Whole-Blood and Peripheral Mononuclear Cell Transcriptional Response to Prolonged Altitude Exposure in Well-Trained Runners.

BACKGROUND: Recombinant human erythropoietin (rHuEpo) abuse by athletes threatens the integrity of sport. Due to the overlap in physiological response to rHuEpo and altitude exposure, it remains difficult to differentiate changes in hematological variables caused by rHuEpo or altitude, and therefore, other molecular methods to enhance anti-doping should be explored. OBJECTIVE: To identify the hematological and transcriptomic response to prolonged altitude exposure typical of practices used by elite athletes. DESIGN: Longitudinal study. SETTING: University of Cape Town and Altitude Training Centre in Ethiopia. PARTICIPANTS AND INTERVENTION: Fourteen well-trained athletes sojourned to an altitude training camp in Sululta, Ethiopia (∼2400-2500 m above sea level) for 27 days. Blood samples were taken before arrival, 24 hours, and 9, 16, and 24 days after arrival at altitude in addition to 24 hours and 6, 13, and 27 days upon return to sea level. MAIN OUTCOME MEASURES: Blood samples were analyzed for hemoglobin concentration, hematocrit, and reticulocyte percentage. The transcriptomic response in whole blood and peripheral blood mononuclear cells (PBMC) were analyzed using gene expression microarrays. RESULTS: A unique set of 29 and 10 genes were identified to be commonly expressed at every altitude time point in whole blood and PBMC, respectively. There were no genes identified upon return to sea level in whole blood, and only one gene within PBMC. CONCLUSIONS: The current study has identified a series of unique genes that can now be integrated with genes previously validated for rHuEpo abuse, thereby enabling the differentiation of rHuEpo from altitude exposure.

An observational human study investigating the effect of anabolic androgenic steroid use on the transcriptome of skeletal muscle and whole blood using RNA-Seq.

BACKGROUND: The effects of Anabolic Androgenic Steroids (AAS) are largely illustrated through Androgen Receptor induced gene transcription, yet RNA-Seq has yet to be conducted on human whole blood and skeletal muscle. Investigating the transcriptional signature of AAS in blood may aid AAS detection and in muscle further understanding of AAS induced hypertrophy. METHODS: Males aged 20-42 were recruited and sampled once: sedentary controls (C), resistance trained lifters (RT) and resistance trained current AAS users (RT-AS) who ceased exposure ≤ 2 or ≥ 10 weeks prior to sampling. RT-AS were sampled twice as Returning Participants (RP) if AAS usage ceased for ≥ 18 weeks. RNA was extracted from whole blood and trapezius muscle samples. RNA libraries were sequenced twice, for validation purposes, on the DNBSEQ-G400RS with either standard or CoolMPS PE100 reagents following MGI protocols. Genes were considered differentially expressed with FDR < 0.05 and a 1.2- fold change. RESULTS: Cross-comparison of both standard reagent whole blood (N = 55: C = 7, RT = 20, RT-AS ≤ 2 = 14, RT-AS ≥ 10 = 10, RP = 4; N = 46: C = 6, RT = 17, RT-AS ≤ 2 = 12, RT-AS ≥ 10 = 8, RP = 3) sequencing datasets, showed that no genes or gene sets/pathways were differentially expressed between time points for RP or between group comparisons of RT-AS ≤ 2 vs. C, RT, or RT-AS ≥ 10. Cross-comparison of both muscle (N = 51, C = 5, RT = 17, RT-AS ≤ 2 = 15, RT-AS ≥ 10 = 11, RP = 3) sequencing (one standard & one CoolMPS reagent) datasets, showed one gene, CHRDL1, which has atrophying potential, was upregulated in RP visit two. In both muscle sequencing datasets, nine differentially expressed genes, overlapped with RT-AS ≤ 2 vs. RT and RT-AS ≤ 2 vs. C, but were not differentially expressed with RT vs. C, possibly suggesting they are from acute doping alone. No genes seemed to be differentially expressed in muscle after the long-term cessation of AAS, whereas a previous study found long term proteomic changes. CONCLUSION: A whole blood transcriptional signature of AAS doping was not identified. However, RNA-Seq of muscle has identified numerous differentially expressed genes with known impacts on hypertrophic processes that may further our understanding on AAS induced hypertrophy. Differences in training regimens in participant groupings may have influenced results. Future studies should focus on longitudinal sampling pre, during and post-AAS exposure to better control for confounding variables.

Rapid Roll Out of a Pacemaker Home Monitoring Programme: A Patient Perspective.

OBJECTIVE: To assess the safety, efficacy, and patient acceptability of a pacemaker home monitoring (HM) service. METHODS: All patients receiving a new Biotronik (Biotronik, Berlin, Germany) pacemaker between March 2020 and February 2021 were contacted for participation. Participants were surveyed on their experience of pacemaker HM. HM alerts and remote wound monitoring rates were also assessed. RESULTS: Of the patients contacted, 77% responded, with a mean age of 80.6±9.9 years. Of these, 95.8% agreed that the home monitoring (HM) has been beneficial. Two thirds preferred HM to face-to-face follow-up and two thirds felt safe with HM. Three themes were identified from the comments: reassurance, technology and data security. Forty-one percent (41%) of respondents would like more reassurance that their HM is working, 18% mentioned technology with mixed responses, and 4.7% cited cybersecurity or the use of their personal data as a concern. The average one-way patient journey saved was 24.3±16.7 km (15.1±10.4 miles). One in three HM alerts required action but only 3.4% were urgent. Remote wound review was successful in 59%. CONCLUSIONS: The majority of patients prefer HM and almost all think it has been beneficial. It saves significant travel time and provides actionable alerts. The patient experience could be improved by reassuring patients that their device is being monitored.

Metabolomic Profiling of Recombinant Erythropoietin (rHuEpo) in Trained Caucasian Athletes.

OBJECTIVE: Recombinant human erythropoietin (rHuEpo) is prohibited by the World Anti-Doping Agency but remains the drug of choice for many cheating athletes wishing to evade detection using current methods. The aim of this study was to identify a robust metabolomics signature of rHuEpo using an untargeted approach in blood (plasma and serum) and urine. DESIGN: Longitudinal study. SETTING: University of Glasgow. PARTICIPANTS: Eighteen male participants regularly engaged in predominantly endurance-based activities, such as running, cycling, swimming, triathlon, and team sports, were recruited. INTERVENTIONS: Each participant received 50 IU·kg -1 body mass of rHuEpo subcutaneously every 2 days for 4 weeks. Samples were collected at baseline, during rHuEpo administration (over 4 weeks) and after rHuEpo administration (week 7-10). The samples were analyzed using hydrophilic interaction liquid chromatography mass spectrometry. MAIN OUTCOME MEASURES: Significant metabolic signatures of rHuEpo administration were identified in all biofluids tested in this study. RESULTS: Regarding metabolomics data, 488 plasma metabolites, 694 serum metabolites, and 1628 urinary metabolites were identified. Reproducible signatures of rHuEpo administration across all biofluids included alterations of pyrimidine metabolism (orotate and dihydroorotate) and acyl-carnitines (palmitoyl-carnitine and elaidic carnitine), metabolic pathways that are associated with erythropoiesis or erythrocyte membrane function, respectively. CONCLUSIONS: Preliminary metabolic signatures of rHuEpo administration were identified. Future studies will be required to validate these encouraging results in independent cohorts and with orthogonal techniques, such as integration of our data with signatures derived from other "omics" analyses of rHuEpo administration (eg, transcriptomics).

The MMAAS Project: An Observational Human Study Investigating the Effect of Anabolic Androgenic Steroid Use on Gene Expression and the Molecular Mechanism of Muscle Memory.

OBJECTIVE: It remains unknown whether myonuclei remain elevated post anabolic-androgenic steroid (AAS) usage in humans. Limited data exist on AAS-induced changes in gene expression. DESIGN: Cross-sectional/longitudinal. SETTING: University. PARTICIPANTS: Fifty-six men aged 20 to 42 years. INDEPENDENT VARIABLES: Non-resistance-trained (C) or resistance-trained (RT), RT currently using AAS (RT-AS), of which if AAS usage ceased for ≥18 weeks resampled as Returning Participants (RP) or RT previously using AAS (PREV). MAIN OUTCOME MEASURES: Myonuclei per fiber and cross-sectional area (CSA) of trapezius muscle fibers. RESULTS: There were no significant differences between C (n = 5), RT (n = 15), RT-AS (n = 17), and PREV (n = 6) for myonuclei per fiber. Three of 5 returning participants (RP1-3) were biopsied twice. Before visit 1, RP1 ceased AAS usage 34 weeks before, RP2 and RP3 ceased AAS usage ≤2 weeks before, and all had 28 weeks between visits. Fiber CSA decreased for RP1 and RP2 between visits (7566 vs 6629 µm 2 ; 7854 vs 5677 µm 2 ) while myonuclei per fiber remained similar (3.5 vs 3.4; 2.5 vs 2.6). Respectively, these values increased for RP3 between visits (7167 vs 7889 µm 2 ; 2.6 vs 3.3). CONCLUSIONS: This cohort of past AAS users did not have elevated myonuclei per fiber values, unlike previous research, but reported AAS usage was much lower. Training and AAS usage history also varied widely among participants. Comparable myonuclei per fiber numbers despite decrements in fiber CSA postexposure adheres with the muscle memory mechanism, but there is variation in usage relative to sampling date and low numbers of returning participants.

Recommendations for Face Coverings While Exercising During the COVID-19 Pandemic.

In an effort to reduce transmission and number of infections of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) virus, governments and official bodies around the world have produced guidelines on the use of face masks and face coverings. While there is a growing body of recommendations for healthcare professionals and the wider population to use facial protection in "enclosed spaces" where minimal distancing from other individuals is not possible, there is a dearth of clear guidelines for individuals undertaking exercise and sporting activity. The present viewpoint aims to propose recommendations for face coverings while exercising during the COVID-19 pandemic that consider physical distancing, the environment, the density of active cases associated with the specific sports activity, and the practical use of face coverings in order to reduce potential viral transmission. Recommendations are provided on the basis of very limited available evidence in conjunction with the extensive collective clinical experience of the authors and acknowledging the need to consider the likelihood of the presence of the SARS-CoV-2 in the general population. We recommend that face coverings should be used in any environment considered to be of a high or moderate transmission risk, where tolerated and after individual risk assessment. In addition, as national caseloads fluctuate, individual sporting bodies should consider up to date guidance on the use of face coverings during sport and exercise, alongside other preventative measures.

Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement.

Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.

Communication in the intensive care unit during COVID-19: early experience with the Nightingale Communication Method.

OBJECTIVE: To assess the utility and frequency of use of the Nightingale Communication Method, during the early operational phase of the Nightingale Hospital London (NHL) 4000-bed field hospital's intensive care unit. DESIGN: Survey-based cross-sectional assessment. SETTING: The intensive care unit at the Nightingale London hospital. PARTICIPANTS: Staff working in the clinical area and therefore requiring full personal protective equipment (PPE). INTERVENTION: Survey of all staff members sampled from a single shift at the Nightingale Hospital. This investigated perceived utility and actual use of identification methods (name and role labels on visors and gowns, coloured role identification tapes) and formal hand signals as an adjunctive communication method. MAIN OUTCOME MEASURE: Self-reported frequency of use and perceived utility of each communication and personnel identification adjunct. RESULTS: Fifty valid responses were received (72% response rate), covering all clinical professional groups. Prominent name/role identifications and coloured role identification tapes were very frequently used and were perceived as being highly useful. Formal hand signals were infrequently used and not perceived as being beneficial, with respondents citing use of individual hand signals only in specific circumstances. CONCLUSION: PPE is highly depersonalizing, and interpersonal identification aids are very useful. Despite being difficult, verbal communication is not completely prohibited, which could explain the low utility of formal hand signals. The methods developed at the Nightingale hospital have enhanced communication in the critical care, field hospital setting. There is potential for wider application to a variety of healthcare settings, in both the current situation and future pandemic scenarios.

The Use of Technology to Protect the Health of Athletes During Sporting Competitions in the Heat.

During the 2019 IAAF World Championships in Athletics in Doha and the 2020 Olympic Games in Tokyo, minimum daily temperatures are expected to be in excess of 30°C. Due to the metabolic demands of the sporting events and the high environmental temperatures, the risk of exertional heat stroke (EHS) is high. Careful planning by event organizers are needed to ensure that athletes are protected from irreversible long-term health damage, or even death during sporting competitions in the heat. Efforts typically have included standard medical plans, equipment, protocols, and expert medical teams. In addition, the importance of responding quickly to a hyperthermic athlete cannot be understated, as minimizing treatment time will greatly improve the chances of full recovery. Treatment time can be minimized by notifying medical personnel about the health status of the athlete and the extent of any pre-competition heat acclimatization. Technology that allows the live transmission of physiological, biomechanical, and performance data to alert medical personnel of potential indicators of EHS should be considered. Real time monitoring ecosystems need to be developed that integrate information from numerous sensors such as core temperature-monitoring "pills" to relay information on how an athlete is coping with competing in intense heat. Medical/support staff would be alerted if an athlete's responses were indicating signs of heat stress or EHS signs and the athlete could be withdrawn under exceptional circumstances. This technology can also help provide more rapid, accurate and dignified temperature assessment at the road/track side in medical emergencies.

The Performance Effects of Microdose Recombinant Human Erythropoietin Administration and Carbon Monoxide Rebreathing.

Frequent, low doses of recombinant human erythropoietin (rHuEpo) have been shown to increase the oxygen carrying capacity of an athlete and enhance endurance performance, although its effect on repeated sprint ability (RSA) remains unknown. If the mechanisms behind improved RSA performance reside within the augmented O2 carrying capacity, then carbon monoxide (CO) inhalation should inhibit RSA. Purpose: The aim of this study was to assess the effects on maximal oxygen uptake (V˙O2max) and RSA of two interventions known to differentially influence blood oxygen carrying capacity. Methods: Fourteen endurance-trained individuals were administered microdoses of rHuEpo (20-40 IUkg) or placebo twice per week for 7 wk using a randomized, crossover design. V˙O2max and RSA were measured at baseline and after rHuEpo administration. Total hemoglobin mass (tHb-mass) was measured twice at baseline (14 and 7 d before the first injection), three times during rHuEpo administration (10, 24, and 38 d after the first rHuEpo injection) and twice after the cessation of rHuEpo administration (7 and 21 d after the final injection) using the optimized CO rebreathing method. V˙O2max and RSA also were assessed in a separate cohort of 11.

The role of vitamin D testing and replacement in fibromyalgia: a systematic literature review.

BACKGROUND: Fibromyalgia is a debilitating condition, characterized by extensive muscular pain and fatigue. Vitamin D is essential for overall health, with ubiquitous involvement in various inflammatory and pain pathways. Little is known about its role in fibromyalgia. We performed a systematic literature review to determine if vitamin D contributes to the pathology and disability of patients with fibromyalgia, and to assess the role of vitamin D supplementation in disease management. METHODS: We searched Medline, EMBASE and the Cochrane Library for clinical studies and randomized controlled trials published in English during January 2000 to June 2017, using the terms vitamin D or hypovitaminosis D combined with fibromyalgia or FMS. References were reviewed manually and articles were only included if they were specific in their diagnosis of fibromyalgia and used appropriate control groups. RESULTS: Four hundred and sixty-six studies were retrieved, of which fourteen fulfilled the inclusion criteria. Six studies, of which two had the best quality evidence, found that patients with fibromyalgia have low levels of vitamin D compared to healthy controls. Conflicting results were obtained on the effect of vitamin D on pain or symptom control, with no clear consensus as to the role of supplementation in the management of fibromyalgia. CONCLUSIONS: Our results highlight an association between vitamin D deficiency and fibromyalgia. However, its role in the pathophysiology of fibromyalgia and the clinical relevance of identifying and treating this requires further elucidation with appropriately controlled studies.

What do Sport and Exercise Medicine (SEM) doctors look like online? A cross-sectional exploration of the social media presence of SEM doctors in the UK.

OBJECTIVES: To explore the social media presence of Sport and Exercise Medicine (SEM) doctors from the UK. Secondary aims were to identify whether there were any differences in years since qualification or specialisation between those with and without social media profiles and websites. METHODS: A cross-sectional design was used to investigate the social media presence of UK-based doctors listed as Fellows of the Faculty of Sport and Exercise Medicine. These SEM doctors were identified via their presence on publicly available member lists. Data collected for each SEM Fellow included the presence of profiles on major social media platforms (Twitter, LinkedIn, YouTube and professional Facebook profiles) demonstrated by active profile use and the number of followers/subscribers per platform. The ownership of professional websites and websites hosted by private healthcare providers was also examined. RESULTS: A total of 175 SEM Fellows were identified and included for analysis. LinkedIn was the most popular platform for this cohort (n=115), followed by Twitter (n=73), while YouTube had far fewer profiles among the SEM Fellows (n=9). No professional Facebook profiles were identified for the SEM Doctors in this study. Almost a third (n=49) of SEM Fellows did not have a profile on any of the social media platforms examined in this study. CONCLUSION: Social media is a powerful tool for health promotion and education. The use of these platforms by SEM Doctors and healthcare organisations warrants ongoing guidance and support to enable these practitioners to maximise the utility of these innovative technologies.

Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration.

BACKGROUND: Recombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo. METHODS: Forty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively). Differential gene expression analysis was carried out following normalisation and significance declared following application of a 5% false discovery rate (FDR) and a 1.5 fold-change. Adaptive model analysis was also applied to incorporate these markers for the detection of rHuEpo. RESULTS: ALAS2, BCL2L1, DCAF12, EPB42, GMPR, SELENBP1, SLC4A1, TMOD1 and TRIM58 were differentially expressed during and throughout the post phase of microdose rHuEpo administration. The CD247 and TRIM58 genes were significantly up- and down-regulated, respectively, immediately following exercise when compared with the baseline both before and after rHuEpo/placebo. No significant gene expression changes were found 30 min after exercise in either rHuEpo or placebo groups. ALAS2, BCL2L1, DCAF12, SLC4A1, TMOD1 and TRIM58 tended to be significantly expressed in the elite runners ten days after arriving at altitude and one week after returning from altitude (FDR > 0.059, fold-change varying from 1.39 to 1.63). Following application of the adaptive model, 15 genes showed a high sensitivity (≥ 93%) and specificity (≥ 71%), with BCL2L1 and CSDA having the highest sensitivity (93%) and specificity (93%). CONCLUSIONS: Current results provide further evidence that transcriptional biomarkers can strengthen the ABP approach by significantly prolonging the detection window and improving the sensitivity and specificity of blood doping detection. Further studies are required to confirm, and if necessary, integrate the confounding effects of altitude training on blood doping.