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Purpose: This study examined the influence of blood-flow restriction (BFR) on the distribution of pace, physiological demands, and perceptual responses during self-paced cycling. Methods: On separate days, 12 endurance cyclists/triathletes were instructed to produce the greatest average power output during 8-minute self-paced cycling trials with BFR (60% arterial occlusion pressure) or without restriction (CON). Power output and cardiorespiratory variables were measured continuously. Perceived exertion, muscular discomfort, and cuff pain were recorded every 2 minutes. Results: Linear regression analysis of the power output slope was statistically significant (ie, deviated from the intercept) for CON (2.7 [3.2] W·30 s−1; P = .009) but not for BFR (−0.1 [3.1] W·30 s−1; P = .952). Absolute power output was ∼24% (12%) lower at all time points (P P P P = .008) were reduced during BFR compared with CON, whereas muscular discomfort (25% [35%]; P = .003) was greater. Cuff pain was rated as “strong” (5.3 [1.8] au; 0–10 scale) for BFR. Conclusion: Trained cyclists adopted a more even distribution of pace when BFR was applied compared with a negative distribution during CON. By presenting a unique combination of physiological and perceptual responses, BFR is a useful tool to understand how the distribution of pace is self-regulated.

Purpose Matrix metalloproteinase-2 (MMP-2) and -3 (MMP-3), and osteopontin (OPN) are associated with adipose-tissue expansion and development of metabolic disease. The purpose of the current study was to assess the circulating concentration of these markers, along with adiponectin and glucose concentrations, in response to acute exercise in individuals with overweight or obesity. Methods Fourteen sedentary males with overweight or obesity (29.0 ± 3.1 kg/m2) completed two separate, 3-day trials in randomised and counterbalanced order. An oral glucose tolerance test (OGTT) was performed on each day of the trial. Day two of each trial consisted of a single 30 min workload-matched bout of either high-intensity interval exercise (HIIE; alternating 100% and 50% of peak pulmonary oxygen uptake, $$\mathop {\text{V}}\limits^{.}$$ V . O2peak) or continuous moderate intensity (CME; 60% $$\mathop {\text{V}}\limits^{.}$$ V . O2peak) cycling completed 1 h prior to the OGTT. Glucose and physical activity were continuously monitored, while MMP-2, MMP-3, OPN and adiponectin were measured pre-, 0 h post-, 1 h post- and 25 h post-exercise. Results Exercise transiently increased MMP-3 and decreased OPN (both p p Conclusion Acute cycling exercise decreased OPN, which is consistent with longer term improvements in cardiometabolic health and increased MMP-3, which is consistent with its role in tissue remodelling. Interestingly, exercise performed prior to the morning OGTT augmented the glucose concentrations in males. Trial registration ACTRN12613001086752.

This study investigated whether walking with blood flow restriction (BFR) increases acute cardio-respiratory demands to the point that it can be considered an alternative for jogging. Sixteen physically active adults completed five experimental sessions (order randomised), comprising 10 min of treadmill exercise. Two sessions included unrestricted walking, two sessions required walking with BFR cuffs positioned on the lower limbs inflated to 60% of individualised arterial occlusion pressure, and one session was conducted at a jogging pace. Comfortable walking and jogging speeds were calculated during the familiarisation session. Walking speeds were individualised to either 100% (speed: 6.0 ± 0.3km·h-1[low-intensity]) or 120% (speed: 7.2 ± 0.3km·h-1[moderate-intensity]) of comfortable walking speed. The jogging session was unrestricted (speed: 9.1 ± 0.7km·h-1). Initial analysis compared walking conditions across heart rate, left cardiac work index, systolic blood pressure, relative oxygen consumption, minute ventilation, rating of perceived exertion and limb discomfort. Secondary analysis compared the walking session with the highest cardio-respiratory demands to jogging. Initial analysis identified that moderate-intensity with BFR induced the highest cardio-respiratory and perceptual responses compared with any other walking sessions (

Identify whether the application of blood flow restriction (BFR) during walking influences fraction of expired oxygen (FRandomised cross-over.On separate visits, sixteen participants completed four experimental sessions (order randomised), each comprising 10 min of treadmill exercise; i.e., with or without BFR (60% arterial occlusion pressure) combined with two different intensity levels (100% or 120% comfortable walking speed). For data analysis, walking speeds within the same condition (with or without BFR) were pooled, and the speed variance was controlled within the statistical model. The FCondition × time interactions were observed for FThe increase of F

Rapamycin and FK506 are macrocyclic natural products with an extraordinary mode of action—they form binary complexes with FKBP through a shared FKBP-binding domain before forming ternary complexes with their respective targets, mTOR and calcineurin, respectively. Inspired by this, we sought to build a rapamycin-like macromolecule library to target new cellular proteins by replacing the effector domain of rapamycin with a combinatorial library of oligopeptides. We developed a robust macrocyclization method using ring-closing metathesis and synthesized a 45,000-compound library of hybrid macrocycles that are named rapafucins using optimized FKBP-binding domains. Screening of the rapafucin library in human cells led to the discovery of rapadocin, an inhibitor of nucleoside uptake. Rapadocin is a potent, isoform-specific and FKBP-dependent inhibitor of the equilibrative nucleoside transporter 1 and is efficacious in an animal model of kidney ischemia reperfusion injury. Together, these results demonstrate that rapafucins are a new class of chemical probes and drug leads that can expand the repertoire of protein targets well beyond mTOR and calcineurin., Graphical abstract

Physical activity and exercise can improve cognitive function and reduce the risk for dementia. Other lifestyle factors, including sleep, are associated with cognitive function and dementia risk, and exercise is an effective therapeutic strategy for improving sleep. Based on these associations, it has been hypothesised that sleep might be an important mediator for the effects of exercise on cognition. Here, we review the current literature to evaluate whether sleep and physical activity are independently or jointly associated with cognitive function. The extant literature in this area is minimal, and the causal relationships between physical activity, sleep and cognition have not been examined. A small number of cross-sectional studies in this area suggest that physical activity may attenuate some of the negative impact that poor sleep has on cognition, and also that sleep may be a mechanism through which physical activity improves cognitive abilities. Further research may enable the development of individually tailored intervention programs to result in the greatest cognitive benefit, ultimately delaying the onset of Alzheimer’s disease.

Purpose: To examine the influence of temporal location of high-intensity interval training (HIIT) within a cycling session on the time spent ≥90% of maximal oxygen consumption and physiological and perceptual responses. Methods: In a randomized, crossover design, 16 trained cyclists (male, n = 13 and female, n = 3) completed three 90-minute cycling sessions with HIIT placed at the beginning, middle, or end of the session (13, 36, and 69 min, respectively). Intervals consisted of three 3-minute efforts at 90% of the power output associated with maximal oxygen consumption interspersed with 3 minutes of recovery. Oxygen consumption, minute ventilation, respiratory rate, and heart rate were recorded continuously during work intervals. Rate of perceived exertion was recorded at the end of work intervals, and sessional rate of perceived exertion was collected 20 minutes after session completion. Results: No differences were observed for mean oxygen consumption (P = .479) or time spent ≥90% maximal oxygen consumption (P = .753) between condition. The mean rate of perceived exertion of all intervals were greater in the Middle (P P P = .015, effect size = 0.63). However, no differences in mean respiratory rate were observed between conditions (P = .297). Conclusions: Temporal location of HIIT has no impact on oxygen consumption or cardiovascular stress within a cycling session. However, HIIT performed later in the session resulted in higher ventilation, which may indicate the need for greater anaerobic contribution to these intervals.

Background There is a paucity of interventional research that systematically assesses the role of exercise intensity and cardiorespiratory fitness, and their relationship with executive function in older adults. To address this limitation, we have examined the effect of a systematically manipulated exercise intervention on executive function. Methods Ninety-nine cognitively normal participants (age = 69.10 ± 5.2 years; n = 54 female) were randomized into either a high-intensity cycle-based exercise, moderate-intensity cycle-based exercise, or no-intervention control group. All participants underwent neuropsychological testing and fitness assessment at baseline (preintervention), 6-month follow-up (postintervention), and 12-month postintervention. Executive function was measured comprehensively, including measures of each subdomain: Shifting, Updating/ Working Memory, Inhibition, Verbal Generativity, and Nonverbal Reasoning. Cardiorespiratory fitness was measured by analysis of peak aerobic capacity; VO2peak. Results First, the exercise intervention was found to increase cardiorespiratory fitness (VO2peak) in the intervention groups, in comparison to the control group (F =10.40, p≤0.01). However, the authors failed to find mean differences in executive function scores between the high-intensity, moderate intensity, or inactive control group. On the basis of change scores, cardiorespiratory fitness was found to associate positively with the executive function (EF) subdomains of Updating/Working Memory (β = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (β = 0.30, p = 0.03, r = 0.28) for intervention, but not control participants. Conclusion At the aggregate level, the authors failed to find evidence that 6-months of high-intensity aerobic exercise improves EF in older adults. However, it remains possible that individual differences in experimentally induced changes in cardiorespiratory fitness may be associated with changes in Updating/ Working Memory and Verbal Generativity.

Hughes, LJ, Peiffer, JJ, and Scott, BR. Reliability and validity of using the Push Band v2.0 to measure repetition velocity in free-weight and Smith machine exercises. J Strength Cond Res XX(X): 000-000, 2019-The purpose of this study was to investigate the test-retest reliability and concurrent validity of using the Push Band device 2.0 (PUSH) to quantify repetition velocity across 4 common resistance training exercises performed using free-weight and Smith machine training modalities. Twenty well-trained men (age: 25.1 ± 2.9 years, height: 182.4 ± 6.0 cm, body mass: 77.9 ± 12.0 kg, training age: 5.2 ± 1.4 years) visited the laboratory on 6 occasions (3 free-weight and 3 Smith machine sessions). Baseline strength assessments were conducted in the first session with each modality for squat, bench press, overhead press, and prone row exercises. The subsequent sessions featured repetitions performed with 30, 60, and 90% 1-repetition maximum. During these sessions, velocity was measured simultaneously using a validated linear position transducer (LPT; considered the criterion for this study) and 2 PUSH devices, one in body mode (PUSHBODY) and the other bar mode (PUSHBAR). Test-retest reliability was examined using the intraclass correlation coefficient (ICC) and coefficient of variation (CV). The LPT demonstrated slightly greater reliability (ICC = 0.80-0.98, CV = 0.4-5.1%) than the PUSHBODY (ICC = 0.65-0.95, CV = 0.8-6.9%) and PUSHBAR (ICC = 0.50-0.93, CV = 0.7-7.1%) devices. Near-perfect correlations existed between velocity measured using LPT and PUSH devices (r = 0.96-0.99). No significant differences existed between mean velocity measures obtained using LPT and either PUSH device. The PUSH device can be used in either bar or body mode to obtain reliable and valid repetition velocity measures across a range of loads and exercises performed using either free weights or a Smith machine.

The purpose of this investigation was to assess the acute changes in growth factors associated with cognitive health following two ecologically valid, intense resistance exercise sessions. Twenty-nine late-middle-aged adults performed one session of either (a) moderate-load resistance exercise or (b) high-load resistance exercise. Venous blood was collected prior to warm-up, immediately following exercise and 30 min following exercise. Serum was analyzed for brain-derived neurotrophic factor, insulin-like growth factor 1, and vascular endothelial growth factor. Session intensity was determined by blood lactate concentration and session rating of perceived exertion. Postexercise blood lactate was greater following moderate-load when compared with high-load resistance exercise. Subjective session intensity was rated higher by the session rating of perceived exertion following moderate-load when compared with high-load resistance exercise. No differences were observed in serum growth factor levels between groups. Ecologically valid and intense moderate-load or high-load exercise methods do not alter serum growth factor levels in late-middle-aged adults.

This study aimed to determine differences in the validity and reliability of 1RM predictions made using load-velocity relationships in Smith machine and free-weight exercise. Twenty well-trained males attended six sessions, comprising the Smith machine and free-weight squat, bench press, prone row and overhead press. Load-velocity relationship-based 1RM predictions were performed using minimal velocity threshold (1RM

Hughes, LJ, Peiffer, JJ, and Scott, B. Estimating repetitions in reserve in four commonly used resistance exercises. J Strength Cond Res XX(X): 000-000, 2020-This study aimed to determine the accuracy and reliability of estimating repetitions in reserve (RIR) across the squat, bench press, overhead press, and prone row exercises, using both free-weight and Smith machine modalities. Twenty-one trained men attended the laboratory on 14 occasions. They were assessed for 1 repetition maximum (1RM) for the squat, bench press, prone row, and overhead press exercises and subsequently completed 6 RIR testing sessions using 65, 75, and 85% 1RM. In these trials, subjects indicated when they reached 2 RIR (i.e., perceive they could only perform 2 more repetitions), before continuing the set to failure. The same process was then replicated using the alternative equipment modality. To determine accuracy of 2-RIR estimates, 1-sample t-tests assessed differences between 2 and the actual number of repetitions completed after subjects indicated they had reached 2 RIR. Intraclass correlation coefficients were used to determine the reliability of test-retest RIR estimated. There were no clear differences in the accuracy or reliability of estimating RIR between free-weight and Smith machine exercises. Load, however, proved an important factor with the highest accuracy associated with RIR estimations performed when using 85%, followed by 75 and 65% 1RM, respectively. When using loads of 75 and 65% 1RM, it was increasingly likely that individuals would underestimate RIR by >1 repetition, which would practically lead to an undesired reduction in training volume. These results highlight that although estimates of 2 RIR may be accurate and reliable in heavy load resistance training (≥85% 1RM), practitioners should be wary of using this measure with lighter loads.

Introduction: Evidence suggests that maintaining a higher level of cardiorespiratory fitness (CRF) later in life can offer some protection against brain volume loss as we age. By contrast, mild traumatic brain injury (mTBI) could accelerate age-related cortical atrophy. The current study sought to examine whether variations in the CRF level modified the association between mTBI history and brain volumetric measures in a sample of older adults. Methods: Seventy-nine community-dwelling older adults (mean age 68.7 ± 4.3 years, 54.4% female) were assessed for their mTBI history: 25 participants (32%) reported sustaining at least one lifetime mTBI. Participants also underwent a CRF assessment and magnetic resonance imaging (MRI) to obtain global and region-of-interest volumes. Results: Analysis of covariance, controlling for age, sex, education, and apolipoprotein (APOE) ε4 allele carriage, revealed that participants with a history of mTBI had a significantly larger total mean grey matter volume (582.21 ± 12.46 cm3) in comparison to participants with no mTBI history (571.08 ± 17.21 cm3, p = 0.01 after correction for multiple comparisons). However, no differences between groups based on mTBI history were found for total white matter volume or in any other cortical or subcortical structures examined. A subsequent moderation analysis found that CRF was predominantly non-influential on the association between mTBI history and the MRI-quantified measures of brain volume. Conclusion: While unexpected, the findings suggest that a history of mTBI can lead to grey matter alterations in the ageing brain. However, concurrent variations in the CRF level did not influence the differences in brain volume found based on mTBI exposure status.

Purpose: This study compared training loads and internal:external load ratios from an aerobic interval session at the highest perceptually sustainable intensity with and without blood flow restriction (BFR). Methods: On separate days, 14 endurance cyclists/triathletes completed four 4-minute self-paced aerobic cycling intervals at their highest sustainable intensity, with and without BFR (60% of arterial occlusion pressure). Internal training load was quantified using 3 training impulses (TRIMP; Banister, Lucia, and Edwards) and sessional ratings of perceived exertion. External load was assessed using total work done (TWD). Training load ratios between all internal loads were calculated relative to TWD. Results: Lucia TRIMP was lower for the BFR compared with non-BFR session (49 [9] vs 53 [8] arbitrary units [au], P = .020, dz = −0.71). No between-conditions differences were observed for Banister TRIMP (P = .068), Edwards TRIMP (P = .072), and training load in sessional ratings of perceived exertion (P = .134). The TWD was lower for the BFR compared with non-BFR session (223 [52] vs 271 [58] kJ, P dz = −1.27). Ratios were greater for the BFR session compared with non-BFR for Lucia TRIMP:TWD (0.229 [0.056] vs 0.206 [0.056] au, P dz = 1.21), Edwards TRIMP:TWD (0.396 [0.105] vs 0.370 [0.088] au, P = .031, dz = 0.66), and training load in sessional ratings of perceived exertion:TWD (1.000 [0.266] vs 0.890 [0.275] au, P = .044, dz = 0.60), but not Banister TRIMP:TWD (P = .306). Conclusions: Practitioners should consider both internal and external loads when monitoring BFR exercise to ensure the demands are appropriately captured. These BFR-induced changes were reflected by the Lucia TRIMP:TWD and Edwards TRIMP:TWD ratio, which could be used to monitor aerobic BFR training loads. The Lucia TRIMP:TWD ratio likely represents BFR-induced changes more appropriately compared with ratios involving either Edwards or Banister TRIMP.

BackgroundGrey matter atrophy occurs as a function of ageing and is accelerated in dementia. Previous research suggests physical activity attenuates grey matter loss; however, there appears to be individual variability in this effect. Understanding factors that can affect the relationship between physical activity and brain volume may enable prediction of individual response, and aid in identifying those that gain the greatest neural benefits from physical activity. The current study examined the relationship between objectively-measured physical activity and brain volume; and whether this relationship is moderated by age, sex, or a priori candidate genetic factors.MethodsData from 10,083 men and women (50 years and over) of the UK Biobank were used to examine: 1) the relationship between objectively-measured physical activity and brain volume; and 2) whether the relationship between objectively-measured physical activity and brain volume is moderated by age, sex, brain-derived neurotrophic factor (BDNF) Val66Met, or apolipoprotein (APOE) ε4 allele carriage. All participants underwent a magnetic resonance imaging scan to quantify grey matter volumes, physical activity monitoring via accelerometry, and genotyping.ResultsPhysical activity was associated with total grey matter volume (B = 0.14, p = 0.001, q = 0.005) and right hippocampal volume (B = 1.45, p = 0.008, q = 0.016). The physical activity*sex interaction predicted cortical grey matter (B = 0.22, p = 0.003, q = 0.004), total grey matter (B = 0.30, p < 0.001, q = 0.001), and right hippocampal volume (B = 3.60, p = 0.001, q = 0.002). Post-hoc analyses revealed males received benefit from higher physical activity levels, in terms of greater cortical grey matter volume (B = 0.13, p = 0.01), total grey matter volume (B=0.23, p < 0.001), and right hippocampal volume (B = 3.05, p = 0.008). No moderating effects of age, APOE ε4 allele carriage, or BDNF Val66Met genotype were observed.DiscussionOur results indicate that in males, but not females, an association exists between objectively-measured physical activity and grey matter volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of sex-effects on the relationship between physical activity and brain volume.

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neuhi), but low levels of CD8+ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neuhi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.

Objective:Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults.Methods:Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention.Results:The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = β = 0.29, p = 0.036, r = 0.27), right supplementary motor area (β = 0.30, p = 0.031, r = 0.29), and both right (β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups.Conclusions:At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.

Some studies have linked bilingualism with a later onset of dementia, Alzheimer's disease (AD), and mild cognitive impairment (MCI). Not all studies have observed such relationships, however. Differences in study outcomes may be due to methodological limitations and the presence of confounding factors within studies such as immigration status and level of education. We conducted the first systematic review with meta-analysis combining cross-sectional studies to explore if bilingualism might delay symptom onset and diagnosis of dementia, AD, and MCI. Primary outcomes included the age of symptom onset, the age at diagnosis of MCI or dementia, and the risk of developing MCI or dementia. A secondary outcome included the degree of disease severity at dementia diagnosis. There was no difference in the age of MCI diagnosis between monolinguals and bilinguals [mean difference: 3.2; 95% confidence intervals (CI): -3.4, 9.7]. Bilinguals vs. monolinguals reported experiencing AD symptoms 4.7 years (95% CI: 3.3, 6.1) later. Bilinguals vs. monolinguals were diagnosed with dementia 3.3 years (95% CI: 1.7, 4.9) later. Here, 95% prediction intervals showed a large dispersion of effect sizes (-1.9 to 8.5). We investigated this dispersion with a subgroup meta-analysis comparing studies that had recruited participants with dementia to studies that had recruited participants with AD on the age of dementia and AD diagnosis between mono- and bilinguals. Results showed that bilinguals vs. monolinguals were 1.9 years (95% CI: -0.9, 4.7) and 4.2 (95% CI: 2.0, 6.4) older than monolinguals at the time of dementia and AD diagnosis, respectively. The mean difference between the two subgroups was not significant. There was no significant risk reduction (odds ratio: 0.89; 95% CI: 0.68-1.16) in developing dementia among bilinguals vs. monolinguals. Also, there was no significant difference (Hedges' g = 0.05; 95% CI: -0.13, 0.24) in disease severity at dementia diagnosis between bilinguals and monolinguals, despite bilinguals being significantly older. The majority of studies had adjusted for level of education suggesting that education might not have played a role in the observed delay in dementia among bilinguals vs. monolinguals. Although findings indicated that bilingualism was on average related to a delayed onset of dementia, the magnitude of this relationship varied across different settings. This variation may be due to unexplained heterogeneity and different sources of bias in the included studies. Registration: PROSPERO CRD42015019100.

Objectives: To examine the associations between physical activity duration and intensity, cardiorespiratory fitness, and executive function in older adults. Methods: Data from 99 cognitively normal adults (age = 69.10 ± 5.1 years; n = 54 females) were used in the current study. Physical activity (intensity and duration) was measured with the International Physical Activity Questionnaire, and fitness was measured by analysis of maximal aerobic capacity, VO2peak. Executive function was measured comprehensively, including measures of Shifting, Updating, Inhibition, Generativity, and Nonverbal Reasoning. Results: Higher levels of cardiorespiratory fitness were associated with better performance on Generativity (B = .55; 95% confidence interval [.15, .97]). No significant associations were found between self-reported physical activity intensity/duration and executive functions. Discussion: To our knowledge, this study is the first to identify an association between fitness and Generativity. Associations between physical activity duration and intensity and executive function requires further study, using objective physical activity measures and longitudinal observations.

There is growing evidence for a preventative effect of resistance training on cognitive decline through physiological mechanisms; yet, the effect of resistance training on resting growth factors and homocysteine levels is incompletely understood. This study aimed to investigate the effect of intense resistance training, for 12 weeks, on changes in peripheral growth factors and homocysteine in late middle-aged adults. 45 healthy adults were enrolled into the single-site parallel groups’ randomized-controlled trial conducted at the Department of Exercise Science, Strength and Conditioning Laboratory, Murdoch University. Participants were allocated to the following conditions: (1) high-load resistance training (n = 14), or (2) moderate-load resistance training (n = 15) twice per week for 12 weeks; or (3) non-exercising control group (n = 16). Data were collected from September 2016 to December 2017. Fasted blood samples were collected at baseline and within 7 days of trial completion for the analysis of resting serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1, vascular endothelial growth factor, and plasma homocysteine levels. No differences in baseline to post-intervention change in serum growth factors or plasma homocysteine levels were observed between groups. A medium effect was calculated for BDNF change within the high-load condition alone (+ 12.9%, g = 0.54). High-load or moderate-load resistance training twice per week for 12 weeks has no effect on peripheral growth factors or homocysteine in healthy late middle-aged adults. Australian New Zealand Clinical Trials Registry: ACTRN12616000690459.

Smith, NDW, Scott, BR, Girard, O, and Peiffer, JJ. Aerobic training with blood flow restriction for endurance athletes: potential benefits and considerations of implementation. J Strength Cond Res XX(X): 000-000, 2021-Low-intensity aerobic training with blood flow restriction (BFR) can improve maximal oxygen uptake, delay the onset of blood lactate accumulation, and may provide marginal benefits to economy of motion in untrained individuals. Such a training modality could also improve these physiological attributes in well-trained athletes. Indeed, aerobic BFR training could be beneficial for those recovering from injury, those who have limited time for training a specific physiological capacity, or as an adjunct training stimulus to provide variation in a program. However, similarly to endurance training without BFR, using aerobic BFR training to elicit physiological adaptations in endurance athletes will require additional considerations compared with nonendurance athletes. The objective of this narrative review is to discuss the acute and chronic aspects of aerobic BFR exercise for well-trained endurance athletes and highlight considerations for its effective implementation. This review first highlights key physiological capacities of endurance performance. The acute and chronic responses to aerobic BFR exercise and their impact on performance are then discussed. Finally, considerations for prescribing and monitoring aerobic BFR exercise in trained endurance populations are addressed to challenge current views on how BFR exercise is implemented.

Background and aims We conducted a comprehensive serum transcriptomic analysis to explore the roles of microRNAs (miRNAs) in alcohol-associated hepatitis (AH) pathogenesis and their prognostic significance. Approach and results Serum miRNA profiling was performed in 15 controls, 20 heavy drinkers without liver disease, and 65 patients with AH and compared to publicly available hepatic miRNA profiling in AH patients. Among the top 26 miRNAs, expression of miR-30b-5p, miR-20a-5p, miR-146a-5p, and miR-26b-5p were significantly reduced in both serum and liver of AH patients. Pathway analysis of the potential targets of these miRNAs uncovered the genes related to DNA synthesis and cell-cycle progression pathways, including ribonucleotide reductase regulatory subunit M2 (RRM2), cyclin D1 (CCND1), cyclin D2 (CCND2), MYC proto-oncogene (MYC), and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1). We found a significant increase in the protein expression of RRM2, CCND1, and CCND2, but not MYC and PMAIP1, in AH patients who underwent liver transplantation; miR-26b-5p and miR-30b-5p inhibited the 3'-UTR (untranslated region) luciferase activity of RRM2 and CCND2, and miR-20a-5p reduced the 3'-UTR luciferase activity of CCND1 and CCND2. During a median follow-up of 346 days, 21% of AH patients died; these patients had higher body mass index (BMI), Model for End-Stage Liver Disease (MELD), and serum miR-30b-5p, miR-20a-5p, miR-146a-5p, and miR-26b-5p than those who survived. Cox regression analysis showed that BMI, MELD score, miR-20a-5p, miR-146a-5p, and miR-26b-5p predicted mortality. Conclusions Patients with AH attempt to deal with hepatocyte injury by down-regulating specific miRNAs and up-regulating genes responsible for DNA synthesis and cell-cycle progression. Higher expression of these miRNAs, suggestive of a diminished capacity in liver regeneration, predicts short-term mortality in AH patients.

INTRODUCTION Persistent diplopia following orbital fracture is a well-recognized problem. While observation is the standard-of-care, symptoms may be protracted. Orthoptic vision therapy is a form of ocular physical therapy that achieves functional rehabilitation through targeted exercises. This study presents a protocol for post-traumatic orthoptics and describes preliminary results. MATERIALS AND METHODS Protocols for home-therapy/office-assessment were developed using commercial software and exercises targeting motility and fusion. Office-assessment also included validated questionnaire chronicling symptomatology. Healthy-volunteers (n = 10) trailed the protocol three times (n = 30) and normative data was compiled. Comparative measurements were made in chronic (>1year; n = 8) and acute (

BACKGROUND: Physical inactivity has been consistently linked to increased risk of cognitive decline; however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements; however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition. In addition, we investigated individual variability in exercise response by examining effects of relevant genetic factors and changes in cardiorespiratory fitness on cognitive change.METHODS: This multi-arm randomised clinical trial investigated the effects of 6-months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12-months post-intervention. Ninety-nine cognitively normal men and women (aged 60 – 80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e., high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test. Apolipoprotein e4 genotype and brain-derived neurotrophic factor Val66Met carriage were identified.RESULTS: There was a dose-dependent effect of exercise intensity on cardiorespiratory fitness; whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition. We observed an association between changes in global cognition and executive function and changes in cardiorespiratory fitness from pre- to post-intervention: this relationship was strongest in brain-derived neurotrophic factor non-Met carriers.CONCLUSIONS We did not observe a direct effect of exercise on cognition. Nevertheless, our data suggests genetics may moderate the relationship between fitness and cognitive change following exercise, and this should be examined further in larger trials.TRIAL REGISTRATION: This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered 3rd May 2017 - retrospectively registered. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372780

Mansfield, Sean, K, Peiffer, Jeremiah, J, Hughes, Liam, J, and Scott Brendan, R. Estimating repetitions in reserve for resistance exercise: an analysis of factors which impact on prediction accuracy. J Strength Cond Res XX(X): 000-000, 2020-The purpose of this study was to examine the influence of knowing the load being lifted on the accuracy of repetitions-in-reserve (RIR) estimates, during both moderate- (60% 1 repetition maximum [RM]) and heavy-load (80% 1RM) exercise. Twenty trained men (age: 25.9 ± 4.5 years, height: 181 ± 7 cm, body mass: 86.5 ± 13.7 kg) were assessed for 1RM in bench press (98.4 ± 16.4 kg) and prone row (72.0 ± 11.7 kg), before being randomized into control (i.e., informed of the load; n = 10) or blinded (noninformed; n = 10) conditions. Subjects then completed 2 protocols in a randomized order: 3 sets at 80% 1RM and 3 sets at 60% 1RM. During each set of these protocols, subjects were asked to estimate their RIR before continuing the set to failure. Differences in estimated and actual RIR between sets and conditions were determined via 3-way repeated measures analysis of variance for the 60 and 80% 1RM protocols independently. No differences in RIR accuracy were observed between blinded vs nonblinded conditions. Repetitions-in-reserve estimates were lower than actual RIR for the first set of both exercises in 60 and 80% protocols (p ≤ 0.007, effect size [ES]: 1.30-2.89 [moderate-large]) and for set 2 of the 80% bench press protocol (p = 0.046, ES: 0.39 [small]). Knowing the load during resistance exercise or the %1RM of the load lifted did not influence the estimates of RIR. The ability to accurately determine RIR in the 60 and 80% 1RM protocols improved from sets 1-3, indicating that estimation of RIR is enhanced when an individual is estimating RIR at a closer point to actual failure.

Objectives To investigate the effects of acute branched-chain amino acid (BCAA) supplementation on cycling performance and neuromuscular fatigue during a prolonged, self-paced cycling time-trial. Design Randomised double-blind counterbalanced crossover. Methods Eighteen recreationally active men (mean ± SD; age: 24.7 ± 4.8 years old; body-weight, BW: 67.1 ± 6.1 kg; height: 171.7 ± 4.9 cm) performed a cycling time-trial on an electromagnetically-braked cycle ergometer. Participants were instructed to complete the individualised total work in the shortest time possible, while ingesting either BCAAs (pre-exercise: 0.084 g kg−1 BW; during exercise: 0.056 g kg−1 h−1) or a non-caloric placebo solution. Rating of perceived exertion, power, cadence and heart rate were recorded throughout, while maximal voluntary contraction, muscle voluntary activation level and electrically evoked torque using single and doublet stimulations were assessed at baseline, immediately post-exercise and 20-min post-exercise. Results Supplementation with BCAA reduced (287.9 ± 549.7 s; p = 0.04) time-to-completion and ratings of perceived exertion (p ≤ 0.01), while concomitantly increasing heart rate (p = 0.02). There were no between-group differences (BCAA vs placebo) in any of the neuromuscular parameters, but significant decreases (All p ≤ 0.01) in maximal voluntary contraction, muscle voluntary activation level and electrically evoked torque (single and doublet stimulations) were recorded immediately following the trial, and these did not recover to pre-exercise values by the 20 min recovery time-point. Conclusions Compared to a non-caloric placebo, acute BCAA supplementation significantly improved performance in cycling time-trial among recreationally active individuals without any notable changes in either central or peripheral factors. This improved performance with acute BCAA supplementation was associated with a reduced rating of perceived exertion.

BACKGROUND: Backpacks are the most popular way of carrying additional weight; however, it puts the body under physical stress and may cause discomfort. It may also increase oxygen demand and energy cost. Manipulation of load placement may relieve the effects carrying a backpack has on the body. OBJECTIVE: This study investigated physiological and self-reported measures of exertion, movement economy and efficiency, carrying a loaded backpack in high and low load placement compared to a control condition. METHOD: Fifteen healthy adults were examined under three load conditions: no load, carrying a 20% of body weight in high and low load placement. Dependent variables were measured using a metabolic measurement system and participants rated their perceived exertion on a Borg scale. RESULT: Carrying load produced a significant increase in VO2, minute ventilation, heart rate, movement economy and overall perceived exertion in both load placements compared with the no backpack condition. However, no difference was observed between the high and low load placement conditions. CONCLUSION: While altering load placement did not influence physiological variables or overall exertion, participants reported lower perceived exertion on the shoulders in low load placement and low load placement might be preferable in this respect.

Purpose: To examine the power-output distribution and sprint characteristics of professional female road cyclists. Methods: A total of 31 race files, representing top 5 finishes, were collected from 7 professional female cyclists. Files were analyzed for sprint characteristics, including mean and peak power output, velocity, and duration. The final 20 min before the sprint was analyzed to determine the mean maximal power output (MMP) consistent with durations of 5, 15, 30, 60, 240, and 600 s. Throughout the race, the number of efforts for each duration exceeding 80% of its corresponding final 20-min MMP (MMP80) was determined. The number of 15-s efforts exceeding 80% of the mean final sprint power output (MSP80) was determined. Results: Sprint finishes lasted 21.8 (6.7) s with mean and peak power outputs of 679 (101) and 886 (91) W, respectively. Throughout the race, additional 5-, 15-, and 30-s efforts above MMP80 were completed in the 5th compared with the 1st–4th quintiles of the race. The 60-s efforts were greater during the 5th quintile compared with the 1st, 2nd, and 4th quintiles, and during the 3rd compared with the 4th quintile. More 240-s efforts were recorded during the 5th compared with the 1st and 4th quintiles. About 82% of the 15-s efforts above MSP80 were completed in the 2nd, 3rd, and 5th quintiles of the race. Conclusions: These data demonstrate the variable nature of women’s professional cycling and the physical demands necessary for success, thus providing information that could enhance in-race decision making and the development of race-specific training programs.

Although complex in nature, a number of metabolites have been implicated in the onset of exercise-induced fatigue. The purpose of this study was to identify changes in the plasma metabolome and specifically, to identify candidate metabolites associated with the onset of fatigue during prolonged cycling. Eighteen healthy and recreationally active men (mean ± SD; age: 24.7 ± 4.8 yr; mass 67.1 ± 6.1 kg; body mass index: 22.8 ± 2.2; peak oxygen uptake: 40.9 ± 6.1 ml·kg−1·min−1) were recruited to this study. Participants performed a prolonged cycling time-to-exhaustion (TTE) test at an intensity corresponding to a fixed blood lactate concentration (3 mmol/l). Plasma samples collected at 10 min of exercise, before fatigue (last sample before fatigue NEW & NOTEWORTHY Metabolites have long been implicated in the onset of fatigue. This study applied a metabolomic approach to track 80 plasma-borne metabolites during a cycle to fatigue task. Of these, 68 metabolites demonstrated significant change, with the plasma metabolome at fatigue being clearly distinguishable from other time points. Six unique clusters of metabolites were identified, and free fatty acids were strongly associated with fatigue onset therein lending support to the central fatigue hypothesis.

Introduction Leg order during sequential single-leg cycling (i.e., exercising both legs independently within a single session) may affect local muscular responses potentially influencing adaptations. This study examined the cardiovascular and skeletal muscle hemodynamic responses during double-leg and sequential single-leg cycling. Methods Ten young healthy adults (28 ± 6 yr) completed six 1-min double-leg intervals interspersed with 1 min of passive recovery and, on a separate occasion, 12 (six with one leg followed by six with the other leg) 1-min single-leg intervals interspersed with 1 min of passive recovery. Oxygen consumption, heart rate, blood pressure, muscle oxygenation, muscle blood volume, and power output were measured throughout each session. Results Oxygen consumption, heart rate, and power output were not different between sets of single-leg intervals, but the average of both sets was lower than the double-leg intervals. Mean arterial pressure was higher during double-leg compared with sequential single-leg intervals (115 ± 9 vs 104 ± 9 mm Hg, P < 0.05) and higher during the initial compared with second set of single-leg intervals (108 ± 10 vs 101 ± 10 mm Hg, P < 0.05). The increase in muscle blood volume from baseline was similar between the active single leg and the double leg (267 ± 150 vs 214 ± 169 μM·cm, P = 0.26). The pattern of change in muscle blood volume from the initial to second set of intervals was significantly different (P < 0.05) when the leg was active in the initial (−52.3% ± 111.6%) compared with second set (65.1% ± 152.9%). Conclusions These data indicate that the order in which each leg performs sequential single-leg cycling influences the local hemodynamic responses, with the inactive muscle influencing the stimulus experienced by the contralateral leg.

Numerous animal studies have reported exercise reduces the accumulation of Alzheimer's disease pathology, including amyloid-β (Aβ) and tau. Furthermore, we previously reported a relationship between higher levels of physical activity (PA) and lower brain Aβ burden in a human population. The recent advent of tau positron emission tomography (PET) tracers enables us to extend our investigations into the evaluation of the relationship between PA and brain tau burden. Utilizing data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, we have examined the cross-sectional relationship between habitual PA and PET-quantified tau burden. Forty-three cognitively healthy older adults were categorized into low-moderate PA (LMPA; n = 16) or high PA (HPA; n = 27), based on self-reported PA levels. Tau PET imaging with the AV1451 tracer was conducted on all participants. The LMPA group had significantly higher neocortical tau burden (presented as a z-score; 1.22±1.98), compared to the HPA group (z-score: - 0.28±1.18). The difference between the LMPA and HPA groups was also evident when examining regional tau burden in the temporoparietal cortex and the prefrontal cortex. Our results suggest an association between self-reported PA level and brain tau burden. Future longitudinal and interventional studies utilizing larger samples sizes are vital to further investigate the nature of the relationship between tau and PA.

Mild traumatic brain injury (mTBI) accounts for a large majority of traumatic brain injuries sustained globally each year. Older adults, who are already susceptible to age-related declines to neurocognitive health, appear to be at an increased risk of both sustaining an mTBI and experiencing slower or impaired recovery. There is also growing evidence that mTBI is a potential risk factor for accelerated cognitive decline and neurodegeneration. Lifestyle-based interventions are gaining prominence as a cost-effective means of maintaining cognition and brain health with age. Consequently, inter-individual variations in exercise, sleep, and dietary patterns could influence the trajectory of post-mTBI neurocognitive recovery, particularly in older adults. This review synthesises the current animal and human literature centred on the mechanisms through which lifestyle-related habits and behaviours could influence acute and longer-term neurocognitive functioning following mTBI. Numerous neuroprotective processes which are impacted by lifestyle factors have been established in animal models of TBI. However, the literature is characterised by a lack of translation to human samples and limited appraisal of the interaction between ageing and brain injury. Further research is needed to better establish the therapeutic utility of applying lifestyle-based modifications to improve post-mTBI neurocognitive outcomes in older adults.

Brain-derived neurotrophic factor (BDNF) has been shown to increase in an intensity dependent manner in response to aerobic exercise. However, previous research investigating the use of resistance exercise to increase BDNF levels has been less conclusive, likely due to the low intensity nature of traditional resistance exercise programs. This study examined the influence of acute resistance exercise to-fatigue on serum BDNF levels and blood lactate.Acute crossover study.Eleven untrained to intermediately trained males (age: 25.0±1.3 year) and five untrained females (age: 23.2±1.1 year) were recruited to undertake two bouts of resistance exercise. Strength (five sets of five repetitions, 180s recovery) and hypertrophy (three sets of ten repetitions, 60s recovery) based resistance exercise was implemented to-fatigue to examine the effect on serum BDNF and blood lactate levels immediately post-, and 30min post-exercise.An interaction (p0.01; ES=0.52) was observed between conditions immediately post-exercise, with hypertrophy resulting in significantly greater BDNF levels when compared with strength exercise. Changes in lactate and BDNF from baseline to post- exercise were positively correlated following hypertrophy exercise (r=0.70; p0.01), but not correlated following strength exercise (r=0.18; p=0.56).The use of a to-fatigue hypertrophy based resistance exercise protocol provides the necessary stimulus to increase peripheral serum BDNF. Mechanistically, the presence of lactate does not appear to drive the BDNF response during resistance exercise.

Objectives Actical® actigraphy is commonly used to monitor athlete sleep. The proprietary software, called Actiware®, processes data with three different sleep-wake thresholds (Low, Medium or High), but there is no standardisation regarding their use. The purpose of this study was to examine validity and bias of the sleep-wake thresholds for processing Actical® sleep data in team sport athletes. Design Validation study comparing actigraph against accepted gold standard polysomnography (PSG). Methods Sixty seven nights of sleep were recorded simultaneously with polysomnography and Actical® devices. Individual night data was compared across five sleep measures for each sleep-wake threshold using Actiware® software. Accuracy of each sleep-wake threshold compared with PSG was evaluated from mean bias with 95% confidence limits, Pearson moment-product correlation and associated standard error of estimate. Results The Medium threshold generated the smallest mean bias compared with polysomnography for total sleep time (8.5 min), sleep efficiency (1.8%) and wake after sleep onset (−4.1 min); whereas the Low threshold had the smallest bias (7.5 min) for wake bouts. Bias in sleep onset latency was the same across thresholds (−9.5 min). The standard error of the estimate was similar across all thresholds; total sleep time ∼25 min, sleep efficiency ∼4.5%, wake after sleep onset ∼21 min, and wake bouts ∼8 counts. Conclusions Sleep parameters measured by the Actical® device are greatly influenced by the sleep-wake threshold applied. In the present study the Medium threshold produced the smallest bias for most parameters compared with PSG. Given the magnitude of measurement variability, confidence limits should be employed when interpreting changes in sleep parameters.

The post‐exercise hepcidin response during prolonged ( > 2 weeks) hypoxic exposure is not well understood. We compared plasma hepcidin levels 3 h after exercise [6 × 1000 m at 90% of maximal aerobic running velocity (vVO2max)] performed in normoxia and normobaric hypoxia (3000 m simulate altitude) 1 week before, and during 14 days of normobaric hypoxia [196.2 ± 25.6 h (median: 200.8 h; range: 154.3–234.8 h) at 3000 m simulated altitude] in 10 well‐trained distance runners (six males, four females). Venous blood was also analyzed for hepcidin after 2 days of normobaric hypoxia. Hemoglobin mass (Hbmass) was measured via CO rebreathing 1 week before and after 14 days of hypoxia. Hepcidin was suppressed after 2 (Cohen's d = −2.3, 95% confidence interval: [−2.9, −1.6]) and 14 days of normobaric hypoxia (d = −1.6 [−2.6, −0.6]). Hepcidin increased from baseline, 3 h post‐exercise in normoxia (d = 0.8 [0.2, 1.3]) and hypoxia (d = 0.6 [0.3, 1.0]), both before and after exposure (normoxia: d = 0.7 [0.3, 1.2]; hypoxia: d = 1.3 [0.4, 2.3]). In conclusion, 2 weeks of normobaric hypoxia suppressed resting hepcidin levels, but did not alter the post‐exercise response in either normoxia or hypoxia, compared with the pre‐exposure response.