Associations between Cerebrovascular Function and the Expression of Genes Related to Endothelial Function in Hormonal Migraine.

There is evidence to suggest that hormonal migraine is associated with altered cerebrovascular function. We aimed to investigate whether the expression of genes related to endothelial function in venous blood (1) might influence cerebrovascular function, (2) differs between hormonal migraineur and non-migraineur women, and (3) changes following resveratrol supplementation. This study utilised data obtained from 87 women (59 hormonal migraineurs and 28 controls) where RNA from venous blood was used to quantify gene expression and transcranial Doppler ultrasound was used to evaluate cerebrovascular function. Spearman's correlation analyses were performed between gene expression, cerebrovascular function, and migraine-related disability. We compared the expression of genes associated with endothelial function between migraineurs and non-migraineurs, and between resveratrol and placebo. The expression of several genes related to endothelial function was associated with alterations in cerebrovascular function. Notably, the expression of CALCA was associated with increased neurovascular coupling capacity (p = 0.013), and both CALCA (p = 0.035) and VEGF (p = 0.014) expression were associated with increased cerebral blood flow velocity in the overall study population. Additionally, VCAM1 expression correlated with decreased pulsatility index (a measure of cerebral arterial stiffness) (p = 0.009) and headache impact test-6 scores (p = 0.007) in the migraineurs. No significant differences in gene expression were observed between migraineurs and controls, or between placebo and resveratrol treatments in migraineurs. Thus, altering the expression of genes related to endothelial function may improve cerebrovascular function and decrease migraine-related disability.

Resveratrol-Induced Suppression of C-type Natriuretic Peptide Associates With Increased Vertebral Bone Density in Postmenopausal Women.

C-type natriuretic peptide (CNP) is a paracrine growth factor essential in driving endochondral bone growth in mammals including humans. Despite evidence from animal experiments and tissues that CNP signaling stimulates osteoblast proliferation and osteoclast activity, whether CNP participates in bone remodeling in the mature skeleton is unknown. Using stored plasma samples from a previous randomized controlled clinical trial (RESHAW) of resveratrol supplementation in postmenopausal women exhibiting mild osteopenia, we have studied changes in plasma aminoterminal proCNP (NTproCNP) and concurrent change in bone turnover markers of formation (osteocalcin [OC] and alkaline phosphatase [ALP]) and resorption (C-terminal telopeptide type 1 collagen [CTX]) with bone mineral density (BMD) over a 2-year period of study in 125 subjects. In year one, subjects received placebo or resveratrol, switching to resveratrol or placebo, respectively, in year two. Across all time points, there were no significant associations of NTproCNP with CTX, ALP, or OC. During year one, plasma NTproCNP declined significantly in both groups. In the crossover comparison, analysis of change within individuals showed that, compared with placebo, NTproCNP declined after resveratrol (p = 0.011) and ALP increased (p = 0.008), whereas CTX and OC were unchanged. Inverse association of NTproCNP (r = -0.31; p = 0.025) and positive association of OC (r = 0.32, p = 0.022) with BMD at the lumbar spine were identified after resveratrol but not found after placebo. Decline in NTproCNP was independently associated with resveratrol treatment. This is the first evidence that CNP is modulated during a period of increasing BMD in postmenopausal women. Further study of NTproCNP and associations with drivers of bone formation or resorption can be expected to clarify CNP's role during other interventions directed to bone health in adults. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The benefits of regular aerobic exercise training on cerebrovascular function and cognition in older adults.

We compared the differences in cerebrovascular and cognitive function between 13 aerobic exercise trained, older adults and 13 age-, height- and sex-matched sedentary, untrained controls. We determined whether other measures accounted for differences in cerebrovascular and cognitive function between these groups and examined the associations between these functions. Participants undertook anthropometric, mood, cardiovascular, exercise performance, strength, cerebrovascular, and cognitive measurements, and a blood collection. Transcranial Doppler ultrasonography determined cerebrovascular responsiveness (CVR) to hypercapnia and cognitive stimuli. The trained group had a higher CVR to hypercapnia (80.3 ± 7.2 vs 35.1 ± 6.7%, P < 0.001), CVR to cognitive stimuli (30.1 ± 2.9 vs 17.8 ± 1.4%, P = 0.001) and total composite cognitive score (117 ± 2 vs 98 ± 4, P < 0.001) than the controls. These parameters no longer remained statistically different between the groups following adjustments for covariates. There were positive correlations between the total composite cognitive score and CVR to hypercapnia (r = 0.474, P = 0.014) and CVR to cognitive stimuli (r = 0.685, P < 0.001). We observed a relationship between cerebrovascular and cognitive function in older adults and an interaction between regular lifelong aerobic exercise training and cardiometabolic factors that may directly influence these functions.

Geographic and demographic variation in worry about extreme heat and COVID-19 risk in summer 2020.

Extreme heat is a major health hazard that is exacerbated by ongoing human-caused climate change. However, how populations perceive the risks of heat in the context of other hazards like COVID-19, and how perceptions vary geographically, are not well understood. Here we present spatially explicit estimates of worry among the U.S. public about the risks of heat and COVID-19 during the summer of 2020, using nationally representative survey data and a multilevel regression and poststratification (MRP) model. Worry about extreme heat and COVID-19 varies both across states and across demographic groups, in ways that reflect disparities in the impact of each risk. Black or African American and Hispanic or Latino populations, who face greater health impacts from both COVID-19 and extreme heat due to institutional and societal inequalities, also tend to be much more worried about both risks than white, non-Hispanic populations. Worry about heat and COVID-19 were correlated at the individual and population level, and patterns tended to be related to underlying external factors associated with the risk environment. In the face of a changing climate there is an urgent need to address disparities in heat risk and develop responses that ensure the most at-risk populations are protected.

Exploring the effects of resveratrol supplementation on cerebrovascular function in hormonal migraineurs: A pilot study.

Background: Past research suggests that hormonal migraineurs may have poorer cerebrovascular function than women who do not suffer from migraine. Resveratrol, a vasoactive phytoestrogen, has been shown to improve cerebrovascular function in several populations but has never been tested in hormonal migraineurs. Aim: To investigate the effects of 3-month resveratrol supplementation on the cerebrovascular function of hormonal migraineurs. Methods: We conducted a randomised, double-blind, placebo-controlled, crossover intervention pilot study with resveratrol (150 mg/d for 3 months) in ten hormonal migraineurs (mean age: 37.2 ± 2.6 years). Participants visited the University of Newcastle's Clinical Nutrition Research Centre where quality of life and disability, and cerebrovascular function were assessed. Quality of life and disability were examined using Migraine-Specific Quality of Life, Headache Impact Test-6 and the Migraine Disability Assessment. Cerebrovascular function was determined using transcranial Doppler ultrasound to bilaterally measure blood flow velocity in the middle and posterior cerebral arteries at rest and in response to a hypercapnic stimulus. Cerebrovascular responsiveness to a cognitive task battery was also measured bilaterally in the middle cerebral arteries. Results: Compared to placebo, blood flow velocity in the right posterior cerebral artery was significantly higher (P = 0.041) following resveratrol supplementation. No other significant differences in cerebrovascular function between resveratrol and placebo treatments were observed. Baseline correlation analyses revealed higher blood flow velocities in the middle and posterior cerebral arteries were associated with better quality of life and less disability. However, higher cerebrovascular responsiveness to hypercapnia in the posterior circulation was associated with higher migraine-related disability and poorer migraine-related quality of life. Conclusion: In this pilot we found evidence that resveratrol may increase blood flow velocity in the right posterior cerebral artery in hormonal migraineurs. Larger cohorts are required confirm this effect and its potential relationship to migraine in premenopausal women.

Structural Elucidation of Agrochemicals and Related Derivatives Using Infrared Ion Spectroscopy.

Agrochemicals frequently undergo various chemical and metabolic transformation reactions in the environment that often result in a wide range of derivates that must be comprehensively characterized to understand their toxicity profiles and their persistence and outcome in the environment. In the development phase, this typically involves a major effort in qualitatively identifying the correct chemical isomer(s) of these derivatives from the many isomers that could potentially be formed. Liquid chromatography-mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy are often used in attempts to characterize such environment transformation products. However, challenges in confidently correlating chemical structures to detected compounds in mass spectrometry data and sensitivity/selectivity limitations of NMR frequently lead to bottlenecks in identification. In this study, we use an alternative approach, infrared ion spectroscopy, to demonstrate the identification of hydroxylated derivatives of two plant protection compounds (azoxystrobin and benzovindiflupyr) contained at low levels in tomato and spinach matrices. Infrared ion spectroscopy is an orthogonal tandem mass spectrometry technique that combines the sensitivity and selectivity of mass spectrometry with structural information obtained by infrared spectroscopy. Furthermore, IR spectra can be computationally predicted for candidate molecular structures, enabling the tentative identification of agrochemical derivatives and other unknowns in the environment without using physical reference standards.

The Effects of Aerobic Exercise Training on Cerebrovascular and Cognitive Function in Sedentary, Obese, Older Adults.

Cerebrovascular function and cognition decline with age and are further exacerbated by obesity and physical inactivity. This decline may be offset by aerobic exercise training (AT). We investigated the effects of 16 weeks AT on cerebrovascular and cognitive function in sedentary, obese, older adults. Twenty-eight participants were randomly allocated to AT or a control group. Before and after the intervention, transcranial Doppler ultrasonography was used to measure the cerebrovascular responsiveness (CVR) to physiological (hypercapnia, 5% carbon dioxide) and cognitive stimuli. AT increased the CVR to hypercapnia (98.5 ± 38.4% vs. 58.0 ± 42.0%, P = 0.021), CVR to cognitive stimuli (25.9 ± 6.1% vs. 16.4 ± 5.4%, P < 0.001) and total composite cognitive score (111 ± 14 vs. 104 ± 14, P = 0.004) compared with the control group. A very strong relationship was observed between the number of exercise sessions completed and CVR to cognitive stimuli (r = 0.878, P < 0.001), but not for CVR to hypercapnia (r = 0.246, P = 0.397) or total composite cognitive score (r = 0.213, P = 0.465). Cerebrovascular function and cognition improved following 16 weeks of AT and a dose-response relationship exists between the amount of exercise sessions performed and CVR to cognitive stimuli.

A Randomised, Double-Blind, Placebo-Controlled Crossover Trial of Resveratrol Supplementation for Prophylaxis of Hormonal Migraine.

Resveratrol, a vasoactive phytoestrogen, has beneficial effects on cerebrovascular function. Previous research has shown that hormonal migraineurs have poorer cerebrovascular function than non-migraineur women. We aimed to investigate if resveratrol supplementation for three months could reduce the hormonal migraine burden index (HMBI: the number of days with menstrual migraine per month), reduce migraine-related disability and improve migraine-related quality of life. A randomised, double-blind, placebo-controlled, crossover, intervention trial was conducted in 62 hormonal migraineurs (mean age: 37.5 ± 0.8 years). Participants consumed 75 mg of resveratrol or matching placebo capsules twice daily for three months before crossing over to the other treatment arm. Participants completed a daily diary and the Headache Impact Test-6™, Migraine Disability Assessment and Migraine-Specific Quality of Life questionnaires at months 0, 3 and 6. The HMBI was the primary outcome and was calculated using data extracted from the participant's diary. No differences in the HMBI (p = 0.895), the Headache Impact Test-6™, the Migraine Disability Assessment and Migraine-Specific Quality of Life were found between the resveratrol and placebo treatments. Resveratrol supplementation for three months did not affect the HMBI, the migraine-related disability or quality of life measures in our cohort of hormonal migraineurs.

Cerebrovascular Function in Hormonal Migraine: An Exploratory Study.

Background: Migraineurs, particularly young premenopausal women, are at increased risk of cerebrovascular disease; however, there is currently limited evidence as to whether hormonal migraine is associated with poor cerebrovascular function. Objectives: The objectives of this study were to: (1) investigate the potential association of cerebrovascular function with hormonal migraine and (2) determine whether abnormalities of cerebrovascular function in hormonal migraineurs are associated with migraine-related disability and/or quality of life. Method: A cross-sectional study was undertaken in 50 hormonal migraineurs (mean age: 38.7 ± 1.2 years) and 29 controls (mean age: 35.6 ± 1.8 years). Data were collected at a single point in time from all participants during the inter-ictal period when they were free from migraine and not menstruating. Transcranial Doppler ultrasound was used to measure resting blood flow velocity and cerebrovascular responsiveness (CVR) to hypercapnia and cognitive stimulation (neurovascular coupling) in the left and right middle cerebral artery (MCA). Additionally, hormonal migraineurs completed three questionnaires to assess migraine-related disability and quality of life as well as migraine frequency and intensity: Headache Impact Test-6™, Migraine-Specific Quality of Life and Migraine Disability Assessment. Results: Hormonal migraineurs had lower resting mean blood flow velocity (MBFV) (P = 0.009) and neurovascular coupling during cognitive stimulation (P = 0.010) in the left MCA than controls. No such differences were found in the right MCA. Additionally, heart rate (P = 0.004) was higher in hormonal migraineurs than controls. However, no differences in CVR to hypercapnia were found between hormonal migraineurs and controls. Multi-variate analysis revealed age to be a significant (P = 0.012) predictor of MBFV in the left MCA. Negative correlations between headache frequency and CVR to hypercapnia in the left (P = 0.026) and right MCA (P = 0.044) were found. Additionally, negative correlations between neurovascular coupling during the 2-Back 1.5 s task in the right MCA and the MSQoL emotional (P = 0.013) and role-function restrictive (P = 0.039) domains were found. Conclusions: This is the first study to show that hormonal migraineurs have poorer cerebrovascular function, as represented by lower resting MBFV and impaired neurovascular coupling in the left MCA. Future studies should investigate whether improving cerebrovascular function can prevent hormonal migraine and improve quality of life. Clinical Trial Registration: ACTRN12618001230246.

Social media reveal ecoregional variation in how weather influences visitor behavior in U.S. National Park Service units.

Daily weather affects total visitation to parks and protected areas, as well as visitors' experiences. However, it is unknown if and how visitors change their spatial behavior within a park due to daily weather conditions. We investigated the impact of daily maximum temperature and precipitation on summer visitation patterns within 110 U.S. National Park Service units. We connected 489,061 geotagged Flickr photos to daily weather, as well as visitors' elevation and distance to amenities (i.e., roads, waterbodies, parking areas, and buildings). We compared visitor behavior on cold, average, and hot days, and on days with precipitation compared to days without precipitation, across fourteen ecoregions within the continental U.S. Our results suggest daily weather impacts where visitors go within parks, and the effect of weather differs substantially by ecoregion. In most ecoregions, visitors stayed closer to infrastructure on rainy days. Temperature also affects visitors' spatial behavior within parks, but there was not a consistent trend across ecoregions. Importantly, parks in some ecoregions contain more microclimates than others, which may allow visitors to adapt to unfavorable conditions. These findings suggest visitors' spatial behavior in parks may change in the future due to the increasing frequency of hot summer days.

Benefits of exercise training on cerebrovascular and cognitive function in ageing.

Derangements in cerebrovascular structure and function can impair cognitive performance throughout ageing and in cardiometabolic disease states, thus increasing dementia risk. Modifiable lifestyle factors that cause a decline in cardiometabolic health, such as physical inactivity, exacerbate these changes beyond those that are associated with normal ageing. The purpose of this review was to examine cerebrovascular, cognitive and neuroanatomical adaptations to ageing and the potential benefits of exercise training on these outcomes in adults 50 years or older. We systematically searched for cross-sectional or intervention studies that included exercise (aerobic, resistance or multimodal) and its effect on cerebrovascular function, cognition and neuroanatomical adaptations in this age demographic. The included studies were tabulated and described narratively. Aerobic exercise training was the predominant focus of the studies identified; there were limited studies exploring the effects of resistance exercise training and multimodal training on cerebrovascular function and cognition. Collectively, the evidence indicated that exercise can improve cerebrovascular function, cognition and neuroplasticity through areas of the brain associated with executive function and memory in adults 50 years or older, irrespective of their health status. However, more research is required to ascertain the mechanisms of action.

Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: A 24-month randomised, double-blind, placebo-controlled, crossover study.

Ageing and menopause contribute to endothelial dysfunction, causing impaired cerebral perfusion, which is in turn associated with accelerated cognitive decline. In a 14-week pilot study, we showed that supplementation with low-dose resveratrol, a phytoestrogen that can enhance endothelial function, improved cerebrovascular and cognitive functions in postmenopausal women. We sought to confirm these benefits in a larger, longer-term trial. A 24-month randomized, placebo-controlled crossover trial was undertaken in 125 postmenopausal women, aged 45-85 years, who took 75 mg trans-resveratrol or placebo twice-daily for 12 months and then crossover to the alternative treatment for another 12 months. We evaluated within individual differences between each treatment period in measures of cognition (primary outcome), cerebrovascular function in the middle cerebral artery (cerebral blood flow velocity: CBFV, cerebrovascular responsiveness: CVR) and cardio-metabolic markers as secondary outcomes. Subgroup analyses examined effects of resveratrol by life stages. Compared to placebo, resveratrol supplementation resulted a significant 33% improvement in overall cognitive performance (Cohen's d = 0.170, P = 0.005). Women ≥65 years of age showed a relative improvement in verbal memory with resveratrol compared to those younger than 65 years. Furthermore, resveratrol improved secondary outcomes including resting mean CBFV (d = 0.275, P = 0.001), CVR to hypercapnia (d = 0.307, P = 0.027), CVR to cognitive stimuli (d = 0.259, P = 0.032), fasting insulin (d = 0.174, P = 0.025) and insulin resistance index (d = 0.102, P = 0.034). Regular supplementation with low-dose resveratrol can enhance cognition, cerebrovascular function and insulin sensitivity in postmenopausal women. This may translate into a slowing of the accelerated cognitive decline due to ageing and menopause, especially in late-life women. Further studies are warranted to observe whether these cognitive benefits of resveratrol can reduce the risk of dementia.

Profiling cerebrovascular function in migraine: A systematic review and meta-analysis.

Previous studies have investigated whether migraine is a circulatory disorder, as migraineurs are at heightened risk of cerebrovascular disease. However, in most cases, systemic vascular function was evaluated, which may not reflect abnormalities in the cerebral circulation. Therefore, we aimed to determine whether cerebrovascular function differs between migraineurs and controls. A systematic literature search was conducted across three electronic databases to search for studies that compared cerebrovascular function in migraineurs to controls. Where applicable, meta-analyses were used to determine standardised mean differences (SMD) between migraineurs and controls. Seventy articles were identified, 40 of which contained quantitative data. Meta-analyses showed pulsatility index (PI) was higher (SMD = 0.23; 95%CI = 0.05 to 0.42, P = 0.01) and cerebrovascular responsiveness (CVR) to hypercapnia was lower (SMD=-0.34; 95%CI=-0.67 to -0.01, P = 0.04) in the posterior circulation of migraineurs, particularly those without aura. The meta-analyses also indicated that migraineurs have higher resting mean blood flow velocity in both anterior (SMD = 0.14; 95%CI = 0.05 to 0.23, P = 0.003) and posterior circulations (SMD = 0.20; 95%CI = 0.05 to 0.34, P = 0.007). Compared to healthy controls, migraineurs have altered cerebrovascular function, evidenced by elevated PI (representing arterial stiffness) and impaired CVR to hypercapnia (representing cerebral vasodilator function). Future studies should investigate whether improvement of cerebrovascular function is able to alleviate migraine.

Evaluation of Cognitive Performance following Fish-Oil and Curcumin Supplementation in Middle-Aged and Older Adults with Overweight or Obesity.

BACKGROUND: Obesity accelerates age-related cognitive decline, which is partly mediated by vascular dysfunction. OBJECTIVE: The aim was to test the hypothesis that supplementation with fish oil and curcumin can enhance cognitive performance by improving cerebral circulatory function in overweight or obese middle-aged to older adults. METHODS: In a 16-wk double-blind, placebo-controlled intervention trial, adults [50-80 y; BMI (kg/m2): 25-40] were randomly assigned to either fish oil (2000 mg/d DHA + 400 mg/d EPA), curcumin (160 mg/d), or a combination. Effects on cerebrovascular function (primary outcome) and cardiovascular risk factors were reported previously. Effects on cognitive performance and cerebrovascular responsiveness (CVR) to cognitive stimuli are reported herein. One-factor ANOVA with post hoc analyses was conducted between groups in the whole cohort and in males and females separately. Two-factor ANOVA was conducted to assess independent effects of fish oil and curcumin and a potential interaction. Correlations between outcomes (those obtained herein and previously reported) were also examined. RESULTS: Compared with placebo, fish oil improved CVR to a processing speed test (4.4% ± 1.9% vs. -2.2% ± 2.1%; P = 0.023) and processing speed in males only (Z-score: 0.6 ± 0.2 vs. 0.1 ± 0.2; P = 0.043). Changes in processing speed correlated inversely with changes in blood pressure (R = -0.243, P = 0.006) and C-reactive protein (R = -0.183, P = 0.046). Curcumin improved CVR in a working memory test (3.6% ± 1.2% vs. -0.2% ± 0.2%, P = 0.026) and, in males only, performance of a verbal memory test compared with placebo (Z-score: 0.2 ± 0.1 vs. -0.5 ± 0.2, P = 0.039). Combining fish oil with curcumin did not produce additional benefits. CONCLUSIONS: Improvements in processing speed following fish-oil supplementation in middle-aged to older males might be mediated by improvements in circulatory function. Mechanisms underlying the cognitive benefit seen with curcumin are unknown. As cognitive benefits were found in males only, further evaluation of sex differences in responsiveness to supplementation is warranted. This trial was registered at the Australian and New Zealand Clinical Trial Register at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370788 as ACTRN12616000732482p.

Long-term resveratrol supplementation improves pain perception, menopausal symptoms, and overall well-being in postmenopausal women: findings from a 24-month randomized, controlled, crossover trial.

OBJECTIVE: Following concerns about hormone therapy, postmenopausal women need alternative options to manage menopause-related symptoms and improve their well-being. A 14-week pilot study has shown that supplementation with resveratrol, a phytoestrogen with circulatory benefits, can improve aspects of well-being including chronic pain, which is a common complaint in postmenopausal women. We aimed to confirm these benefits in a larger, long-term study. METHODS: The Resveratrol for Healthy Ageing in Women study, a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention trial of resveratrol supplementation (75 mg BID) was conducted in 125 healthy postmenopausal women to evaluate effects on cognitive performance (results published elsewhere). Aspects of well-being including pain perception, mood and depressive symptoms, menopausal symptoms, sleep quality, and quality of life were assessed with questionnaires as secondary outcomes of the study. Cerebrovascular responsiveness to hypercapnia was measured as a surrogate marker of cerebrovascular function. RESULTS: Resveratrol supplementation reduced composite pain score (P < 0.001), especially in overweight individuals; this was associated with improvements in cerebrovascular responsiveness to hypercapnia (R = -0.329, P = 0.014). Somatic menopausal symptoms (P = 0.024) and general well-being (P = 0.010) were also improved after resveratrol supplementation. CONCLUSIONS: These results confirm the pilot study finding that resveratrol supplementation can reduce chronic pain in age-related osteoarthritis and improve menopause-related quality of life in postmenopausal women. These improvements are sustained by supplementation for at least 12 months and are associated with enhancement of circulatory function. CLINICAL TRIAL REGISTRATION: ACTRN12616000679482p.

Video Summary:http://links.lww.com/MENO/A638.

Fish oil supplementation reduces osteoarthritis-specific pain in older adults with overweight/obesity.

OBJECTIVES: OA is a leading cause of chronic pain and disability. Next to inflammation, vascular pathology has been hypothesized to play a role in its aetiology and progression. Owing to side effects and the low efficacy of pharmacological treatments, dietary supplements are popular as alternative treatments, but evidence of efficacy is limited. We tested whether fish oil and curcumin supplementation can reduce chronic pain and OA burden in older adults. METHODS: A 16-week randomized, double-blind, placebo-controlled, 2 × 2 factorial design supplementation trial with fish oil (2000 mg/day docosahexaenoic acid + 400 mg/day eicosapentaenoic acid), curcumin (160 mg/day) or a combination of both was undertaken in sedentary overweight/obese older adults. Secondary outcomes included treatment-induced changes in self-reported chronic pain and OA burden and whether changes were related to changes in small artery elasticity (surrogate marker for microvascular function), CRP (inflammatory marker) and well-being. RESULTS: The majority of participants (131 of 152) reported chronic pain, which was predominantly OA specific. Fish oil significantly reduced OA-specific pain (P = 0.002, Cohen's d = 0.56) and burden (P = 0.015, Cohen's d = 0.45) compared with no fish oil treatment; reductions were correlated with improvements in microvascular function and well-being. Curcumin, alone or in combination with fish oil, did not reduce pain measures. CONCLUSION: Our findings indicate potential for fish oil to alleviate OA pain and burden in overweight/obese older adults. Further investigations should be undertaken in patients with clinically diagnosed OA to evaluate fish oil alone and as an adjunct to conventional pharmacotherapy and to investigate underlying mechanisms. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370788, ACTRN12616000732482p.

Recent developments in the use of fluorine NMR in synthesis and characterisation.

A review of developments in fluorine NMR of relevance to synthesis, characterisation and industrial applications of small organic molecules. Developments considered include those in spectrometer technology, computational methods and pulse sequences. The review of 80 references outlines applications in areas of identification, quantitation, mixture analysis, reaction monitoring, environmental studies and fragment-based drug design.

An Exploratory Analysis of Changes in Mental Wellbeing Following Curcumin and Fish Oil Supplementation in Middle-Aged and Older Adults.

Curcumin has previously been shown to enhance mood in non-depressed older adults. However, observed benefits were limited to short-term supplementation (4 weeks). In a 16 week randomized, double-blind, placebo-controlled, 2 × 2 factorial design trial, we supplemented overweight or obese non-depressed adults (50-80 years) with curcumin (160 mg/day), fish oil (2000 mg docosahexaenoic acid +400 mg eicosapentaenoic acid/day), or a combination of both. Secondary outcomes included mental wellbeing measures (mood states and subjective memory complaints (SMCs)) and quality of life (QoL). Furthermore, plasma apolipoprotein E4 (APOE4) was measured to determine whether APOE4 status influences responses to fish oil. Curcumin improved vigour (p = 0.044) compared to placebo and reduced SMCs compared to no curcumin treatment (p = 0.038). Fish oil did not affect any mood states, SMCs or QoL; however, responses to fish oil were affected by APOE4 status. In APOE4 non-carriers, fish oil increased vigour (p = 0.030) and reduced total mood disturbances (p = 0.048) compared to placebo. Improvements in mental wellbeing were correlated with increased QoL. Combining curcumin with fish oil did not result in additive effects. This exploratory analysis indicates that regular supplementation with either curcumin or fish oil (limited to APOE4 non-carriers) has the potential to improve some aspects of mental wellbeing in association with better QoL.

Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial.

Resveratrol, a naturally occurring polyphenol in red grapes and berries, can act as a phytoestrogen. It has been shown to improve both systemic and cerebral circulatory functions, possibly through activation of endothelial estrogen receptors. in vitro and in vivo studies in rodent models also indicate a bone-protective role for resveratrol, particularly in ovariectomized rat models that mimic postmenopausal osteoporosis caused by estrogen deficiency. Hypothesizing a circulatory benefit of resveratrol in bone tissue, we investigated whether resveratrol supplementation could improve bone health in postmenopausal women. The Resveratrol for Healthy Aging in Women (RESHAW) trial was a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention conducted to evaluate the effects of resveratrol (75 mg twice daily) on cognition, cerebrovascular function, bone health, cardiometabolic markers, and well-being in postmenopausal women. After 12 months of supplementation with resveratrol versus placebo, there were positive effects on bone density in the lumbar spine (+0.016 ± 0.003 g/cm2 ) and neck of femur (+0.005 ± 0.002 g/cm2 ), which were accompanied by a 7.24% reduction in C-terminal telopeptide type-1 collagen levels, a bone resorption marker, compared with placebo. The increase in bone mineral density in the femoral neck resulted in an improvement in T-score (+0.070 ± 0.018) and a reduction in the 10-year probability of major and hip fracture risk. The magnitude of improvement was higher in women with poor bone health biomarker status. Importantly, the improvement in femoral neck T-score with resveratrol correlated with improvement in perfusion. Our subanalysis also revealed that the bone-protective benefit of resveratrol was greater in participants who supplemented with vitamin D plus calcium. Regular supplementation with 75 mg of resveratrol twice daily has the potential to slow bone loss in the lumbar spine and femoral neck, common fracture sites in postmenopausal women without overt osteoporosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Sustained Cerebrovascular and Cognitive Benefits of Resveratrol in Postmenopausal Women.

Deficits in the cerebral microcirculation contribute to age-related cognitive decline. In a pilot study of postmenopausal women, we found that supplementation with a low dose of resveratrol, a phytoestrogen, for 14 weeks improved cerebrovascular and cognitive functions. We have since undertaken a larger, longer term study to confirm these benefits. Postmenopausal women aged 45-85 years (n = 129) were randomized to take placebo or 75 mg trans-resveratrol twice daily for 12 months. Effects on cognition, cerebral blood flow, cerebrovascular responsiveness (CVR) and cardiometabolic markers (blood pressure, diabetes markers and fasting lipids) were assessed. Compared to placebo, resveratrol improved overall cognitive performance (P < 0.001) and attenuated the decline in CVR to cognitive stimuli (P = 0.038). The latter effect was associated with reduction of fasting blood glucose (r = -0.339, P = 0.023). This long-term study confirms that regular consumption of resveratrol can enhance cognitive and cerebrovascular functions in postmenopausal women, with the potential to slow cognitive decline due to ageing and menopause.