Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma.

In the pivotal ZUMA-5 trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients. Here, outcomes from ZUMA-5 are compared with the international SCHOLAR-5 cohort, which applied key ZUMA-5 trial eligibility criteria simulating randomized controlled trial conditions. SCHOLAR-5 data were extracted from institutions in 5 countries, and from 1 historical clinical trial, for r/r FL patients who initiated a third or higher line of therapy after July 2014. Patient characteristics were balanced through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. Time-to-event outcomes were evaluated using weighted Kaplan-Meier analysis. Overall response rate (ORR) and complete response (CR) rate were compared using weighted odds ratios. The 143 ScHOLAR-5 patients reduced to an effective sample of 85 patients after SMR weighting vs 86 patients in ZUMA-5. Median follow-up time was 25.4 and 23.3 months for SCHOLAR-5 and ZUMA-5. Median overall survival (OS) and progression-free survival (PFS) in SCHOLAR-5 were 59.8 months and 12.7 months and not reached in ZUMA-5. Hazard ratios for OS and PFS were 0.42 (95% confidence interval [CI], 0.21-0.83) and 0.30 (95% CI, 0.18-0.49). The ORR and CR rate were 49.9% and 29.9% in SCHOLAR-5 and 94.2% and 79.1% in ZUMA-5, for odds ratios of 16.2 (95% CI, 5.6-46.9) and 8.9 (95% CI, 4.3-18.3). Compared with available therapies, axi-cel demonstrated an improvement in meaningful clinical endpoints, suggesting axi-cel addresses an important unmet need for r/r FL patients. This trial was registered at www.clinicaltrials.gov as #NCT03105336.

Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study.

The SCHOLAR-5 study examines treatment patterns and outcomes of real-world follicular lymphoma (FL) patients on 3rd line of treatment (LoT) or higher, for whom existing data are limited. SCHOLAR-5 is a retrospective cohort study using data from adults (≥ 18 years) with grade 1-3a FL, initiating ≥3rd LoT after June 2014 at major lymphoma centers in the US and Europe. Objective response rate (ORR), complete response (CR), progression-free survival (PFS) and overall survival (OS) were analyzed by LoT. Time-to-event outcomes were assessed using Kaplan-Meier methods. Of 128 patients, 87 initiated 3rd LoT, 63 initiated 4th LoT, and 47 initiated 5th LoT. At 1st eligible LoT, 31% progressed within 24-months of 1st LoT anti-CD20 combination therapy, 28% had prior autologous stem cell transplantation, and 31% were refractory to the previous LoT. The most common regimen in each LoT was chemoimmunotherapy; however, experimental drugs were increasingly used at later LoT. In the US, anti-CD20 monotherapy was more common at ≥3rd LoT compared to Europe, where stem cell transplants were more common. ORR at 3rd LoT was 68% (CR 44%), but decreased after each LoT to 37% (CR 22%) in ≥5 LoT. Median OS and PFS at 3rd LoT were 68 and 11 months, respectively, and reduced to 43 and 4 months at ≥5 LoT. Treatments were heterogenous at each LoT in both the US and Europe. Few FL patients achieved CR in later LoT, and duration of response and survival diminished with each subsequent line.

Effects of a mediterranean diet on the gut microbiota and microbial metabolites: A systematic review of randomized controlled trials and observational studies.

Consumption of the Mediterranean dietary pattern (MedDiet) is associated with reduced risk of numerous non-communicable diseases. Modulation of the composition and metabolism of the gut microbiota represents a potential mechanism through which the MedDiet elicits these effects. We conducted a systematic literature search (Prospero registration: CRD42020168977) using PubMed, The Cochrane Library, MEDLINE, SPORTDiscuss, Scopus and CINAHL databases for randomized controlled trials (RCTs) and observational studies exploring the impact of a MedDiet on gut microbiota composition (i.e., relative abundance of bacteria or diversity metrics) and metabolites (e.g., short chain fatty acids). Seventeen RCTs and 17 observational studies were eligible for inclusion in this review. Risk of bias across the studies was mixed but mainly identified as low and unclear. Overall, RCTs and observational studies provided no clear evidence of a consistent effect of a MedDiet on composition or metabolism of the gut microbiota. These findings may be related to the diverse methods across studies (e.g., MedDiet classification and analytical techniques), cohort characteristics, and variable quality of studies. Further, well-designed studies are warranted to advance understanding of the potential effects of the MedDiet using more detailed examination of microbiota and microbial metabolites with reference to emerging characteristics of a healthy gut microbiome.

Analytical Performance of the Factory-Calibrated Flash Glucose Monitoring System FreeStyle Libre2TM in Healthy Women.

Continuous glucose monitoring (CGM) is used clinically and for research purposes to capture glycaemic profiles. The accuracy of CGM among healthy populations has not been widely assessed. This study assessed agreement between glucose concentrations obtained from venous plasma and from CGM (FreeStyle Libre2TM, Abbott Diabetes Care, Witney, UK) in healthy women. Glucose concentrations were assessed after fasting and every 15 min after a standardized breakfast over a 4-h lab period. Accuracy of CGM was determined by Bland-Altman plot, 15/15% sensor agreement analysis, Clarke error grid analysis (EGA) and mean absolute relative difference (MARD). In all, 429 valid CGM readings with paired venous plasma glucose (VPG) values were obtained from 29 healthy women. Mean CGM readings were 1.14 mmol/L (95% CI: 0.97 to 1.30 mmol/L, p < 0.001) higher than VPG concentrations. Ratio 95% limits of agreement were from 0.68 to 2.20, and a proportional bias (slope: 0.22) was reported. Additionally, 45% of the CGM readings were within ±0.83 mmol/L (±15 mg/dL) or ±15% of VPG, while 85.3% were within EGA Zones A + B (clinically acceptable). MARD was 27.5% (95% CI: 20.8, 34.2%), with higher MARD values in the hypoglycaemia range and when VPG concentrations were falling. The FreeStyle Libre2TM CGM system tends to overestimate glucose concentrations compared to venous plasma samples in healthy women, especially during hypoglycaemia and during glycaemic swings.

Comparative efficacy of ravulizumab and eculizumab in the treatment of atypical hemolytic uremic syndrome: An indirect comparison using clinical trial data.

Ravulizumab and eculizumab are approved terminal complement inhibitor treatments for atypical hemolytic uremic syndrome (aHUS). Ravulizumab was engineered from eculizumab to have an increased half-life allowing for reduced dosing frequency (8-weekly vs. 2-weekly). To account for differences in respective clinical trials, a validated balancing technique was used to enable an indirect comparison of ravulizumab and eculizumab treatment efficacy in aHUS. Patient-level data from four eculizumab clinical trials were available for pooling and comparison with data from two ravulizumab trials. In the primary analysis, adult native kidney data were compared. Propensity scores were calculated from baseline characteristics (dialysis status, estimated glomerular filtration rate, platelet count, serum lactate dehydrogenase). Stabilized inverse probability weighting was used to balance groups. Changes in outcomes from baseline to 26 weeks were compared between treatment groups. Sensitivity and subgroup analyses were conducted to assess the robustness of findings. Overall, 85 patients (46 ravulizumab, 39 eculizumab) were included in the primary analysis. Demographic and clinical characteristics were well balanced after weighting at baseline. At 26 weeks, clinical outcomes (including renal function, hematological markers, and dialysis prevalence), and fatigue and quality of life measures were improved with eculizumab and ravulizumab treatment. No differences between treatment groups reached statistical significance, although confidence intervals were wide. Sensitivity and subgroup analysis results were consistent with those of the primary analysis. Using appropriate methodology for indirect comparison of studies, no differences in outcomes were seen between ravulizumab and eculizumab, although, owing to small sample sizes, confidence intervals were wide.

The effect of rugby training on indirect markers of gut permeability and gut damage in academy level rugby players.

PURPOSE: To assess indirect markers of intestinal endothelial cell damage and permeability in academy rugby players in response to rugby training at the beginning and end of preseason. METHODS: Blood and urinary measures (intestinal fatty acid binding protein and lactulose:rhamnose) as measures of gastrointestinal cell damage and permeability were taken at rest and after a standardised collision-based rugby training session in 19 elite male academy rugby players (age: 20 ± 1 years, backs: 89.3 ± 8.4 kg; forwards: 111.8 ± 7.6 kg) at the start of preseason. A subsample (n = 5) repeated the protocol after six weeks of preseason training. Gastrointestinal symptoms (GIS; range of thirteen standard symptoms), aerobic capacity (30-15 intermittent fitness test), and strength (1 repetition maximum) were also measured. RESULTS: Following the rugby training session at the start of preseason, there was an increase (median; interquartile range) in intestinal fatty acid binding protein (2140; 1260-2730 to 3245; 1985-5143 pg/ml, p = 0.003) and lactulose:rhamnose (0.31; 0.26-0.34 to 0.97; 0.82-1.07, p < 0.001). After six weeks of preseason training players physical qualities improved, and the same trends in blood and urinary measures were observed within the subsample. Overall, the frequency and severity of GIS were low and not correlated to markers of endothelial damage. CONCLUSIONS: Rugby training resulted in increased intestinal endothelial cell damage and permeability compared to rest. A similar magnitude of effect was observed after six weeks of pre-season training. This was not related to the experience of GIS.

Isolated & Combined Wearable Technology Underestimate the Total Energy Expenditure of Professional Young Rugby League Players; A Doubly Labelled Water Validation Study.

ABSTRACT: Costello, N, Deighton, K, Cummins, C, Whitehead, S, Preston, T, and Jones, B. Isolated & combined wearable technology underestimate the total energy expenditure of professional young rugby league players; a doubly labelled water validation study. J Strength Cond Res 36(12): 3398-3403, 2022-Accurately determining total energy expenditure (TEE) enables the precise manipulation of energy balance within professional collision-based sports. Therefore, this study investigated the ability of isolated or combined wearable technology to determine the TEE of professional young rugby league players across a typical preseason and in-season period. Total energy expenditure was measured via doubly labelled water, the criterion method, across a fourteen-day preseason ( n = 6) and 7-day in-season ( n = 7) period. Practical measures of TEE included SenseWear Pro3 Armbands in isolation and combined with metabolic power derived from microtechnology units. SenseWear Pro3 Armbands significantly under-reported preseason (5.00 [2.52] MJ·d -1 ; p = 0.002) and in-season (2.86 [1.15] MJ·d -1 ; p < 0.001) TEE, demonstrating a large and extremely large standardized mean bias, and a very large and large typical error, respectively. Combining metabolic power with SenseWear Pro3 Armbands almost certainly improved preseason (0.95 [0.15] MJ·d -1 ; Effect size = 0.32 ± 0.04; p < 0.001) and in-season (1.01 [0.15] MJ·d -1 ; ES = 0.88 ± 1.05; p < 0.001) assessment. However, SenseWear Pro3 Armbands combined with metabolic power continued to significantly under-report preseason (4.04 [2.38] MJ·d -1 ; p = 0.004) and in-season (2.18 [0.96] MJ·d -1 ; p = 0.002) expenditure, demonstrating a large and very large standardized mean bias, and a very large and large typical error, respectively. These findings demonstrate the limitations of utilizing isolated or combined wearable technology to accurately determine the TEE of professional collision-based sport athletes across different stages of the season.

Galactose Ingested with a High-Fat Beverage Increases Postprandial Lipemia Compared with Glucose but Not Fructose Ingestion in Healthy Men.

BACKGROUND: Fructose ingestion with a high-fat beverage increases postprandial lipemia when compared with glucose. It is unknown whether other sugars, such as galactose, also increase postprandial lipemia. OBJECTIVES: The objective was to assess whether galactose ingestion within a high-fat beverage increases postprandial lipemia relative to glucose or fructose. METHODS: Two experiments were conducted, which contrasted different test drinks under otherwise standardized conditions. In Experiment 1, 10 nonobese men (age: 22 ± 1 y; BMI, 23.5 ± 2.2 kg/2) ingested either galactose or glucose (0.75 g supplemented carbohydrate per⋅kilogram body mass) within a high-fat test drink (0.94 g fat per kilogram body mass). In Experiment 2, a separate group of 9 nonobese men (age: 26 ± 6 y; BMI: 23.5 ± 2.6 kg/m2) ingested either galactose or fructose (identical doses as those in Experiment 1) within the same high-fat test drink. Capillary blood was sampled before and at frequent intervals after ingestion of the test drinks for a 300-min period to determine plasma triacylglycerol, glucose, lactate, nonesterified fatty acid, and insulin concentrations. Paired t tests and 2-way, repeated-measures ANOVA were used to compare conditions within each experiment. RESULTS: The incremental AUC for triacylglycerol was greater following galactose ingestion compared with glucose (127 ± 59 compared with 80 ± 48 mmol⋅L-1 × 300 min, respectively; P = 0.04) but not compared with fructose (136 ± 74 compared with 133 ± 63 mmol⋅L-1 ×300 min, respectively; P = 0.91). Plasma lactate concentrations also increased to a greater extent with galactose compared with glucose ingestion (time-condition interaction: P < 0.001) but not fructose ingestion (time-condition interaction: P = 0.17). CONCLUSIONS: Galactose ingestion within a high-fat beverage exacerbates postprandial lipemia and plasma lactate concentrations compared with glucose but not fructose in nonobese men. These data suggest that galactose metabolism may be more similar to fructose than to glucose, providing a rationale to reassess the metabolic fate of galactose ingestion in humans. This trial was registered at clinicaltrials.gov as NCT03439878.

Appetite and energy intake responses to breakfast consumption and carbohydrate supplementation in hypoxia.

PURPOSE: The purpose of experiment one was to determine the appetite, acylated ghrelin and energy intake response to breakfast consumption and omission in hypoxia and normoxia. Experiment two aimed to determine the appetite, acylated ghrelin and energy intake response to carbohydrate supplementation after both breakfast consumption and omission in hypoxia. METHODS: In experiment one, twelve participants rested and exercised once after breakfast consumption and once after omission in normobaric hypoxia (4300 m: FiO2 ~11.7%) and normoxia. In experiment two, eleven participants rested and exercised in normobaric hypoxia (4300 m: FiO2 ~11.7%), twice after consuming a high carbohydrate breakfast and twice after breakfast omission. Participants consumed both a carbohydrate (1.2g·min-1 glucose) and a placebo beverage after breakfast consumption and omission. Measures of appetite perceptions and acylated ghrelin were taken at regular intervals throughout both experiments and an ad-libitum meal was provided post-exercise to quantify energy intake. RESULTS: Breakfast consumption had no significant effect on post exercise energy intake or acylated ghrelin concentrations, despite reductions in appetite perceptions. As such, breakfast consumption increased total trial energy intake compared with breakfast omission in hypoxia (7136 ± 2047 kJ vs. 5412 ± 1652 kJ; p = 0.02) and normoxia (9276 ± 3058 vs. 6654 ± 2091 kJ; p < 0.01). Carbohydrate supplementation had no effect on appetite perceptions or acylated ghrelin concentrations after breakfast consumption or omission. As such, carbohydrate supplementation increased total energy intake after breakfast consumption (10222 ± 2831 kJ vs. 7695 ± 1970 kJ p < 0.01) and omission (8058 ± 2574 kJ vs. 6174 ± 2222 kJ p = 0.02). CONCLUSION: Both breakfast consumption and carbohydrate supplementation provide beneficial dietary interventions for increasing energy intake in hypoxic conditions.

Differences in circulating appetite-related hormone concentrations between younger and older adults: a systematic review and meta-analysis.

Ageing is associated with reduced appetite and energy intakes. However, the mechanisms underlying this phenomenon are not fully understood. This systematic review and meta-analysis quantified differences in circulating concentrations of appetite-related hormones between healthy older and younger adults. Six databases were searched through 12th June 2018 for studies that compared appetite-related hormone concentrations between older and younger adults. Data were pooled using random-effects meta-analysis and are presented as standardised mean difference (Hedges' g) with 95% confidence intervals (95% CI). Thirty-five studies were included involving 710 older adults (mean ± SD; age: 73 ± 5 years) and 713 younger adults (age: 28 ± 7 years). Compared with younger adults, older adults exhibited higher fasted and postprandial concentrations of the anorectic hormones cholecystokinin (Fasted: SMD 0.41 (95% CI 0.24, 0.57); p < 0.001. Postprandial: SMD 0.41 (0.20, 0.62); p < 0.001), leptin [Fasted: SMD 1.23 (0.15, 2.30); p = 0.025. Postprandial: SMD 0.62 (0.23, 1.01); p = 0.002] and insulin [Fasted: SMD 0.24 (- 0.02, 0.50); p = 0.073. Postprandial: SMD 0.16 (0.01, 0.32); p = 0.043]. Higher postprandial concentrations of peptide-YY were also observed in older adults compared with younger adults [SMD 0.31 (- 0.03, 0.65); p = 0.075]. Compared with younger adults, older adults had lower energy intakes [SMD - 0.98 (- 1.74, - 0.22); p = 0.011], and lower hunger perceptions in the fasted [SMD - 1.00 (- 1.54, - 0.46); p < 0.001] and postprandial states [SMD - 0.31, (- 0.64, 0.02); p = 0.064]. Higher circulating concentrations of insulin, leptin, cholecystokinin and peptide-YY accord with reduced appetite and energy intakes in healthy older adults. Interventions to reduce circulating levels of these hormones may be beneficial for combatting the anorexia of ageing.

How well do activity monitors estimate energy expenditure? A systematic review and meta-analysis of the validity of current technologies.

OBJECTIVE: To determine the accuracy of wrist and arm-worn activity monitors' estimates of energy expenditure (EE). DATA SOURCES: SportDISCUS (EBSCOHost), PubMed, MEDLINE (Ovid), PsycINFO (EBSCOHost), Embase (Ovid) and CINAHL (EBSCOHost). DESIGN: A random effects meta-analysis was performed to evaluate the difference in EE estimates between activity monitors and criterion measurements. Moderator analyses were conducted to determine the benefit of additional sensors and to compare the accuracy of devices used for research purposes with commercially available devices. ELIGIBILITY CRITERIA: We included studies validating EE estimates from wrist-worn or arm-worn activity monitors against criterion measures (indirect calorimetry, room calorimeters and doubly labelled water) in healthy adult populations. RESULTS: 60 studies (104 effect sizes) were included in the meta-analysis. Devices showed variable accuracy depending on activity type. Large and significant heterogeneity was observed for many devices (I2 >75%). Combining heart rate or heat sensing technology with accelerometry decreased the error in most activity types. Research-grade devices were statistically more accurate for comparisons of total EE but less accurate than commercial devices during ambulatory activity and sedentary tasks. CONCLUSIONS: EE estimates from wrist and arm-worn devices differ in accuracy depending on activity type. Addition of physiological sensors improves estimates of EE, and research-grade devices are superior for total EE. These data highlight the need to improve estimates of EE from wearable devices, and one way this can be achieved is with the addition of heart rate to accelerometry. PROSPEROREGISTRATION NUMBER: CRD42018085016.

Body composition differences by age and playing standard in male rugby union and rugby league: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to determine differences in body compositionn between playing standard and age in male rugby union and rugby league athletes. The MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines for design, implementation, and reporting were followed. Studies were required to be in male rugby union or league and have body composition as the primary or secondary outcome. Data was required to be presented separately for positional groups and body composition presented as whole-body. A systematic search was performed in PubMed, Cochrane Library, MEDLINE, SPORTDiscus, and CINHAHL via EBSCOhost. 57 studies were included for meta-analysis. Results highlighted significantly higher fat-free mass in senior elite than senior sub-elite or junior elite athletes for all RU and RL forwards. Small and non-significant differences were found in fat mass between rugby union playing standards and age categories. Rugby league senior elite forwards had less fat mass than junior elite forwards. Practitioners should prioritise training and nutritional strategies that maximise fat-free mass development, especially in junior elite cohorts.

A single day of mixed-macronutrient overfeeding does not elicit compensatory appetite or energy intake responses but exaggerates postprandial lipaemia during the next day in healthy young men.

Discrete episodes of overconsumption may induce a positive energy balance and impair metabolic control. However, the effects of an ecologically relevant, single day of balanced macronutrient overfeeding are unknown. Twelve healthy men (of age 22 (sd 2) years, BMI 26·1 (sd 4·2) kg/m2) completed two 28 h, single-blind experimental trials. In a counterbalanced repeated measures design, participants either consumed their calculated daily energy requirements (energy balance trial (EB): 10 755 (sd 593) kJ) or were overfed by 50 % (overfeed trial (OF): 16 132 (sd 889) kJ) under laboratory supervision. Participants returned to the laboratory the next day, after an overnight fast, to complete a mixed-meal tolerance test (MTT). Appetite was not different between trials during day 1 (P>0·211) or during the MTT in the fasted or postprandial state (P>0·507). Accordingly, plasma acylated ghrelin, total glucagon-like peptide-1 and total peptide YY concentrations did not differ between trials during the MTT (all P>0·335). Ad libitum energy intake, assessed upon completion of the MTT, did not differ between trials (EB 6081 (sd 2260) kJ; OF 6182 (sd 1960) kJ; P=0·781). Plasma glucose and insulin concentrations were not different between trials (P>0·715). Fasted NEFA concentrations were lower in OF compared with EB (P=0·005), and TAG concentrations increased to a greater extent on OF than on EB during the MTT (P=0·009). The absence of compensatory changes in appetite-related variables after 1 d of mixed macronutrient overfeeding highlights the limited physiological response to defend against excess energy intake. This supports the concept that repeated discrete episodes of overconsumption may promote weight gain, while elevations in postprandial lipaemia may increase CVD risk.

Erythropoietic responses to a series of repeated maximal dynamic and static apnoeas in elite and non-breath-hold divers.

PURPOSE: 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. METHODS: 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 30 s post each maximal effort. Blood samples were collected at 30, 90, and 180 min after each protocol for EPO, haemoglobin and haematocrit concentrations. RESULTS: 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. CONCLUSIONS: 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.

Substrate oxidation and the influence of breakfast in normobaric hypoxia and normoxia.

PURPOSE: Previous research has reported inconsistent effects of hypoxia on substrate oxidation, which may be due to differences in methodological design, such as pre-exercise nutritional status and exercise intensity. This study investigated the effect of breakfast consumption on substrate oxidation at varying exercise intensities in normobaric hypoxia compared with normoxia. METHODS: Twelve participants rested and exercised once after breakfast consumption and once after omission in normobaric hypoxia (4300 m: FiO2 ~ 11.7%) and normoxia. Exercise consisted of walking for 20 min at 40%, 50% and 60% of altitude-specific [Formula: see text]O2max at 10-15% gradient with a 10 kg backpack. Indirect calorimetry was used to calculate carbohydrate and fat oxidation. RESULTS: The relative contribution of carbohydrate oxidation to energy expenditure was significantly reduced in hypoxia compared with normoxia during exercise after breakfast omission at 40% (22.4 ± 17.5% vs. 38.5 ± 15.5%, p = 0.03) and 60% [Formula: see text]O2max (35.4 ± 12.4 vs. 50.1 ± 17.6%, p = 0.03), with a trend observed at 50% [Formula: see text]O2max (23.6 ± 17.9% vs. 38.1 ± 17.0%, p = 0.07). The relative contribution of carbohydrate oxidation to energy expenditure was not significantly different in hypoxia compared with normoxia during exercise after breakfast consumption at 40% (42.4 ± 15.7% vs. 48.5 ± 13.3%, p = 0.99), 50% (43.1 ± 11.7% vs. 47.1 ± 14.0%, p = 0.99) and 60% [Formula: see text]O2max (54.6 ± 17.8% vs. 55.1 ± 15.0%, p = 0.99). CONCLUSIONS: Relative carbohydrate oxidation was significantly reduced in hypoxia compared with normoxia during exercise after breakfast omission but not during exercise after breakfast consumption. This response remained consistent with increasing exercise intensities. These findings may explain some of the disparity in the literature.

Non-targeted metabolomics in sport and exercise science.

Metabolomics incorporates the study of metabolites that are produced and released through physiological processes at both the systemic and cellular levels. Biological compounds at the metabolite level are of paramount interest in the sport and exercise sciences, although research in this field has rarely been referred to with the global 'omics terminology. Commonly studied metabolites in exercise science are notably within cellular pathways for adenosine triphosphate production such as glycolysis (e.g., pyruvate and lactate), ß-oxidation of free fatty acids (e.g., palmitate) and ketone bodies (e.g., ß-hydroxybutyrate). Non-targeted metabolomic technologies are able to simultaneously analyse the large numbers of metabolites present in human biological samples such as plasma, urine and saliva. These analytical technologies predominately employ nuclear magnetic resonance spectroscopy and chromatography coupled to mass spectrometry. Performing experiments based on non-targeted methods allows for systemic metabolite changes to be analysed and compared to a particular physiological state (e.g., pre-/post-exercise) and provides an opportunity to prospect for metabolite signatures that offer beneficial information for translation into an exercise science context, for both elite performance and public health monitoring. This narrative review provides an introduction to non-targeted metabolomic technologies and discusses current and potential applications in sport and exercise science.

Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials.

BACKGROUND: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. METHODS: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. RESULTS: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: - 0.10, (95% CI - 0.17, - 0.03); p = 0.007], VLDL (ES: - 0.26 (- 0.51, - 0.01); p = 0.044], triglycerides (ES: - 0.39 (- 0.55, - 0.24; p ≤ 0.001] and HbA1c (ES: - 0.27 (- 0.48, - 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: - 0.59 (- 1.17, - 0.01); p = 0.045] and IL-6 (ES: - 1.67 (- 3.14, - 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). CONCLUSIONS: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802.

Collision activity during training increases total energy expenditure measured via doubly labelled water.

PURPOSE: Collision sports are characterised by frequent high-intensity collisions that induce substantial muscle damage, potentially increasing the energetic cost of recovery. Therefore, this study investigated the energetic cost of collision-based activity for the first time across any sport. METHODS: Using a randomised crossover design, six professional young male rugby league players completed two different 5-day pre-season training microcycles. Players completed either a collision (COLL; 20 competitive one-on-one collisions) or non-collision (nCOLL; matched for kinematic demands, excluding collisions) training session on the first day of each microcycle, exactly 7 days apart. All remaining training sessions were matched and did not involve any collision-based activity. Total energy expenditure was measured using doubly labelled water, the literature gold standard. RESULTS: Collisions resulted in a very likely higher (4.96 ± 0.97 MJ; ES = 0.30 ± 0.07; p = 0.0021) total energy expenditure across the 5-day COLL training microcycle (95.07 ± 16.66 MJ) compared with the nCOLL training microcycle (90.34 ± 16.97 MJ). The COLL training session also resulted in a very likely higher (200 ± 102 AU; ES = 1.43 ± 0.74; p = 0.007) session rating of perceived exertion and a very likely greater (- 14.6 ± 3.3%; ES = - 1.60 ± 0.51; p = 0.002) decrease in wellbeing 24 h later. CONCLUSIONS: A single collision training session considerably increased total energy expenditure. This may explain the large energy expenditures of collision-sport athletes, which appear to exceed kinematic training and match demands. These findings suggest fuelling professional collision-sport athletes appropriately for the "muscle damage caused" alongside the kinematic "work required".

The effects of hypoxia on hunger perceptions, appetite-related hormone concentrations and energy intake: A systematic review and meta-analysis.

Exposure to hypoxia appears to depress appetite and energy intake, however the mechanisms are not fully understood. The aim of this review was to determine the magnitude of changes in hunger and energy intake in hypoxic compared with normoxic environments, and establish any alterations in appetite-related hormone concentrations. PubMed and The Cochrane Library as well as MEDLINE, SPORTDiscus, PsycINFO and CINAHL, via EBSCOhost, were searched through 1st April 2017 for studies that evaluated hunger, energy intake and/or appetite-related hormones in normoxia and during hypoxic exposure in a within-measures design. A total of 28 studies (comprising 54 fasted and 22 postprandial comparisons) were included. A random-effects meta-analysis was performed to establish standardised mean difference (SMD) with 95% confidence intervals. Hypoxic exposure resulted in a trivial but significant decrease in postprandial hunger scores (SMD: -0.15, 95% CI: -0.29 to -0.01; n = 14; p = 0.043) and a moderate decrease in energy intake (SMD: -0.50, 95% CI: -0.85 to -0.15; n = 8; p = 0.006). Hypoxic exposure resulted in a decrease (albeit trivial) in postprandial acylated ghrelin concentrations (SMD: -0.16, 95% CI: -0.25 to -0.08; n = 7; p < 0.0005), and a moderate increase in fasted insulin concentrations (SMD: 0.41, 95% CI: 0.17 to 0.65; n = 34; p = 0.001). Meta-regression revealed a decrease in postprandial acylated ghrelin concentrations (p = 0.010) and an increase in fasted insulin concentrations (p = 0.020) as hypoxic severity increased. Hypoxic exposure reduces hunger and energy intake, which may be mediated by decreased circulating concentrations of acylated ghrelin and elevated insulin concentrations. PROSPERO registration number: CRD42015017231.

Using Contemporary Behavior Change Science to Design and Implement an Effective Nutritional Intervention Within Professional Rugby League.

Designing and implementing successful dietary intervention is integral to the role of sport nutrition professionals as they attempt to positively change the dietary behavior of athletes. High-performance sport is a time-pressured environment where immediate results can often supersede pursuit of the most effective evidence-based practice. However, efficacious dietary intervention necessitates comprehensive, systematic, and theoretical behavioral design and implementation, if the habitual dietary behaviors of athletes are to be positively changed. Therefore, this case study demonstrates how the Behaviour Change Wheel was used to design and implement an effective nutritional intervention within a professional rugby league. The eight-step intervention targeted athlete consumption of a high-quality dietary intake of 25.1 MJ each day to achieve an overall body mass increase of 5 kg across a 12-week intervention period. The capability, opportunity, motivation, and behavior model and affordability, practicability, effectiveness/cost-effectiveness, acceptability, safety, and equity criteria were used to identify population-specific intervention functions, policy categories, behavior change techniques, and modes of intervention delivery. The resulting intervention was successful, increasing the average daily energy intake of the athlete to 24.5 MJ, which corresponded in a 6.2 kg body mass gain. Despite consuming 0.6 MJ less per day than targeted, secondary outcome measures of diet quality, strength, body composition, and immune function all substantially improved, supporting sufficient energy intake and the overall efficacy of a behavioral approach. Ultimately, the Behaviour Change Wheel provides sport nutrition professionals with an effective and practical stepwise method to design and implement effective nutritional interventions for use within high-performance sport.