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

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

Baseline azithromycin resistance in the gut microbiota of preterm born infants.

BACKGROUND: Macrolides, including azithromycin, are increasingly used in preterm-born infants to treat Ureaplasma infections. The baseline carriage of macrolide resistance genes in the preterm stool microbiota is unknown. OBJECTIVES: Identify carriage of azithromycin resistant bacteria and the incidence of macrolide resistant genes. METHODS: Azithromycin resistant bacteria were isolated from serial stool samples obtained from preterm infants (≤32 weeks' gestation) by culturing aerobically/anaerobically, in the presence/absence of azithromycin. Using quantitative PCR, we targeted 6 common macrolide resistance genes (erm(A), erm(B), erm(C), erm(F), mef(A/E), msr(A)) in DNA extracted from selected bacteria resistant to azithromycin. RESULTS: From 89 stool samples from 37 preterm-born infants, 93.3% showed bacterial growth in aerobic or anaerobic conditions. From the 280 azithromycin resistant isolates that were identified, Staphylococcus (75%) and Enterococcus (15%) species dominated. Macrolide resistance genes were identified in 91% of resistant isolates: commonest were erm(C) (46% of isolates) and msr(A) (40%). Multiple macrolide resistance genes were identified in 18% of isolates. CONCLUSION: Macrolide resistance is common in the gut microbiota of preterm-born infants early in life, most likely acquired from exposure to the maternal microbiota. It will be important to assess modulation of macrolide resistance, if macrolide treatment becomes routine in the management of preterm infants. IMPACT STATEMENT: Azithromycin resistance is present in the stool microbiota in the first month of life in preterm infants 91% of azithromycin resistant bacteria carried at least one of 6 common macrolide resistant genes Increasing use of macrolides in the preterm population makes this an important area of study.

Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter?

BACKGROUND: Whether changes in blood pressure (BP) over women's midlife are more driven by chronological aging or the menopause transition has been debated. We sought to determine whether women can be classified into distinct trajectory groups based on pattern and level of systolic BP (SBP), diastolic BP, pulse pressure (PP), and mean arterial pressure (MAP) over the menopause transition, and to assess whether menopause-related factors predict the group and level of BP measures. METHODS: Participants were from the SWAN (Study of Women's Health Across the Nation). Group-based trajectory modeling was used to identify women who shared distinct BP trajectories over time relative to menopause onset and to assess associations of menopause-related factors with trajectory group and level of BP measures. An accelerated rise relative to menopause onset suggests a menopause contribution. RESULTS: The study included 3302 multiracial and multiethnic women with BP measures over 17 follow-up visits (baseline age [SD]: 46.3 [2.7]). Women were classified into either low, medium, or high trajectory group in each BP measure. The low SBP, PP, and MAP trajectories (in 35%, 53%, and 28% of the cohort, respectively) were rising slowly before menopause but showed a significant accelerated rise 1 year after menopause, indicating a menopause contribution. The remaining BP trajectories were rising up until menopause and either continued with the same rise or declined after menopause. A younger menopause age predicted the low SBP, PP, and MAP trajectories. A greater follicle-stimulating hormone level predicted lower SBP and PP levels, while vasomotor symptoms occurrence predicted higher SBP, PP, and MAP levels over time. Estradiol did not predict trajectory or level of any BP measure. CONCLUSIONS: Distinct BP trajectories over the menopause transition exist that revealed a group of women whose SBP, PP, and MAP trajectories are consistent with a menopause contribution. Our findings support frequent monitoring of BP during the menopause transition.

Assessing frailty amongst older people admitted to hospital in a low-income setting: a multicentre study in northern Tanzania.

BACKGROUND: Populations are ageing globally and Low- and Middle-Income Countries (LMICs) are experiencing the fastest rates of demographic change. Few studies have explored the burden of frailty amongst older people in hospital in LMICs, where healthcare services are having to rapidly adapt to align with the needs of older people. This study aimed to measure the prevalence of frailty amongst older people admitted to hospital in Tanzania and to explore their demographic and clinical characteristics. METHODS: This study had a prospective observational design. Over a six-month period, all adults ≥ 60 years old admitted to medical wards in four hospitals in northern Tanzania were invited to participate. They were screened for frailty using the Clinical Frailty Scale (CFS) and the Frailty Phenotype (FP). Demographic and clinical characteristics of interest were recorded in a structured questionnaire. These included the Barthel Index, the Identification of Elderly Africans Instrumental Activities of Daily Living (IADEA-IADL) and Cognitive (IDEA-Cog) screens, the EURO-D depression scale and Confusion Assessment Method. RESULTS: 540 adults aged ≥ 60 were admitted, and 308 completed assessment. Frailty was present in 66.6% using the CFS and participants with frailty were significantly older, with lower levels of education and literacy, greater disability, greater comorbidity, poorer cognition and higher levels of delirium. Using the FP, 57.0% of participants were classed as frail though a majority of participants (n = 159, 51.6%) could not be classified due to a high proportion of missing data. CONCLUSIONS: This study indicates that the prevalence of frailty on medical wards in northern Tanzania is high according to the CFS. However, the challenges in operationalising the FP in this setting highlight the need for future work to adapt frailty screening tools for an African context. Future investigations should also seek to correlate frailty status with long-term clinical outcomes after admission in this setting.

Reproductive hormones in relation to white matter hyperintensity volumes among midlife women.

INTRODUCTION: Although reproductive hormones are implicated in cerebral small vessel disease in women, few studies consider measured hormones in relation to white matter hyperintensity volume (WMHV), a key indicator of cerebral small vessel disease. Even fewer studies consider estrone (E1), the primary postmenopausal estrogen, or follicle-stimulating hormone (FSH), an indicator of ovarian age. We tested associations of estradiol (E2), E1, and FSH to WMHV among women. METHODS: Two hundred twenty-two women (mean age = 59) underwent hormone assays (E1, E2, FSH) and 3T brain magnetic resonance imaging. Associations of hormones to WMHV were tested with linear regression. RESULTS: Higher E2 (B[standard error (SE)] = -0.17[0.06], P = 0.008) and E1 (B[SE] = -0.26[0.10], P = 0.007) were associated with lower whole-brain WMHV, and higher FSH (B[SE] = 0.26[0.07], P = 0.0005) with greater WMHV (covariates age, race, education). When additionally controlling for cardiovascular disease risk factors, associations of E1 and FSH to WMHV remained. DISCUSSION: Reproductive hormones, particularly E1 and FSH, are important to women's cerebrovascular health. HIGHLIGHTS: Despite widespread belief that sex hormones are important to women's brain health, little work has considered how these hormones in women relate to white matter hyperintensities (WMH), a major indicator of cerebral small vessel disease. We considered relations of estradiol (E2), estrone (E1), and follicle-stimulating hormone (FSH) to WMH in midlife women. Higher E2 and E1 were associated with lower whole-brain WMH volume (WMHV), and higher FSH with higher whole-brain WMHV. Associations of E1 and FSH, but not E2, to WMHV persisted with adjustment for cardiovascular disease risk factors. Findings underscore the importance of E2 and FSH to women's cerebrovascular health.

Carotid intima media thickness and white matter hyperintensity volume among midlife women.

INTRODUCTION: Carotid atherosclerosis may be associated with brain white matter hyperintensities (WMH). Few studies consider women at midlife, a critical time for women's cardiovascular and brain health. We tested the hypothesis that higher carotid intima media thickness (IMT) would be associated with greater WMH volume (WMHV) among midlife women. We explored interactions by apolipoprotein E (APOE) ε4 status. METHODS: Two hundred thirty-nine women aged 45 to 67 underwent carotid artery ultrasound, phlebotomy, and magnetic resonance imaging (MRI). One hundred seventy participants had undergone an ultrasound 5 years earlier. RESULTS: Higher IMT was associated with greater whole brain (B[standard error (SE)] = 0.77 [.31], P = 0.01; multivariable) and periventricular (B[SE] = 0.80 [.30], P = 0.008; multivariable) WMHV. Associations were observed for IMT assessed contemporaneously with the MRI and 5 years prior to the MRI. Associations were strongest for APOE ε4-positive women. DISCUSSION: Among midlife women, higher IMT was associated with greater WMHV. Vascular risk is critical to midlife brain health, particularly for APOE ε4-positive women.

The quantity and quality of cardiovascular fat at mid-life and future cognitive performance among women: The SWAN cardiovascular fat ancillary study.

INTRODUCTION: Cardiovascular fat is a novel risk factor that may link to dementia. Fat volume and radiodensity are measurements of fat quantity and quality, respectively. Importantly, high fat radiodensity could indicate healthy or adverse metabolic processes. METHODS: The associations of cardiovascular fat (including epicardial, paracardial, and thoracic perivascular adipose tissue [PVAT]) quantity and quality assessed at mean age of 51 with subsequent cognitive performance measured repeatedly over 16 years of follow-up were examined using mixed models among 531 women. RESULTS: Higher thoracic PVAT volume was associated with a higher future episodic memory (ß[standard error (SE)] = 0.08 [0.04], P = 0.033), while higher thoracic PVAT radiodensity with lower future episodic (ß[SE] = -0.06 [0.03], P = 0.045) and working (ß[SE] = -0.24 [0.08], P = 0.003) memories. The latter association is prominent at higher volume of thoracic PVAT. DISCUSSION: Mid-life thoracic PVAT may have a distinct contribution to future cognition possibly due to its distinct adipose tissue type (brown fat) and anatomical proximity to the brain circulation. HIGHLIGHTS: Higher mid-life thoracic perivascular adipose tissue (thoracic PVAT) volume is related to a better future episodic memory in women. Higher mid-life thoracic PVAT radiodensity is related to worse future working and episodic memories. Negative association of high thoracic PVAT radiodensity with working memory is prominent at higher thoracic PVAT volume. Mid-life thoracic PVAT is linked to future memory loss, an early sign of Alzheimer's disease. Mid-life women's epicardial and paracardial fat are not related to future cognition.

Determining the Impact of a Community-Based Intervention on Knowledge Gained and Attitudes Towards the HPV Vaccine in Virginia.

HPV vaccination series completion rates have increased steadily in the USA, yet specific areas continue to be burdened by HPV-related cancers, including rural areas of Virginia. The primary purpose of this study is to compare the impact of an community driven educational film about HPV on intention to vaccinate and knowledge gained in urban and rural areas of Virginia. From October 2016 to September 2019, the CDC-approved documentary "Someone You Love: The HPV Epidemic" was screened and followed by a Q&A session. Intention to vaccinate and knowledge gained after seeing the DVD intervention were measured through a pre-post-survey and analyzed data using chi-squared tests. The sample included males and females of all races and ages 18+ that identified as either student, parent/guardian, and/or healthcare provider from rural and urban geographical areas. Changes in knowledge about HPV were statistically significant in two out of seven questions (p < 0.05). Changes in attitude were statistically significant in every attitude-based question about HPV (p < 0.05). There were significant differences in knowledge gained and attitudes towards the HPV vaccine when comparing urban and rural locations as well. More research is needed to explore the efficacy of community-based interventions to increase uptake and series completion of HPV vaccination, particularly in rural areas most impacted by HPV-associated cancers.

Predictors of cervical cancer screening for refugee women attending an international family medicine clinic in the United States.

PURPOSE: Cervical cancer screening (CCS) rates are lower for foreign-born women in the United States (U.S.) compared with the overall population. This study aimed to determine the CCS rate and predictors among refugees who were identified as female attending a family medicine clinic. METHODS: A retrospective chart review included refugee individuals aged 21+, seen in the previous 3 years (3/23/2015-3/20/2018), without hysterectomy (n = 525). Lab results determined CCS rate. Chi-square and logistic regression models explored predictors of CCS. RESULTS: Overall, 60.0% were up-to-date (UTD) on CCS. Individuals aged 30-49, married, and with [Formula: see text] 1 child had higher odds of being UTD. Ten or more years living in the U.S. was a significant bivariate predictor of CCS, and approached significance in the multivariate model. CONCLUSION: This study begins to fill gaps in knowledge about cervical cancer control among individuals who resettled in the U.S. as refugees and, given that CCS rates are suboptimal, informs clinical practice improvements and directions for future research.

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

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

The Cardiovascular Cost of Silence: Relationships Between Self-silencing and Carotid Atherosclerosis in Midlife Women.

BACKGROUND: Individuals engage in a range of behaviors to maintain close relationships. One behavior is self-silencing or inhibiting self-expression to avoid relationship conflict or loss. Self-silencing is related to poor mental health and self-reported physical health in women but has not been examined in relation to cardiovascular health, particularly using direct measures of the vasculature. PURPOSE: To test associations between self-silencing and carotid atherosclerosis in midlife women; secondary analyses examined moderation by race/ethnicity. METHODS: Women (N = 290, ages 40-60) reported on self-silencing in intimate relationships and underwent physical measurements, blood draw, and ultrasound assessment of carotid intima-media thickness (IMT) and plaque. Associations between self-silencing and mean IMT and plaque index (0, 1, ≥2) were tested in linear regression and multinomial logistic regression models, respectively, followed by interaction terms between self-silencing and race, adjusted for demographic factors, CVD risk factors, partner status, depression, physical activity, and diet. RESULTS: Forty-seven percent of women demonstrated carotid plaque. Greater self-silencing was related to increased odds of plaque index ≥2 (e.g., for each additional point, odds ratio [95% confidence interval] = 1.16 [1.03-1.31], p = .012), relative to no plaque). Moderation analyses indicated that self-silencing was related to odds of plaque index ≥2 in non-white women (1.15 [1.05-1.26], p = .004), but there was no significant relationship in white women (1.01 [0.97-1.06], p = .550). No associations emerged for IMT. CONCLUSIONS: Among midlife women, self-silencing was associated with carotid plaque, independent of CVD risk factors, depression, and health behaviors. Emotional expression in relationships may be important for women's cardiovascular health.

Macroscopic current generated by local division and apoptosis in a minimal model of tissue dynamics.

It has been known that the motion of self-propelled particles inside an asymmetric channel can be rectified to give rise to a macroscopic and unidirectional current. In this paper, we show that division and apoptosis process alone (which are ubiquitous in all living systems), without any self-propulsion, are sufficient to give rise to a macroscopic and unidirectional current in a similar channel. More specifically, we consider a minimal computational model of two-dimensional living tissues, with two active ingredients: local particle division and apoptosis, and we found a net steady state current along the channel. This mechanism is fundamentally different from that of self-propelled particles, since this requires the system to be dense. Finally, our results might have applications in tissue engineering such as controlling tissue growth via a geometrically non-uniform substrate.

A quantitative systems pharmacology model for simulating OFF-Time in augmentation trials for Parkinson's disease: application to preladenant.

The clinical impact of therapeutic interventions in Parkinson's disease is often measured as a reduction in OFF-time when the beneficial effects of the standard-of-care L-DOPA formulations wanes off. We investigated the pharmacodynamic interactions of augmentation therapy to standard-of-care using a quantitative systems pharmacology (QSP) model of the basal ganglia motor circuit, essentially a computer model of neuronal firing in the different subregions with anatomically informed connectivity, cell-specific expression of 17 different G-protein coupled receptors and corresponding coupling to voltage-gated ion channel effector proteins based on experimentally observed intracellular signaling. The calculated beta/gamma (b/g) power spectrum of the local field potentials in the subthalamic nucleus was previously calibrated on the clinically relevant Unified Parkinson's Disease Rating Scale (UPDRS). When combining this QSP model with PK modeling of different formulations of L-DOPA, we calculated the b/g fluctuations over a 16 h awake period and used a weighted distance from a specific threshold to determine the cumulative liability of OFF-Time. Prediction of OFF-time with clinical observations of different L-DOPA formulations showed a significant correlation. Simulations show that augmentation with the adenosine A2A antagonist preladenant reduces OFF-time with 6 min for carbidopa/levodopa 950 mg 5-times daily to 37 min for 100 mg L-DOPA - 3 or 5 times daily. Exploring delays between preladenant and L-DOPA intake did not improve the outcome. Hypothetical A2A antagonists with an ideal PK and pharmacology profile can achieve OFF-Time reductions ranging from 9.5 min with DuoDopa to 55 min with low dose L-DOPA formulations. Combination of the QSP model with PK modeling can predict the anticipated OFF-Time reduction of novel A2A antagonists with standard of care. With the large number of GPCR in the model, this combination can support both the design of clinical trials with new therapeutic agents and the optimization of combination therapy in clinical practice.

Explaining Government Policy Inaction on International Student Housing in Australia: The Perspectives of Stakeholders.

Housing is a major concern for many international students. This is especially so in those countries where students are mostly dependent on the private market for their accommodation. Australia is one such country, and is one of the world's major destinations for international students. This article analyses governmental failure to address problems relating to international student housing affordability and conditions. Using theory on 'policy inaction' to frame the analysis, we draw on 20 interviews with policy stakeholders to explain the Australian government's reliance on: (1) market-based housing provision for international students, and (2) a longstanding policy preference not to provide support. Interviewees were widely critical of the lack of action to address international student housing problems and understood inaction in relation, rather than in opposition, to the dominance of market-based action in housing and higher education. However, analysis of stakeholder perspectives also illuminates how policy-making action benefiting some emerges as inaction for others left behind or overlooked by the status quo. The interview data points to the need for government to overhaul its policy framework, and in doing so, to collaborate with higher education providers in revising the market-based regulatory approach. The main implications for theory and policy are discussed.

Race/Ethnicity, Cumulative Midlife Loss, and Carotid Atherosclerosis in Middle-Aged Women.

African-American women have elevated rates of cardiovascular disease compared with women of other races or ethnicities, and race/ethnicity-related stressors may play a role. We examined the association between a race/ethnicity-related stressor, midlife loss, and a marker of cardiovascular risk, carotid intima media thickness (IMT), in 1,410 African-American, White, Chinese, and Hispanic women from the Study of Women's Health Across the Nation. Participants were queried about losses annually over 12 years (1996-2013), with IMT assessed in year 12-13 via ultrasound. Linear regression models were used to examine associations between cumulative upsetting losses and IMT, adjusting for covariates. In minimally adjusted models in the full cohort, 3 or more upsetting losses (vs. none) were associated with IMT (ß = 0.03, 95% confidence interval (CI): 0.01, 0.05; P = 0.0003). Results were more robust among African-American women (ß = 0.042, 95% CI: 0.01, 0.07; P < 0.01) than White (ß = 0.014, 95% CI: -0.01, 0.03; P = 0.21), Chinese (ß = 0.036, 95% CI: -0.03, 0.10; P = 0.25), or Hispanic (ß = 0.036, 95% CI: -0.07, 0.14; P = 0.51) women, although associations among women from racial/ethnic minorities overall were of similar magnitude. Results persisted in fully adjusted models (P for interaction with race/ethnicity = 0.04). Midlife loss may be a pathway through which race/ethnicity influences cardiovascular risk for African-American women and, potentially, Chinese and Hispanic women.

Gestational Weight Gain and Long-term Maternal Obesity Risk: A Multiple-Bias Analysis.

BACKGROUND: Lifecourse research provides an important framework for chronic disease epidemiology. However, data collection to observe health characteristics over long periods is vulnerable to systematic error and statistical bias. We present a multiple-bias analysis using real-world data to estimate associations between excessive gestational weight gain and mid-life obesity, accounting for confounding, selection, and misclassification biases. METHODS: Participants were from the multiethnic Study of Women's Health Across the Nation. Obesity was defined by waist circumference measured in 1996-1997 when women were age 42-53. Gestational weight gain was measured retrospectively by self-recall and was missing for over 40% of participants. We estimated relative risk (RR) and 95% confidence intervals (CI) of obesity at mid-life for presence versus absence of excessive gestational weight gain in any pregnancy. We imputed missing data via multiple imputation and used weighted regression to account for misclassification. RESULTS: Among the 2,339 women in this analysis, 937 (40%) experienced obesity in mid-life. In complete case analysis, women with excessive gestational weight gain had an estimated 39% greater risk of obesity (RR = 1.4, CI = 1.1, 1.7), covariate-adjusted. Imputing data, then weighting estimates at the guidepost values of sensitivity = 80% and specificity = 75%, increased the RR (95% CI) for obesity to 2.3 (2.0, 2.6). Only models assuming a 20-point difference in specificity between those with and without obesity decreased the RR. CONCLUSIONS: The inference of a positive association between excessive gestational weight gain and mid-life obesity is robust to methods accounting for selection and misclassification bias.

Blood-flow-restricted exercise: Strategies for enhancing muscle adaptation and performance in the endurance-trained athlete.

NEW FINDINGS: What is the topic of this review? Blood-flow-restricted (BFR) exercise represents a potential approach to augment the adaptive response to training and improve performance in endurance-trained individuals. What advances does it highlight? When combined with low-load resistance exercise, low- and moderate-intensity endurance exercise and sprint interval exercise, BFR can provide an augmented acute stimulus for angiogenesis and mitochondrial biogenesis. These augmented acute responses can translate into enhanced capillary supply and mitochondrial function, and subsequent endurance-type performance, although this might depend on the nature of the exercise stimulus. There is a requirement to clarify whether BFR training interventions can be used by high-performance endurance athletes within their structured training programme. ABSTRACT: A key objective of the training programme for an endurance athlete is to optimize the underlying physiological determinants of performance. Training-induced adaptations are governed by physiological and metabolic stressors, which initiate transcriptional and translational signalling cascades to increase the abundance and/or function of proteins to improve physiological function. One important consideration is that training adaptations are reduced as training status increases, which is reflected at the molecular level as a blunting of the acute signalling response to exercise. This review examines blood-flow-restricted (BFR) exercise as a strategy for augmenting exercise-induced stressors and subsequent molecular signalling responses to enhance the physiological characteristics of the endurance athlete. Focus is placed on the processes of capillary growth and mitochondrial biogenesis. Recent evidence supports that BFR exercise presents an intensified training stimulus beyond that of performing the same exercise alone. We suggest that this has the potential to induce enhanced physiological adaptations, including increases in capillary supply and mitochondrial function, which can contribute to an improvement in performance of endurance exercise. There is, however, a lack of consensus regarding the potency of BFR training, which is invariably attributable to the different modes, intensities and durations of exercise and BFR methods. Further studies are needed to confirm its potential in the endurance-trained athlete.

Arterial Stiffness Accelerates Within 1 Year of the Final Menstrual Period: The SWAN Heart Study.

OBJECTIVE: Menopause may augment age-dependent increases in arterial stiffness, with black women having greater progression in midlife compared with white women. We sought to determine whether and when women experience changes in arterial stiffness relative to the final menstrual period (FMP) and whether these changes differ between black and white midlife women. Approach and Results: We evaluated 339 participants from the SWAN (Study of Women's Health Across the Nation) Heart Ancillary study (Study of Women's Health Across the Nation). Women had ≤2 carotid-femoral pulse-wave velocity (cfPWV) exams over a mean±SD of 2.3±0.5 years of follow-up. Annual percentage changes in cfPWV were estimated in 3 time segments relative to FMP and compared using piecewise linear mixed-effects models. At baseline, women were 51.1±2.8 years of age and 36% black. Annual percentage change (95% CI) in cfPWV varied by time segments: 0.9% (-0.6% to 2.3%) for >1 year before FMP, 7.5% (4.1% to 11.1%) within 1 year of FMP, and -1.0% (-2.8% to 0.8%) for >1 year after FMP. Annual percentage change in cfPWV within 1 year of FMP was significantly greater than the other 2 time segments; P<0.05 for both comparisons. Adjusting for concurrent cardiovascular disease risk factors explained part of the change estimates but did not eliminate the difference. Black women had greater increase in cfPWV compared with white women in the first segment; P for interaction, 0.04. CONCLUSIONS: The interval within 1 year of FMP is a critical period for women when vascular functional alterations occur. These findings underscore the importance of more intensive lifestyle modifications in women transitioning through menopause.

The effect of soy isoflavones on arterial stiffness: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Some but not all randomized controlled trials (RCTs) of soy isoflavones showed their beneficial effect on arterial stiffness, a predictor of cardiovascular events, dementia, and all-cause mortality, independent of traditional risk factors. To test the hypothesis that supplementation of soy isoflavones reduces arterial stiffness, we performed a systematic review and meta-analysis of RCTs of soy isoflavones on arterial stiffness. METHODS: The protocol of this systematic review was registered with PROSPERO (CRD42019126128) and written in accordance with PRISMA. The PubMed, Embase, and clinicaltrials.gov databases were searched using the following criteria: human subjects, soy isoflavones as intervention, and arterial stiffness as primary outcome. A random-effects meta-analysis was used to pool estimates across studies. Standardized mean difference (SMD) was used to synthesize quantitative results. RESULTS: Among 998 articles retrieved, 8 articles met our criteria. Duration of intervention was relatively short (maximum of 12 weeks). Outcome measurements extracted were pulse wave velocity (PWV), systemic arterial compliance (SAC), augmentation index (AI), and cardio-ankle vascular index (CAVI). Soy isoflavones reduced arterial stiffness compared to placebo (standardized mean difference - 0.33, 95% confidence interval - 0.47, - 0.19). Subgroup analyses showed no difference between treatment effects for intervention duration (< 6 weeks vs. ≥ 6 weeks) or gender (women only vs. men only vs. combined). Sensitivity analysis showed no difference in the effect of soy isoflavones between PWV, CAVI, SAC, and AI. CONCLUSION: Supplementation of soy isoflavones reduced arterial stiffness. Longer duration trials with larger number of participants are warranted.

Globally altered sleep patterns and physical activity levels by confinement in 5056 individuals: ECLB COVID-19 international online survey.

Symptoms of psychological distress and disorder have been widely reported in people under quarantine during the COVID-19 pandemic; in addition to severe disruption of peoples' daily activity and sleep patterns. This study investigates the association between physical-activity levels and sleep patterns in quarantined individuals. An international Google online survey was launched in April 6th, 2020 for 12-weeks. Forty-one research organizations from Europe, North-Africa, Western-Asia, and the Americas promoted the survey through their networks to the general society, which was made available in 14 languages. The survey was presented in a differential format with questions related to responses "before" and "during" the confinement period. Participants responded to the Pittsburgh Sleep Quality Index (PSQI) questionnaire and the short form of the International Physical Activity Questionnaire. 5056 replies (59.4% female), from Europe (46.4%), Western-Asia (25.4%), America (14.8%) and North-Africa (13.3%) were analysed. The COVID-19 home confinement led to impaired sleep quality, as evidenced by the increase in the global PSQI score (4.37 ± 2.71 before home confinement vs. 5.32 ± 3.23 during home confinement) (p < 0.001). The frequency of individuals experiencing a good sleep decreased from 61% (n = 3063) before home confinement to 48% (n = 2405) during home confinement with highly active individuals experienced better sleep quality (p < 0.001) in both conditions. Time spent engaged in all physical-activity and the metabolic equivalent of task in each physical-activity category (i.e., vigorous, moderate, walking) decreased significantly during COVID-19 home confinement (p < 0.001). The number of hours of daily-sitting increased by ~2 hours/days during home confinement (p < 0.001). COVID-19 home confinement resulted in significantly negative alterations in sleep patterns and physical-activity levels. To maintain health during home confinement, physical-activity promotion and sleep hygiene education and support are strongly warranted.