Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males

Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function

A pilot sequential multiple assignment randomized trial (SMART) protocol for developing an adaptive coaching intervention around a mobile application for athletes to improve carbohydrate periodization behavior

Background: It has recently been identified that manipulating carbohydrate availability around exercise activity can enhance training-induced metabolic adaptations. Despite this approach being accepted in the athletic populations, athletes do not systematically follow the guidelines. Digital environments appear to allow nutritionists to deliver this intervention at scale, reducing expensive human coaching time. Yet, digitally delivered dietary behavior change interventions for athletes and the coaching strategy to support them are still novel concepts within sports nutrition. Methods/design: We aim to recruit 900 athletes across the UK. 500 athletes will be recruited to test the feasibility of a novel menu planner mobile application with coaching for 6 weeks. 250 athletes with pre-existing nutritionist support will also be recruited as control. We will then conduct a 4-week pilot sequential multiple assignment randomized trial (SMART) with an additional 150 athletes. In the SMART, athletes will be given the application and additional coaching according to their engagement responses. The primary outcomes are the mobile application and coach uptake, retention, engagement, and success in attaining carbohydrate periodization behavior. Secondary outcomes are changes in goal, weight, carbohydrate periodization self-efficacy, and beliefs about consequences. Due to the high attrition nature of digital interventions, all quantitative analyses will be carried out based on both the intention-to-treat and per-protocol principles. Discussion: This study will be the first to investigate improving carbohydrate periodization using a digital approach and tailored coaching strategies under this context. Foundational evidence from this study will provide insights into the feasibility of the digital approach

Muscle glycogen utilisation during Rugby match play: Effects of pre-game carbohydrate

Objectives: Although the physical demands of Rugby League (RL) match-play are well-known, the fuel sources supporting energy-production are poorly understood. We therefore assessed muscle glycogen utilisation and plasma metabolite responses to RL match-play after a relatively high (HCHO) or relatively low CHO (LCHO) diet. Design: Sixteen (mean ± SD age; 18 ± 1 years, body-mass; 88 ± 12 kg, height 180 ± 8 cm) professional players completed a RL match after 36-h consuming a non-isocaloric high carbohydrate (n = 8; 6 g kg day−1) or low carbohydrate (n = 8; 3 g kg day−1) diet. Methods: Muscle biopsies and blood samples were obtained pre- and post-match, alongside external and internal loads quantified using Global Positioning System technology and heart rate, respectively. Data were analysed using effects sizes ±90% CI and magnitude-based inferences. Results: Differences in pre-match muscle glycogen between high and low carbohydrate conditions (449 ± 51 and 444 ± 81 mmol kg−1 d.w.) were unclear. High (243 ± 43 mmol kg−1 d.w.) and low carbohydrate groups (298 ± 130 mmol kg−1 d.w.) were most and very likely reduced post-match, respectively. For both groups, differences in pre-match NEFA and glycerol were unclear, with a most likely increase in NEFA and glycerol post-match. NEFA was likely lower in the high compared with low carbohydrate group post-match (0.95 ± 0.39 mmol l−1 and 1.45 ± 0.51 mmol l−1, respectively), whereas differences between the 2 groups for glycerol were unclear (98.1 ± 33.6 mmol l−1 and 123.1 ± 39.6 mmol l−1) in the high and low carbohydrate groups, respectively. Conclusions: Professional RL players can utilise ∼40% of their muscle glycogen during a competitive match regardless of their carbohydrate consumption in the preceding 36-h

Postexercise High-Fat Feeding Supresses p70S6K1 Activity in Human Skeletal Muscle.

PURPOSE: To examine the effects of reduced CHO but high post-exercise fat availability on cell signalling and expression of genes with putative roles in regulation of mitochondrial biogenesis, lipid metabolism and muscle protein synthesis (MPS). METHODS: Ten males completed a twice per day exercise model (3.5 h between sessions) comprising morning high-intensity interval (HIT) (8 x 5-min at 85% VO2peak) and afternoon steady-state (SS) running (60 min at 70% VO2peak). In a repeated measures design, runners exercised under different isoenergetic dietary conditions consisting of high CHO (HCHO: 10 CHO, 2.5 Protein and 0.8 Fat g.kg per whole trial period) or reduced CHO but high fat availability in the post-exercise recovery periods (HFAT: 2.5 CHO, 2.5 Protein and 3.5 Fat g.kg per whole trial period). RESULTS: Muscle glycogen was lower (P<0.05) at 3 (251 vs 301 mmol.kgdw) and 15 h (182 vs 312 mmol.kgdw) post-SS exercise in HFAT compared to HCHO. AMPK-α2 activity was not increased post-SS in either condition (P=0.41) though comparable increases (all P<0.05) in PGC-1α, p53, CS, Tfam, PPAR and ERRα mRNA were observed in HCHO and HFAT. In contrast, PDK4 (P=0.003), CD36 (P=0.05) and CPT1 (P=0.03) mRNA were greater in HFAT in the recovery period from SS exercise compared with HCHO. p70S6K activity was higher (P=0.08) at 3 h post-SS exercise in HCHO versus HFAT (72.7 ± 51.9 vs 44.7 ± 27 fmol.min mg). CONCLUSION: Post-exercise high fat feeding does not augment mRNA expression of genes associated with regulatory roles in mitochondrial biogenesis though it does increase lipid gene expression. However, post-exercise p70S6K1 activity is reduced under conditions of high fat feeding thus potentially impairing skeletal muscle remodelling processes

Leucine-enriched protein feeding does not impair exercise-induced free fatty acid availability and lipid oxidation: beneficial implications for training in carbohydrate-restricted states

Given that the enhanced oxidative adaptations observed when training in carbohydrate (CHO) restricted states are potentially regulated through free fatty acid (FFA) mediated signalling and that leucine rich protein elevates muscle protein synthesis, the present study aimed to test the hypothesis that leucine enriched protein feeding enhances circulating leucine concentration but does not impair FFA availability nor whole body lipid oxidation 56 during exercise. Nine males cycled for 2 h at 70% VO2peak when fasted (PLACEBO) or having consumed a whey protein solution (WHEY) or a leucine enriched whey protein gel (GEL), administered as 22 g 1 hour pre-exercise, 11 g/h during and 22 g thirty minutes post-exercise. Total leucine administration was 14.4 g and 6.3 in GEL and WHEY, respectively. Mean plasma leucine concentrations were elevated in GEL (P= 0.001) compared 60 with WHEY and PLACEBO (375 ± 100, 272 ± 51, 146 ± 14 μmol.L-1 respectively). No differences (P= 0.153) in plasma FFA (WHEY 0.53 ± 0.30, GEL 0.45 ± 0.25, PLACEBO 0.65 ± 0.30, mmol.L-1) or whole body lipid oxidation during exercise (WHEY 0.37 ± 0.26, GEL 0.36 ± 0.24, PLACEBO 0.34 ± 0.24 g/min) were apparent between trials, despite elevated (P= 0.001) insulin in WHEY and GEL compared with PLACEBO (38 ± 16, 35 ± 16, 22 ± 11 pmol.L-1 respectively). We conclude that leucine enriched protein feeding does not impair FFA availability nor whole body lipid oxidation during exercise, thus having practical applications for athletes who deliberately train in CHO restricted states to promote skeletal muscle adaptations

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society