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Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Purpose: Acute prolonged bouts of sitting reduce popliteal artery blood flow and flow-mediated dilation (FMD). Individuals with higher aerobic fitness have enhanced popliteal FMD. Conflicting evidence regarding whether more aerobically fit individuals are protected from the negative impacts of sitting on popliteal endothelial function in male-dominated studies have been reported. We further explored the relationship between aerobic fitness and sitting-induced impairments in popliteal blood flow and FMD in a more sex-balanced cohort., Methods: Relative peak oxygen consumption (V̇O 2 peak) was assessed using a cycling-based incremental test in 21 healthy adults (eight males; 23 ± 2 years; 23.9 ± 2.9 kg/m 2 ). Popliteal blood flow and relative FMD (%) were measured via duplex ultrasonography before and after 3 h of uninterrupted sitting. Pearson correlations were performed separately between V̇O 2 peak versus pre-sitting and sitting-induced reductions in popliteal outcomes., Results: Aerobic fitness (41.0 ± 9.7 ml/kg/min) was positively correlated with pre-sitting popliteal blood flow (65 ± 23 mL/min; R = 0.59, P = 0.005) and relative FMD (4.2 ± 1.5%; R = 0.49, P = 0.03). As expected, sitting reduced resting blood flow (19 ± 11 mL/min) and FMD (1.9 ± 0.7%) (both, P < 0.001). V̇O 2 peak was inversely related to sitting-induced declines in blood flow (Δ-46 ± 23 mL/min; R = - 0.71, P < 0.001) and FMD (Δ-2.4 ± 1.5%; R = - 0.51, P = 0.02)., Conclusions: Although higher aerobic fitness was associated with more favorable popliteal endothelial-dependent vasodilator responses, it also corresponded with larger sitting-induced impairments in FMD. This suggests that being more aerobically fit does not protect against sitting-induced vascular endothelial dysfunction. As such, all young adults should minimize habitual prolonged sedentary bouts, regardless of their aerobic fitness level., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The activPAL linear cadence-metabolic equivalents (METs) equation poorly estimates activity intensity. The magnitude of acceleration in three directional planes may be a superior predictor of activity intensity than stepping cadence, with accelerometry count thresholds developed in children/adolescent populations. We extracted the proprietary accelerometer-derived information to develop a counts-METs model and cross-validates it in laboratory and free-living conditions. Forty adults (25±6 years) wore an activPAL during a 7-stage progressive treadmill protocol (criterion: indirect calorimetry). Tri-axial accelerometry-derived activity counts (vector magnitude) and METs data from a subset of participants (n = 20) were modelled (R 2 =0.76) and the regression equation evaluated in the remaining participants (n = 20). Thirty-two of these participants wore the activPAL during free-living conditions (n = 192-d; criterion: PiezoRxD monitor). The absolute percent error of the counts-METs model in the laboratory cross-validation was 18±13%, with equivalence testing determinining equivalent MET values to indirect calorimetry during the slowest (1.5 mph) and fastest (4.0-4.5 mph) stages. In free-living conditions, the model accurately quantified light- and moderate-intensity physical activity but underestimated vigorous-intensity activity (6.5±11.3 vs. 5.5±20.8 mins/day; p < 0.001). We developed and present a data analysis method using the activPAL tri-axial accelerometry counts to improve estimations of physical activity intensity in controlled laboratory settings and uncontrolled free-living settings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The sympathetic nervous system is important for the beat-by-beat regulation of arterial blood pressure and the control of blood flow to various organs. Microneurographic recordings of pulse-synchronous muscle sympathetic nerve activity (MSNA) are used by numerous laboratories worldwide. The transduction of hemodynamic and vascular responses elicited by spontaneous bursts of MSNA provides novel, mechanistic insight into sympathetic neural control of the circulation. Although some of these laboratories have developed in-house software programs to analyze these sympathetic transduction responses, they are not openly available and most require higher level programming skills and/or costly platforms. In the present paper, we present an open-source, Microsoft Excel-based analysis program designed to examine the pressor and/or vascular responses to spontaneous resting bursts of MSNA, including across longer, continuous MSNA burst sequences, as well as following heartbeats not associated with MSNA bursts. An Excel template with embedded formulas is provided. Detailed written and video-recorded instructions are provided to help facilitate the user and promote its implementation among the research community. Open science activities such as the dissemination of analytical programs and instructions may assist other laboratories in their pursuit to answer novel and impactful research questions regarding sympathetic neural control strategies in human health and disease. NEW & NOTEWORTHY The pressor responses to spontaneous bursts of muscle sympathetic nerve activity provide important information regarding sympathetic regulation of the circulation. Many laboratories worldwide quantify sympathetic neurohemodynamic transduction using in-house, customized software requiring high-level programming skills and/or costly computer programs. To overcome these barriers, this study presents a simple, open-source, Microsoft Excel-based analysis program along with video instructions to assist researchers without the necessary resources to quantify sympathetic neurohemodynamic transduction.

As with blood pressure, age-related changes in muscle sympathetic nerve activity (MSNA) may differ nonlinearly between sexes. Data acquired from 398 male (age: 39±17; range: 18-78 years [mean±SD]) and 260 female (age: 37±18; range: 18-81 years) normotensive healthy nonmedicated volunteers were analyzed using linear regression models with resting MSNA burst frequency as the outcome and the predictors sex, age, MSNA, blood pressure, and body mass index modelled with natural cubic splines. Age and body mass index contributed 41% and 11%, respectively, of MSNA variance in females and 23% and 1% in males. Overall, changes in MSNA with age were sigmoidal. At age 20, mean MSNA of males and females were similar, then diverged significantly, reaching in women a nadir at age 30. After 30, MSNA increased nonlinearly in both sexes. Both MSNA discharge and blood pressure were lower in females until age 50 (17±9 versus 25±10 bursts·min -1 ; P <1×10 -19 ; 106±11/66±8 versus 116±7/68±9 mm Hg; P <0.01) but converged thereafter (38±11 versus 35±12 bursts·min -1 ; P =0.17; 119±15/71±13 versus 120±13/72±9 mm Hg; P >0.56). Compared with age 30, MSNA burst frequency at age 70 was 57% higher in males but 3-fold greater in females; corresponding increases in systolic blood pressure were 1 (95% CI, -4 to 5) and 12 (95% CI, 6-16) mm Hg. Except for concordance in females beyond age 40, there was no systematic change with age in any resting MSNA-blood pressure relationship. In normotensive adults, MSNA increases after age 30, with ascendance steeper in women.

Background: Existing analytical approaches used to measure free-living stepping cadence (steps per minute; spm) characterize stepping two-ways: 1) 60 s epochs without considering time spent stepping during the epoch (step accumulation; SA), or 2) a bout-based analysis that considers both number of steps and time spent stepping during stepping bouts (total event cadence; TEC). SA and TEC may incorrectly characterize cadence in epochs that do not consist of continuous stepping or if there are marked changes in cadence within a stepping bout, respectively., Research Question: How does a bout-based analytical method that examines each stepping bout individually and considers within-bout changes in stepping cadence during epochs ≥120 s (Bout Cadence; BC) compare to SA and TEC?, Methods: ActivPAL™-derived data from 122 participants were analyzed (790 total days). SA and TEC were calculated according to previous literature. BC calculated cadence bout-by-bout and stride-by-stride for bouts lasting <120 s and ≥120 s, respectively. Time spent stepping between 0-140 spm (divided into 20 spm bins) or >140 spm were determined for each method. Time spent in slow (0-80 spm), medium (80-120 spm) and fast (>120 spm) cadences for each method were compared via Bland-Altman analyses., Results: Almost half (43 %) of the total number of 60 s epochs included ≥2 stepping bouts, and 37 % of total stepping time was accumulated in continuous stepping bouts ≥120 s. Compared to TEC, BC identified more daily time spent in the 20-40 spm and >120 spm cadence bins, but less time spent in the 60-120 spm range. Both SA (fixed bias: -11.0 ± 12.4 min/day) and TEC (fixed bias: -10.0 ± 13.6 min/day) underestimated faster stepping cadences compared to BC., Significance: Existing analytical approaches largely underestimate faster stepping cadences, resulting in inaccurate measurements of vigorous-intensity stepping activity. The BC better characterizes higher intensity stepping activity, which could have important implications for assessing participants' true habitual stepping activity levels., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Reviews on cardiovascular fitness and cognition in older adults suggest that a higher level of cardiorespiratory fitness may protect the brain against the effects of aging. Although studies reveal positive effects of cardiorespiratory fitness on executive function, more research is needed to clarify the underlying mechanisms of these effects in older adults. The aim of the current study was to assess the association between cardiorespiratory fitness level, cerebral oxygenation, and cognitive performance in older adults (OAs). Seventy-four OAs (68 ± 6.3 years) gave their written, informed consent to participate in the study. Complete data was collected from 66 participants. All participants underwent a cycle ergometer maximal continuous graded exercise test in order to assess their peak power output (PPO) and a neuropsychological paper and pencil tests (Trail Making Test A and B) while changes in left prefrontal cortex oxygenation were measured with functional near-infrared spectroscopy (fNIRS). The results reveal increased cardiorespiratory fitness was associated with decreased response time (i.e., better performance) on the Trail Making Test (B) (standardized β = - 0.42, p < 0.05). Cerebral oxygenation in higher fit older adults mediated the relationship with improved executive functioning (standardized β = - 0.08, p < 0.05). Specifically, in older adults with higher cardiorespiratory fitness (based on a median split), cerebral oxygenation was related to executive functioning but no such relationship existed in lower fit adults.

Virgin coconut oil (VCO) is high in antioxidants, which reduce reactive oxygen species-induced conversion of vascular endothelial-derived nitric oxide (NO) to toxic peroxynitrite. As such, flow-mediated dilation (FMD, a surrogate marker of NO bioavailability) and exercise-mediated hyperemia may be enhanced following VCO treatment. Animal research supports these findings, but direct assessments of FMD after short-term VCO use in humans are unknown. We tested the hypotheses that a 4-week VCO supplement (30 mL·d -1 ) would improve popliteal artery (PA) FMD and the hyperemic response to aerobic exercise. Thirty-four young adults were divided into VCO (n = 19, 9 women, 22 ± 2 years, 24 ± 3 kg·m -2 ) and control (CON: n = 15, 7 women, 24 ± 2 years, 24 ± 3 kg·m - 2 ) groups. PA-FMD and blood flow were assessed via high-resolution duplex ultrasonography (Vivid i, GE Healthcare, Mississauga, Ontario, Canada). PA blood flow was measured at rest and for 5 minutes following a 10-minute bout of moderate-intensity (60% heart rate reserve) cycling exercise. Total PA blood volume was calculated as the integral of the 5-minute postexercise PA blood flow response. After 4 weeks, PA-FMD increased (P = .04) following VCO supplementation (4.9% ± 0.9% to 5.5% ± 1.2%) with no change (P > .9) in the CON group (5.7% ± 2.1% to 5.8% ± 1.9%). There were no differences (both P > .28) in the postexercise total PA blood volume response in either group (VCO: 495 ± 355 to 598 ± 384 mL; CON: 562 ± 362 to 488 ± 229 mL). Short-term VCO supplementation does not alter aerobic exercise-mediated blood flow responses in young adults. However, the augmented popliteal FMD response observed in the VCO supplement group indicates that short-term VCO supplementation improves vascular endothelial function in young, healthy adults., (Copyright © 2019. Published by Elsevier Inc.)

Long-term endurance training is associated with an increased risk of atrial arrhythmia in older adults (OA). We tested the hypothesis that Aerobically-Fit OA would have prolonged indices related to atrial arrhythmias (e.g. PR-intervals and P durations) compared to younger adults (YA) and Aerobically-Unfit OA. 10-minute stable supine electrocardiogram (ECG) recordings were collected at 1000 Hz in 15 YA (4F, 22 ± 2 years, 50.7 ± 8.5 ml/kg/min), 11 Aerobically-Unfit OA (6♀, 63 ± 7 years, 25.2 ± 2.3 ml/kg/min) and 10 Aerobically-Fit OA (4F, 64 ± 3 years, 45.5 ± 7.0 ml/kg/min) to assess ECG morphology and spectral indices of heart rate variability. In the pooled sample, age was a predictor of PR-interval (r = 0.75) and P wave duration (r = 0.80) (both, p < 0.01). Regardless of age, aerobic fitness was positively associated with PR interval duration (r = 0.81; p < 0.01). Aerobically-Fit OA had prolonged PR-intervals (187 ± 17 vs 161 ± 14 vs. 168 ± 20 ms) and P-wave durations (123 ± 9 vs. 97 ± 9 vs. 96 ± 9 ms) compared to YA and Aerobically-Unfit OA, respectively (all, p < 0.05). In addition, Aerobically-Fit OA had greater normalized high-frequency (HF) power compared to Aerobically-Unfit OA (40.7 ± 4.5nu vs. 30.1 ± 14.2 ± nu; p = 0.03) suggestive of enhance parasympathetic tone. These data highlight that the combination of age-related electrical remodeling and enhanced vagal tone in OA with higher aerobic fitness may contribute to prolongation of atrial-related ECG indices. This is further supported by the correlation between HF power and PR-interval duration (r = 0.45; p = 0.02). These findings may help identify older individuals at risk for atrial arrhythmias who are otherwise free of cardiovascular disease., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Effective regulation of central blood volume and arterial pressure is critical for optimal cardiovascular homeostasis. Inadequate regulation of mean arterial pressure has important pathophysiological implications including syncope, end organ damage, and stroke. Such regulation requires appropriate central integration of barosensory afferents and reflex autonomic control of the heart and blood vessels. The neural pathways involved with the baroreflex include brainstem nuclei that receive modulatory input from higher brain centres. Studies in anesthetized animals have highlighted the role of a central autonomic network involved with baroreflex control. The refinement of functional neuroimaging techniques has provided the opportunity to confirm and extend these findings in awake humans. Such methods have provided information about the temporal and spatial neural patterns associated with changes in barosensory afferent activity and reflex autonomic and cardiovascular responses. This review focuses on human neuroimaging investigations that utilized volitional (e.g., respiratory challenges) and/or non-volitional (e.g. lower body suction) methods to study baroreflex control. The cumulative evidence points to the importance of a baroreflex autonomic network that includes the insular cortex, anterior cingulate cortex, medial prefrontal cortex, amygdala and cerebellum. Future work is required to further delineate the brain regions involved specifically with sensing barosensory afferents versus reflex efferent responses. The use of functional electrophysiological imaging techniques (e.g. MEG) may provide an opportunity to: 1) expand the methods and physiologic measures used to study central baroreflex function in humans, and 2) enhance the temporal precision required to delineate the order of activation within higher brain regions involved with baroreflex control., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of the study was to assess the validity and reliability of using the Portapres ® to measure toe blood pressure during rest and exercise. Construct validity, concurrent validity, and interday reliability were assessed by measuring toe (Portapres ®) ) and brachial blood pressure in 16 nondisabled participants on consecutive days. Construct validity was assessed by pedaling on a cycle ergometer (6 revolutions per minute) and comparing the measured toe blood pressure to an estimated value based on orthostatic factors. Concurrent validity was assessed by comparing toe and brachial blood pressure during supine rest and following 10 min of cycling exercise. Interday reliability was assessed by recording toe and brachial blood pressure during supine rest on a second day. Construct validity analysis shows that the toe blood pressure signal was moderately correlated with the changes in heart-toe distance and that changes in toe blood pressure during slow cycling were similar to the estimated value. Resting toe and brachial mean arterial blood pressure showed concurrent validity with only a fixed bias explained by the change in orthostatic pressure and the toe-brachial index. Furthermore, cycling exercise was associated with an increase in brachial and a decrease in toe mean blood pressure. The interday reliability analysis showed no proportional or fixed bias for mean arterial blood pressure. Our study showed the feasibility of using the Portapres ® to measure toe blood pressure during movement and can be used to study the effect of movement-related forces during cycling on toe blood pressure., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: The purpose of this study was to examine the influence of fast tempo music (FM) on self-paced running performance (heart rate, running speed, ratings of perceived exertion), and slow tempo music (SM) on post-exercise heart rate and blood lactate recovery rates., Methods: Twelve participants (5 women) completed three randomly assigned conditions: static noise (control), FM and SM. Each condition consisted of self-paced treadmill running, and supine postexercise recovery periods (20 min each). Average running speed, heart rate (HR) and ratings of perceived exertion (RPE) were measured during the treadmill running period, while HR and blood lactate were measured during the recovery period., Results: Listening to FM during exercise resulted in a faster self-selected running speed (10.8±1.7 vs. 9.9±1.4 km•hour-1, P<0.001) and higher peak HR (184±12 vs. 177±17 beats•min-1, P<0.01) without a corresponding difference in peak RPE (FM, 16.8±1.8 vs. SM 15.7±1.9, P=0.10). Listening to SM during the post-exercise period resulted in faster HR recovery throughout (main effect P<0.001) and blood lactate at the end of recovery (2.8±0.4 vs. 4.7±0.8 mmol•L-1, P<0.05)., Conclusions: Listening to FM during exercise can increase self-paced intensity without altering perceived exertion levels while listening to SM after exercise can accelerate the recovery rate back to resting levels.

Background: To determine whether angiotensin II (ANG II) contributes to the reflex skeletal muscle sympathoexcitation elicited by isometric and isotonic exercise, we tested the hypothesis that angiotensin AT(1) receptor blockade (ARB) would attenuate reflex sympathoneural responses to handgrip (HG) and to post-handgrip ischemia (PHGI)., Methods: Seventeen healthy men were studied before and 1 week after random double-blind crossover allocation to oral losartan (100 mg daily) and placebo. Heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded at rest, and during 2 min bouts of isotonic HG at 50% maximum voluntary contraction (MVC) and isometric HG at 30% MVC, performed randomly, each followed by 2 min of PHGI., Results: At rest, losartan doubled plasma renin (P = 0.01) and ANG II (P = 0.03) concentrations, and lowered BP (P < 0.01) yet had no effect on MSNA burst frequency or incidence. HR trended higher (P = 0.060). Losartan's hypotensive effect persisted throughout each exercise bout (P < 0.045). MSNA and HR responses to isotonic exercise and postexercise ischemia were not affected by losartan. Isometric exercise and postexercise ischemia increased MSNA on both sessions (all P < 0.01). Losartan augmented the HR response (P ≤ 0.03), and after losartan MSNA burst frequency (P < 0.01) and incidence (P < 0.04) were significantly higher at all time points, but the magnitude of the MSNA response to isometric exercise and postexercise ischemia was unchanged., Conclusion: In healthy men, short-term ARB does not attenuate reflex sympathoneural responses to HG or PHGI.