Explainer: what is gene doping – and will any athletes at Rio 2016 have tried it?

Gene doping is simply gene therapy in people who don’t need it. The aim of gene therapy is to permanently cure sick individuals of their conditions by altering their genetic makeup. The aim of gene doping, meanwhile, is to artificially enhance an individual – to make them better than themselves, perhaps even everyone – by altering their genetic makeup. In many respects, gene doping is similar to conventional performance enhancing drugs – they too are often misused medical treatments. However, gene doping could potentially have permanent effects, good and bad, and be much harder to detect. Access this article on The Conversation website: https://theconversation.com/explainer-what-is-gene-doping-and-will-any-athletes-at-rio-2016-have-tried-it-6323

Tour de France Champions born or made: where do we take the genetics of performance?

Cyclists in the Tour de France are endurance specialists. Twin and family studies have shown that approximately 50% of the variance in a number of performance-related phenotypes (whether measured at baseline, i.e., natural talent, or in response to training) including those important to cycling can be explained by genetic variation. Research into the specific genetic variants that are responsible has identified over 200 genes containing common genetic variants involved in the genetic predisposition to physical performance. However, typically these explain only a small portion of the variance, perhaps 1–2% and collectively they rarely explain anything approaching the 50% of the variance identified in the twin and family studies. Thus, there is a gap in our understanding of the relationship between heritability and performance. This gap may be bridged by investigation of rare variants or epigenetic variation or by altering study designs through increased collaborations to pool existing cohorts together. Initial findings from such efforts show promising results. This mini-review will touch on the genetics and epigenetics of sporting performance, how they relate to cyclists in the Tour de France and where best future efforts may be directed as well as discuss some preliminary research findings

When kids run for 15 minutes in school every day, here’s what happens to their health

First paragraph: If you haven’t heard of the Daily Mile yet, your time has come. Now taking place in 3,600 primary schools each day in 35 countries around the world, it takes children outside during normal lesson time to run or walk laps of the playground for 15 minutes. The ones who run cover around a mile each day. The initiative has an endearing back story. It was developed six years ago by St Ninians Primary School in Stirling in central Scotland after children and teachers felt the pupils needed to be fitter

Exercise-Conditioned Plasma and DNMT3B Concentration in PBMCs

DNA methylation is modifiable by acute and chronic exercise. DNA methyltransferases (DNMT) catalyze this process; however, there is a lack of literature concerning the specific mechanisms by which exercise‐induced modifications occur. Interleukin 6 (IL‐6) stimulation of various cell lines has been shown to augment DNMT expression and nuclear translocation, which suggests a possible pathway by which exercise is able to elicit changes in epigenetic enzymes. The present study sought to elucidate the response of thede novomethyltransferases DNMT3A and DNMT3B to circulatory factors found in plasma isolated from whole blood before and after 120‐min of treadmill running at an intensity of 60% of individual velocity at(v) interspersed with 30‐sec sprints at 90% of vevery 10‐min. Peripheral blood mononuclear cells (PBMCs) isolated from a resting participant were incubated with plasma isolated from exercising participants (n=10) or recombinant IL‐6 (rIL‐6), followed by nuclear protein extraction and quantification of DNMT3A and DNMT3B concentrations. Nuclear concentrations of DNMT3B significantly decreased following the experimental protocol (P=0.03), with no change observed in DNMT3A (P=0.514).Various concentrations of rIL‐6 caused an elevation in both DNMT3A and DNMT3B nuclear concentration compared with the blank control. The conflicting results between exercising and rIL‐6 conditions suggests that IL‐6 does regulate DNMT nuclear transport, however, other plasma mediators may also exert significant influence on the nuclear concentrations of these enzymes

Genetic influence on East African running success

East African athletes now dominate international distance running events from the 800 m to the marathon. Explanations for their phenomenal success have included optimal environmental conditions for developing distance running performance, psychological advantage and advantageous physiological characteristics. It is well established that genetics plays a role in determining inter-individual differences in exercise performance and adaptation to training stimuli. It is not known, however, to what extent inter-population differences (i.e. between ‘races’ and/or ethnic groups) in exercise performance can be attributed to genetics. There have been considerations that ‘black’ athletes are genetically adapted towards performance, given the concurrent success of athletes of West African ancestry in sprint events. However, the current notion of ‘race’ is not universally accepted, and genetic differences within and between populations are not clearly delineated by geographical or ethnic categorizations. Recent findings from mitochondrial DNA show that the populations from which Ethiopian athletes are drawn have not been isolated populations and are not genetically distinct from other Ethiopians. Y-chromosome analysis of the same population shows concurrent results, although some differences are present between athletes and the general Ethiopian population, suggesting an influence of the Y chromosome on athlete status in Ethiopia. It is concluded that there may be a role for genetics in the success of East African athletes; however, any genetic component to their success is unlikely to be limited to East Africans and is more likely to be found in other populations. At present it is unjustified to implicate a role for genetics in the success of East African runners when no genes have been identified as being important to their performance

2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy.

Thyroid dysfunction (TD) frequently occurs as an autoimmune complication of immune reconstitution therapy (IRT), especially in individuals with multiple sclerosis treated with alemtuzumab, a pan-lymphocyte depleting drug with subsequent recovery of immune cell numbers. Less frequently, TD is triggered by highly active antiretroviral therapy (HAART) in patients infected with human immunodeficiency virus (HIV), or patients undergoing bone-marrow/hematopoietic-stem-cell transplantation (BMT/HSCT). In both alemtuzumab-induced TD and HIV/HAART patients, the commonest disorder is Graves' disease (GD), followed by hypothyroidism and thyroiditis; Graves' orbitopathy is observed in some GD patients. On the contrary, GD is rare post-BMT/HSCT, where hypothyroidism predominates probably as a consequence of the associated radiation damage. In alemtuzumab-induced TD, the autoantibodies against the thyrotropin receptor (TRAb) play a major role, and 2 main aspects distinguish this condition from the spontaneous form: (1) up to 20% of GD cases exhibit a fluctuating course, with alternating phases of hyper- and hypothyroidism, due to the coexistence of TRAb with stimulating and blocking function; (2) TRAb are also positive in about 70% of hypothyroid patients, with blocking TRAb responsible for nearly half of the cases. The present guidelines will provide up-to-date recommendations and suggestions dedicated to all phases of IRT-induced TD: (1) screening before IRT (recommendations 1-3); (2) monitoring during/after IRT (recommendations 4-7); (3) management of TD post-IRT (recommendations 8-17). The clinical management of IRT-induced TD, and in particular GD, can be challenging. In these guidelines, we propose a summary algorithm which has particular utility for nonspecialist physicians and which is tailored toward management of alemtuzumab-induced TD. However, we recommend prompt referral to specialist endocrinology services following diagnosis of any IRT-induced TD diagnosis, and in particular for pregnant women and those considering pregnancy

Plasma microRNA levels differ between endurance and strength athletes

Aim: MicroRNAs (miRNAs) are stable in the circulation and are likely to function in inter-organ communication during a variety of metabolic responses that involve changes in gene expression, including exercise training. However, it is unknown whether differences in circulating-miRNA (c-miRNA) levels are characteristic of training modality. Methods: We investigated whether levels of candidate c-miRNAs differ between elite male athletes of two different training modalities (n = 10 per group) - endurance (END) and strength (STR) - and between these groups and untrained controls (CON; n = 10). Fasted, non-exercised, morning plasma samples were analysed for 14 c-miRNAs (miR-1, miR-16-2, miR-20a-1, miR-21, miR-93, miR-103a, miR-133a, miR-146a, miR-192, miR-206, miR-221, miR-222, miR-451, miR-499). Moreover, we investigated whether c-miRNA levels were associated with quantitative performance-related phenotypes within and between groups. Results: miR-222 was present at different levels in the three participant groups (p = 0.028) with the highest levels being observed in END and the lowest in STR. A number of other c-miRNAs were present at higher levels in END than in STR (relative to STR, ± 1 SEM; miR-222: 1.94 fold (1.73-2.18), p = 0.011; miR-21: 1.56 fold (1.39-1.74), p = 0.013; miR-146a: 1.50 fold (1.38-1.64), p = 0.019; miR-221: 1.51 fold (1.34-1.70), p = 0.026). Regression analyses revealed several associations between candidate c-miRNA levels and strength-related performance measures before and after adjustment for muscle or fat mass, but not following adjustment for group. Conclusion: Certain c-miRNAs (miR-222, miR-21, miR-146a and miR-221) differ between endurance- and resistance-trained athletes and thus have potential as useful biomarkers of exercise training and / or play a role in exercise mode-specific training adaptations. However, levels of these c-miRNAs are probably unrelated to muscle bulk or fat reserves

2019 European thyroid association guidelines on the management of thyroid dysfunction following immune reconstitution therapy

Thyroid dysfunction (TD) frequently occurs as an autoimmune complication of immune reconstitution therapy (IRT), especially in individuals with multiple sclerosis treated with alemtuzumab, a pan-lymphocyte depleting drug with subsequent recovery of immune cell numbers. Less frequently, TD is triggered by highly active antiretroviral therapy (HAART) in patients infected with human immunodeficiency virus (HIV), or patients undergoing bone-marrow/hematopoietic-stem-cell transplantation (BMT/HSCT). In both alemtuzumab-induced TD and HIV/HAART patients, the commonest disorder is Graves’ disease (GD), followed by hypothyroidism and thyroiditis; Graves’ orbitopathy is observed in some GD patients. On the contrary, GD is rare post-BMT/HSCT, where hypothyroidism predominates probably as a consequence of the associated radiation damage. In alemtuzumab-induced TD, the autoantibodies against the thyrotropin receptor (TRAb) play a major role, and 2 main aspects distinguish this condition from the spontaneous form: (1) up to 20% of GD cases exhibit a fluctuating course, with alternating phases of hyper- and hypothyroidism, due to the coexistence of TRAb with stimulating and blocking function; (2) TRAb are also positive in about 70% of hypothyroid patients, with blocking TRAb responsible for nearly half of the cases. The present guidelines will provide up-to-date recommendations and suggestions dedicated to all phases of IRT-induced TD: (1) screening before IRT (recommendations 1–3); (2) monitoring during/after IRT (recommendations 4–7); (3) management of TD post-IRT (recommendations 8–17). The clinical management of IRT-induced TD, and in particular GD, can be challenging. In these guidelines, we propose a summary algorithm which has particular utility for nonspecialist physicians and which is tailored toward management of alemtuzumab-induced TD. However, we recommend prompt referral to specialist endocrinology services following diagnosis of any IRT-induced TD diagnosis, and in particular for pregnant women and those considering pregnancy

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment