The effect of anabolic-androgenic hormones on postprandial triglyceridaemia and lipoprotein profiles in man

It has been hypothesised that endogenous testosterone and AAS may predispose humans to premature CHD. However, there is no direct evidence to link these hormones with a greater prevalence of premature CHD. The aim of this thesis was to better describe atherosclerotic risk associated with these hormones by clarifying their effect on additional risk factors for premature atherosclerosis. Little is known about the effect of testosterone and AAS on 'atherogenic dyslipidaemia', a phenotype characterised by elevated postprandial triglyceridaemia, small dense LDL and a low HDLC concentration, which confers a high risk of CHD. Accordingly, the magnitude of postprandial triglyceridaemia, LDL and HDL particle size, and LDLC, HDLC and Lp(a) concentration were compared in male (n=9) and female (n=3) bodybuilders after self administration of AAS for 5-6 weeks (ON cycle) and again after a 4-6 week 'washout' period (OFF cycle), and in normal males (T) (n=10) before and during a reversible suppression of endogenous testosterone, induced using a GnRH agonist (triptorelin), and in a control group (C) (n=8). Lipoprotein size was assessed by gradient gel electrophoresis (GGE), lipoprotein concentrations by immuno and enzymatic assay, and postprandial triglyceridaemia by a standardised oral fat tolerance test (65g/m² ). HDLC decreased in male bodybuilders (0.94±0.30 vs 0.70±0.27 mmol/L, p=0.004; x ± SD) and female bodybuilders (1.3±0.5 vs 0.8±0.2 mmol/L) ON cycle. GGE studies suggested that mostly HDL₂ was reduced. There were no significant reductions in LDL particle size ON cycle. Two males had larger LDL species ON cycle. Lp(a) decreased in male bodybuilders (124.7±128.0 to 69.3±73.3 U/L, p=0.008). ON cycle postprandial triglyceride excursion was unchanged in female bodybuilders and reduced (11.6±10.0 vs 7.5±5.4 mmol/L.hr; p=0.027) in male bodybuilders. In the triptorelin study, HDLC was increased in T (1.07±0.18 vs 1.41±0.28 mmol/L, p=0.002) and not in C. GGE studies indicated an increase of HDL₂ in five T subjects and no increase in C. Total cholesterol increased in T (4.77±0.80 vs 5.24±1.04 mmol/L, p=0.039) but not in C. LDL size increased in four T subjects, and not in C. Lp(a) increased in T (277.9±149.l vs 376.5±222.2 U/L, p=0.004), but not in C. Postprandial triglyceridaemia was unchanged in both T and C. The results of these studies did not show any additional atherogenic effects of endogenous testosterone or AAS in humans. Rather, a suppression of Lp(a) may be an antiatherogenic effect of these hormones. A reduced postprandial triglyceridaemia and increased LDL size in individuals who are predisposed to 'atherogenic dyslipidaemia', may be further antiatherogenic effects of AAS use

A novel Markov model projecting costs and outcomes of providing antiretroviral therapy to public patients in private practices versus public clinics in south Africa

Introduction Providing private antiretroviral therapy (ART) care for public sector patients could increase access to ART in low- and middle-income countries. We compared the costs and outcomes of a private-care and a public-care ART program in South Africa. METHODS: A novel Markov model was developed from the public-care program. Patients were first tunneled for 6 months in their baseline CD4 category before being distributed into a dynamic CD4 and viral load model. Patients were allowed to return to ART care from loss to follow up (LTFU). We then populated this modeling framework with estimates derived from the private-care program to externally validate the model. RESULTS: Baseline characteristics were similar in the two programs. Clinic visit utilization was higher and death rates were lower in the first few years on ART in the public-care program. After 10 years on ART we estimated the following outcomes in the public-care and private-care programs respectively: viral load 500 cells/μl 33% and 37%, LTFU 14% and 14%, and death 27% and 32%. Lifetime undiscounted survival estimates were 14.1 (95%CI 13.2-14.9) and (95%CI 12.7-14.5) years with costs of 18,734 (95%CI 12,588-14,022) and 13,062 (95%CI 12,077-14,047) USD in the private-care and public-care programs respectively. When clinic visit utilization in the public-care program was reduced by two thirds after the initial 6 months on ART, which is similar to their current practice, the costs were comparable between the programs. CONCLUSIONS: Using a novel Markov model, we determined that the private-care program had similar outcomes but lower costs than the public-care program, largely due to lower visit frequencies. These findings have important implications for increasing and sustaining coverage of patients in need of ART care in resource-limited settings

Visible-Light Photoswitchable Benzimidazole Azo-Arenes as beta-Arrestin2-Biased Selective Cannabinoid 2 Receptor Agonists

Acknowledgements The authors would like to acknowledge Dr. Andrea Holme for excellent technical support and the Iain Fraser Cytometry Centre (University of Aberdeen) for providing access to their equipment. The authors would like to thank Dr. Matthias Scheiner for his contributions towards the development of the calcium mobilization assay and Dr. Valérie Jahns for her efforts towards faster automated analysis of the obtained results. Nick Verhavert is acknowledged for his assistance with the NanoBiT® assay. Diego Rodriguez-Soacha is acknowledged for establishing the rCB1R radioligand binding assay in our laboratory. Special thanks to Dr. Rangan Maitra and RTI International for providing the G16 coupled hCB1 and hCB2 CHO-K1 cell lines. The authors thank Nadine Yurdagül-Hemmrich and Annette Hannawacker for excellent technical support. This project was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft under DFG DE1546/10-1). J. N. Hislop’s financing support was given by NHS Grampian. The research visit of S. A. M. Steinmüller in Dr. Hislop’s laboratory was funded by the Elite Network of Bavaria (grant N° K-BM-2013-247). J. Fender and A. Tutov were supported by the International Doctoral Program “Receptor Dynamics” funded within the framework of the Elite Network of Bavaria (grant N° K-BM-2013- 247). M. H. Deventer was funded by the Research FoundationFlanders (FWO; grant 1S54521N).Peer reviewe

Bridging the Binding Sites : Dualsteric Ligands for the Cannabinoid 2 Receptor (CB2R)

Acknowledgements This project was financially supported by the German Research Foundation (Deutsche Forschungsgemeinschaft under DFG DE1546/10-1). Gratitude is expressed to the International Doctorate Program “Receptor Dynamics” of the Elite Network of Bavaria (ENB) for financial support of A.T. and S.A.M.S. (grant No. K-BM-2013-247). Y.A.R. was granted a scholarship by the German Academic Exchange Service (Deutscher Akademischer Austauschdienst, DAAD) program “Research stays for university academics and scientists.” D.A.R.-S. was awarded a Ph.D. scholarship by the DAAD. J.N.H. was financially supported by NHS Grampian. Furthermore, the authors thank Professor Dr. Kristina Lorenz (Institute of Pharmacology and Toxicology, University of Würzburg) for enabling them to conduct in vitro experiments in her laboratory. Open access funding enabled and organized by Projekt DEAL.Peer reviewedPublisher PD

The consumption of zooplankton by early life stages of fish in the North Sea

Previous work has shown that during the 1970s, fish and carnivorous macrozooplankton together consumed ~22 gC m-2 year-1 of mesozooplankton, principally copepods. Consumption declined to ~17 gC m-2 year-1 during the 1990s, mainly because of a reduction in fish production. The zooplankton production required to meet this demand seems to be approximately accounted for by estimates of new primary production, but there are additional sinks for zooplankton production attributable to predation by, for example, gelatinous species. Additionally, the consumption of zooplankton by early life stages of fish is difficult to assess and could be larger than implied by the earlier analysis. Here, the role of fish early life stages in zooplankton consumption is reassessed, and found to be approximately double that previously estimated. Some 28% of the zooplankton consumption by fish is now estimated to be attributable to early life stages, resulting in an estimate of zooplankton consumption by the fish community as a whole 14% higher. Taken overall, the consumption of zooplankton production by fish and other planktivorous predators is now estimated to be 19-25 gC m-2 year-1

The Extragalactic Distance Scale without Cepheids IV

The Cepheid period-luminosity relation is the primary distance indicator used in most determinations of the Hubble constant. The tip of the red giant branch (TRGB) is an alternative basis. Using the new ANU SkyMapper Telescope, we calibrate the Tully Fisher relation in the I band. We find that the TRGB and Cepheid distance scales are consistent.Comment: ApJ in press 201

Ground State and Resonances in the Standard Model of Non-relativistic QED

We prove existence of a ground state and resonances in the standard model of the non-relativistic quantum electro-dynamics (QED). To this end we introduce a new canonical transformation of QED Hamiltonians and use the spectral renormalization group technique with a new choice of Banach spaces.Comment: 50 pages change

Applied Sport Science for Male Age-Grade Rugby Union in England

Rugby union (RU) is a skill-collision team sport played at junior and senior levels worldwide. Within England, age-grade rugby governs the participation and talent development of youth players. The RU player development pathway has recently been questioned, regarding player performance and well-being, which sport science research can address. The purpose of this review was to summarise and critically appraise the literature in relation to the applied sport science of male age-grade RU players in England focussing upon (1) match-play characteristics, (2) training exposures, (3) physical qualities, (4) fatigue and recovery, (5) nutrition, (6) psychological challenges and development, and (7) injury. Current research evidence suggests that age, playing level and position influence the match-play characteristics of age-grade RU. Training exposures of players are described as 'organised chaos' due to the multiple environments and stakeholders involved in coordinating training schedules. Fatigue is apparent up to 72 h post match-play. Well-developed physical qualities are important for player development and injury risk reduction. The nutritional requirements are high due to the energetic costs of collisions. Concerns around the psychological characteristics have also been identified (e.g. perfectionism). Injury risk is an important consideration with prevention strategies available. This review highlights the important multi-disciplinary aspects of sport science for developing age-grade RU players for continued participation and player development. The review describes where some current practices may not be optimal, provides a framework to assist practitioners to effectively prepare age-grade players for the holistic demands of youth RU and considers areas for future research