Effect of a program of short bouts of exercise on bone health in adolescents involved in different sports: the PRO-BONE study protocol

This is the author accepted manuscript. The final version is available from BioMed Central via the DOI in this record.Background: Osteoporosis is a skeletal disease associated with high morbidity, mortality and increased economic costs. Early prevention during adolescence appears to be one of the most beneficial practices. Exercise is an effective approach for developing bone mass during puberty, but some sports may have a positive or negative impact on bone mass accrual. Plyometric jump training has been suggested as a type of exercise that can augment bone, but its effects on adolescent bone mass have not been rigorously assessed. The aims of the PRO-BONE study are to: 1) longitudinally assess bone health and its metabolism in adolescents engaged in osteogenic (football), non-osteogenic (cycling and swimming) sports and in a control group, and 2) examine the effect of a 9 month plyometric jump training programme on bone related outcomes in the sport groups. Methods/Design: This study will recruit 105 males aged 12-14 years who have participated in sport specific training for at least 3 hours per week during the last 3 years in the following sports groups: football (n=30), cycling (n=30) and swimming (n=30). An age-matched control group (n=15) that does not engage in these sports more than 3 hours per week will also be recruited. Participants will be measured on 5 occasions: 1) at baseline; 2) after 12 months of sport specific training where each sport group will be randomly allocated into two sub-groups: intervention group (sport + plyometric jump training) and sport group (sport only); 3) exactly after the 9 months of intervention; 4) 6 months following the intervention; 5) 12 months following the intervention. Body composition (dual energy X-ray absorptiometry, air displacement plethysmography and bioelectrical impedance), bone stiffness index (ultrasounds), physical activity (accelerometers), diet (24 h recall questionnaire), pubertal maturation (Tanner stage), physical fitness (cardiorespiratory and muscular) and biochemical markers of bone formation and resorption will be measured at each visit. Discussion: The PRO-BONE study is designed to investigate the impact of osteogenic and non-osteogenic sports on bone development in adolescent males during puberty, and how a plyometric jump training programme is associated with body composition parameters.European Union Seventh Framework Programme [FP7/2007-2013

Effect of maturational timing on bone health in male adolescent athletes engaged in different sports: The PRO-BONE study

This is the author accepted manuscript. the final version is available from Elsevier via the DOI in this recordObjectives: To describe differences in bone outcomes according to biological age in male athletes participating in osteogenic (OS) or non-osteogenic (NOS) sports. Design: Longitudinal (12-months). Methods: 104 adolescents (12–14 years) were measured at baseline and after 1y: OS group (n = 37 football or soccer players) and NOS group (n = 39 swimmers, n = 28 cyclists). Years from peak height velocity (PHV, −2 to +2) was used as a maturational landmark. Bone mineral content (BMC) was assessed using DXA. Hip structural analysis estimated cross-sectional area (CSA), cross-sectional moment of inertia (CSMI) and section modulus (Z) at the femoral neck (FN). Trabecular bone score (TBS) estimated lumbar spine (LS) texture. Quantitative ultrasound measured bone stiffness. Multilevel regression models adjusted by hours of training were fitted. Results: Compared to NOS, OS had significantly greater total body (less head) BMC from PHV to +2 years from PHV (from 9.5% to 11.3%, respectively); LS BMC from −1 years from PHV to PHV (from 9.8% to 9.9%); hip BMC (from 11.6% to 22.9%), FN BMC (from 12.0% to 15.9%), TBS (from 4.2% to 4.8%) and stiffness index (from 11.9% to 23.3%) from −1 years from PHV to +2 years from PHV; and CSA (from 8.4% to 18.8%), Z (from 5.5% to 22.9%) and CSMI (from 10.6% to 23.3%) from −2 years from PHV to +2 years from PHV. There was a significant trend for the between-group differences to increase with biological age except for LS BMC and TBS. Conclusions: These findings underline the differential bone response to different sports throughout the years surrounding PHV in male adolescent athletes. Clinical trial registration: ISRCTN17982776.European Union Seventh Framework ProgrammeUniversity of Castilla-La ManchaUniversity of Granad

The impact of sport participation on bone mass and geometry in adolescent males

Exercise is an effective approach for developing bone mass and adolescence is a key period to optimize bone health. However, sports specific training may have different effects on bone outcomes. This study examined the differences on bone outcomes between osteogenic (football) and non-osteogenic (swimming and cycling) sports and a control group in adolescent males. Methods: One hundred twenty one males (13.1±0.1 years) were measured: 41 swimmers, 37 footballers, 29 cyclists and 14 controls. Dual energy X-ray absorptiometry measured bone mineral density (BMD) and content (BMC) at lumbar spine, right and left hip and total body. Hip structural analysis evaluated bone geometry at the femoral neck. Quantitative ultrasound evaluated bone stiffness at both feet. Results: Footballers had significantly higher BMD at total body less head (7-9%), total hip (12-2%) and legs (7-11%) compared to all groups and significantly higher BMD at the femoral neck than controls (14%). Cyclists had higher BMD at the trochanter (10%) and BMC at the arms (10%) compared to controls. Geometrical analysis showed that footballers had significantly higher cross-sectional area (8-19%) compared to all groups, cross-sectional moment of inertia (17 %) compared to controls and section modulus compared to cyclists (11%) and controls (21%). Footballers had significantly higher bone stiffness compared to all groups (10-20%) at the dominant foot and (12-13%) at the nondominant foot compared to swimmers and controls. Conclusions: Adolescent male footballers exhibited higher bone density, geometry and stiffness compared to swimmers, cyclists and controls. Although swimmers and cyclists had higher bone outcomes compared to controls, these differences were not significant.The research leading to these results has received funding from the European Union Seventh Framework Programme ([FP7/2007-2013] under grant agreement n°. PCIG13-GA-2013-618496

Determinants of bone outcomes in adolescent athletes at baseline: the PRO-BONE study

This is the author accepted manuscript. The final version is available from the American College of Sports Medicine (ACSM) via the DOI in this record.Purpose: The determinants of areal bone mineral density (aBMD) and hip geometry 26 estimates in adolescent athletes are poorly understood. This study aimed to identify the 27 determinants of aBMD and hip geometry estimates in adolescent male athletes. Methods: 28 One hundred twenty one males (13.1±0.1 years) were measured: 41 swimmers, 37 29 footballers, 29 cyclists and 14 controls. Dual energy X-ray absorptiometry (DXA) measured 30 aBMD at lumbar spine, femoral neck (FN) and total body. Hip structural analysis evaluated 31 hip geometry estimates at the FN. Multiple linear regression examined the contribution of the 32 sports practised, stature, lean and fat mass, serum calcium and vitamin D, moderate to 33 vigorous physical activity (MVPA), vertical jump and cardiorespiratory fitness (CRF) with 34 aBMD and hip geometry estimates. Results: Region specific lean mass was the strongest 35 positive predictor of aBMD (β = 0.614 - 0.931) and football participation was the next 36 strongest predictor (β = 0.304 - 0.579). Stature (β = 0.235 - 0.380), fat mass (β = 0.189), 37 serum calcium (β = 0.103), serum vitamin D (β = 0.104 - 0.139) and vertical jump (β = 0.146 38 - 0.203) were associated with aBMD across various specific sites. All hip geometry estimates 39 were associated with lean mass (β = 0.370 - 0.568) and stature (β = 0.338 - 0.430). Football 40 participation was associated with hip cross-sectional area (β = 0.322) and MVPA (β = 0.140 - 41 0.142). CRF (β = 0.183 - 0.207) was associated with section modulus and cross-sectional 42 moment of inertia. Conclusions: Region specific lean mass is the strongest determinant of 43 aBMD and hip geometry estimates in adolescent male athletes. Football participation and 44 stature were important determinants for aBMD and hip geometry estimates while the 45 contribution of the other predictors was site specific.The research leading to these results has received funding from the European Union Seventh Framework Programme ([FP7/2007-2013] under grant agreement n°. PCIG13-GA-2013-61849

Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

Conducting retrospective impact analysis to inform a medical research charity’s funding strategies: The case of Asthma UK

© 2013 Hanney et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. METHODS: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. RESULTS: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. CONCLUSIONS: We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.This study was funded by Asthma UK

Does physical activity moderate the association between shorter leukocyte telomere length and incident coronary heart disease? Data from 54,180 UK Biobank participants

This is the final version. Available on open access from Springer via the DOI in this recordData availability: Data used in this project are available via application to UK Biobank.Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association between shorter leukocyte telomere length (LTL) relatively in the population sample and incident CHD. Data were from the UK Biobank participants with well-calibrated accelerometer data for at least 6.5 days (n = 54,180). Relative mean LTL at baseline (5-6 years prior to aPA assessment) was measured in T/S ratio, using a multiplex quantitative polymerase chain reaction (qPCR) technology, by comparing the amount of the telomere amplification product (T) to that of a single-copy gene (S). aPA measures included total number of events (at least 10-s continued physical activity > 32 milligravities [mg]), total volume, mean duration, mean intensity, and peak intensity of all events. LTL, aPA measures, and their interactions were associated with incident CHD (mean follow-up 6.8 years) using Cox proportional hazards models adjusting for covariates. Longer LTL (relative to the sample distribution) was associated with reduced incidence of CHD (adjusted hazard ratio [aHR] = 0.94 per standard deviation [SD] increase in LTL, [95% CI, 0.90 to 0.99], P = .010). Incidence of CHD was reduced by higher total volume of aPA (aHR = 0.82 per SD increase in LTL, [95% CI, 0.71 to 0.95], P = .010) but increased by higher total number of events (aHR = 1.11 per SD increase in LTL, [95% CI, 1.02 to 1.21], P = .020) after controlling for other aPA measures and covariates. However, none of the interactions between LTL and aPA measures was statistically significant (P = .171).National Institute of Nursing Research, National Institutes of Healt

Children, parents and pets exercising together (CPET) : exploratory randomised controlled trial

Levels of physical activity (PA) in UK children are much lower than recommended and novel approaches to its promotion are needed. The Children, Parents and Pets Exercising Together (CPET) study is the first exploratory randomised controlled trial (RCT) to develop and evaluate an intervention aimed at dog-based PA promotion in families. CPET aimed to assess the feasibility, acceptability and potential efficacy of a theory-driven, family-based, dog walking intervention for 9-11 year olds

The mode of school transportation in pre-pubertal children does not influence the accrual of bone mineral or the gain in bone size - two year prospective data from the paediatric osteoporosis preventive (POP) study

<p>Abstract</p> <p>Background</p> <p>Walking and cycling to school are one source of regular physical activity. The aim of this two years observational study in pre-pubertal children was to evaluate if walking and cycling to school was associated with higher total amount of physical activity and larger gain in bone mineral content (BMC) and bone width than when going by car or bus.</p> <p>Methods</p> <p>133 boys and 99 girls aged 7-9 years were recruited to the Malmö Prospective Paediatric Osteoporosis Prevention (POP) study. BMC (g) was measured by dual X-ray absorptiometry (DXA) in total body, lumbar spine (L2-L4) and femoral neck (FN) at baseline and after 24 months. Bone width was measured in L2-L4 and FN. Skeletal changes in the 57 boys and 48 girls who consistently walked or cycled to school were compared with the 24 boys and 17 girls who consistently went by bus or car. All children remained in Tanner stage I. Level of everyday physical activity was estimated by accelerometers worn for four consecutive days and questionnaires. Comparisons were made by independent student's t-tests between means and Fisher's exact tests. Analysis of covariance (ANCOVA) was used to adjust for group differences in age at baseline, duration of organized physical activity, annual changes in length and BMC or bone width if there were differences in these traits at baseline.</p> <p>Results</p> <p>After the adjustments, there were no differences in the annual changes in BMC or bone width when comparing girls or boys who walked or cycled to school with those who went by car or bus. Furthermore, there were no differences in the levels of everyday physical activity objectively measured by accelerometers and all children reached above the by the United Kingdom Expert Consensus Group recommended level of 60 minutes moderate to vigorous physical activity per day.</p> <p>Conclusion</p> <p>A physical active transportation to school for two years is in pre-pubertal children not associated with a higher accrual of BMC or bone width than a passive mode of transportation, possibly due to the fact that the everyday physical activity in these pre-pubertal children, independent of the mode of school transportation, was high.</p

Pichia pastoris versus Saccharomyces cerevisiae:a case study on the recombinant production of human granulocyte-macrophage colony-stimulating factor

BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is a glycoprotein that has been approved by the FDA for the treatment of neutropenia and leukemia in combination with chemotherapies. Recombinant hGM-CSF is produced industrially using the baker's yeast, Saccharomyces cerevisiae, by large-scale fermentation. The methylotrophic yeast, Pichia pastoris, has emerged as an alternative host cell system due to its shorter and less immunogenic glycosylation pattern together with higher cell density growth and higher secreted protein yield than S. cerevisiae. In this study, we compared the pipeline from gene to recombinant protein in these two yeasts. RESULTS: Codon optimization in silico for both yeast species showed no difference in frequent codon usage. However, rhGM-CSF expressed from S. cerevisiae BY4742 showed a significant discrepancy in molecular weight from those of P. pastoris X33. Analysis showed purified rhGM-CSF species with molecular weights ranging from 30 to more than 60 kDa. Fed-batch fermentation over 72 h showed that rhGM-CSF was more highly secreted from P. pastoris than S. cerevisiae (285 and 64 mg total secreted protein/L, respectively). Ion exchange chromatography gave higher purity and recovery than hydrophobic interaction chromatography. Purified rhGM-CSF from P. pastoris was 327 times more potent than rhGM-CSF from S. cerevisiae in terms of proliferative stimulating capacity on the hGM-CSF-dependent cell line, TF-1. CONCLUSION: Our data support a view that the methylotrophic yeast P. pastoris is an effective recombinant host for heterologous rhGM-CSF production