Post-exercise hot or cold water immersion does not alter perception of effort or neuroendocrine responses during subsequent moderate-intensity exercise.

Post-exercise hot (HWI) and cold (CWI) water immersion are popular strategies used by athletes in a range of sporting contexts, such as enhancing recovery or adaptation. However, prolonged heating bouts increase neuroendocrine responses that are associated with perceptions of fatigue. Fourteen endurance-trained runners performed three trials consisting of two 45-min runs at 95% lactate threshold on a treadmill separated by 6 h of recovery. Following the first run, participants completed one of HWI (30 min, 40°C), CWI (15 min, 14°C) or control (CON, 30 min rest in ambient conditions) in a randomised order. Perceived effort and recovery were measured using ratings of perceived exertion (RPE) and the Acute Recovery and Stress Scale (ARSS), whilst physiological responses including venous concentrations of a range of neuroendocrine markers, superficial femoral blood flow, heart rate and rectal temperature were measured. Exercise increased neuroendocrine responses of interleukin-6, adrenaline and noradrenaline (all P < 0.001). Additionally, perceptions of overall recovery (P < 0.001), mental performance capacity (P = 0.02), physical performance capability (P = 0.01) and emotional balance (P = 0.03) were reduced prior to the second run. However, there was no effect of condition on these variables (P > 0.05), nor RPE (P = 0.68), despite differences in rectal temperature, superficial femoral blood flow following the first run, and participants' expected recovery prior to the intervention (all P < 0.001). Therefore, athletes may engage in post-exercise hot or cold-water immersion without negatively impacting moderate-intensity training sessions performed later the same day.

FLOW-MEDIATED DILATION IS MODIFIED BY EXERCISE TRAINING STATUS DURING CHILDHOOD AND ADOLESCENCE: PRELIMINARY EVIDENCE OF THE YOUTH ATHLETE'S ARTERY.

Chronic exercise training is associated with an 'athlete's artery' phenotype in young adults and an attenuated age-related decline in endothelium-dependent arterial function. Adolescence is associated with an influx of sex-specific hormones that may exert divergent effects on endothelial function, but whether training adaptations interact with biological maturation to produce a 'youth athlete's artery' has not been explored. We investigated the influence of exercise training-status on endothelium-dependent arterial function during childhood and adolescence. Brachial artery flow mediated dilation (FMD) was assessed in n=102 exercise-trained (males: n=25, females: n=29) and untrained (males: n=23, females: n=25) youths, characterised as pre- (males: n=25, females: n=26) or post- (males: n=23, females: n=28) predicted age at peak height velocity (PHV). Baseline brachial artery diameter was larger in post- compared to pre-PHV youths (P≤0.001), males compared to females (P≤0.001), and trained compared to untrained youths (3.26 ± 0.51mm vs 3.11 ± 0.42mm; P=0.041). Brachial FMD was similar in pre- and post-PHV youths (P=0.298), and males and females (P=0.946). However, exercise trained youths demonstrated higher FMD when compared to untrained counterparts (5.3 ± 3.3% vs 3.0 ± 2.6%; P≤0.001). Furthermore, brachial artery diameter (r2=0.142; P=0.007 vs r2=0.004; P=0.652) and FMD (r2=0.138; P=0.008 vs r2=0.003; P=0.706) were positively associated with cardiorespiratory fitness in post-, but not pre-PHV youths, respectively. Collectively, our data indicate that exercise training is associated with brachial artery remodeling and enhanced endothelial function during youth. However, arterial remodeling and endothelium-dependent function are only associated with elevated cardiorespiratory fitness during later stages of adolescence.

Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Exercise is recommended for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training. METHODS: We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12-20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI-measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness. RESULTS: Eighty-eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5-fold (OR [95%CI]: 4.86 [1.72, 13.8], p = .002) greater odds of ≥30% relative reduction in MRI-measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight). CONCLUSION: Exercise training led to clinically meaningful improvements in surrogate serum- and imaging-based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight-neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.

The effect of underwater massage during hot water immersion on acute cardiovascular and mood responses.

PURPOSE: There is emerging evidence that demonstrates the health benefits of hot water immersion including improvements to cardiovascular health and reductions in stress and anxiety. Many commercially available hot tubs offer underwater massage systems which purport to enhance many benefits of hot water immersion, however, these claims have yet to be studied. METHODS: Twenty participants (4 females) completed three, 30-min sessions of hot-water immersion (beginning at 39 °C) in a crossover randomized design: with air massage (Air Jet), water massage (Hydro Jet) or no massage (Control). Cardiovascular responses comprising; heart rate, blood pressure and superficial femoral artery blood flow and shear rate were measured. State trait anxiety, basic affect, and salivary cortisol were recorded before and after each trial. Data were analysed using a mixed effects model. RESULTS: Post immersion, heart rate increased (Δ31bpm, P < 0.001, d = 1.38), mean arterial blood pressure decreased (Δ16 mmHg, P < 0.001, d = -0.66), with no difference between conditions. Blood flow and mean shear rate increased following immersion (P < 0.001, Δ362 ml/min, d = 1.20 and Δ108 s-1, d = 1.00), but these increases were blunted in the Air Jet condition (P < 0.001,Δ171 ml/min, d = 0.43 and Δ52 s-1, d = 0.52). Anxiety and salivary cortisol were reduced (P = 0.003, d = -0.20, P = 0.014, d = -0.11), but did not vary between conditions. Enjoyment did not vary between conditions. CONCLUSION: These data demonstrate positive acute responses to hot water immersion on markers of cardiovascular function, anxiety, and stress. There was no additional benefit of water-based massage, while air-based massage blunted some positive vascular responses due to lower heat conservation of the water.

Semmaphorin 3 A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells.

Semaphorin-3A (SEMA3A) functions as a chemorepulsive signal during development and can affect T cells by altering their filamentous actin (F-actin) cytoskeleton. The exact extent of these effects on tumour-specific T cells are not completely understood. Here we demonstrate that Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 are upregulated on stimulated CD8+ T cells, allowing tumour-derived SEMA3A to inhibit T cell migration and assembly of the immunological synapse. Deletion of NRP1 in both CD4+ and CD8+ T cells enhance CD8+ T-cell infiltration into tumours and restricted tumour growth in animal models. Conversely, over-expression of SEMA3A inhibit CD8+ T-cell infiltration. We further show that SEMA3A affects CD8+ T cell F-actin, leading to inhibition of immune synapse formation and motility. Examining a clear cell renal cell carcinoma patient cohort, we find that SEMA3A expression is associated with reduced survival, and that T-cells appear trapped in SEMA3A rich regions. Our study establishes SEMA3A as an inhibitor of effector CD8+ T cell tumour infiltration, suggesting that blocking NRP1 could improve T cell function in tumours.

Oncogenic Cell Tagging and Single-Cell Transcriptomics Reveal Cell Type-Specific and Time-Resolved Responses to Vhl Inactivation in the Kidney.

Defining the initial events in oncogenesis and the cellular responses they entrain, even in advance of morphologic abnormality, is a fundamental challenge in understanding cancer initiation. As a paradigm to address this, we longitudinally studied the changes induced by loss of the tumor suppressor gene von Hippel Lindau (VHL), which ultimately drives clear cell renal cell carcinoma. Vhl inactivation was directly coupled to expression of a tdTomato reporter within a single allele, allowing accurate visualization of affected cells in their native context and retrieval from the kidney for single-cell RNA sequencing. This strategy uncovered cell type-specific responses to Vhl inactivation, defined a proximal tubular cell class with oncogenic potential, and revealed longer term adaptive changes in the renal epithelium and the interstitium. Oncogenic cell tagging also revealed markedly heterogeneous cellular effects including time-limited proliferation and elimination of specific cell types. Overall, this study reports an experimental strategy for understanding oncogenic processes in which cells bearing genetic alterations can be generated in their native context, marked, and analyzed over time. The observed effects of loss of Vhl in kidney cells provide insights into VHL tumor suppressor action and development of renal cell carcinoma. SIGNIFICANCE: Single-cell analysis of heterogeneous and dynamic responses to Vhl inactivation in the kidney suggests that early events shape the cell type specificity of oncogenesis, providing a focus for mechanistic understanding and therapeutic targeting.

Lung Ultrasound Reproducibly Outperforms Computed Tomography in the Detection of Extravascular Lung Water in Patients Undergoing Haemodialysis.

BACKGROUND: Lung ultrasound (LUS) is increasingly used as an extension of physical examination, informing clinical diagnosis, and decision making. There is particular interest in the assessment of patients with pulmonary congestion and extravascular lung water, although gaps remain in the evidence base underpinning this practice as a result of the limited evaluation of its inter-rater reliability and comparison with more established radiologic tests. METHODS: 30 patients undergoing haemodialysis were prospectively recruited to an observational cohort study (NCT01949402). Patients underwent standardised LUS assessment before, during and after haemodialysis; their total LUS B-line score was generated, alongside a binary label of whether appearances were consistent with an interstitial syndrome. LUS video clips were recorded and independently scored by two blinded expert clinician sonographers. Low-dose non-contrast thoracic CT, pre- and post dialysis, was used as a "gold standard" radiologic comparison. RESULTS: LUS detected a progressive reduction in B-line scores in almost all patients undergoing haemodialysis, correlating with the volume of fluid removed once individuals with no or minimal B-lines upon pre-dialysis examination were discounted. When comparing CT scans pre- and post dialysis, radiologic evidence of the change in fluid status was only identified in a single patient. CONCLUSIONS: This is the first study to demonstrate that LUS detects changes in extravascular lung water caused by changing fluid status during haemodialysis using a blinded outcome assessment and that LUS appears to be more sensitive than CT for this purpose. Further research is needed to better understand the role of LUS in this and similar patient populations, with the aim of improving clinical care and outcomes.

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.

The influence of physical activity and sex on carotid artery longitudinal wall motion in younger healthy adults.

Carotid artery longitudinal wall motion (CALM) is a novel preclinical marker for atherosclerosis that describes the axial anterograde and retrograde motion of the intima-media complex. While regular physical activity and sex are known to independently influence arterial stiffness, their roles on axial arterial wall behaviour are unknown. The purpose of this study is to examine whether physical activity and sex impact CALM. We hypothesized that CALM retrograde displacement and total amplitude would be greater in females and active individuals, as a function of arterial stiffness. Fifty-seven young healthy adults (30 females; aged 22 ± 3 years) were evaluated for CALM outcomes and arterial stiffness and grouped by physical activity based on active (V̇O2 = 44.2 ± 8.9 mL/kg/min) or sedentary (V̇O2 = 33.7 ± 6.7 mL/kg/min) lifestyles defined by the Canadian 24-Hour Movement Guidelines. Arterial stiffness and CALM were measured by carotid-femoral pulse wave velocity (cfPWV) and vascular ultrasound at the right common carotid artery with speckle tracking analysis, respectively. cfPWV was greater in males (p < 0.01) with no interaction between sex and physical activity (p = 0.90). CALM anterograde displacement was greater in males (p = 0.03) resulting in a forward shift in total CALM pattern, which became less prominent when controlling for mean arterial pressure (p = 0.06). All other CALM outcomes were not different between activity and sex. V̇O2max was not correlated to any CALM outcome (all p > 0.05). Apparent sex differences in vascular function extend to novel CALM outcomes but may be confounded by blood pressure. We recommend sex-balanced design and reporting in future studies due to possible anterograde-shifted CALM patterns in healthy males.

The influence of maturation and sex on intracranial blood velocities during exercise in children.

Cerebral blood velocity (CBv) increases in response to moderate exercise in humans, but the magnitude of change is smaller in children compared with postpubertal adolescents and adults. Whether sex differences exist in the anterior or posterior CBv response to exercise across pubertal development remains to be determined. We assessed middle cerebral artery (MCAv) and posterior cerebral artery (PCAv) blood velocity via transcranial Doppler in 38 prepubertal (18 males) and 48 postpubertal (23 males) with cerebrovascular and cardiorespiratory measures compared at baseline and ventilatory threshold. At baseline, MCAv was higher in both sexes pre- versus postpuberty. Females demonstrated a greater MCAv (P < 0.001) than their male counterparts (prepubertal females; 78 ± 11 cm·s-1 vs. prepubertal males; 72 ± 8 cm·s-1, and postpubertal females; 68 ± 10 cm·s-1 vs. postpubertal males; 62 ± 7 cm·s-1). During exercise, MCAv remained higher in postpubertal females versus males (81 ± 15 cm·s-1 vs. 73 ± 11 cm·s-1), but there were no differences in prepuberty. The relative increase in PCAv was greater in post- versus prepubertal females (51 ± 9 cm·s-1 vs. 45 ± 11 cm·s-1; P = 0.032) but was similar in males and females. Our findings suggest that biological sex alters anterior cerebral blood velocities at rest in both pre- and postpubertal youth, but the response to submaximal exercise is only influenced by sex postpuberty.NEW & NOTEWORTHY Cerebral blood velocity (CBv) in the anterior circulation was higher in females compared with males irrespective of maturational stage, but not in the posterior circulation. In response to exercise, females demonstrated a greater CBv compared with males, especially post-peak height velocity (post-PHV) where the CBv response to exercise was more pronounced. Our findings suggest that both CBv at rest and in response to acute submaximal exercise are altered by biological sex in a maturity-dependent manner.

Pharmacological modulation of vascular ageing: A review from VascAgeNet.

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.

A peer-volunteer led active ageing programme to prevent decline in physical function in older people at risk of mobility disability (Active, Connected, Engaged [ACE]): study protocol for a randomised controlled trial.

BACKGROUND: The Active Connected Engaged [ACE] study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial [RCT] with an internal pilot phase. The ACE study incorporates a multi-level mixed methods process evaluation including a systems mapping approach and an economic evaluation. ACE aims to test the effectiveness and cost-effectiveness of a peer-volunteer led active ageing intervention designed to support older adults at risk of mobility disability to become more physically and socially active within their communities and to reduce or reverse, the progression of functional limitations associated with ageing. METHODS/DESIGN: Community-dwelling, older adults aged 65 years and older (n = 515), at risk of mobility disability due to reduced lower limb physical functioning (Short Physical Performance Battery (SPPB) score of 4-9 inclusive) will be recruited. Participants will be randomised to receive either a minimal control intervention or ACE, a 6-month programme underpinned by behaviour change theory, whereby peer volunteers are paired with participants and offer them individually tailored support to engage them in local physical and social activities to improve lower limb mobility and increase their physical activity. Outcome data will be collected at baseline, 6, 12 and 18 months. The primary outcome analysis (difference in SPPB score at 18 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals. DISCUSSION: ACE is the largest, pragmatic, community-based randomised controlled trial in the UK to target this high-risk segment of the older population by mobilising community resources (peer volunteers). A programme that can successfully engage this population in sufficient activity to improve strength, coordination, balance and social connections would have a major impact on sustaining health and independence. ACE is also the first study of its kind to conduct a full economic and comprehensive process evaluation of this type of community-based intervention. If effective and cost-effective, the ACE intervention has strong potential to be implemented widely in the UK and elsewhere. TRIAL REGISTRATION: ISRCTN, ISRCTN17660493. Registered on 30 September 2021. Trial Sponsor: University of Birmingham, Contact: Dr Birgit Whitman, Head of Research Governance and Integrity; Email: researchgovernance@contacts.bham.ac.uk. Protocol Version 5 22/07/22.

Cerebral blood flow and cerebrovascular reactivity are modified by maturational stage and exercise training status during youth.

NEW FINDINGS: What is the central question of this study? Gonadal hormones modulate cerebrovascular function while insulin-like growth factor 1 (IGF-1) facilitates exercise-mediated cerebral angiogenesis; puberty is a critical period of neurodevelopment alongside elevated gonadal hormone and IGF-1 activity: but whether exercise training across puberty enhances cerebrovascular function is unkown. What is the main finding and its importance? Cerebral blood flow is elevated in endurance trained adolescent males when compared to untrained counterparts. However, cerebrovascular reactivity to hypercapnia is faster in trained vs. untrained children, but not adolescents. Exercise-induced improvements in cerebrovascular function are attainable as early as the first decade of life. ABSTRACT: Global cerebral blood flow (gCBF) and cerebrovascular reactivity to hypercapnia ( CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) are modulated by gonadal hormone activity, while insulin-like growth factor 1 facilitates exercise-mediated cerebral angiogenesis in adults. Whether critical periods of heightened hormonal and neural development during puberty represent an opportunity to further enhance gCBF and CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ is currently unknown. Therefore, we used duplex ultrasound to assess gCBF and CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ in n = 128 adolescents characterised as endurance-exercise trained (males: n = 30, females: n = 36) or untrained (males: n = 29, females: n = 33). Participants were further categorised as pre- (males: n = 35, females: n = 33) or post- (males: n = 24, females: n = 36) peak height velocity (PHV) to determine pubertal or 'maturity' status. Three-factor ANOVA was used to identify main and interaction effects of maturity status, biological sex and training status on gCBF and CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ . Data are reported as group means (SD). Pre-PHV youth demonstrated elevated gCBF and slower CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ mean response times than post-PHV counterparts (both: P ≤ 0.001). gCBF was only elevated in post-PHV trained males when compared to untrained counterparts (634 (43) vs. 578 (46) ml min-1 ; P = 0.007). However, CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ mean response time was faster in pre- (72 (20) vs. 95 (29) s; P ≤ 0.001), but not post-PHV (P = 0.721) trained youth when compared to untrained counterparts. Cardiorespiratory fitness was associated with gCBF in post-PHV youth (r2  = 0.19; P ≤ 0.001) and CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ mean response time in pre-PHV youth (r2  = 0.13; P = 0.014). Higher cardiorespiratory fitness during adolescence can elevate gCBF while exercise training during childhood primes the development of cerebrovascular function, highlighting the importance of exercise training during the early stages of life in shaping the cerebrovascular phenotype.

Aortic stiffness contributes to greater pressor responses during static hand grip exercise in healthy young and middle-aged normotensive men.

Central arterial stiffness can influence exercise blood pressure (BP) by increasing the rise in arterial pressure per unit increase in aortic inflow. Whether central arterial stiffness influences the pressor response to isometric handgrip exercise (HG) and post-exercise muscle ischemia (PEMI), two common laboratory tests to study sympathetic control of BP, is unknown. We studied 46 healthy non-hypertensive males (23 young and 23 middle-aged) during HG (which increases in cardiac output [Q̇c]) and isolated metaboreflex activation PEMI (no change or decreases in Q̇c). Aortic stiffness (aortic pulse wave velocity [aPWV]; applanation tonometry via SphygmoCor) was measured during supine rest and was correlated to the pressor responses to HG and PEMI. BP (photoplethysmography) and muscle sympathetic nerve activity (MSNA) were continuously recorded at rest, during HG to fatigue (35 % maximal voluntary contraction) and 2-min of PEMI. aPWV was higher in middle-aged compared to young males (7.1 ± 0.9 vs 5.4 ± 0.7 m/s, P < 0.001). Middle-aged males also exhibited greater increases in systolic pressure (∆30 ± 11 vs 10 ± 8 mmHg) and MSNA (∆2313 ± 2006 vs 1387 ± 1482 %/min) compared to young males during HG (both, P < 0.03); with no difference in the Q̇c response (P = 0.090). Responses to PEMI were not different between groups. Sympathetic transduction during these stressors (MSNA-diastolic pressure slope) was not different between groups (P > 0.341). Middle-aged males displayed a greater increase in SBP per unit change of Q̇c during HG (∆SBP/∆Q̇c; 21 ± 18 vs 6 ± 10 mmHg/L/min, P = 0.004), with a strong and moderate relationship between the change in systolic (r = 0.53, P < 0.001) and diastolic pressure (r = 0.34, P = 0.023) and resting aPWV, respectively; with no correlation during PEMI. Central arterial stiffness can modulate pressor responses during stimuli associated with increases in cardiac output and sympathoexcitation in healthy males.

Neurovascular coupling and cerebrovascular hemodynamics are modified by exercise training status at different stages of maturation during youth.

Neurovascular coupling (NVC) is mediated via nitric oxide signaling, which is independently influenced by sex hormones and exercise training. Whether exercise training differentially modifies NVC pre- versus postpuberty, where levels of circulating sex hormones will differ greatly within and between sexes, remains to be determined. Therefore, we investigated the influence of exercise training status on resting intracranial hemodynamics and NVC at different stages of maturation. Posterior and middle cerebral artery velocities (PCAv and MCAv) and pulsatility index (PCAPI and MCAPI) were assessed via transcranial Doppler ultrasound at rest and during visual NVC stimuli. N = 121 exercise-trained (males, n = 32; females, n = 32) and untrained (males, n = 28; females, n = 29) participants were characterized as pre (males, n = 33; females, n = 29)- or post (males, n = 27; females, n = 32)-peak height velocity (PHV). Exercise-trained youth demonstrated higher resting MCAv (P = 0.010). Maturity and training status did not affect the ΔPCAv and ΔMCAv during NVC. However, pre-PHV untrained males (19.4 ± 13.5 vs. 6.8 ± 6.0%; P ≤ 0.001) and females (19.3 ± 10.8 vs. 6.4 ± 7.1%; P ≤ 0.001) had a higher ΔPCAPI during NVC than post-PHV untrained counterparts, whereas the ΔPCAPI was similar in pre- and post-PHV trained youth. Pre-PHV untrained males (19.4 ± 13.5 vs. 7.9 ± 6.0%; P ≤ 0.001) and females (19.3 ± 10.8 vs. 11.1 ± 7.3%; P = 0.016) also had a larger ΔPCAPI than their pre-PHV trained counterparts during NVC, but the ΔPCAPI was similar in trained and untrained post-PHV youth. Collectively, our data indicate that exercise training elevates regional cerebral blood velocities during youth, but training-mediated adaptations in NVC are only attainable during early stages of adolescence. Therefore, childhood provides a unique opportunity for exercise-mediated adaptations in NVC.NEW & NOTEWORTHY We report that the change in cerebral blood velocity during a neurovascular coupling task (NVC) is similar in pre- and postpubertal youth, regardless of exercise-training status. However, prepubertal untrained youth demonstrated a greater increase in cerebral blood pulsatility during the NVC task when compared with their trained counterparts. Our findings highlight that childhood represents a unique opportunity for exercise-mediated adaptations in cerebrovascular hemodynamics during NVC, which may confer long-term benefits in cerebrovascular function.

Microscopy with heralded Fock states.

We consider a microscopy setting where quantum light is used for illumination. Spontaneous parametric down conversion (SPDC) is used as a source of a heralded single photon, which is quantum light prepared in a Fock state. We present analytical formulas for the spatial mode tracking along with the heralded and non-heralded mode widths. The obtained analytical results are supported by numerical calculations and the following discussion taking into account realistic setup parameters such as finite-size optics and finite-size single-photon detectors. This allows us to observe that the diffraction limit can be approached with simultaneous alleviation of the photon loss leading to increased signal-to-noise ratio - a factor limiting practical applications of quantum light. Additionally, it is shown that the spatial resolution can be manipulated by carefully preparing the amplitude and phase of the spatial mode profile of the single photon at the input to the microscope objective. Here, the spatial entanglement of the biphoton wavefunction or adaptive optics can be applied for spatial mode shaping. Analytical dependencies between the incident and focused spatial mode profiles parameters are provided.

Physical Activity and Nonalcoholic Fatty Liver Disease: A Roundtable Statement from the American College of Sports Medicine.

ABSTRACT: Although physical activity (PA) is crucial in the prevention and clinical management of nonalcoholic fatty liver disease, most individuals with this chronic disease are inactive and do not achieve recommended amounts of PA. There is a robust and consistent body of evidence highlighting the benefit of participating in regular PA, including a reduction in liver fat and improvement in body composition, cardiorespiratory fitness, vascular biology, and health-related quality of life. Importantly, the benefits of regular PA can be seen without clinically significant weight loss. At least 150 min of moderate or 75 min of vigorous intensity PA are recommended weekly for all patients with nonalcoholic fatty liver disease, including those with compensated cirrhosis. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. In this roundtable document, the benefits of PA are discussed, along with recommendations for 1) PA assessment and screening; 2) how best to advise, counsel, and prescribe regular PA; and 3) when to refer to an exercise specialist.