Dr Oliver Wilson

Synaptosomal-associated protein 23 (SNAP23) is a SNARE protein expressed abundantly in human skeletal muscle. Its established role is to mediate insulin-stimulated docking and fusion of glucose transporter 4 (GLUT4) with the plasma membrane. Recent in vitro research has proposed that SNAP23 may also play a role in the fusion of growing lipid droplets (LDs) and the channeling of LD-derived fatty acids (FAs) into neighboring mitochondria for β-oxidation. This study investigates the subcellular distribution of SNAP23 in human skeletal muscle using immunofluorescence microscopy to confirm that SNAP23 localization supports the three proposed metabolic roles. Percutaneous biopsies were obtained from the m. vastus lateralis of six lean, healthy males in the rested, overnight fasted state. Cryosections were stained with antibodies targeting SNAP23, the mitochondrial marker cytochrome c oxidase and the plasma membrane marker dystrophin, whereas intramuscular LDs were stained using the neutral lipid dye oil red O. SNAP23 displayed areas of intense punctate staining in the intracellular regions of all muscle fibers and continuous intense staining in peripheral regions of the cell. Quantitation of confocal microscopy images showed colocalization of SNAP23 with the plasma membrane marker dystrophin (Pearson's correlation coefficient r = 0.50 ± 0.01). The intense punctate intracellular staining colocalized primarily with the mitochondrial marker cytochrome C oxidase (r = 0.50 ± 0.012) and to a lesser extent with LDs (r = 0.21 ± 0.01) visualized with oil red O. We conclude that the observed subcellular distribution of SNAP23 in human skeletal muscle supports the three aforementioned metabolic roles.

BACKGROUND: Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. PURPOSE: To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. METHODS: Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15-60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30-45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. RESULTS: Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. CONCLUSIONS: HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.

Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in part as a result of the translocation of glucose transporter 4 (GLUT4) from intracellular stores to the plasma membrane (PM). This study aimed to use immunofluorescence microscopy in human skeletal muscle to quantify GLUT4 redistribution from intracellular stores to the PM in response to glucose feeding and exercise. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of ten insulin-sensitive men in the basal state and following 30 min of cycling exercise (65% VO2 max). Muscle biopsy samples were also taken from a second cohort of ten age-, BMI- and VO2 max-matched insulin-sensitive men in the basal state and 30 and 60 min following glucose feeding (75 g glucose). GLUT4 and dystrophin colocalization, measured using the Pearson's correlation coefficient, was increased following 30 min of cycling exercise (baseline r = 0.47 ± 0.01; post exercise r = 0.58 ± 0.02; P < 0.001) and 30 min after glucose ingestion (baseline r = 0.42 ± 0.02; 30 min r = 0.46 ± 0.02; P < 0.05). Large and small GLUT4 clusters were partially depleted following 30 min cycling exercise, but not 30 min after glucose feeding. This study has, for the first time, used immunofluorescence microscopy in human skeletal muscle to quantify increases in GLUT4 and dystrophin colocalization and depletion of GLUT4 from large and smaller clusters as evidence of net GLUT4 translocation to the PM.

Within animal skeletal muscle, focal adhesion kinase (FAK) has been associated with load-dependent molecular and metabolic adaptation including the regulation of insulin sensitivity. This study aimed to generate the first visual images of the localisation of FAK within human skeletal muscle fibres and its associated microvasculature using widefield and confocal immunofluorescence microscopy. Percutaneous muscle biopsies, taken from five lean, active males, were frozen and 5-lm cryosections were incubated with FAK antibodies for visualisation in muscle fibres and the microvasculature. Anti-myosin heavy chain type I was used for fibre-type differentiation. Muscle sections were also incubated with anti-dihydropyridine receptor (DHPR) to investigate co-localisation of FAK with the t-tubules. FITC-conjugated Ulex europaeus Agglutinin I stained the endothelium of the capillaries, whilst anti-smooth muscle actin stained the vascular smooth muscle of arterioles. Fibre-type differences in the intensity of FAK immunofluorescence were determined with image analysis software. In transversely and longitudinally orientated fibres, FAK was localised at the sarcolemmal regions. In longitudinally orientated fibres, FAK staining also showed uniform striations across the fibre and co-staining with DHPR suggests FAK associates with the t-tubules. There was no fibre-type difference in sarcoplasmic FAK content. Within the capillary endothelium and arteriolar smooth muscle, FAK was distributed heterogeneously as clusters. This is the first study to visualise FAK in human skeletal muscle microvasculature and within the (sub)sarcolemmal and t-tubule regions using immunofluorescence microscopy. This technique will be an important tool for investigating the role of FAK in the intracellular signalling of human skeletal muscle and the endothelium of its associated microvasculature. © Springer-Verlag 2012.

Focal adhesion kinase (FAK) and paxillin are functionally linked hormonal- and mechano-sensitive proteins. We aimed to describe paxillin's subcellular distribution using widefield and confocal immunofluorescence microscopy and test the hypothesis that FAK and paxillin colocalise in human skeletal muscle and its associated microvasculature. Percutaneous muscle biopsies were collected from the m. vastus lateralis of seven healthy males, and 5-μm cryosections were stained with anti-paxillin co-incubated with anti-dystrophin to identify the sarcolemma, anti-myosin heavy chain type I for fibre-type differentiation, anti-dihydropyridine receptor to identify T-tubules, lectin UEA-I to identify the endothelium of microvessels and anti-α-smooth muscle actin to identify vascular smooth muscle cells (VSMC). Colocalisation of anti-paxillin with anti-dystrophin or anti-FAK was quantified using Pearson's correlation coefficient on confocal microscopy images. Paxillin was primarily present in (sub)sarcolemmal regions of skeletal muscle fibres where it colocalised with dystrophin (r = 0.414 ± 0.026). The (sub)sarcolemmal paxillin immunofluorescence intensity was ~2.4-fold higher than in sarcoplasmic regions (P < 0.001) with sarcoplasmic paxillin immunofluorescence intensity ~10 % higher in type I than in type II fibres (P < 0.01). In some longitudinally orientated fibres, paxillin formed striations that corresponded to the I-band region. Paxillin immunostaining was highest in endothelial and VSMC and distributed heterogeneously in both cell types. FAK and paxillin colocalised at (sub)sarcolemmal regions and within the microvasculature (r = 0.367 ± 0.036). The first images of paxillin in human skeletal muscle suggest paxillin is present in (sub)sarcolemmal and I-band regions of muscle fibres and within the microvascular endothelium and VSMC. Colocalisation of FAK and paxillin supports their suggested role in hormonal and mechano-sensitive signalling. © 2014 Springer-Verlag.

Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.

Using guidance from the RE-AIM evaluation framework, we aimed to qualitatively evaluate the participant experiences of a high intensity interval training (HIIT) workplace intervention. Twelve previously insufficiently active individuals (4 male, 8 females) were interviewed once as part of 3 focus groups. Perceptions of program satisfaction, barriers to and facilitators of adherence and persistence to exercise were explored. HIIT initiates interest because of its novelty, provides a sense of accomplishment and overcomes the barriers of perceived lack of time. The feeling of relatedness between the participants can attenuate negative unpleasant responses during the HIIT sessions. HIIT, in this workplace setting, is an acceptable intervention for physically inactive adults. However, participants were reluctant to maintain the same mode of exercise, believing that HIIT sessions were for the very fit. Key words: High-intensity interval training, evaluation, qualitative, health promotion, physical activity

Purpose This study examined the influence of dynamic apnoea training on splenic volume and haematological responses in non-breath-hold divers (BHD). Methods Eight non-BHD performed ten maximal dynamic apnoeas, four times a week for six weeks. Splenic volumes were assessed ultrasonically, and blood samples were drawn for full blood count analysis, erythropoietin, iron, ferritin, albumin, protein and osmolality at baseline, 24 h post the completion of each week’s training sessions and seven days post the completion of the training programme. Additionally, blood samples were drawn for haematology at 30, 90, and 180 min post session one, twelve and twenty-four. Results Erythropoietin was only higher than baseline (6.62 ± 3.03 mlU/mL) post session one, at 90 (9.20 ± 1.88 mlU/mL, p = 0.048) and 180 min (9.04 ± 2.35 mlU/mL, p = 0.046). Iron increased from baseline (18 ± 3 µmol/L) post week five (23 ± 2 µmol/L, p = 0.033) and six (21 ± 6 µmol/L; p = 0.041), whereas ferritin was observed to be lower than baseline (111 ± 82 µg/L) post week five (95 ± 75 µg/L; p = 0.016), six (84 ± 74 µg/L; p = 0.012) and one week post-training (81 ± 63 µg/L; p = 0.008). Reticulocytes increased from baseline (57 ± 12 × 109/L) post week one (72 ± 17 × 109/L, p = 0.037) and six (71 ± 17 × 109/L, p = 0.021) while no changes were recorded in erythrocytes (p = 0.336), haemoglobin (p = 0.124) and splenic volumes (p = 0.357). Conclusions Six weeks of dynamic apnoeic training increase reticulocytes without altering mature erythrocyte concentration and splenic volume.

Background: Sarcopenia is characterised by losses in muscle mass, strength and function. It is a contributing factor to numerous non-communicable diseases and frailty. Screening for sarcopenia typically requires measurements of handgrip strength, functional performance, and skeletal muscle mass. However, available tools do not tend to measure strength of the lower extremities. The aim of this study was to investigate associations between these measures and lower extremity strength with skeletal muscle mass in healthy young and older adults. Methods: Fifty younger (mean ± SD age = 22.7 ± 5.4 years) and 50 older (age = 69.9 ± 4.3 years) individuals received the following measurements after an overnight fast: Skeletal Muscle Index (SMI) derived by dual-energy X-ray absorptiometry, gait speed, handgrip strength (HGS), and unilateral one-repetition maximum (1RM) leg extension strength. Muscle quality (MQ), was also determined as the ratio of grip strength to appendicular lean mass of the upper body. Results: One older female and one older male were pre-sarcopenic and sarcopenic. Upper extremity MQ was below established cutpoints in 21 older participants. SMI was positively associated with upper and lower extremity strength in all groups except older men, and negatively associated with upper extremity MQ in young males. By multiple regression analysis, dominant HGS and dominant leg extension 1RM strength predicted SMI in the complete sample, accounting for 70.3% of the variance (B = 0.469 and 0.421, respectively; P < 0.00001). The equation for SMI is as follows: 4.568 + 0.025 x dominant leg extension 1RM + 0.059 x dominant grip strength. Discussion: Since muscle mass is the foremost variable in determining sarcopenia, we support the inclusion of lower extremity strength testing in addition to that of handgrip strength to enable better prediction of SMI in both older and younger individuals. MQ determination is also recommended since established algorithms may fail to identify individuals with muscle weakness.

Introduction: This thesis addresses a critical gap in track cycling research, presenting the first academic study focused on identifying performance factors in the elite men’s Omnium Points Race, a field where, until now, coaches have largely relied on experiential insights, or extrapolated data from other cycling disciplines. Grounded in the author’s dual role as a coach and analyst with national cycling teams from Japan and the USA, the thesis is shaped by three primary aims: (1) to investigate elite coaches' perceptions regarding key performance factors in the Points Race, and the role of data in competitive decision making and outcomes; (2) to analyse physical, tactical, and strategic performance factors in the Points Race; and (3) to develop an actionable framework to support coaches and analysts in integrating insights from data to enhance training, competition strategies, and overall performance.Methodology: A multi-method approach was employed, including semi-structured interviews with elite coaches and video-based performance analysis of seven world-class Points Races from the 2019/20 season. These data informed the development of the Racecraft Framework – a systems informed conceptual model that reflects the complexity of Omnium racing, mapping how multiple interdependent factors underpin race outcomes.Results: In Chapter 5, coaches of elite male Omnium cyclists revealed that performance is conceptualised as a multifaceted combination of physical attributes (e.g., power and aerobic capacity), tactical intelligence, strategic awareness, and psychological resilience. Chapter 6 reveals that repeatable access to high speed, rather than peak speed alone, is more indicative of performance, aligning with a view of racing as a dynamic system of shifting demands. Chapter 7 highlights that there was a variation in the speed of points scoring sprint ranks throughout the subsectionTenLaps leading into each intermediate sprint highlighting a variety of tactics used. Positional analysis showed the top-ranked cyclists achieving advanced positions earlier in the subsection to make the most of point scoring opportunities. Analysis of successful lap gains reveal that they often occur as part of broader strategic plays that include intermediate point accumulation, with most lap gains made by small groups, and most frequently take between 9.5-10.5, or 15.5-16.5 laps to complete. Chapter 8 then explores the strategies among cyclists, emphasising the systems thinking needed to manage energy, positioning, and point scoring over time. High-ranking cyclists score consistently across intermediate sprints and secure positions by capitalising on speed variations throughout the race, often establishing an unassailable lead before the final sprint.Practical Applications: The Racecraft Framework, developed iteratively through a review of and reflection on existing literature, interviews with coaches, video analysis, and the authors own experiences of working as a track cycling coach and performance analyst at the highest level, provides a conceptual model for coaches and analysts to evaluate the physical, tactical, and strategic complexity of Points Race performance. Its real-world utility was demonstrated in athlete preparation for the Tokyo Olympics. A final reflections chapter draws together methodological, applied, and personal insights, reinforcing the thesis’s value as both an academic and practical contribution to enhancing track cycling performance.

We appreciate the opportunity to respond to the comments raised by Silva and Cipriano [1] regarding our recently published systematic review and meta-analysis on acute sarcopenia [2]. Constructive discussions such as this help clarify methodological considerations and enhance scientific understanding. Firstly, regarding knee extensor strength measurement, Silva and Cipriano [1] note that our review stated their study [3] did not assess knee extensor strength. We acknowledge that they measured strength using neuromuscular electrical stimulation to evoke peak force. However, our review excluded studies using electrically evoked contractions, as voluntary contractions are the recognised standard for sarcopenia assessments. This exclusion criterion was applied consistently across all studies, ensuring methodological alignment. Although we did not explicitly state this in our inclusion/exclusion criteria, we appreciate the opportunity to clarify this point. To further justify our stance on excluding this, we would like to highlight conclusions from Jenkins et al. [4] who acknowledged that voluntary and evoked contractions offer unique information to each other and should not be used interchangeably. Secondly, with reference to the sample size inclusion, we included only the control group from Silva et al.'s study, as per our inclusion criteria that specified that only control groups from intervention studies would be included. Although their total sample size was 60 participants, we reported only the control group (n = 30) as our review focused on muscle changes during hospitalisation independent of interventions. We acknowledge that this distinction could have been stated more clearly. We respectfully disagree with the claim that our review contains inaccuracies that could compromise the integrity of the scientific record. Our methodological decisions were carefully considered, transparent, and aligned with standard sarcopenia assessment practices. The exclusion of electrically evoked contraction measures was a deliberate methodological choice, as voluntary contractions are the established standard. Although this criterion was not explicitly outlined in our inclusion/exclusion criteria, it reflects a methodological decision rather than an inaccuracy. We appreciate the opportunity to clarify this and believe our approach remains clear to researchers familiar with standard assessment methods. We thank Silva et al. for their engagement and the opportunity to address these points.

Background: The benefits of exercise for people with rheumatoid arthritis (RA) are now widely recognised [1]. However, exercise participation among people with RA remains low. A key reason for that could be the commonly held belief that exercise, may exacerbate disease activity while acutely increasing levels of joint pain. The association of acute exercise with pain has not been established in RA and especially in people with a recent diagnosis. Objectives: This study investigated the impact of acute aerobic-and resistance-type exercise on perceptions of pain in people with early RA. Methods: Following local NHS ethical approval, ten people with RA volunteered for the study (Age=46±13years; BMI=29.4±8.6kg/m2, RA diagnosis= 13±9months, mean±SD). Inclusion criteria were RA diagnosis (2010 EULAR criteria) within the last two years and not engaging in regular physical activity (i.e. no participation in structured exercise >2 times per week). They were assessed for maximal aerobic capacity and maximal strength at chest press, leg press and wide-grip lateral pulldown to determine intensities for exercise conditions. Thereafter they completed one no-exercise control trial (CON) and four exercise trials: 30 minutes of sub-maximal cycling at a workload equivalent to 65% VO2max (CYCLE); high intensity interval exercise consisting of 10x1 minutes cycling intervals at a workload equivalent to 95% VO2max (HIIE); resistance exercise consisting of three sets of 12-15 repetitions at 70%1RM (RES-70); resistance exercise consisting of three sets of repetitions to failure at 30%1RM (RES-30). All trials were randomised and separated by a washout period of 3-7 days. Participants completed a a visual analogue scale (VAS) for pain at baseline then 2-and 24-hours post exercise; they also completed a questionnaire related to exercise enjoyment 2-and 24-hours post exercise. Results: Currently four RA participants have completed the study and all participants completed the prescribed exercises in full. Perceived pain was low at 2 hours (0.7±0.4) and 24 hours post-exercise (1.2±0.8) for all exercise conditions (see table 1). Importantly, a difference in heart rate between the aerobic conditions (heart rate during HIIE was 16% higher than during CYCLE), and a difference in workload between the resistance conditions (RES-30 was 117% higher than RES-70) did not result in a difference in pain perception. One participant reported increased pain at 24 hours (7cm vs 1cm at 2 hours) post RES-30, but claimed that this was purely muscular and not joint pain. Interestingly, all participants enjoyed the exercises with comparable high results across the exercise conditions (see table 1). Conclusion: This study identified minimal exercise effect on perceived pain at 2 hours-and 24 hours-post exercise among participants with early RA. This suggests that exercise did not exacerbate pain and importantly, high intensities and high loads did not cause additional pain. Nevertheless, further larger studies are required to examine the role of acute exercise on disease activity, e.g. inflammation, and the association with perceived pain in people with early RA. References: [1]Combe B, et al. 2016 update of the EULAR recommendations for the management of early arthritis. Annals of the Rheumatic Diseases 2016; 76: 948-959. Disclosure of Interests: None declared Table 1 Pain and Enjoyment Descriptives Trial Baseline VAS pain (cm) 2-hour VAS pain (cm) 24-hour VAS pain (cm) 2-hour exercise enjoyment (1-119) 24-hour exercise enjoyment (1-119) CON 0.1±0.3 0.1±0.3 0.3±0.3 63.8±13.0 63.8±13.0 CYCLE 0.1±0.3 0.5±0.4 0.9±1.2 86.8±11.0 88.0±8.8 HIIE 0.1±0.3 1.3±1.9 1.1±1.7 85.0±27.8 88.3±19.1 RES-70 0.1±0.3 0.4±0.4 0.5±0.4 91.3±13.0 88.3±6.6 RES-30 0.1±0.3 0.4±0.5 2.4±3.1 88.5±17.1 85.0±13.1 (mean±SD)

PURPOSE: Beneficial effects of carbohydrate (CHO) ingestion on exogenous CHO oxidation and endurance performance require a well-functioning gastrointestinal (GI) tract. However, GI complaints are common during endurance running. This study investigated the effect of a CHO solution-containing sodium alginate and pectin (hydrogel) on endurance running performance, exogenous and endogenous CHO oxidation and GI symptoms. METHODS: Eleven trained male runners, using a randomised, double-blind design, completed three 120-minute steady state runs at 68% V̇O2max, followed by a 5-km time-trial. Participants ingested 90 g·h-1 of 2:1 glucose:fructose (13C enriched) either as a CHO hydrogel, a standard CHO solution (non-hydrogel), or a CHO-free placebo during the 120 minutes. Fat oxidation, total and exogenous CHO oxidation, plasma glucose oxidation and endogenous glucose oxidation from liver and muscle glycogen were calculated using indirect calorimetry and isotope ratio mass spectrometry. GI symptoms were recorded throughout the trial. RESULTS: Time-trial performance was 7.6% and 5.6% faster after hydrogel ([minutes:seconds]19:29±2:24; p<0.001) and non-hydrogel (19:54±2:23, p=0.002), respectively, versus placebo (21:05±2:34). Time-trial performance after hydrogel was 2.1% faster (p=0.033) than non-hydrogel. Absolute and relative exogenous CHO oxidation was greater with hydrogel (68.6±10.8g, 31.9±2.7%; p=0.01) versus non-hydrogel (63.4±8.1g, 29.3±2.0%; p=0.003). Absolute and relative endogenous CHO oxidation were lower in both CHO conditions compared with placebo (p<0.001), with no difference between CHO conditions. Absolute and relative liver glucose and muscle glycogen oxidation were not different between CHO conditions. Total GI symptoms were not different between hydrogel and placebo, but GI symptoms was higher in non-hydrogel compared with placebo and hydrogel (p<0.001). CONCLUSION: Ingestion of glucose and fructose in hydrogel form during running benefited endurance performance, exogenous CHO oxidation and GI symptoms, compared with a standard CHO solution.

Serum erythropoietin (EPO) concentration is increased following static apnoea-induced hypoxia. However, the acute erythropoietic responses to a series of dynamic apnoeas in non-divers (ND) or elite breath-hold divers (EBHD) are unknown. Participants were stratified into EBHD (n=8), ND (n=10) and control (n=8) groups. On two separate occasions EBHD and ND performed a series of five maximal dynamic apnoeas (DYN) or two sets of five maximal static apnoeas (STA). Control performed a static eupnoeic (STE) protocol to control against any effects of water immersion and diurnal variation on EPO. Peripheral oxygen saturation (SpO2) levels were monitored up to 20s post each maximal effort. Blood samples were collected at 30, 90, and 180-min after each protocol for EPO, haemoglobin and haematocrit concentrations. No between group differences were observed at baseline (p>0.05). For EBHD and ND, mean end-apnoea SpO2 was lower in DYN (EBHD,62±10%,p=0.024;ND,85±6%;p=0.020) than STA (EBHD,76±7%;ND,96±1%) and control (98±1%) protocols. EBHD attained lower end-apnoeic SpO2 during DYN and STA than ND (p<0.001). Serum EPO increased from baseline following the DYN protocol in EBHD only (EBHD,p<0.001;ND,p=0.622). EBHD EPO increased from baseline (6.85±0.9mlU/mL) by 60% at 30-min (10.82±2.5mlU/mL,p=0.017) and 63% at 180-min (10.87±2.1mlU/mL,p=0.024). Serum EPO did not change after the STA (EBHD,p=0.534;ND,p=0.850) and STE (p=0.056) protocols. There was a significant negative correlation (r=-0.49,p=0.003) between end-apnoeic SpO2 and peak post-apnoeic serum EPO concentrations. The novel findings demonstrate that circulating EPO is only increased after DYN in EBHD. This may relate to the greater hypoxemia achieved by EBHD during the DYN.

Purpose: This pilot study investigated differences in lean tissue mass, muscle strength, muscle quality (strength per unit of muscle mass; MQ), and functional performance in healthy younger and older individuals. The most robust predictors of appendicular lean mass (ALM) were then determined in each group.

Splenic contractions occur in response to apnoea‐induced hypoxia with and without facial water immersion. However, the splenic responses to a series of static (STA) or dynamic (DYN) apnoeas with whole‐body water immersion in non‐divers (NDs) and elite breath‐hold divers (EBHDs) are unknown. EBHD (n = 8), ND (n = 10) and control participants (n = 8) were recruited. EBHD and ND performed a series of five maximal DYN or STA on separate occasions. Control performed a static eupnoeic (STE) protocol to control against any effects of water immersion and diurnal variation on splenic volume and haematology. Heart rate (HR) and peripheral oxygen saturation (SpO2) were monitored for 30 s after each apnoea. Pre‐ and post‐apnoeic splenic volumes were quantified ultrasonically, and blood samples were drawn for haematology. For EBHD and ND end‐apnoeic HR was higher (P < 0.001) and SpO2 was lower in DYN (P = 0.024) versus STA. EBHD attained lower end‐apnoeic SpO2 during DYN and STA than NDs (P < 0.001). Splenic contractions occurred following DYN (EBHD, −47 ± 6%; ND, −37 ± 4%; P < 0.001) and STA (EBHD, −26 ± 4%; ND, −26 ± 8%; P < 0.01). DYN‐associated splenic contractions were greater than STA in EBHD only (P = 0.042). Haemoglobin concentrations were higher following DYN only (EBHD, +5 ± 8g/L , +4 ± 2%; ND, +8 ± 3 g/L , +4.9 ± 3%; P = 0.019). Haematocrit remained unchanged after each protocol. There were no between group differences in post‐apnoeic splenic volume or haematology. In both groups, splenic contractions occurred in response to STA and DYN when combined with whole‐body immersion. DYN apnoeas, were effective at increasing haemoglobin concentrations but not STA apnoeas. Thus, the magnitude of the splenic response relates to the hypoxemic stress encountered during apnoeic epochs.

Purpose The aim of the study was to provide an evaluation of the oxygen transport, exchange and storage capacity of elite breath-hold divers (EBHD) compared with non-divers (ND). Methods Twenty-one healthy males’ (11 EBHD; 10 ND) resting splenic volumes were assessed by ultrasound and venous blood drawn for full blood count analysis. Percutaneous skeletal muscle biopsies were obtained from the m. vastus lateralis to measure capillarisation, and fibre type-specific localisation and distribution of myoglobin and mitochondrial content using quantitative immunofluorescence microscopy. Results Splenic volume was not different between groups. Reticulocytes, red blood cells and haemoglobin concentrations were higher (+ 24%, p < 0.05; + 9%, p < 0.05; + 3%, p < 0.05; respectively) and mean cell volume was lower (− 6.5%, p < 0.05) in the EBHD compared with ND. Haematocrit was not different between groups. Capillary density was greater (+ 19%; p < 0.05) in the EBHD. The diffusion distance (R95) was lower in type I versus type II fibres for both groups (EBHD, p < 0.01; ND, p < 0.001), with a lower R95 for type I fibres in the EBHD versus ND (− 13%, p < 0.05). Myoglobin content was higher in type I than type II fibres in EBHD (+ 27%; p < 0.01) and higher in the type I fibres of EBHD than ND (+ 27%; p < 0.05). No fibre type differences in myoglobin content were observed in ND. Mitochondrial content was higher in type I than type II fibres in EBHD (+ 35%; p < 0.05), with no fibre type differences in ND or between groups. Conclusions In conclusion, EBDH demonstrate enhanced oxygen storage in both blood and skeletal muscle and a more efficient oxygen exchange capacity between blood and skeletal muscle versus ND.

Background: Acute sarcopenia is sarcopenia lasting less than six months, typically following acute illness or injury. It may impact patient recovery and quality of life, advancing to chronic sarcopenia. However, its development and assessment remain poorly understood, particularly during hospitalisation. This systematic review aimed to elucidate the incidence of acute sarcopenia and examine changes in muscle parameters during hospitalisation. Methods: Eighty-eight papers were included in the narrative synthesis; 33 provided data for meta-analyses on the effects of hospitalisation on handgrip strength (HGS), rectus femoris cross-sectional area (RFCSA) and various muscle function tests. Meta-regressions were performed for length of hospital stay (LoS) and age for all meta-analyses; sex was also considered for HGS. Results: Acute sarcopenia development was assessed in four studies with a pooled incidence of 18% during hospitalisation. Incidence was highest among trauma patients in intensive care (59%) while it was lower among medical and surgical patients (15-20%). Time of development ranged from 4-44 days. HGS remained stable during hospitalisation (SMD = 0.05, 95% CI = -0.18:0.28, P = 0.67) as did knee extensor strength. LoS affected HGS performance (θ = 0.04, 95% CI = 0.001:0.09, P = 0.045) but age (P = 0.903) and sex (P = 0.434) did not. RFCSA, reduced by 16.5% over 3 to 21 days (SMD = -0.67, 95% CI = -0.92:-0.43, P <0.001); LoS or time between scans did significantly predict the reduction (θ = -0.04, 95% CI = -0.077:-0.011, P = 0.012). Indices of muscle quality also reduced. Muscle function improved when assessed by the short physical performance battery (SMD = 0.86, 95% CI = 0.03:1.69, P = 0.046); there was no change in 6-minute walk (P = 0.22), timed up-and-go (P = 0.46) or gaitspeed tests (P = 0.98). The only significant predictor of timed up-and-go performance was age (θ = -0.11, 95% CI = -0.018:-0.005, P = 0.009). Conclusions: Assessment and understanding of acute sarcopenia in clinical settings is limited. Incidence varies between clinical conditions and muscle parameters are affected differently. HGS and muscle function tests may not be sensitive enough to identify acute changes during hospitalisation. Currently, muscle health deterioration may be underdiagnosed impacting recovery, quality of life and overall health following hospitalisation. Further evaluation is necessary to determine the suitability of existing diagnostic criteria of acute sarcopenia. Muscle mass and quality indices might need to become the primary determinants for muscle health assessment in hospitalised populations.

Background: Exercise is advocated in the treatment of rheumatoid arthritis (RA). However, uncertainty around the acute effects of exercise on pain and inflammation may be stopping people with RA from exercising more regularly. Objectives: To determine the acute effects of exercise on pain symptoms, clinical inflammatory markers, and inflammatory cytokines in RA. Design: A systematic review of the literature. Data sources and methods: Five databases were searched (PubMed, Cochrane Library, CINAHL, Scopus and SPORTDiscus); inclusion criteria were studies with acute exercise, a definite diagnosis of RA and disease characteristics assessed by clinical function (i.e., disease activity score, health assessment questionnaire and self-reported pain), clinical markers associated with inflammation (i.e., c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), and inflammatory cytokines (i.e., interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)). Results: From a total of 1544 articles, initial screening and full text assessment left 11 studies meeting the inclusion criteria. A total of 274 people were included in the studies (RA = 186; control = 88). Acute bouts of aerobic, resistance, and combined aerobic and resistance exercise did not appear to exacerbate pain symptoms in people with RA. Conclusion: Post-exercise responses for pain, clinical inflammatory markers and inflammatory cytokines were not different between people with or without RA. Exercise prescription was variable between studies, which limited between-study comparisons. Therefore, future investigations in people with RA are warranted, which combine different exercise modes and intensities to examine acute effects on pain symptoms and inflammatory markers. Registration: The PROSPERO international prospective register of systematic reviews - CRD42018091155.

MicroRNAs (miRNAs) are endogenously generated single-stranded RNAs that play crucial roles in numerous biological processes, such as cell development, proliferation, differentiation, metabolism and apoptosis. They negatively regulate target gene expression by repressing translation of messenger RNA into a functional protein. Several miRNAs have been implicated in the development and progression of RA. They are involved in inflammatory and immune processes and are associated with susceptibility to RA and disease activity. They are also considered to be potential markers of disease activity or even therapeutic targets. Likewise, several miRNAs are affected acutely by exercise and regulate exercise-related adaptations in the skeletal muscle and cardiovascular system and aerobic fitness. Interestingly, some miRNAs affected by exercise are also important in the context of RA. Investigating these might increase our understanding of the effects of exercise in RA and improve exercise prescription and, potentially, disease management. In this review, we focus on the miRNAs that are associated with both RA and exercise and discuss their roles in (and potential interactions between) RA and exercise-induced adaptations.

The COVID-19 pandemic and social distancing restrictions have significantly reduced population-wide physical activity (PA) levels. However, the impact of the pandemic and relevant restrictions on PA participation, and any potential barriers to it, in people with rheumatoid arthritis (RA) are not clear. Furthermore, we are unsure if any such PA changes have affected their body weight, mental wellbeing, and/or quality of life (QoL). Thus, the aim of this study was to examine the impact of the lockdown on PA participation in people with RA, versus people without RA. Participants (n = 128; RA = 27, non-RA = 101) completed a self-administered online survey, which included questions on PA, body weight, mental wellbeing and QoL. PA participation during lockdown was significantly lower among RA versus non-RA participants (p < 0.001). Additionally, a similar profile of results was found where more RA participants vs non-RA participants reported reduced habitual PA (59% vs 33%) and increased body weight (59% vs 35%). Mental wellbeing scores were similarly low in both groups during lockdown (RA: 20.8 ± 4.2; non-RA: 22.2 ± 3.4, p = 0.080). Matched group comparisons identified similar trends to full sample analyses. In the first months of the lockdown, more people with RA reported decreased PA participation and increased body weight than their non-RA counterparts. Access to exercise equipment and facilities appears to be the main cause for these results. Looking beyond COVID-19, specific PA promotion for people with RA will be required to prevent a pandemic of inactivity.

Fatty acids are stored within the muscle as intramyocellular lipids (IMCL). Some, but not all, studies indicate that following a high-fat diet (HFD), IMCL may accumulate and affect insulin sensitivity. This systematic review and meta-analysis aimed to quantify the effects of an HFD on IMCL. It also explored the potential modifying effects of HFD fat content and duration, IMCL measurement technique, physical activity status, and the associations of IMCL with insulin sensitivity. Five databases were systematically searched for studies that examined the effect of ≥3 d of HFD (>35% daily energy intake from fat) on IMCL content in healthy individuals. Meta-regressions were used to investigate associations of the HFD total fat content, duration, physical activity status, IMCL measurement technique, and insulin sensitivity with IMCL responses. Changes in IMCL content and insulin sensitivity (assessed by hyperinsulinemic-euglycemic clamp) are presented as standardized mean difference (SMD) using a random effects model with 95% confidence intervals (95% CIs). Nineteen studies were included in the systematic review and 16 in the meta-analysis. IMCL content increased following HFD (SMD = 0.63; 95% CI: 0.31, 0.94, P = 0.001). IMCL accumulation was not influenced by total fat content (P = 0.832) or duration (P = 0.844) of HFD, physical activity status (P = 0.192), or by the IMCL measurement technique (P > 0.05). Insulin sensitivity decreased following HFD (SMD = –0.34; 95% CI: –0.52, –0.16; P = 0.003), but this was not related to the increase in IMCL content following HFD (P = 0.233). Consumption of an HFD (>35% daily energy intake from fat) for ≥3 d significantly increases IMCL content in healthy individuals regardless of HFD total fat content and duration of physical activity status. All IMCL measurement techniques detected the increased IMCL content following HFD. The dissociation between changes in IMCL and insulin sensitivity suggests that other factors may drive HFD-induced impairments in insulin sensitivity in healthy individuals. This trial was registered at PROSPERO as CRD42021257984.

Age-related sarcopenia is a syndrome characterised by progressive decline in skeletal muscle mass and strength (von Haehling, Morley, & Anker, 2010). The European Working Group on Sarcopenia in Older People recommends the measurement of muscle mass and function as means of diagnosing sarcopenia (Cruz-Jentoft et al., 2010) since sole focus on measurement of muscle mass may be of limited value. The age-associated loss of muscle strength (Dynapenia) cannot be only explained by reductions in muscle size since reductions in strength are more rapid than reductions in muscle (Clark & Manini, 2012). Cawthon et al. (2014) developed cut points for appendicular lean mass (ALM) that would identify individuals with clinically significant weakness taking into account both ALM and strength. Since sarcopenia is a multifaceted syndrome with potentially modifiable factors such as dietary intakes, the aim of this pilot study was to explore the interrelationships between dietary intakes, ALM, and strength. Twenty-five healthy older adults including both female (n=15, age: 68.8 ± 2.9 years) and male (n =10, age 69.5 ± 2.5 years) participants completed a 7-day diet diary before having their handgrip strength and body composition (dual energy X-ray absorptiometry) measured. Males with ALM<19.75 kg and females with ALM<15.02 kg were defined as having low lean muscle mass, whilst cut points of <30 kg and <20 kg (Campbell & Vallis, 2014) were used to identify males and females with low strength. Participants received guidance on recording food and drink by household measures. Energy expenditure was calculated using the World Health Organization/Food and Agriculture Organization equation (Frankenfield, Roth-Yousey, & Compher, 2005) for resting energy expenditure and an activity factor of 1.5. Forty percent (40%) of the females displayed low muscle strength while their male counterparts were all above the 30 kg cut point. ALM was 25.6±3.7 and 15.9±1.7 kg for males and females respectively. Twenty-seven percent (27%) of the females were below the cut point for low lean mass whilst males were all above the equivalent cut point. Energy intake (EI) was 1753±366 kcal for males and 1376±270 kcal for females corresponding to an EI deficit of 27.8±21.7 % and 27.7±6 % for males and females respectively. EI was significantly (P<0.05) lower than recommended EI. Protein intake was 0.97±0.3 g·kg·d-1 for the males and 0.95±0.2 g·kg·d-1 for the females representing 18.8±3.1 and 17.8±2.4 % of EI for males and females respectively. Our findings suggest that females in early retirement years are at greater risk of sarcopenia and dynapenia than their male counterparts. Inadequate energy intake and protein consumption which was below current research led recommendations of 20 % suggest that females may benefit from dietary interventions that would address energy and protein deficits. References Campbell, T. M., & Vallis, L. A. (2014). Predicting fat-free mass index and sarcopenia in assisted-living older adults. Age (Dordr), 36(4), 9674. doi: 10.1007/s11357-014-9674-8 Cawthon, P. M., Peters, K. W., Shardell, M. D., McLean, R. R., Dam, T.-T. L., Kenny, A. M., . . . Guralnik, J. M. (2014). Cutpoints for low appendicular lean mass that identify older adults with clinically significant weakness. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69(5), 567-575. Clark, B. C., & Manini, T. M. (2012). What is dynapenia? Nutrition, 28(5), 495-503. doi: 10.1016/j.nut.2011.12.002 Cruz-Jentoft, A. J., Baeyens, J. P., Bauer, J. M., Boirie, Y., Cederholm, T., Landi, F., . . . European Working Group on Sarcopenia in Older, P. (2010). Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing, 39(4), 412-423. doi: 10.1093/ageing/afq034 Frankenfield, D., Roth-Yousey, L., & Compher, C. (2005). Comparison of predictive equations for resting metabolic rate in healthy nonobese and obese adults: a systematic review. J Am Diet Assoc, 105(5), 775-789. doi: 10.1016/j.jada.2005.02.005 Morley, J. E. (2008). Sarcopenia: diagnosis and treatment. J Nutr Health Aging, 12(7), 452-456. von Haehling, S., Morley, J. E., & Anker, S. D. (2010). An overview of sarcopenia: facts and numbers on prevalence and clinical impact. J Cachexia Sarcopenia Muscle, 1(2), 129-133. doi: 10.1007/s13539-010-0014-2

The ergogenic benefits of carbohydrate (CHO) ingestion in cycling and running have been widely reported. Studies directly comparing the effect of CHO ingestion on CHO oxidation rates in cycling and running suggest no difference in exogenous CHO oxidation between these exercise modes. Potential differences in endogenous fuel use between cycling and running when ingesting CHO may lead to a greater benefit in cycling rather than running time trial (TT) performance. Direct comparisons of the effect of CHO ingestion during endurance exercise on subsequent cycling or running TT performance are limited. This study tested the hypothesis that ingesting CHO during 120 min of constant intensity exercise would benefit subsequent TT performance more in cycling than running. Methods: In a randomised, placebo controlled, double blind crossover trial, 10 male triathletes (VO2 max cycle 51.65±5.53, run 59.07±6.14 mL kg min ) completed 4 separate exercise trials. Each trial consisted of cycling or running at 70% of mode specific VO2max for 120min whilst ingesting either a CHO drink (2:1 glucose: fructose, 90g h ) or an equal volume of taste matched 0% CHO placebo (PLA) (750mL h ). After 10min recovery, participants completed a TT in the same mode of exercise, running 6km or cycling 16km. The CHO drink was enriched with uniformly labelled C glucose and C fructose isotopes to quantify exogenous and endogenous CHO oxidation. Due to limitations of the tracer methods used in the first hour, only data for the final 60min of exercise are presented. Total CHO and fat oxidation rates were calculated from expired air using stoichiometric equations. Data were analysed using ANOVA, values are means±SD. Results: From 60 120 min of exercise mean fat oxidation rates did not differ between exercise modes (PLA cycle 0.52±0.17, run 0.56±0.22g min p=0.86; CHO cycle 0.37±0.12 run 0.40±0.17g min , p=0.82). CHO ingestion reduced fat oxidation within cycling (p<0.01) and running trials (p=0.02) compared to PLA. Mean total CHO oxidation rates did not differ between trials (PLA cycle 2.52±0.74, run 2.21±0.46g min , p=0.23, CHO cycle 2.95±0.40, run 2.77±0.55g min , p=0.47). Mean exogenous CHO oxidation did not differ with CHO ingestion (cycle 0.87±0.22 run 0.75±0.31g min , p=0.31). CHO ingestion reduced endogenous CHO oxidation in cycling (PLA 2.52±0.74, CHO 2.10±0.41g min , p=0.03) but not running (PLA 2.21±0.46, CHO 2.00±0.61g min , p=0.44). TT performance improved 10% in cycling and 3% in running after CHO ingestion (p<0.01). TT performance improvement was greater in cycling than running (p=0.04, ES=1.45). Conclusions: This study demonstrates a greater improvement in cycling versus running TT performance after CHO ingestion. This may relate to the greater sparing of endogenous CHO in cycling versus running during the previous exercise period when CHO is ingested.

We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signalling in healthy younger (28 ± 4 years) and older (71 ± 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE; following the consumption of two 50 mL EAA gels (40% leucine, 15 g total EAA); and following RE with EAA (combination; COM). Protein content and the phosphorylation status of key anabolic signalling proteins were determined via immunoblotting. Irrespective of age, during EAA and COM peak leucinemia (younger: 454 ± 32 µM and 537 ± 111 µM; older: 417 ± 99 µM and 553 ± 136 µM) occurred ~60 – 120 min post-ingestion (younger: 66 ± 6 min and 120 ± 60 min; older: 90 ± 13 min and 78 ± 12 min). In the pooled sample, area under the curve for plasma leucine and the sum of branched-chain amino acids was significantly greater in EAA and COM compared with RE. For intramyocellular signalling, significant main effects were found for condition (mTOR (Ser2481), rpS6 (Ser235/236)) and age (S6K1 (Thr421/Ser424), 4E-BP1 (Thr37/46)) in age group analyses. The phosphorylation of rpS6 was of similar magnitude (~8-fold) in pooled and age group data 2 h following COM. Our findings suggest that a gel-based, leucine-enriched EAA supplement is associated with aminoacidemia and a muscle anabolic signalling response, thus representing an effective means of stimulating muscle protein anabolism in younger and older adults following EAA and COM.

To establish the criterion-assessed energy and fluid requirements of female netball players, 13 adult players from a senior Netball Super League squad were assessed over 14 days in a cross-sectional design, representing a two- and one-match microcycle, respectively. Total energy expenditure (TEE) and water turnover (WT) were measured by doubly labeled water. Resting and activity energy expenditure were measured by indirect calorimetry and Actiheart, respectively. Mean 14-day TEE was 13.46 ± 1.20 MJ day−1 (95% CI, 12.63–14.39 MJ day−1). Resting energy expenditure was 6.53 ± 0.60 MJ day−1 (95% CI, 6.17–6.89 MJ day−1). Physical activity level was 2.07 ± 0.19 arbitrary units (AU) (95% CI, 1.95–2.18 AU). Mean WT was 4.1 ± 0.9 L day−1 (95% CI, 3.6–4.7 L day−1). Match days led to significantly greater TEE than training (+2.85 ± 0.70 MJ day−1; 95% CI, +1.00– +4.70 MJ day−1; p = 0.002) and rest (+4.85 ± 0.70 MJ day−1; 95% CI, +3.13–+6.56 MJ day−1; p < 0.001) days. Matches led to significantly greater energy expenditure (+1.85 ± 1.27 MJ; 95% CI, +0.95–+2.76 MJ day−1; p = 0.001) than court-based training sessions. There was no significant difference in TEE (+0.03 ± 0.35 MJ day−1; 95% CI, −0.74–+0.80 MJ day−1; p = 0.936) across weeks. Calibrated Actiheart 5 monitors underestimated TEE (−1.92 ± 1.21 MJ day−1). Energy and fluid turnover were greatest on match days, followed by training and rest days, with no difference across weeks. This study provides criterion-assessed energy and fluid requirements to inform dietary guidance for female netball players.

This narrative review examines the mechanisms underlying the development of cardiovascular (CVD) and metabolic diseases (MDs), along with their association with sarcopenia. Furthermore, non-pharmacological interventions to address sarcopenia in patients with these conditions are being suggested. The significance of combined training in managing metabolic disease and secondary sarcopenia in type II diabetes mellitus is emphasized. Additionally, the potential benefits of resistance and aerobic training are being explored. This review emphasises the role of nutrition in addressing sarcopenia in patients with CVD or MDs, focusing on strategies such as optimising protein intake, promoting plant-based protein sources, incorporating antioxidant-rich foods and omega-3 fatty acids, and ensuring sufficient vitamin D levels. Moreover, the potential benefits of targeting gut microbiota through probiotics and prebiotic fibres in sarcopenic individuals are being considered. Multidisciplinary approaches that integrate behavioural science are explored to enhance the uptake and sustainability of behaviour-based sarcopenia interventions. Future research should prioritise high-quality randomized controlled trials to refine exercise and nutritional interventions and investigate the incorporation of behavioural science into routine practices. Ultimately, a comprehensive and multifaceted approach is essential to improve health outcomes, well-being, and quality of life in older adults with sarcopenia and coexisting cardio-vascular and metabolic diseases.