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

Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling

Gallium-68 (68Ga) is a positron-emitting isotope used for clinical PET imaging of peptide receptor expression. 68Ga radiopharmaceuticals used in molecular PET imaging consist of disease-targeting biomolecules tethered to chelators that complex 68Ga3+. Ideally, the chelator will rapidly, quantitatively and stably coordinate 68Ga3+ at room temperature, near neutral pH and low chelator concentration, allowing for simple routine radiopharmaceutical formulation. Identification of chelators that fulfil these requirements will facilitate development of kit-based 68Ga radiopharmaceuticals. Herein the reaction of a range of widely used macrocyclic and acyclic chelators with 68Ga3+ is reported. Radiochemical yields have been measured under conditions of varying chelator concentrations, pH (3.5 and 6.5) and temperature (25 and 90 °C). These chelators are: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7-triazacyclononane macrocycles substituted with phosphonic (NOTP) and phosphinic (TRAP) groups at the amine, bis(2-hydroxybenzyl)ethylenediaminediacetic acid (HBED), a tris(hydroxypyridinone) containing three 1,6-dimethyl-3-hydroxypyridin-4-one groups (THP) and the hexadentate tris(hydroxamate) siderophore desferrioxamine-B (DFO). Competition studies have also been undertaken to assess relative complexation efficiencies of each chelator for 68Ga3+ under different pH and temperature conditions. Performing radiolabelling reactions at pH 6.5, 25 °C and 5–50 μM chelator concentration resulted in near quantitative radiochemical yields for all chelators, except DOTA. Radiochemical yields either decreased or were not substantially improved when the reactions were undertaken at lower pH or at higher temperature, except in the case of DOTA. THP and DFO were the most effective 68Ga3+ chelators at near-neutral pH and 25 °C, rapidly providing near-quantitative radiochemical yields at very low chelator concentrations. NOTP and HBED were only slightly less effective under these conditions. In competition studies with all other chelators, THP demonstrated highest reactivity for 68Ga3+ complexation under all conditions. These data point to THP possessing ideal properties for rapid, one-step kit-based syntheses of 68Ga-biomolecules for molecular PET imaging. LC-MS and 1H, 13C{1H} and 71Ga NMR studies of HBED complexes of Ga3+ showed that under the analytical conditions employed in this study, multiple HBED-bound Ga complexes exist. X-ray diffraction data indicated that crystals isolated from these solutions contained octahedral [Ga(HBED)(H2O)], with HBED coordinated in a pentadentate N2O3 mode, with only one phenolic group coordinated to Ga3+, and the remaining coordination site occupied by a water molecule

ArteFill® Permanent Injectable for Soft Tissue Augmentation: I. Mechanism of Action and Injection Techniques

After more than 25 years of research and development, in October 2006 ArteFill® became the first and only permanent injectable wrinkle filler to receive FDA approval. ArteFill is a third-generation polymeric microsphere-based filler, following its predecessor Artecoll®, which was marketed outside the United States between 1994 and 2006. ArteFill is approved for the correction of nasolabial folds and has been used in over 15,000 patients since its U.S. market introduction in February 2007. No serious side effects have been reported to date according to the FDA’s MAUDE reporting database. ArteFill consists of polymethylmethacrylate (PMMA) microspheres (20% by volume), 30–50 μm in diameter, suspended in 3.5% bovine collagen solution (80% by volume) and 0.3% lidocaine. The collagen carrier is absorbed within 1 month after injection and completely replaced by the patient’s own connective tissue within 3 months. Each cc of ArteFill contains approximately six million microspheres and histological studies have shown that long-term wrinkle correction consists of 80% of the patient’s own connective tissue and 20% microspheres. The standard injection technique is subdermal tunneling that delivers a strand of ArteFill at the dermal–subdermal junction. This strand beneath a wrinkle or fold acts like a support structure that protects against further wrinkling and allows the diminished thickness of the dermis to recover to its original thickness

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

Using Rasch analysis to form plausible health states amenable to valuation: the development of CORE-6D from CORE-OM in order to elicit preferences for common mental health problems

Purpose: To describe a new approach for deriving a preference-based index from a condition specific measure that uses Rasch analysis to develop health states. Methods: CORE-OM is a 34-item instrument monitoring clinical outcomes of people with common mental health problems. CORE-OM is characterised by high correlation across its domains. Rasch analysis was used to reduce the number of items and response levels in order to produce a set of unidimensionally-behaving items, and to generate a credible set of health states corresponding to different levels of symptom severity using the Rasch item threshold map. Results: The proposed methodology resulted in the development of CORE-6D, a 2-dimensional health state description system consisting of a unidimensionally-behaving 5-item emotional component and a physical symptom item. Inspection of the Rasch item threshold map of the emotional component helped identify a set of 11 plausible health states, which, combined with the physical symptom item levels, will be used for the valuation of the instrument, resulting in the development of a preference-based index. Conclusions: This is a useful new approach to develop preference-based measures where the domains of a measure are characterised by high correlation. The CORE-6D preference-based index will enable calculation of Quality Adjusted Life Years in people with common mental health problems

A mobile phone app to support young people in making shared decisions in therapy (Power Up): study protocol

Background: Evidence suggests that young people want to be active participants in their care and involved in decisions about their treatment. However, there is a lack of digital shared decision-making tools available to support young people in child and adolescent mental health services (CAMHS). Objective: The primary aim of this paper is to present the protocol of a feasibility trial for Power Up, a mobile phone app to empower young people in CAMHS to make their voices heard and participate in decisions around their care. Methods: In the development phase, 30 young people, parents, and clinicians will take part in interviews and focus groups to elicit opinions on an early version of the app. In the feasibility testing phase, 60 young people from across 7 to 10 London CAMHS sites will take part in a trial looking at the feasibility and acceptability of measuring the impact of Power Up on shared decision making. Results: Data collection for the development phase ended in December 2016. Data collection for the feasibility testing phase will end in December 2017. Conclusions: Findings will inform the planning of a cluster controlled trial and contribute to the development and implementation of a shared decision-making app to be integrated into CAMHS

Patient information leaflets (PILs) for UK randomised controlled trials : a feasibility study exploring whether they contain information to support decision making about trial participation

Peer reviewedPublisher PD

Disinfection of football protective equipment using chlorine dioxide produced by the ICA TriNova system

<p>Abstract</p> <p>Backround</p> <p>Community-associated methicillin-resistant <it>Staphylococcus aureus </it>outbreaks have occurred in individuals engaged in athletic activities such as wrestling and football. Potential disease reduction interventions include the reduction or elimination of bacteria on common use items such as equipment. Chlorine dioxide has a long history of use as a disinfectant. The purpose of this investigation was to evaluate the ability of novel portable chlorine dioxide generation devices to eliminate bacteria contamination of helmets and pads used by individuals engaged in football.</p> <p>Methods</p> <p>In field studies, the number of bacteria associated with heavily used football helmets and shoulder pads was determined before and after overnight treatment with chlorine dioxide gas. Bacteria were recovered using cotton swabs and plated onto trypticase soy agar plates. In laboratory studies, <it>Staphylococcus aureus </it>was applied directly to pads. The penetration of bacteria into the pads was determined by inoculating agar plates with portions of the pads taken from the different layers of padding. The ability to eliminate bacteria on the pad surface and underlying foam layers after treatment with chlorine dioxide was also determined.</p> <p>Results</p> <p>Rates of recovery of bacteria after treatment clearly demonstrated that chlorine dioxide significantly (p < 0.001) reduce and eliminated bacteria found on the surface of pads. For example, the soft surface of shoulder pads from a university averaged 2.7 × 10³recoverable bacteria colonies before chlorine dioxide treatment and 1.3 × 10²recoverable colonies after treatment. In addition, the gas was capable of penetrating the mesh surface layer and killing bacteria in the underlying foam pad layers. Here, 7 × 10³to 4.5 × 10³laboratory applied <it>S. aureus </it>colonies were recovered from underlying layers before treatment and 0 colonies were present after treatment. Both naturally occurring bacteria and <it>S. aureus </it>were susceptible to the treatment process.</p> <p>Conclusion</p> <p>Results of this study have shown that chlorine dioxide can easily and safely be used to eliminate bacteria contamination of protective pads used by football players. This could serve to reduce exposure to potential pathogens such as the methicillin-resistant <it>Staphylococcus aureus </it>among this group of individuals.</p

A Comparative Approach Linking Molecular Dynamics of Altered Peptide Ligands and MHC with In Vivo Immune Responses

The recognition of peptide in the context of MHC by T lymphocytes is a critical step in the initiation of an adaptive immune response. However, the molecular nature of the interaction between peptide and MHC and how it influences T cell responsiveness is not fully understood.We analyzed the immunological consequences of the interaction of MHC class II (I-Au) restricted 11-mer peptides of myelin basic protein with amino acid substitutions at position 4. These mutant peptides differ in MHC binding affinity, CD4+ T cell priming, and alter the severity of peptide-induced experimental allergic encephalomyelitis. Using molecular dynamics, a computational method of quantifying intrinsic movements of proteins at high resolution, we investigated conformational changes in MHC upon peptide binding. We found that irrespective of peptide binding affinity, MHC deformation appears to influence costimulation, which then leads to effective T cell priming and disease induction. Although this study compares in vivo and molecular dynamics results for three altered peptide ligands, further investigation with similar complexes is essential to determine whether spatial rearrangement of peptide-MHC and costimulatory complexes is an additional level of T cell regulation

AKT1 Loss Correlates with Episomal HPV16 in Vulval Intraepithelial Neoplasia

Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma–HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN) and vulval squamous cell carcinoma (vSCC). We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy