Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus.

BACKGROUND: Patients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR). METHODS: We randomly assigned patients with symptomatic severe aortic stenosis and an aortic-valve annulus area of 430 mm2 or less in a 1:1 ratio to undergo TAVR with either a self-expanding supraannular valve or a balloon-expandable valve. The coprimary end points, each assessed through 12 months, were a composite of death, disabling stroke, or rehospitalization for heart failure (tested for noninferiority) and a composite end point measuring bioprosthetic-valve dysfunction (tested for superiority). RESULTS: A total of 716 patients were treated at 83 sites in 13 countries (mean age, 80 years; 87% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality, 3.3%). The Kaplan-Meier estimate of the percentage of patients who died, had a disabling stroke, or were rehospitalized for heart failure through 12 months was 9.4% with the self-expanding valve and 10.6% with the balloon-expandable valve (difference, -1.2 percentage points; 90% confidence interval [CI], -4.9 to 2.5; P<0.001 for noninferiority). The Kaplan-Meier estimate of the percentage of patients with bioprosthetic-valve dysfunction through 12 months was 9.4% with the self-expanding valve and 41.6% with the balloon-expandable valve (difference, -32.2 percentage points; 95% CI, -38.7 to -25.6; P<0.001 for superiority). The aortic-valve mean gradient at 12 months was 7.7 mm Hg with the self-expanding valve and 15.7 mm Hg with the balloon-expandable valve, and the corresponding values for additional secondary end points through 12 months were as follows: mean effective orifice area, 1.99 cm2 and 1.50 cm2; percentage of patients with hemodynamic structural valve dysfunction, 3.5% and 32.8%; and percentage of women with bioprosthetic-valve dysfunction, 10.2% and 43.3% (all P<0.001). Moderate or severe prosthesis-patient mismatch at 30 days was found in 11.2% of the patients in the self-expanding valve group and 35.3% of those in the balloon-expandable valve group (P<0.001). Major safety end points appeared to be similar in the two groups. CONCLUSIONS: Among patients with severe aortic stenosis and a small aortic annulus who underwent TAVR, a self-expanding supraannular valve was noninferior to a balloon-expandable valve with respect to clinical outcomes and was superior with respect to bioprosthetic-valve dysfunction through 12 months. (Funded by Medtronic; SMART ClinicalTrials.gov number, NCT04722250.).

Skeletal muscle mitochondrial correlates of critical power and W' in healthy active individuals.

The asymptote (critical power; CP) and curvature constant (W') of the hyperbolic power-duration relationship can predict performance within the severe-intensity exercise domain. However, the extent to which these parameters relate to skeletal muscle mitochondrial content and respiratory function is not known. Fifteen males (peak O2 uptake, 52.2 ± 8.7 mL kg-1 min-1; peak work rate, 366 ± 40 W; and gas exchange threshold, 162 ± 41 W) performed three to five constant-load tests to task failure for the determination of CP (246 ± 44 W) and W' (18.6 ± 4.1 kJ). Skeletal muscle biopsies were obtained from the vastus lateralis to determine citrate synthase (CS) activity, as a marker of mitochondrial content, and the ADP-stimulated respiration (P) and maximal electron transfer (E) through mitochondrial complexes (C) I-IV. The CP was positively correlated with CS activity (absolute CP, r = 0.881, P < 0.001; relative CP, r = 0.751, P = 0.001). The W' was not correlated with CS activity (P > 0.05). Relative CP was positively correlated with mass-corrected CI + IIE (r = 0.659, P = 0.038), with absolute CP being inversely correlated with CS activity-corrected CIVE (r = -0.701, P = 0.024). Relative W' was positively correlated with CS activity-corrected CI + IIP (r = 0.713, P = 0.021) and the phosphorylation control ratio (r = 0.661, P = 0.038). There were no further correlations between CP or W' and mitochondrial respiratory variables. These findings support the assertion that skeletal muscle mitochondrial oxidative capacity is positively associated with CP and that this relationship is strongly determined by mitochondrial content.

Influence of nitrate supplementation on motor unit activity during recovery following a sustained ischemic contraction in recreationally active young males.

PURPOSE: Dietary nitrate (NO3-) supplementation enhances muscle blood flow and metabolic efficiency in hypoxia, however, its efficacy on neuromuscular function and specifically, the effect on motor unit (MU) activity is less clear. We investigated whether NO3- supplementation affected MU activity following a 3 min sustained ischemic contraction and whether this is influenced by blood flow restriction (BFR) during the recovery period. METHOD: In a randomized, double-blinded, cross-over design, 14 males (mean ± SD, 25 ± 6 years) completed two trials following 5 days of supplementation with NO3--rich (NIT) or NO3--depleted (PLA) beetroot juice to modify plasma nitrite (NO2-) concentration (482 ± 92 vs. 198 ± 48 nmol·L-1, p < 0.001). Intramuscular electromyography was used to assess MU potential (MUP) size (duration and area) and mean firing rates (MUFR) during a 3 min submaximal (25% MVC) isometric contraction with BFR. These variables were also assessed during a 90 s recovery period with the first half completed with, and the second half completed without, BFR. RESULTS: The change in MUP area and MUFR, did not differ between conditions (all p > 0.05), but NIT elicited a reduction in MUP recovery time during brief isometric contractions (p < 0.001), and during recoveries with (p = 0.002) and without (p = 0.012) BFR. CONCLUSION: These novel observations improve understanding of the effects of NO3- on the recovery of neuromuscular function post-exercise and might have implications for recovery of muscle contractile function. TRIAL REGISTRATION: The study was registered on clinicaltrials.gov with ID of NCT05993715 on August 08, 2023.

Post exercise hot water immersion and hot water immersion in isolation enhance vascular, blood marker, and perceptual responses when compared to exercise alone.

Exercise and passive heating induce some similar vascular hemodynamic, circulating blood marker, and perceptual responses. However, it remains unknown whether post exercise hot water immersion can synergise exercise derived responses and if they differ from hot water immersion alone. This study investigated the acute responses to post moderate-intensity exercise hot water immersion (EX+HWI) when compared to exercise (EX+REST) and hot water immersion (HWI+HWI) alone. Sixteen physically inactive middle-aged adults (nine males and seven females) completed a randomized cross-over counterbalanced design. Each condition consisted of two 30-min bouts separated by 10 min of rest. Cycling was set at a power output equivalent to 50% V̇o2 peak . Water temperature was controlled at 40°C up to the mid sternum with arms not submerged. Venous blood samples and artery ultrasound scans were assessed at 0 (baseline), 30 (immediately post stressor one), 70 (immediately post stressor two), and 100 min (recovery). Additional physiological and perceptual measures were assessed at 10-min intervals. Brachial and superficial femoral artery shear rates were higher after EX+HWI and HWI+HWI when compared with EX+REST (p < 0.001). Plasma nitrite was higher immediately following EX+HWI and HWI+HWI than EX+REST (p < 0.01). Serum interleukin-6 was higher immediately after EX+HWI compared to EX+REST (p = 0.046). Serum cortisol was lower at 30 min in the HWI+HWI condition in contrast to EX+REST (p = 0.026). EX+HWI and HWI+HWI were more enjoyable than EX+REST (p < 0.05). Irrespective of whether hot water immersion proceeded exercise or heating, hot water immersion enhanced vascular and blood marker responses, while also being more enjoyable than exercise alone.

Combined effects of green tea supplementation and eccentric exercise on nuclear factor erythroid 2-related factor 2 activity.

PURPOSE: This study investigated whether combining eccentric exercise and green tea supplementation synergistically increased nuclear factor erythroid 2-related factor 2 (NRF2) activity, a transcription factor responsible for coordinating endogenous antioxidant expression. METHODS: In a double-blinded, randomized, between-subjects design, 24 males (mean [SD]; 23 [3] years, 179.6 [6.1] cm, 78.8 [10.6] kg) performed 100 drop jumps following a 6 days supplementation period with either green tea (poly)phenols (n = 12; 500 mg·d-1) or a placebo (n = 12; inulin). NRF2/antioxidant response element (ARE) binding in peripheral blood mononuclear cells (PBMCs), catalase (CAT) and glutathione reductase (GR) activity, 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion, and differential leukocyte counts were measured pre-, post-, 1 h and 24 h post-exercise. RESULTS: Exercise did not increase NRF2/ARE binding (p = 0.12) (fold change vs rest: green tea = [post] 0.78 ± 0.45, [1 h] 1.17 ± 0.54, [24 h] 1.06 ± 0.56; placebo = [post] 1.40 ± 1.50, [1 h] 2.98 ± 3.70, [24 h] 1.04 ± 0.45). Furthermore, CAT activity (p = 0.12) and 8-OHdG excretion (p = 0.42) were unchanged in response to exercise and were not augmented by green tea supplementation (p > 0.05 for all). Exercise increased GR activity by 30% (p = 0.01), however no differences were found between supplement groups (p = 0.51). Leukocyte and neutrophil concentrations were only elevated post-exercise (p < 0.001 for all). CONCLUSION: Eccentric exercise, either performed alone or in conjunction with green tea supplementation, did not significantly increase NRF2 activity in PBMCs. TRIAL REGISTRATION NUMBER: osf.io/kz37g (registered: 15/09/21).

Acute inorganic nitrate ingestion does not impact oral microbial composition, cognitive function, or high-intensity exercise performance in female team-sport athletes.

The purpose of this study was to investigate the effects of acute nitrate (NO3-)-rich beetroot juice ingestion on explosive and high-intensity exercise performance, oral microbiota composition, and cognitive flexibility (i.e., function), before and after maximal intermittent running exercise. Fifteen women team-sport athletes were assigned in a randomized, double-blind, crossover design to consume concentrated NO3--depleted beetroot juice (PL; 0.1 mmol NO3-) and NO3--rich beetroot juice (BR; 12.0 mmol NO3-) 2.5 h prior to performing a battery of exercise performance tasks and cognitive testing before and after the Yo-Yo intermittent recovery level 1 (YYIR1) running test. Resting plasma [NO3-] and plasma nitrite ([NO2-]) were elevated following BR (P < 0.001). BR did not impact global composition or relative abundance of taxa in the oral microbiome (P > 0.05) or cognitive flexibility before or after exercise (P > 0.05). There was no significant difference in performance during 20-m (PRE, PL: 4.38 ± 0.27 vs. BR: 4.38 ± 0.32 s; POST, PL: 4.45 ± 0.29 vs. BR: 4.43 ± 0.35 s) and 10-m sprints (PRE, PL 2.78 ± 0.15 vs. BR 2.79 ± 0.18 s; POST, PL: 2.82 ± 0.16 vs. BR: 2.81 ± 0.19 s), isokinetic handgrip dynamometry, medicine ball throw, horizontal countermovement jump, or YYIR1 (PL: 355 ± 163 m vs. BR: 368 ± 184 m) between BR and PL (P > 0.05). These findings indicate that acute dietary NO3- may not influence the oral microbiome, explosive and high-intensity exercise performance, or cognitive function in women team-sport athletes.

Plasma biomarkers of endothelial function, inflammation and oxidative stress in individuals with non-freezing cold injury.

NEW FINDINGS: What is the central question of this study? Are biomarkers of endothelial function, oxidative stress and inflammation altered by non-freezing cold injury (NFCI)? What is the main finding and its importance? Baseline plasma [interleukin-10] and [syndecan-1] were elevated in individuals with NFCI and cold-exposed control participants. Increased [endothelin-1] following thermal challenges might explain, in part, the increased pain/discomfort experienced with NFCI. Mild to moderate chronic NFCI does not appear to be associated with either oxidative stress or a pro-inflammatory state. Baseline [interleukin-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosis of NFCI. ABSTRACT: Plasma biomarkers of inflammation, oxidative stress, endothelial function and damage were examined in 16 individuals with chronic NFCI (NFCI) and matched control participants with (COLD, n = 17) or without (CON, n = 14) previous cold exposure. Venous blood samples were collected at baseline to assess plasma biomarkers of endothelial function (nitrate, nitrite and endothelin-1), inflammation [interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor alpha and E-selectin], oxidative stress [protein carbonyl, 4-hydroxy-2-nonenal (4-HNE), superoxide dismutase and nitrotyrosine) and endothelial damage [von Willebrand factor, syndecan-1 and tissue type plasminogen activator (TTPA)]. Immediately after whole-body heating and separately, foot cooling, blood samples were taken for measurement of plasma [nitrate], [nitrite], [endothelin-1], [IL-6], [4-HNE] and [TTPA]. At baseline, [IL-10] and [syndecan-1] were increased in NFCI (P < 0.001 and P = 0.015, respectively) and COLD (P = 0.033 and P = 0.030, respectively) compared with CON participants. The [4-HNE] was elevated in CON compared with both NFCI (P = 0.002) and COLD (P < 0.001). [Endothelin-1] was elevated in NFCI compared with COLD (P < 0.001) post-heating. The [4-HNE] was lower in NFCI compared with CON post-heating (P = 0.032) and lower than both COLD (P = 0.02) and CON (P = 0.015) post-cooling. No between-group differences were seen for the other biomarkers. Mild to moderate chronic NFCI does not appear to be associated with a pro-inflammatory state or oxidative stress. Baseline [IL-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosing NFCI, but it is likely that a combination of tests will be required.

Effects of dietary nitrate supplementation on peak power output: Influence of supplementation strategy and population.

Increasing evidence indicates that dietary nitrate supplementation has the potential to increase muscular power output during skeletal muscle contractions. However, there is still a paucity of data characterizing the impact of different nitrate dosing regimens on nitric oxide bioavailability and its potential ergogenic effects across various population groups. This review discusses the potential influence of different dietary nitrate supplementation strategies on nitric oxide bioavailability and muscular peak power output in healthy adults, athletes, older adults and some clinical populations. Effect sizes were calculated for peak power output and absolute and/or relative nitrate doses were considered where applicable. There was no relationship between the effect sizes of peak power output change following nitrate supplementation and when nitrate dosage when considered in absolute or relative terms. Areas for further research are also recommended including a focus on nitrate dosing regimens that optimize nitric oxide bioavailability for enhancing peak power at times of increased muscular work in a variety of healthy and disease populations.

Effects of dietary nitrate supplementation on muscular power output: Influence of supplementation strategy and population.

Increasing evidence indicates that dietary nitrate supplementation has the potential to increase muscular power output during skeletal muscle contractions. However, there is still a paucity of data characterizing the impact of different nitrate dosing regimens on nitric oxide bioavailability its potential ergogenic effects across various population groups. This narrative review discusses the potential influence of different dietary nitrate supplementation strategies on nitric oxide bioavailability and muscular power output in healthy adults, athletes, older adults and some clinical populations. Areas for further research are also recommended including a focus individualized nitrate dosing regimens to optimize nitric oxide bioavailability and to promote muscular power enhancements in different populations.

Dietary nitrate supplementation increases nitrate and nitrite concentrations in human skin interstitial fluid.

Acute dietary nitrate (NO3-) supplementation can increase [NO3-], but not nitrite ([NO2-]), in human skeletal muscle, though its effect on [NO3-] and [NO2-] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO3--rich beetroot juice (BR; 9.6 mmol NO3-), and 6 young adults ingested 140 mL of a NO3--depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO3-] and [NO2-]. The relative recovery rate of NO3- and NO2- through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO3-] and [NO2-]. Baseline [NO3-] was lower, whereas baseline [NO2-] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO3-] and [NO2-] in the skin interstitial fluid and plasma (all P < 0.001), with the magnitude being smaller in the skin interstitial fluid (e.g., 183 ± 54 vs. 491 ± 62 µM for Δ[NO3-] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO2-] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO2-] post BR ingestion was higher, whereas [NO3-] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO3- and NO2- distribution at rest and indicate that acute BR supplementation increases [NO3-] and [NO2-] in human skin interstitial fluid.

Calf blood flow is augmented in habitually aerobically trained versus untrained postmenopausal women in association with favorable modulation of vasculo-metabolic interactions.

INTRODUCTION: Menopause is associated with vascular dysfunction and increased risk of developing metabolic syndrome. Associations between vascular and metabolic health, and interactions with aerobic exercise training, are unknown in postmenopausal women (PMW). METHODS: In habitually aerobically trained PMW (PMWtr; n = 10; 57 ± 1 years; 40 ± 1 mL/kg/min), strain-gauge plethysmography was used to compare resting and peak calf blood flow (CBFr and CBFpk, respectively) and vascular resistance (CVRr; CVRpk) versus untrained PMW (PMWun; n = 13; 56 ± 1 years; 29 ± 1 mL/kg/min) and premenopausal women (PreM; n = 14; 26 ± 1 years; 40 ± 1 mL/kg/min). Vascular measures were taken before and 1 hour after 45 minutes of aerobic exercise (60% V̇ O2peak ), a known nitric oxide stimulus. Blood analyses included low- (LDLc) and high-density lipoprotein cholesterol (HDLc), insulin, and glucose. RESULTS: Pre-exercise, CBFr and CVRr did not differ (p > 0.05) between PMW groups, nor between PreM and PMWtr. CBFpk was highest (p < 0.05) and CVRpk was lowest (p < 0.05) in PMWtr. Blood markers were similar (p > 0.05) in PMW groups. However, in PMWtr, CBFpk was associated inversely (p < 0.05) with insulin (r = -0.725). Conversely, in PMWun, CBFpk correlated (p < 0.05) inversely with glucose (r = -0.717), positively with HDLc (r = 0.633), and CVRpk positively (p < 0.05) with LDLc (r = 0.568). Post-exercise, CBF increased and CVR decreased (p < 0.05) in all groups, yet CBFpk remained higher and CVRpk lower (p < 0.05) in PMWtr. CONCLUSION: In untrained PMW, peak CBF is associated inversely with circulating pro-atherogenic lipids and glucose. In contrast, peak CBF is associated inversely with insulin levels only in trained PMW. Habitual aerobic exercise may favorably modulate vasculo-metabolic interactions in PMW.

Influence of acute dietary nitrate supplementation timing on nitrate metabolism, central and peripheral blood pressure and exercise tolerance in young men.

PURPOSE: Dietary nitrate (NO3-) supplementation can lower systolic blood pressure (SBP) and improve exercise performance. Salivary flow rate (SFR) and pH are key determinants of oral NO3- reduction and purported to peak in the afternoon. We tested the hypotheses that NO3--rich beetroot juice (BR) would increase plasma [nitrite] ([NO2-]), lower SBP and improve exercise performance to a greater extent in the afternoon (AFT) compared to the morning (MORN) and evening (EVE). METHOD: Twelve males completed six experimental visits in a repeated-measures, crossover design. NO3--depleted beetroot juice (PL) or BR (~ 13 mmol NO3-) were ingested in the MORN, AFT and EVE. SFR and pH, salivary and plasma [NO3-] and [NO2-], brachial SBP and central SBP were measured pre and post supplementation. A severe-intensity exercise tolerance test was completed to determine cycling time to exhaustion (TTE). RESULTS: There were no between-condition differences in mean SFR or salivary pH. The elevation in plasma [NO2-] after BR ingestion was not different between BR-MORN, BR-AFT and BR-EVE. Brachial SBP was unchanged following BR supplementation in all conditions. Central SBP was reduced in BR-MORN (- 3 ± 4 mmHg), BR-AFT (- 4 ± 3 mmHg), and BR-EVE (- 2 ± 3 mmHg), with no differences between timepoints. TTE was not different between BR and PL at any timepoint. CONCLUSION: Acute BR supplementation was ineffective at improving TTE and brachial SBP and similarly effective at increasing plasma [NO2-] and lowering central SBP across the day, which may have implications for informing NO3- supplementation strategies.

Mechanically demanding eccentric exercise increases nuclear factor erythroid 2-related factor 2 activity in human peripheral blood mononuclear cells.

PRE-REGISTRATION NUMBER: osf.io/kz37g.

Ischaemic preconditioning blunts exercise-induced mitochondrial dysfunction, speeds oxygen uptake kinetics but does not alter severe-intensity exercise capacity.

NEW FINDINGS: What is the central question of this study? Ischaemic preconditioning is a novel pre-exercise priming strategy. We asked whether ischaemic preconditioning would alter mitochondrial respiratory function and pulmonary oxygen uptake kinetics and improve severe-intensity exercise performance. What is the main finding and its importance? Ischaemic preconditioning expedited overall pulmonary oxygen uptake kinetics and appeared to prevent an increase in leak respiration, proportional to maximal electron transfer system and ADP-stimulated respiration, that was evoked by severe-intensity exercise in sham-control conditions. However, severe-intensity exercise performance was not improved. The results do not support ischaemic preconditioning as a pre-exercise strategy to improve exercise performance in recreationally active participants. ABSTRACT: We examined the effect of ischaemic preconditioning (IPC) on severe-intensity exercise performance, pulmonary oxygen uptake ( V ̇ O 2 ${\dot V_{{{\rm{O}}_{\rm{2}}}}}$ ) kinetics, skeletal muscle oxygenation (muscle tissue O2 saturation index) and mitochondrial respiration. Eight men underwent contralateral IPC (4 × 5 min at 220 mmHg) or sham-control (SHAM; 20 mmHg) before performing a cycling time-to-exhaustion test (92% maximum aerobic power). Muscle (vastus lateralis) biopsies were obtained before IPC or SHAM and ∼1.5 min postexercise. The time to exhaustion did not differ between SHAM and IPC (249 ± 37 vs. 240 ± 32 s; P = 0.62). Pre- and postexercise ADP-stimulated (P) and maximal (E) mitochondrial respiration through protein complexes (C) I, II and IV did not differ (P > 0.05). Complex I leak respiration was greater postexercise compared with baseline in SHAM, but not in IPC, when normalized to wet mass (P = 0.01 vs. P = 0.19), mitochondrial content (citrate synthase activity, P = 0.003 vs. P = 0.16; CI+IIP, P = 0.03 vs. P = 0.23) and expressed relative to P (P = 0.006 vs. P = 0.30) and E (P = 0.004 vs. P = 0.26). The V ̇ O 2 ${\dot V_{{{\rm{O}}_{\rm{2}}}}}$ mean response time was faster (51.3 ± 15.5 vs. 63.7 ± 14.5 s; P = 0.003), with a smaller slow component (270 ± 105 vs. 377 ± 188 ml min-1 ; P = 0.03), in IPC compared with SHAM. The muscle tissue O2 saturation index did not differ between trials (P > 0.05). Ischaemic preconditioning expedited V ̇ O 2 ${\dot V_{{{\rm{O}}_{\rm{2}}}}}$ kinetics and appeared to prevent an increase in leak respiration through CI, when expressed proportional to E and P evoked by severe-intensity exercise, but did not improve exercise performance.

The effect of dietary (poly)phenols on exercise-induced physiological adaptations: A systematic review and meta-analysis of human intervention trials.

We performed a systematic review and meta-analysis to determine whether (poly)phenol supplementation augments the physiological adaptations to exercise training. Eligible studies administered a (poly)phenol supplement alongside ≥2 weeks of supervised exercise in adult humans. After screening, 22 studies were included in the analysis. Isoflavones and green tea (poly)phenols were administered most frequently. Quality assessments suggested most studies were free from bias. (Poly)phenols had no effect on training-induced adaptations in muscle strength, peak power output, and V̇O2max, but enhanced exercise capacity (SMD: 0.67, 95% CI: 0.25 to 1.09, p < 0.01). (Poly)phenols had no overall effect on fat loss (SMD: 0.10, 95% CI: -0.10 to 0.29; p = 0.97) or lean mass gains (SMD: 0.06, 95% CI: -0.18 to 0.30, p = 0.62) but sub-analysis suggested that isoflavones increased lean mass (SMD: 0.25, 95 CI%: -0.00 to 0.50, p = 0.05). Resveratrol impaired adaptations in two studies, although this was a non-statistically significant finding (SMD: -0.54, 95% CI: -1.15 to 0.07, p = 0.08). Our results suggest that isoflavones may augment aspects of the adaptive response to exercise training, while resveratrol may compromise training adaptations. More high-quality research is needed to resolve the effects of (poly)phenols on exercise training adaptations.

Effect of nitrate supplementation on skeletal muscle motor unit activity during isometric blood flow restriction exercise.

BACKGROUND: Nitrate (NO3-) supplementation has been reported to lower motor unit (MU) firing rate (MUFR) during dynamic resistance exercise; however, its impact on MU activity during isometric and ischemic exercise is unknown. PURPOSE: To assess the effect of NO3- supplementation on knee extensor MU activities during brief isometric contractions and a 3 min sustained contraction with blood flow restriction (BFR). METHODS: Sixteen healthy active young adults (six females) completed two trials in a randomized, double-blind, crossover design. Trials were preceded by 5 days of either NO3- (NIT) or placebo (PLA) supplementation. Intramuscular electromyography was used to determine the M. vastus lateralis MU potential (MUP) size, MUFR and near fibre (NF) jiggle (a measure of neuromuscular stability) during brief (20 s) isometric contractions at 25% maximal strength and throughout a 3 min sustained BFR isometric contraction. RESULTS: Plasma nitrite (NO2-) concentration was elevated after NIT compared to PLA (475 ± 93 vs. 198 ± 46 nmol L-1, p < 0.001). While changes in MUP area, NF jiggle and MUFR were similar between NIT and PLA trials (all p > 0.05), MUP duration was shorter with NIT compared to PLA during brief isometric contractions and the sustained ischemic contraction (p < 0.01). In addition, mean MUP duration, MUP area and NF jiggle increased, and MUFR decreased over the 3 min sustained BFR isometric contraction for both conditions (all p < 0.05). CONCLUSIONS: These findings provide insight into the effect of NO3- supplementation on MUP properties and reveal faster MUP duration after short-term NO3- supplementation which may have positive implications for skeletal muscle contractile performance.

The effect of dietary phytochemicals on nuclear factor erythroid 2-related factor 2 (Nrf2) activation: a systematic review of human intervention trials.

We conducted a systematic review of human trials examining the effects of dietary phytochemicals on Nrf2 activation. In accordance with the PRISMA guidelines, Medline, Embase and CAB abstracts were searched for articles from inception until March 2020. Studies in adult humans that measured Nrf2 activation (gene or protein expression changes) following ingestion of a phytochemical, either alone or in combination were included. The study was pre-registered on the Prospero database (Registration Number: CRD42020176121). Twenty-nine full-texts were retrieved and reviewed for analysis; of these, eighteen were included in the systematic review. Most of the included participants were healthy, obese or type 2 diabetics. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Twelve different compounds were examined in the included studies: curcumin, resveratrol and sulforaphane were the most common (n = 3 each). Approximately half of the studies reported increases in Nrf2 activation (n = 10); however, many were of poor quality and had an unclear or high risk of bias. There is currently limited evidence that phytochemicals activate Nrf2 in humans. Well controlled human intervention trials are needed to corroborate the findings from in vitro and animal studies.

Independent and combined impact of hypoxia and acute inorganic nitrate ingestion on thermoregulatory responses to the cold.

PURPOSE: This study assessed the impact of normobaric hypoxia and acute nitrate ingestion on shivering thermogenesis, cutaneous vascular control, and thermometrics in response to cold stress. METHOD: Eleven male volunteers underwent passive cooling at 10 °C air temperature across four conditions: (1) normoxia with placebo ingestion, (2) hypoxia (0.130 FiO2) with placebo ingestion, (3) normoxia with 13 mmol nitrate ingestion, and (4) hypoxia with nitrate ingestion. Physiological metrics were assessed as a rate of change over 45 min to determine heat loss, and at the point of shivering onset to determine the thermogenic thermoeffector threshold. RESULT: Independently, hypoxia expedited shivering onset time (p = 0.05) due to a faster cooling rate as opposed to a change in central thermoeffector thresholds. Specifically, compared to normoxia, hypoxia increased skin blood flow (p = 0.02), leading to an increased core-cooling rate (p = 0.04) and delta change in rectal temperature (p = 0.03) over 45 min, yet the same rectal temperature at shivering onset (p = 0.9). Independently, nitrate ingestion delayed shivering onset time (p = 0.01), mediated by a change in central thermoeffector thresholds, independent of changes in peripheral heat exchange. Specifically, compared to placebo ingestion, no difference was observed in skin blood flow (p = 0.5), core-cooling rate (p = 0.5), or delta change in rectal temperature (p = 0.7) over 45 min, while nitrate reduced rectal temperature at shivering onset (p = 0.04). No interaction was observed between hypoxia and nitrate ingestion. CONCLUSION: These data improve our understanding of how hypoxia and nitric oxide modulate cold thermoregulation.

Carbohydrate mouth rinsing does not affect 6-min walk test performance and blood glucose responses in older adults.

PURPOSE: Carbohydrate (CHO) mouth rinsing (MR) prior to exercise has been shown to elicit enhanced performance and energy availability in some studies. Previous literature has concentrated on examining CHO MR strategies for improving aerobic endurance performance in younger athletic adults. Knowledge of the impact of CHO MR on functional performance in older adults is scarce. The purpose of this investigation was to determine if CHO MR would improve 6-min walk test (6MWT) performance, perceived exertion, and blood glucose responses in older adults. METHOD: Thirty-three individuals (16 males, 17 females), age ≥ 70 years performed two 6MWT trials, one of which utilized a 6.4% maltodextrin CHO MR and one of which utilized a placebo MR. Participants held the MR in their mouth for 20 s prior to the 6MWT, and trials occurred in a counterbalanced fashion. Total distance walked and rating of perceived exertion (RPE) were recorded upon completion of each 6MWT. Heart rate (HR), peripheral blood oxygen saturation (SpO2), systolic and diastolic blood pressures (BP), blood glucose, and blood lactate were measured before and after each 6MWT. RESULT: CHO MR did not alter the response of any study parameter compared to the placebo MR (p = 0.13-0.94). HR, systolic BP, and blood lactate increased and SpO2 decreased across time (p < 0.01). CONCLUSION: A 6.4% maltodextrin CHO MR did not alter total distance walked, perceived exertion, or other physiological responses elicited by the 6MWT in older adults.

Detection of synchronous brain activity in white matter tracts at rest and under functional loading.

Functional MRI based on blood oxygenation level-dependent (BOLD) contrast is well established as a neuroimaging technique for detecting neural activity in the cortex of the human brain. While detection and characterization of BOLD signals, as well as their electrophysiological and hemodynamic/metabolic origins, have been extensively studied in gray matter (GM), the detection and interpretation of BOLD signals in white matter (WM) remain controversial. We have previously observed that BOLD signals in a resting state reveal structure-specific anisotropic temporal correlations in WM and that external stimuli alter these correlations and permit visualization of task-specific fiber pathways, suggesting variations in WM BOLD signals are related to neural activity. In this study, we provide further strong evidence that BOLD signals in WM reflect neural activities both in a resting state and under functional loading. We demonstrate that BOLD signal waveforms in stimulus-relevant WM pathways are synchronous with the applied stimuli but with various degrees of time delay and that signals in WM pathways exhibit clear task specificity. Furthermore, resting-state signal fluctuations in WM tracts show significant correlations with specific parcellated GM volumes. These observations support the notion that neural activities are encoded in WM circuits similarly to cortical responses.