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What is the central question of this study? We sought to investigate whether peripheral and cerebrovascular function are impaired in early and late postmenopausal females compared with premenopausal females, while also accounting for nitric oxide and estradiol levels. What is the main finding and its importance? We observed no differences in peripheral vascular and cerebrovascular function between healthy and physically active premenopausal females and early and late postmenopausal females. Our findings contradict previous cross-sectional observations of vascular and cerebrovascular dysfunction across menopause. Longitudinal studies assessing vascular and cerebrovascular outcomes across the menopausal transition are warranted.The risk of cardiovascular and cerebrovascular disease increases in ageing females, coinciding with the onset of menopause. Differences in peripheral and cerebrovascular function across menopausal stages, however, are poorly characterized. The aim of this study was to compare peripheral and cerebrovascular function between healthy premenopausal (PRE), early (1-6 years after final menstrual period; E-POST) and late (6 years after final menstrual period; L-POST) postmenopausal females. We also explored the association between reproductive hormones, NO bioavailability and cerebrovascular function. In 39 females (40-65 years of age), we measured arterial stiffness, brachial artery flow-mediated dilatation, and cerebrovascular reactivity (CVR) to hypercapnia in the middle (MCAv) and internal (ICA) carotid arteries. Follicle-stimulating hormone, estradiol, progesterone and plasma nitrate and nitrite concentrations were also measured. Years since final menstrual period (PRE, 0 ± 0 years; E-POST, 3 ± 1 years; L-POST, 11 ± 4 years; P 0.001) and estradiol levels (PRE, 145.5 ± 65.6 pg ml

We observed similar MCA CVR and ICA reactivity in males and females. However, kinetic responses of the MCA to hypercapnia suggest that advancing age slows down the rate at which MCA velocity increases in response to hypercapnia. These data indicate distinct regulatory differences, and an impaired vasomotor control of the cerebrovasculature with advancing age, not detected by traditional methods.

This is the first study to model the MCAv kinetic response to moderate- and heavy-intensity cycling in healthy adults. This study found that the amplitude of the exponential rise in MCAv at exercise onset was greater during heavy-intensity exercise (∼34%) compared with moderate-intensity exercise (∼19%), but the time-based characteristics of the responses were similar between intensities. Higher cardiorespiratory fitness was not associated with a greater or faster MCAv response to moderate- or heavy-intensity exercise.

Purpose Our aim was to compare cerebrovascular and systemic vascular function between older adults with and without mild cognitive impairment (MCI), and to determine which measures of vascular function best predict the presence of MCI. Methods In 41 adults with MCI and 33 adults without MCI (control) we compared middle cerebral artery velocity (MCAv) and cerebrovascular pulsatility index (PI) at rest, cerebrovascular reactivity to CO2, and responsiveness to changes in blood pressure (%∆MCAv/%∆MAP). Systemic vascular function was assessed by flow-mediated dilation (FMD) and stiffness by pulse wave velocity (PWV). Results Cerebrovascular PI was higher in MCI compared with control (mean ± SD: 1.17 ± 0.27 vs. 1.04 ± 0.21), and MCI exhibited a lower %∆MCAv/%∆MAP (1.26 ± 0.44 vs. 1.50 ± 0.55%). Absolute (p = 0.76) and relative cerebrovascular reactivity to CO2 (p = 0.34) was similar between MCI and control. When age was included as a covariate the significant difference in cerebral PI between groups was lost. PWV was higher (13.2 ± 2.2 vs. 11.3 ± 2.5 m s−1) and FMD% (4.41 ± 1.70 vs. 5.43 ± 2.15%) was lower in MCI compared with control. FMD% was positively associated with PI across the cohort. Logistic regression analysis indicated that FMD and PWV significantly discriminated between MCI and controls, independent of age, whereas the inclusion of cerebrovascular measures did not improve the predictive accuracy of the model. Conclusion These findings raise the possibility that early changes in systemic vascular stiffness and endothelial function may contribute to altered cerebrovascular haemodynamics and impaired cognitive function, and present potential targets for prevention and treatment strategies in people with MCI.

Introduction Cancer-related pain is common and undertreated. Exercise is known to have a pain-relieving effect in non-cancer pain. Objectives This systematic review aimed to evaluate (1) the effect of exercise on cancer-related pain in all cancers, and (2) whether the effect of exercise differed according to exercise mode, degree of supervision, intervention duration and timing (during or after cancer treatment), pain types, measurement tool and cancer type. Methods Electronic searches were undertaken in six databases to identify exercise studies evaluating pain in people with cancer, published prior to 11 January 2023. All stages of screening and data extraction were conducted independently by two authors. The Cochrane risk of bias tool for randomised trials (RoB 2) was used and overall strength of evidence was assessed using the GRADE approach. Meta-analyses were performed overall and by study design, exercise intervention and pain characteristics. Results In total, 71 studies reported in 74 papers were eligible for inclusion. The overall meta-analysis included 5877 participants and showed reductions in pain favouring exercise (standardised mean difference − 0.45; 95% confidence interval − 0.62, − 0.28). For most (> 82%) of the subgroup analyses, the direction of effect favoured exercise compared with usual care, with effect sizes ranging from small to large (median effect size − 0.35; range − 0.03 to − 1.17). The overall strength of evidence for the effect of exercise on cancer-related pain was very low. Conclusion The findings provide support that exercise participation does not worsen cancer-related pain and that it may be beneficial. Better pain categorisation and inclusion of more diverse cancer populations in future research would improve understanding of the extent of benefit and to whom. PROSPERO registration number CRD42021266826.

Purpose To systematically synthesise evidence of exercise intervention efficacy for physical/psychosocial outcomes that matter to women during/following treatment for gynaecological cancer. Methods Five databases were searched (PubMed, EMBASE, CINAHL, PsychInfo, Scopus). Exercise-only intervention studies that included women during/ following treatment for any gynaecological cancer, with/ without control comparison, on any physical or psychosocial outcome(s), were included and qualitatively appraised using the Revised Cochrane Risk of Bias tool and a modified Newcastle-Ottawa Scale. Results Seven randomised controlled trials (RCTs), three single-arm pre-post studies, and one prospective cohort study satisfied were included (11 studies). Most studies were completed following treatment (91%), included combined (aerobic and resistance; 36%) and aerobic (36%) training, were fully/mostly (63%) unsupervised, and had a moderate-to-high risk of bias. Overall, 33 outcomes (64% objectively-measured) were assessed. Improvements were observed in aerobic capacity (V̇O2 Peak +1.6 mL/kg/min, 6-minute walk distance +20-27 m), lower- (30-second sit-to-stand +2-4 repetitions) and upper-limb strength (30-second arm curl +5 repetitions; 1RM grip strength/chest press +2.4-3.1 kg), and agility (timed up-and-go -0.6 seconds). However, changes in quality of life, anthropometry/body composition, balance and flexibility were inconsistent. There was no evidence to support worsening of outcomes. Conclusion Preliminary research into the role of exercise post-gynaecological cancer suggests an improvement in exercise capacity, muscular strength, and agility which, in the absence of exercise, typically decline following gynaecological cancer. Future exercise trials involving larger and more diverse gynaecological cancer samples will improve understanding of the potential and magnitude of effect of guideline-recommended exercise on outcomes that matter to patients.

Purpose Cancer treatments exert vascular toxic effects that can lead to the development of cardiovascular disease. Exercise training has the potential to prevent or reduce cancer treatment–induced damage to vascular structure and function. This systematic review with meta-analyses aimed to determine the isolated effects of exercise training on vascular outcomes in people with cancer. Methods Seven electronic databases were searched on 20 September 2021 to identify randomised controlled trials, quasi-randomised trials, pilot and cohort studies. Included studies implemented a structured exercise intervention and assessed vascular structure and/or function in people during or following cancer treatment. Meta-analyses examined the effects of exercise training on endothelial function (via brachial artery flow-mediated dilation) and arterial stiffness (via pulse wave velocity). Methodological quality was assessed using the Cochrane Quality Assessment tool and modified Newcastle-Ottawa Quality Appraisal tool. Grading of Recommendations, Assessment, Development and Evaluations framework was used to assess the certainty of evidence. Results Ten studies (discussed across 11 articles) met the inclusion criteria. Methodological quality of the included studies was moderate (71% average). Exercise improved vascular function when compared to control (standardised mean difference = 0.34, 95% CI (0.01, 0.67); p = 0.044: studies = 5, participants = 171), but not pulse wave velocity (standardised mean difference = − 0.64, 95% CI (− 1.29, 0.02); p = 0.056: studies = 4, participants = 333). The certainty of evidence was moderate for flow-mediated dilation and low for pulse wave velocity. Conclusions Compared to usual care, exercise training significantly improves flow-mediated dilation (endothelial function) but not pulse wave analysis, in people treated for cancer. Implications for Cancer Survivors Exercise may improve vascular health in individuals during and following cancer treatment.

Understanding the contribution of the autonomic nervous system to cerebral blood flow (CBF) control is challenging, and interpretations are unclear. The identification of calcium channels and adrenoreceptors within cerebral vessels has led to common misconceptions that the function of these receptors and actions mirror those of the peripheral vasculature. This review outlines the fundamental differences and complex actions of cerebral autonomic activation compared to the peripheral circulation. Anatomical differences, including the closed nature of the cerebrovasculature, and differential adrenoreceptor subtypes, density, distribution and sensitivity, provide evidence that measures on peripheral sympathetic nerve activity cannot be extrapolated to the cerebrovasculature. Cerebral sympathetic nerve activity seems to act opposingly to the peripheral circulation, mediated at least in part by changes in intracranial pressure and cerebral blood volume. Additionally, heterogeneity in cerebral adrenoreceptor distribution highlights regional-specific autonomic regulation of CBF. Compensatory chemo- and autoregulatory responses throughout the cerebral circulation, and interactions with parasympathetic nerve activity are unique features to the cerebral circulation. This crosstalk between sympathetic and parasympathetic reflexes acts to ensure adequate perfusion of CBF to rising and falling perfusion pressures, optimising delivery of oxygen and nutrients to the brain, whilst attempting to maintain blood volume and intracranial pressure. Herein, we highlight the distinct similarities and differences between autonomic control of cerebral and peripheral blood flow, and the regional specificity of sympathetic and parasympathetic regulation within the cerebrovasculature. Future research directions are outlined with the goal to further our understanding of autonomic control of CBF in humans. This article is protected by copyright. All rights reserved.

This is the first study to observe similar increases in cerebral blood flow during incremental exercise in adolescents and adults. Increases in cerebral blood flow during exercise were smaller in children compared with adolescents and adults and were associated with a greater V̇E/V̇co2 slope. This study also provides the first evidence on the progressive development of the regulatory role of end-tidal CO2 on cerebral blood flow during exercise during the transition from childhood to adulthood.

Menopause and its associated decline in oestrogen is linked to chronic conditions like cardiovascular disease and osteoporosis, which may be difficult to disentangle from the effects of ageing. Further, post-menopausal women are at increased risk of cerebrovascular disease, linked to declines in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), yet the direct understanding of the impact of the menopause on cerebrovascular function is unclear. The aim of this systematic review and meta-analysis was to examine the literature investigating CBF and CVR in pre- compared with post-menopausal women METHODS: Five databases were searched for studies assessing CBF or CVR in pre- and post-menopausal women. Meta-analysis examined the effect of menopausal status on middle cerebral artery velocity (MCAv), and GRADE-assessed evidence certainty RESULTS: Nine studies (n=504) included cerebrovascular outcomes. Six studies (n=239) reported negligible differences in MCAv between pre- and post-menopausal women [2.11cm/s (95% CI: -8.94 to 4.73, p=0.54)], but with a "low" certainty of evidence. MCAv was lower in post-menopausal women in two studies, when MCAv was adjusted for blood pressure. CVR was lower in post- compared with pre-menopausal women in two of three studies, but high-quality evidence is lacking. Across outcomes, study methodology and reporting criteria for menopause were inconsistent CONCLUSIONS: MCAv was similar in post- compared with pre-menopausal women. Methodological differences in characterising menopause and inconsistent reporting of cerebrovascular outcomes make comparisons difficult. Comprehensive assessments of cerebrovascular function of the intra- and extracranial arteries to determine the physiological implications of menopause on CBF with healthy ageing is warranted.

BObjectiveThis study aimed to investigate the effect of exercise intensity on visceral adipose tissue (VAT) and liver fat reduction in patients with coronary artery disease (CAD) over 3 months and the maintenance of improvements over 12 months.MethodsForty‐two participants with CAD were randomized to three sessions/week of either 4 × 4‐minute high‐intensity interval training (HIIT) or 40 minutes of usual care moderate‐intensity continuous training (MICT) for a 4‐week supervised cardiac rehabilitation program, followed by three home‐based sessions/week for 11 months. Liver fat (as intrahepatic lipid) and VAT were measured via magnetic resonance techniques. Data are mean change (95% CI).ResultsHIIT and MICT significantly reduced VAT over 3 months (−350 [−548 to −153] cm3 vs. −456 [−634 to −278] cm3; time × group effect: P = 0.421), with further improvement over 12 months (−545 [−818 to −271] cm3 vs. −521 [−784 to −258] cm3; time × group effect: P = 0.577) and no differences between groups. Both groups improved liver fat over 3 months, with HIIT tending to show greater reduction than MICT (−2.8% [−4.0% to −1.6%] vs. −1.4% [−2.4% to −0.4%]; time × group effect: P = 0.077). After 12 months, improvements were maintained to a similar degree. Higher exercise intensity predicted liver fat reduction (β = −0.3 [−0.7 to 0.0]; P = 0.042).ConclusionsHIIT and MICT reduced VAT over 3 and 12 months. For liver fat, HIIT tended to provide a slightly greater reduction compared with MICT. These findings support HIIT as a beneficial adjunct or alternative to MICT for reducing visceral and liver fat in patients with CAD.

Neurovascular coupling (NVC) is the matching between local neuronal activity and regional cerebral blood flow (CBF), but little is known about the effects of age and sex on NVC. This study aimed to investigate the relationships and interaction between age and sex on NVC. Sixty-four healthy adults (18–85 years, N = 34 female) completed a visual stimulus evoked NVC assessment to a flashing checkerboard. NVC responses were measured in the posterior cerebral artery (PCAv) using transcranial Doppler ultrasound. A hierarchical multiple regression was used to determine the relationships between age, sex, and the age by sex interaction on NVC. There was a significant age by sex interaction for baseline (P = 0.001) and peak PCAv (P = 0.01), with a negative relationship with age in females (P

People with type 2 diabetes (T2D) are at a greater risk of cardiovascular disease than the general population. Both non-modifiable (age) and modifiable (low aerobic fitness, high body fatness) factors are separately predictive of cardiovascular risk, although they often occur concomitantly. This study aimed to examine the (1) association between age and arterial stiffness, a subclinical marker of cardiovascular risk; and (2) effects of body fatness and aerobic fitness on age-related increases in arterial stiffness in people with T2D. Data from 64 individuals with T2D (age 59.8 ± 8.7 years, 40% female, HbA

Objective/background: Elevated arterial stiffness is a characteristic of abdominal aortic aneurysm (AAA), and is associated with AAA growth and cardiovascular mortality. A bout of exercise transiently reduces aortic and systemic arterial stiffness in healthy adults. Whether the same response occurs in patients with AAA is unknown. The effect of moderate- and higher intensity exercise on arterial stiffness was assessed in patients with AAA and healthy adults. Methods: Twenty-two men with small diameter AAAs (36 ± 5 mm; mean age 74 ± 6 years) and 22 healthy adults (mean age 72 ± 5 years) were included. Aortic stiffness was measured using carotid to femoral pulse wave velocity (PWV), and systemic arterial stiffness was estimated from the wave reflection magnitude (RM) and augmentation index (Alx75). Measurements were performed at rest and during 90 min of recovery following three separate test sessions in a randomised order: (i) moderate intensity continuous exercise; (ii) higher intensity interval exercise; or (iii) seated rest. Results: At rest, PWV was higher in patients with AAA than in healthy adults (p < .001), while AIx75 and RM were similar between groups. No differences were observed between AAA patients and healthy adults in post-exercise aortic and systemic arterial stiffness after either exercise protocol. When assessed as the change from baseline (delta, Δ), post-exercise ΔAIx75 was not different to the seated rest protocol. Conversely, post-exercise ΔPWV and ΔRM were both lower at all time points than seated rest (p < .001). ΔPWV was lower immediately after higher intensity than after moderate intensity exercise (p = .015). Conclusion: High resting aortic stiffness in patients with AAA is not exacerbated after exercise. There was a similar post-exercise attenuation in arterial stiffness between patients with AAA and healthy adults compared with seated rest. This effect was most pronounced following higher intensity interval exercise, suggesting that this form of exercise may be a safe and effective adjunctive therapy for patients with small AAAs.

Innate immune cell defects contribute to severe autoimmunity and the pathogenesis of inflammatory disease. Monocyte-derived macrophages typically retain disease related signatures and represent an excellent in vitro model to uncover and validate mechanisms contributing to specific pathological states. Monocyte isolation procedures vary widely in terms of purity, yield, cost, degree of technical difficulty and volume of peripheral blood needed. This paper outlines a novel isolation method that yields monocytes through density gradient centrifugation (Ficoll® and hyperosmotic Percoll®). The protocol has been optimised for small volumes of blood (42 ml) and is simple, reproducible and inexpensive compared to other methods. Monocyte recovery is 70% (relative to monocyte numbers within the buffy coat) and the highly functional macrophages produced are characterised by excellent purity (98.6 ± 0.6%) and intact activation and phagocytic capacities. The method is well suited to investigations involving patient populations where a particular subset of immune cells is known to contribute to the pathogenesis of a specific disease or is aberrant as a consequence of that disease.

Several species from the Clostridium genus show promise as industrial solvent producers and cancer therapeutic delivery vehicles. Previous development of shuttle plasmids and genome editing tools has aided the study of these species and enabled their exploitation in industrial and medical applications. Nevertheless, the precise control of gene expression is still hindered by the limited range of characterized promoters. To address this, libraries of promoters (native and synthetic), 5' UTRs, and alternative start codons were constructed. These constructs were tested in Escherichia coli K-12, Clostridium sporogenes NCIMB 10696, and Clostridium butyricum DSM 10702, using β-glucuronidase (gusA) as a gene reporter. Promoter activity was corroborated using a second gene reporter, nitroreductase (nmeNTR) from Neisseria meningitides. A strong correlation was observed between the two reporters. In C. sporogenes and C. butyricum, respectively, changes in GusA activity between the weakest and strongest expressing levels were 129-fold and 78-fold. Similar results were obtained with the nmeNTR. Using the GusA reporter, translation initiation from six alternative (non-AUG) start codons was measured in E. coli, C. sporogenes, and C. butyricum. Clearly, species-specific differences between clostridia and E. coli in translation initiation were observed, and the performance of the start codons was influenced by the upstream 5' UTR sequence. These results highlight a new opportunity for gene control in recombinant clostridia. To demonstrate the value of these results, expression of the sacB gene from Bacillus subtilis was optimized for use as a novel negative selection marker in C. butyricum. In summary, these results indicate improvements in the understanding of heterologous gene regulation in Clostridium species and E. coli cloning strains. This new knowledge can be utilized for rationally designed gene regulation in Clostridium-mediated industrial and medical applications, as well as fundamental research into the biology of Clostridium species.

NEW FINDINGS What is the central question of the study? What is the reliability of middle cerebral artery velocity cerebrovascular reactivity (CVR) when using traditional and novel outcomes, as measured by transcranial doppler? What is the main finding and its importance? Traditional CVR approaches presented acceptable reproducibility but should be expressed as an absolute CVR. Large within- and between-individual differences in the MCAv response profile support using a dynamic peak, rather than a set time point, for the most reliable interpretation. Our study highlights the utility of novel kinetic CVR outcomes, however, due to increased variability in time-based metrics, this analysis requires larger sample sizes then traditional methods. ABSTRACT Cerebrovascular reactivity of the middle cerebral artery velocity (CVR MCAv) to carbon dioxide (CO2 ) is a common method to assess cerebrovascular function. Yet, the approaches used to calculate CVR outcomes vary. The aim of this study was to explore the within and between-day reliability of traditional CVR outcomes. The second aim was to explore the reliability of novel kinetic-based analyses. Healthy adults (n = 10, 22.3±3.4 years) completed assessments of CVR over four minutes using a fixed fraction of inspired CO2 (6%). This was repeated across four separate visits (between-day), and on one visit measures were repeated 2.5 hours later (within-day). No mean biases were present between assessments for traditional CVR metrics, expressed as absolute (cm/s/mmHg) or relative (%/mmHg) outcomes (minute-3, minute-4, peak 1 second, peak 30 second) (between-day: P>0.14, ηp2 0.22, d>0.27). Absolute, rather than relative CVR, yielded the most reproducible parameters (coefficient of variation: 8.1-13.2% versus 14-83% respectively). There were significant differences between CVR outcomes (P 0.89) dependent on the time point used to determine CVR, as a steady state MCAv response was rarely observed. Furthermore, the MCAv response was not reproducible within an individual (kappa = 0.15, P = 0.09). No mean differences were present for novel kinetic outcomes (amplitude, time-delay, time constant) (between-day: P>0.05, d 0.38, d

We address two aims: Aim 1 (Fitness Review) compares the effect of higher cardiorespiratory fitness (CRF) (e.g., endurance athletes) with lower CRF (e.g., sedentary adults) on cerebrovascular outcomes, including middle cerebral artery velocity (MCAv), cerebrovascular reactivity and resistance, and global cerebral blood flow, as assessed by transcranial Doppler (TCD) or magnetic resonance imaging (MRI). Aim 2 (Exercise Training Review) determines the effect of exercise training on cerebrovascular outcomes. Systematic review of studies with meta-analyses where appropriate. Certainty of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty studies (18 using TCD) met the eligibility criteria for Aim 1, and 14 studies (8 by TCD) were included for Aim 2. There was a significant effect of higher CRF compared with lower CRF on cerebrovascular resistance (effect size = -0.54, 95% confidence interval = -0.91 to -0.16) and cerebrovascular reactivity (0.98, 0.41-1.55). Studies including males only demonstrated a greater effect of higher CRF on cerebrovascular resistance than mixed or female studies (male only: -0.69, -1.06 to -0.32; mixed and female studies: 0.10, -0.28 to 0.49). Exercise training did not increase MCAv (0.05, -0.21 to 0.31) but showed a small nonsignificant improvement in cerebrovascular reactivity (0.60, -0.08 to 1.28; P = 0.09). Exercise training showed heterogeneous effects on regional but little effect on global cerebral blood flow as measured by MRI. High CRF positively effects cerebrovascular function, including decreased cerebrovascular resistance and increased cerebrovascular reactivity; however, global cerebral blood flow and MCAv are primarily unchanged following an exercise intervention in healthy and clinical populations.NEW & NOTEWORTHY Higher cardiorespiratory fitness is associated with lower cerebrovascular resistance and elevated cerebrovascular reactivity at rest. Only adults with a true-high fitness based on normative data exhibited elevated middle cerebral artery velocity. The positive effect of higher compared with lower cardiorespiratory fitness on resting cerebrovascular resistance was more evident in male-only studies when compared with mixed or female-only studies. A period of exercise training resulted in negligible changes in middle cerebral artery velocity and global cerebral blood flow, with potential for improvements in cerebrovascular reactivity.

Endothelial function, assessed using brachial artery flow-mediated dilation (FMD), predicts future cardiovascular disease (CVD) risk. This study established age- and sex-specific reference intervals for brachial artery FMD in healthy individuals and examined the relation with CVD risk factors. In a retrospective study design, we pooled brachial artery FMD (acquired according to expert-consensus guidelines for FMD protocol and analysis) and participant characteristics/medical history from 5362 individuals (4–84 years; 2076 females). Healthy individuals (n=1403 [582 females]) were used to generate age-/sex-specific percentile curves. Subsequently, we included individuals with CVD risk factors, without overt disease (unmedicated n=3167 [1247 females] and medicated n=792 [247 females]). Multiple linear regression tested the relation of CVD risk factors (body mass index, blood pressure, cholesterol, diabetes, dyslipidemia, and smoking) with FMD. Healthy males showed a negative, curvilinear relation between FMD and age, while females revealed a negative linear relation that started higher but declined at a faster rate than males. Age- and sex-specific differences in FMD relate, at least partly, to baseline artery diameter. FMD was related to CVD risk factors in unmedicated (eg, systolic/diastolic blood pressure) and medicated individuals (eg, diabetes/dyslipidemia). Sex mediated some of these effects ( P

NEW FINDINGS What is the topic of this review? We have conducted a systematic review and meta-analysis on the current evidence for the effect of heat therapy on blood pressure and vascular function. What advances does it highlight? We found that heat therapy reduced mean arterial, systolic and diastolic blood pressure. We also observed that heat therapy improved vascular function, as assessed via brachial artery flow-mediated dilatation. Our results suggest that heat therapy is a promising therapeutic tool that should be optimized further, via mode and dose, for the prevention and treatment of cardiovascular disease risk factors. ABSTRACT Lifelong sauna exposure is associated with reduced cardiovascular disease risk. Recent studies have investigated the effect of heat therapy on markers of cardiovascular health. We aimed to conduct a systematic review with meta-analysis to determine the effects of heat therapy on blood pressure and indices of vascular function in healthy and clinical populations. Four databases were searched up to September 2020 for studies investigating heat therapy on outcomes including blood pressure and vascular function. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of evidence. A total of 4522 titles were screened, and 15 studies were included. Healthy and clinical populations were included. Heat exposure was for 30-90 min, over 10-36 sessions. Compared with control conditions, heat therapy reduced mean arterial pressure [n = 4 studies; mean difference (MD): -5.86 mmHg, 95% confidence interval (CI): -8.63, -3.10; P

BackgroundThere is evidence that drinking alcohol increases the risk of recurrent breast cancer. It is unclear whether Australian women with breast cancer are aware of this evidence or modify their alcohol intake accordingly.ObjectiveThis article reports a secondary analysis of data from the Women's Wellness after Cancer Program (WWACP) randomized controlled trial (N = 351). The WWACP aimed to enhance quality of life and reduce chronic disease risk in women previously treated for cancer through lifestyle modification. Here we provide the alcohol-related data from the study's breast cancer participants (n = 269). We analyzed baseline alcohol consumption, the variables associated with alcohol intake, and intervention effect on intake at weeks 12 (end of intervention) and 24 (to determine sustainability).Interventions/methodsMeasures included the Dietary Questionnaire for Epidemiological Studies, Short Form-36, International Physical Activity Questionnaire, Green Climacteric Scale, Pittsburgh Sleep Quality Index, and Center for Epidemiologic Studies Depression Scale.ResultsMost participants practiced safe alcohol consumption. Among drinkers, drinking caffeine, smoking, emotional and physical role limitations, and greater discomfort with vasomotor symptoms were associated with increased intake. Relative to baseline, alcohol consumption decreased from 5.22 g/d to 4.18 g/d in the intervention group, whereas consumption increased among control subjects at 12 weeks. No difference between groups was observed at week 24.ConclusionThe intervention was associated with less alcohol intake at week 12 among drinkers, but this reduction was not sustained at the 24-week follow-up.Implications for practiceFuture iterations of the WWACP will emphasize stronger messaging and supports regarding alcohol consumption after breast cancer treatment.

ObjectiveThis randomized controlled trial tested a digitally-delivered whole-of-lifestyle program for women previously treated for cancer. We investigated (1) associations between self-reported physical activity (PA) and menopausal symptoms and (2) if the intervention was associated with beneficial changes in PA and menopausal symptoms.MethodsWomen were randomized to intervention (n = 142) or control (n = 138). The intervention targeted lifestyle behavior including PA. Self-reported PA (International Physical Activity Questionnaire - Short Form) and menopausal symptom (Green Climacteric Scale, GCS) data were collected at baseline, with measures repeated at 12 weeks (end of intervention) and 24 weeks (to assess sustainability). Generalized estimating equation models explored associations between PA and GCS scores. Mixed-effects generalized equation models analyzed changes within and between groups in PA and GCS scores.ResultsTotal GCS scores were 1.83 (95% CI: 0.11-3.55) and 2.72 (95% CI: 1.12-4.33) points lower in women with medium and high levels of PA, respectively, than in women with low levels of PA. Total average GCS scores were 1.02 (0.21-2.26) and 1.61 (0.34-2.87) points lower in those undertaking moderate or vigorous intensity PA, respectively. Time spent walking, and performing moderate and vigorous PA were not different between intervention and control. The average GCS decrease of 0.66 points (95% CI: 0.03-1.29; p time = 0.03) over 24 weeks was not different between groups.ConclusionThis exploratory study established a stepwise association between moderate and vigorous PA and a lower total menopausal symptom score. The intervention did not appear to increase self-reported PA in women treated for early stage breast, reproductive, and blood cancers.

The results of a mesocosm study are team-reviewed by staff scientists and statisticians to ensure that data used in an ecological risk assessment are scientifically acceptable. Structural and functional variables of plankton communities, macroinvertebrate communities, and fish populations are measured. These variables are analyzed for statistical significance, and biological trends are reviewed to determine if the results have demonstrated safety.

Impairments in skeletal muscle microvascular function are frequently reported in patients with various cardiometabolic conditions for which older age is a risk factor. Whether aging per se predisposes the skeletal muscle to microvascular dysfunction is unclear. We used contrast‐enhanced ultrasound (CEU) to compare skeletal muscle microvascular perfusion responses to cuff occlusion and leg exercise between healthy young (n = 12, 26 ± 3 years) and older (n = 12, 68 ± 7 years) adults. Test–retest reliability of CEU perfusion parameters was also assessed. Microvascular perfusion (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after: (a) 5‐min of thigh‐cuff occlusion, and (b) 5‐min of submaximal intermittent isometric plantar‐flexion exercise (400 N) using CEU. Whole‐leg blood flow was measured using strain‐gauge plethysmography. Repeated measures were obtained with a 15‐min interval, and averaged responses were used for comparisons between age groups. There were no differences in post‐occlusion whole‐leg blood flow and muscle microvascular perfusion between young and older participants (p > .05). Similarly, total whole‐leg blood flow during exercise and post‐exercise peak muscle microvascular perfusion did not differ between groups (p > .05). The overall level of agreement between the test–retest measures of calf muscle perfusion was excellent for measurements taken at rest (intraclass correlation coefficient [ICC] 0.85), and in response to cuff occlusion (ICC 0.89) and exercise (ICC 0.95). Our findings suggest that healthy aging does not affect muscle perfusion responses to cuff‐occlusion and submaximal leg exercise. CEU muscle perfusion parameters measured in response to these provocation tests are highly reproducible in both young and older adults., We used contrast‐enhanced ultrasound (CEU) to compare skeletal muscle microvascular perfusion responses to cuff occlusion and leg exercise between healthy young (n = 12, 26 ± 3 years) and older (n = 12, 68 ± 7 years) adults. There were no differences in post‐occlusion whole‐leg blood flow and muscle microvascular perfusion between young and older participants (p > .05). Similarly, total whole‐leg blood flow during exercise and post‐exercise peak muscle microvascular perfusion did not differ between groups (p > .05).

This review sought to evaluate the role of exercise in patients with obesity and comorbid hypertension, with a focus on contemporary literature (since January 2015). No reviews have included patients classified with both obesity and hypertension and there is a paucity of randomised controlled trials examining the benefits of exercise in this population. Moreover, just one of 19 reviews examining the role of exercise on blood pressure included studies that met pre-defined inclusion criterion for hypertension, although seven conducted subgroup analyses stratified by mean baseline blood pressure. These demonstrated significantly larger reductions in blood pressure in hypertensive than pre-hypertensive and normotensive samples. There is a significant research-practice gap for understanding and influencing the role of exercise for patients with obesity and hypertension. This review provides recommendations for future research and consensus-based recommendations that promote exercise as a principle therapy for patients with obesity and hypertension.

BackgroundIncomplete restoration of myocardial blood flow (MBF) is reported in up to 30% of ST-segment elevation myocardial infarction (STEMI) despite prompt mechanical revascularization. Experimental hyperinsulinemic euglycemia (HE) increases MBF reserve (MBFR). If fully exploited, this effect may also improve MBF to ischemic myocardium. Using insulin-dextrose infusions to induce HE, we conducted four experiments to determine (1) how insulin infusion duration, dose, and presence of insulin resistance affect MBFR response; and (2) the effect of an insulin-dextrose infusion given immediately following revascularization of STEMI on myocardial perfusion.MethodsThe MBFR was determined using myocardial contrast echocardiography. Experiment 1 (insulin duration): 12 participants received an insulin-dextrose or saline infusion for 120 minutes. MBFR was measured at four time intervals during infusion. Experiment 2 (insulin dose): 22 participants received one of three insulin doses (0.5, 1.5, 3.0 mU/kg/minute) for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 3 (insulin resistance): five metabolic syndrome and six type 2 diabetes (T2DM) participants received 1.5 mU/kg/minute of insulin-dextrose for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 4 (STEMI): following revascularization for STEMI, 20 patients were randomized to receive either 1.5 mU/kg/minute insulin-dextrose infusion for 120 minutes or standard care. Myocardial contrast echocardiography was performed at four time intervals to quantify percentage contrast defect length.ResultsExperiment 1: MBFR increased with time through to 120 minutes in the insulin-dextrose group and did not change in controls. Experiment 2: compared with baseline, MBFR increased in the 1.5 (2.42 ± 0.39 to 3.25 ± 0.77, P = .002), did not change in the 0.5, and decreased in the 3.0 (2.64 ± 0.25 to 2.16 ± 0.33, P = .02) mU/kg/minute groups. Experiment 3: compared with baseline, MBFR increase was only borderline significant in metabolic syndrome and T2DM participants (1.98 ± 0.33 to 2.59 ± 0.45, P = .04, and 1.67 ± 0.35 to 2.14 ± 0.21, P = .05). Experiment 4: baseline percentage contrast defect length was similar in both groups but with insulin decreased with time and was significantly lower than in controls at 60 minutes (2.8 ± 5.7 vs 13.7 ± 10.6, P = .02).ConclusionsPresence of T2DM, insulin infusion duration, and dose are important determinants of the MBFR response to HE. When given immediately following revascularization for STEMI, insulin-dextrose reduces perfusion defect size at one hour. Hyperinsulinemic euglycemia may improve MBF following ischemia, but further studies are needed to clarify this.

Evidence of prospective associations between participation in sports and recreational activities (SRAs) and health outcomes at the population level is scarce. We investigated the associations between participation in SRAs and 6-year incidence of hypertension, diabetes, and obesity in a cohort of mid-age Australian adults. We analyzed data from the HABITAT study (n = 8784), a cohort of adults aged 40+ years living in Brisbane, Australia. Mail surveys in 2007, 2009, 2011, and 2013 were used to collect data on participation in 11 SRAs in the past 12 months, as well as self-reported hypertension, diabetes, height, and weight. Obesity was defined as BMI ≥ 30.0 kg/m2. Logistic generalized estimating equation models with a 2-year lag were used. Participation in SRAs in 2007, 2009, and 2011 was matched with outcomes measured in 2009, 2011, and 2013. From 2007 to 2013, the cumulative incidence of hypertension, diabetes, and obesity was 14.9%, 3.2%, and 11%, respectively. Running, tennis, team sports, exercise classes, and resistance training were associated with reduced odds of hypertension. Running, cycling, resistance training, and yoga/tai chi were associated with reduced odds of diabetes. Cycling, tennis, home-based exercises, resistance training, and yoga/tai chi were associated with lower odds of obesity. Participation in SRAs was associated with lower incidence of hypertension, diabetes, and obesity in mid-age adults over six years. These findings support current efforts to promote wider and continuing participation in SRAs at this life stage.

Introduction Aging is associated with impaired cerebrovascular blood flow and function, attributed to reduced vasodilatory capacity of the cerebrovascular network. Older adults may also have an impaired relationship between changes in blood pressure and cerebral blood flow; however, previous reports conflict. This study aimed to compare the blood pressure and cerebral blood flow responses to both repeated and sustained stand‐to‐sit transitions in young and older adults, and to assess the relationship with cerebrovascular reactivity. Methods In 20 young (age: 24 ± 4 years) and 20 older (age: 71 ± 7 years) adults we compared middle cerebral artery flow velocity (MCAv), end‐tidal partial pressure of carbon dioxide (PETCO2), and blood pressure (mean arterial blood pressure [MAP]) during repeated stand‐to‐sit (10 s standing and 10 s sitting) and sustained stand‐to‐sit (3 min standing followed by 2 min sitting) transitions. Cerebrovascular reactivity to changes in carbon dioxide levels was assessed using a repeated breath‐hold test. Results The % change in MCAv per % change in MAP (%∆MCAv/%∆MAP) was higher in the older adults than in the young adults during repeated stand‐to‐sit transitions. During the sustained protocol the %∆MCAv/%∆MAP response was similar in both age groups. A high %∆MCAv/%∆MAP response during the repeated stand‐to‐sit protocol was associated with low cerebrovascular reactivity to CO2 (r = −.39; p, Aging and age‐related cerebrovascular diseases are associated with impaired cerebrovascular function. The novel finding of this study is that older adults showed higher pressure–flow responses during repeated stand–sit transitions compared to younger adults, and that a high pressure–flow response was associated with low cerebrovascular reactivity to CO2. These results suggest that impaired vascular function and increased arterial stiffness may contribute to the pressure–flow responses observed in the older adults.

Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of the lower limb arteries. Although leg blood flow is limited in PAD, it remains unclear whether skeletal muscle microvascular perfusion is affected. We compared whole leg blood flow and calf muscle microvascular perfusion after cuff occlusion and submaximal leg exercise between patients with PAD ( n = 12, 69 ± 9 yr) and healthy age-matched control participants ( n = 12, 68 ± 7 yr). Microvascular blood flow (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after the following: 1) 5 min of thigh-cuff occlusion, and 2) a 5-min bout of intermittent isometric plantar-flexion exercise (400 N) using real-time contrast-enhanced ultrasound. Whole leg blood flow was measured after thigh-cuff occlusion and during submaximal plantar-flexion exercise using strain-gauge plethysmography. Postocclusion whole leg blood flow and calf muscle microvascular perfusion were lower in patients with PAD than control participants, and these parameters were strongly correlated ( r = 0.84, P < 0.01). During submaximal exercise, total whole leg blood flow and vascular conductance were not different between groups. There were also no group differences in postexercise calf muscle microvascular perfusion, although microvascular blood volume was higher in patients with PAD than control participants (12.41 ± 6.98 vs. 6.34 ± 4.98 arbitrary units, P = 0.03). This study demonstrates that the impaired muscle perfusion of patients with PAD during postocclusion hyperemia is strongly correlated with disease severity and is likely mainly determined by the limited conduit artery flow. In response to submaximal leg exercise, microvascular flow volume was elevated in patients with PAD, which may reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery during recovery from exercise. NEW & NOTEWORTHY This study suggests that peripheral arterial disease (PAD) has different effects on the microvascular perfusion responses to cuff occlusion and submaximal leg exercise. Patients with PAD have impaired microvascular perfusion after cuff occlusion, similar to that previously reported after maximal exercise. In response to submaximal exercise, however, the microvascular flow volume response was elevated in patients with PAD compared with control. This finding may reflect a compensatory mechanism to maintain perfusion and oxygen delivery during recovery from exercise.

Captive breeding has contributed to successful restoration of many species of birds of prey. Avicultural techniques pioneered by raptor breeders include double clutching, direct fostering, cross-fostering, hatch and switch, hacking, imprinting male and female falcons for semen collection, and artificial insemination techniques. However, reproductive failure occurs related to management problems, including hygiene measures, food quality issues, breeding flock structure, or individual health issues of breeding birds. These may result in non-egg laying females, low-quality eggs, or infertile eggs caused by male infertility. Veterinary care of breeding collections is extremely important. This article provides an overview of veterinary involvement in raptor breeding projects.

Background: Assessment of endothelial function using brachial artery flow-mediated dilation (FMD) predicts future cardiovascular disease (CVD) risk. However, poor adherence to protocol guidelines and lack of reference values hinders widespread FMD use. This study established age- and sex-specific reference intervals for brachial artery FMD in healthy individuals and examined the relation with CVD risk factors. Methods: Collected according to expert-consensus guidelines, we combined brachial artery FMD and subject characteristics/medical history from 5,362 individuals (4–84 years; 2,076 females). We first examined healthy individuals (n = 1,403 [582 females]) to generate age-/sex-specific percentile curves. Subsequently, we included subjects with CVD risk factors but without disease (un-medicated n = 3,167 [1,247 females], and medicated n = 792 [247 females]). Multiple linear regression tested the relation of CVD risk factors with FMD. Results: Healthy men showed a negative, curvilinear relation between FMD and age, whilst females revealed a linear relation that started higher, but declined at a faster rate. Age-/sex-related differences in FMD, at least partly, relate to baseline artery diameter. FMD was affected by CVD risk factors in un-medicated (e.g. systolic-/diastolic blood pressure, diabetes) and medicated subjects (e.g. dyslipidaemia). Importantly, sex mediated these effects (p < 0.05), with (supra) normalisation of FMD in medicated men, but not in women (except for blood pressure). Conclusion: Sex alters the age-related decline in FMD, which is partly explained through differences in artery diameter. Sex also altered the effect of some CVD risk factors and medication on FMD. This work improves interpretation and future use of the FMD technique when strictly adhering to FMD protocol guidelines.

Abdominal aortic aneurysm (AAA) is associated with inflammation and oxidative stress, the latter of which contributes to activation of macrophages, a prominent cell type in AAA. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to limit oxidative stress in animal models of AAA. The aim of this study was to evaluate the effect of the n-3 PUFA docosahexaenoic acid (DHA) on antioxidant defence in macrophages from patients with AAA. Cells were obtained from men with small AAA (diameter 3.0–4.5 cm, 75 ± 6 yr, n = 19) and age- matched male controls (72 ± 5 yr, n = 41) and incubated with DHA for 1 h before exposure to 0.1 µg/mL lipopolysaccharide (LPS) for 24 h. DHA supplementation decreased the concentration of tumour necrosis factor-α (TNF-α; control, 42.1 ± 13.6 to 5.1 ± 2.1 pg/ml, p

Menopausal hot flushes negatively impact quality of life and may be a biomarker of cardiovascular and metabolic disease risk; therefore understanding the physiology of hot flushes is important. Current thinking is that a small elevation (∼0.03-0.05C) in core temperature surpasses a sweating threshold (that is reduced in the menopause), sweating is activated, and a hot flush ensues. Nevertheless, more recent studies examining thermoregulatory control question whether core temperature per se can explain the trigger for a hot flush. The primary aim of this study was to assess the contribution of increases in core temperature on the occurrence of menopausal hot flushes.For this purpose, 108 hot flushes were objectively assessed in a laboratory setting in 72 symptomatic postmenopausal women (aged 45.8 ± 5.1 years; body mass index 25.9 ± 4.5 kg/m) from five previously reported studies. Women rested, wearing a tube-lined suit (or trousers), which was perfused with 34C water. A subset then underwent mild heat stress (48°C water). Sweat rate, skin blood flow, blood pressure, heart rate, skin, and core temperature were measured continuously throughout. A hot flush was objectively identified during rest (spontaneous hot flush) or mild heating as an abrupt increase in sternal sweat rate. Further, a subset of symptomatic postmenopausal women (n = 22) underwent whole-body passive heating for 60 minutes to identify core temperature thresholds and sensitivities for sweat rate and cutaneous vasodilation, which were compared to a subset of premenopausal women (n = 18). Data were analyzed using t tests and/or general linear modeling, and are presented as mean (95% confidence interval).In the 20 minutes before a spontaneous hot flush, core temperature increased by 0.03 ± 0.12C (P 0.05), but only 51% of hot flushes were preceded by an increase in core temperature. During mild heating, 76% of hot flushes were preceded by an increase in core temperature. The temperature thresholds for sweating were similar, but the vasodilatory threshold was higher in postmenopausal compared with premenopausal women (37.1 ± 0.2 vs 36.8 ± 0.3°C; P = 0.06).We provide new evidence that menopausal hot flushes are unlikely triggered by an increase in core temperature. These findings provide important information about the physiology of hot flushes that have implications for treatment and management options for menopausal hot flushes.

Aging is often associated with reduced leg blood flow, increased arterial stiffness, and endothelial dysfunction, all of which are related to declining nitric oxide (NO) bioavailability. Flow mediated dilatation (FMD) and passive leg movement (PLM) hyperaemia are two techniques used to measure NO-dependent vascular function. We hypothesised that acute dietary nitrate (NO3&minus, ) supplementation would improve NO bioavailability, leg FMD, and PLM hyperaemia. Fifteen healthy older men (69 &plusmn, 4 years) attended two experiment sessions and consumed either 140 mL of concentrated beetroot juice (800 mg NO3&minus, ) or placebo (NO3&minus, depleted beetroot juice) in a randomised, double blind, cross-over design study. Plasma nitrite (NO2&minus, ) and NO3&minus, blood pressure (BP), augmentation index (AIx75), pulse wave velocity (PWV), FMD of the superficial femoral artery, and PLM hyperaemia were measured immediately before and 2.5 h after consuming NO3&minus, and placebo. Placebo had no effect but NO3&minus, led to an 8.6-fold increase in plasma NO2&minus, which was accompanied by an increase in FMD (NO3&minus, +1.18 &plusmn, 0.94% vs. placebo: 0.23 &plusmn, 1.13%, p = 0.002), and a reduction in AIx75 (NO3&minus, &minus, 8.7 &plusmn, 11.6% vs. placebo: &minus, 4.6 &plusmn, 5.5%, p = 0.027). PLM hyperaemia, BP, and PWV were unchanged during both trials. This study showed that a dose of dietary NO3&minus, improved NO bioavailability and enhanced endothelial function as measured by femoral artery FMD. These findings provide insight into the specific central and peripheral vascular responses to dietary NO3&minus, supplementation in older adults.