate, left internal and external capsule. Fractional anisotropy reductions within these tracts were explained by increased radial diffusivity, which may suggest demyelination of white matter tracts. Mean diffusivity and axial diffusivity did not differ between the groups. Conclusion/interpretation Our data shows that adolescent obesity alone results in reduced gray matter volume and that adolescent type 2 diabetes is associated with both white and gray matter abnormalities

    Quantitative MRI brain in congenital adrenal hyperplasia: in vivo assessment of the cognitive and structural impact of steroid hormones

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    Abstract Context Brain white matter hyper-intensities are seen on routine clinical imaging in 46% of adults with congenital adrenal hyperplasia (CAH). The extent and functional relevance of these abnormalities have not been studied using quantitative MRI analysis. Objective To examine white matter microstructure, neural volumes and CNS metabolites in CAH due to 21-hydroxylase deficiency (21OHD) and to determine whether identified abnormalities are associated with cognition, glucocorticoid and androgen exposure. Design, setting and participants A cross-sectional study at a tertiary hospital including 19 females (18-50 years) with 21OHD and 19 age-matched healthy females. Main outcome measure Recruits underwent cognitive assessment and brain imaging including; diffusion weighted imaging of white matter, T1-weighted volumetry and magnetic resonance spectroscopy for neural metabolites. We evaluated white matter microstructure using tract-based spatial statistics. We compared cognitive scores, neural volumes and metabolites between groups and relationships between glucocorticoid exposure, MRI and neurologic outcomes. Results Patients with 21OHD had widespread reductions in white matter structural integrity, reduced volumes of right hippocampus, bilateral thalami, cerebellum and brainstem, and reduced mesial temporal lobe total choline content. Working memory, processing speed, and digit span and matrix reasoning scores were reduced in patients with 21OHD, despite similar education and intelligence to controls. 21OHD individuals exposed to higher glucocorticoid doses had greater abnormalities in white matter microstructure and cognitive performance. Conclusion For the first time we demonstrate that 21OHD and current glucocorticoid replacement regimens have a profound impact on brain morphology and function. If reversible, these CNS markers represent a potential target for treatment

    Treatment adherence and BMI reduction are key predictors of HbA1c one year after diagnosis of childhood Type 2 Diabetes in UK

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    Background/Objective: Type 2 Diabetes (T2DM) is increasing in childhood especially among females and South-Asians. Our objective was to report outcomes from a national cohort of children and adolescents with T2DM 1 year following diagnosis. Methods: Clinician reported, 1-year follow-up of a cohort of children (<17 years) diagnosed with T2DM reported through the British Paediatric Surveillance Unit (BPSU) (April 2015-April 2016). Results: One hundred (94%) of 106 baseline cases were available for review. Of these, five were lost to follow up and one had a revised diagnosis. Mean age at follow up was 15.3 years. Median BMI standard deviation scores (SDS) was 2.81 with a decrease of 0.13 SDS over a year. HbA1c <48 mmol/mol (UK target) was achieved in 38.8%. logHbA1c was predicted by clinician reported compliance and attendance concerns (β = 0.12, P = <0.0001) and change in body mass index (BMI) SDS at 1-year (β = 0.13, P=0.007). In over 50%, clinicians reported issues with compliance and attendance. Mean clinic attendance was 75%. Metformin was the most frequently used treatment at baseline (77%) and follow-up (87%). Microalbuminuria prevalence at 1-year was 16.4% compared to 4.2% at baseline and was associated with a higher HbA1c compared to those without microalbuminuria (60 vs 49 mmol/mol, P = 0.03). Conclusions: Adherence to treatment and a reduction in BMI appear key to better outcomes a year after T2DM diagnosis. Retention and clinic attendance are concerning. The prevalence of microalbuminuria has increased 4-fold in the year following diagnosis and was associated with higher HbA1c

    EURO-WABB: an EU rare diseases registry for Wolfram syndrome, Alström syndrome and Bardet-Biedl syndrome

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    Background: Wolfram, Alström and Bardet-Biedl (WABB) syndromes are rare diseases with overlapping features of multiple sensory and metabolic impairments, including diabetes mellitus, which have caused diagnostic confusion. There are as yet no specific treatments available, little or no access to well characterized cohorts of patients, and limited information on the natural history of the diseases. We aim to establish a Europe-wide registry for these diseases to inform patient care and research. Methods: EURO-WABB is an international multicenter large-scale observational study capturing longitudinal clinical and outcome data for patients with WABB diagnoses. Three hundred participants will be recruited over 3 years from different sites throughout Europe. Comprehensive clinical, genetic and patient experience data will be collated into an anonymized disease registry. Data collection will be web-based, and forms part of the project's Virtual Research and Information Environment (VRIE). Participants who haven't undergone genetic diagnostic testing for their condition will be able to do so via the project. Conclusions: the registry data will be used to increase the understanding of the natural history of WABB diseases, to serve as an evidence base for clinical management, and to aid the identification of opportunities for intervention to stop or delay the progress of the disease. The detailed clinical characterisation will allow inclusion of patients into studies of novel treatment interventions, including targeted interventions in small scale open label studies; and enrolment into multi-national clinical trials. The registry will also support wider access to genetic testing, and encourage international collaborations for patient benefit

    Untangling the drivers of energy reduction in the UK productive sectors: Efficiency or offshoring?

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    The UK has been one of the few countries that has successfully decoupled final energy consumption from economic growth over the past 15 years. This study investigates the drivers of final energy consumption in the UK productive sectors between 1997 and 2013 using a decomposition analysis that incorporates two novel features. Firstly, it investigates to what extent changes in thermodynamic efficiency have contributed to overall changes in sectoral energy intensities. Secondly, it analyses how much of the structural change in the UK economy is driven by the offshoring of energy-intensive production overseas. The results show that energy intensity reductions are the strongest factor reducing energy consumption. However, only a third of the energy savings from energy intensity reductions can be attributed to reductions in thermodynamic efficiency with re- ductions in the exergy intensity of production making up the reminder. In addition the majority of energy savings from structural change are a result of offshoring, which constitutes the second biggest factor reducing energy consumption. In recent years the contributions of all decomposition factors have been declining with very little change in energy consumption after 2009. This suggests that a return to the strong reductions in energy consumption observed between 2001 and 2009 in the UK productive sectors should not be taken for granted. Given that further reductions in UK final energy consumption are needed to achieve global targets for climate change mitigation, additional policy interventions are needed. Such policies should adopt a holistic approach, taking into account all sectors in the UK economy as well as the relationship between the structural change in the UK and in the global supply chains delivering the goods and service for consumption and investment in the UK
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