We tested whether chronic supplementation with resveratrol (a phytoestrogen) could improve cerebrovascular function, cognition and mood in post-menopausal women. Eighty post-menopausal women aged 45–85 years were randomised to take trans-resveratrol or placebo for 14 weeks and the effects on cognitive performance, cerebral blood flow velocity and pulsatility index (a measure of arterial stiffness) in the middle cerebral artery (using transcranial Doppler ultrasound), and cerebrovascular responsiveness (CVR) to both cognitive testing and hypercapnia were assessed. Mood questionnaires were also administered. Compared to placebo, resveratrol elicited 17% increases in CVR to both hypercapnic (p = 0.010) and cognitive stimuli (p = 0.002). Significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020), which correlated with the increase in CVR (r = 0.327; p = 0.048). Mood tended to improve in multiple measures, although not significantly. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.

Objective. To determine whether symptomatic (painful/problematic) joints pre-total knee replacement (TKR) surgery influence 1) pre-and 12-month post-TKR patient-reported outcomes (pain, physical function, and mood [fatigue, anxiety, and depression]) and 2) postsurgical pain and function mediated through mood. Methods. A total of 494 participants completed the patient-reported outcome measures pre-and 12-months post-TKR. Symptomatic (painful/problematic) joints affected by arthritis were indicated on a homunculus presurgery. Covariate data included age, sex, educational attainment, body mass index, and comorbidity. Pre-and postsurgical outcome scores were regressed on symptomatic joint sites and covariates using linear regression analyses; postsurgical scores additionally were regressed on presurgery scores. Path analyses examined whether the effects of symptomatic joint sites on postsurgical pain and function were mediated through mood. Results. The age range was 35-88 years (mean 65 years) and 65% were women. Forty-six percent reported >4 symptomatic joints (other than the surgical knee). Pre-and postsurgery, worse outcome scores were observed with increasing joint count. Adjusted for covariates, individuals reporting symptomatic ankles/feet/toes, neck, and spine/lower back had worse presurgery fatigue and anxiety. Adjusted for covariates and presurgery status, worse fatigue for the neck and spine/lower back and worse depression, pain, and function for the ankles/feet/toes and neck were observed postsurgery. The influence of symptomatic ankles/feet/toes on postsurgical pain and function was in part direct and partially mediated through depression. Full mediation was found for the neck through fatigue, anxiety, and depression, and for the spine/lower back through fatigue. Conclusion. Findings suggest that a comprehensive approach to osteoarthritis management/care is warranted, and identify important associations between symptomatic joints and mood that negatively impact post-TKR pain and physical function.

Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a multi-functional kinase that controls a range of cellular functions, including proliferation, differentiation and apoptosis. The biological properties of CaMKII are regulated by multi-site phosphorylation. However, the role that CaMKII phosphorylation plays in cancer cell metastasis has not been examined. We demonstrate herein that CaMKII expression and phosphorylation at T286 is increased in breast cancer when compared to normal breast tissue, and that increased CAMK2 mRNA is associated with poor breast cancer patient prognosis (worse overall and distant metastasis free survival). Additionally, we show that overexpression of WT, T286D and T286V forms of CaMKII in MDA-MB-231 and MCF-7 breast cancer cells increases invasion, migration and anchorage independent growth, and that overexpression of the T286D phosphomimic leads to a further increase in the invasive, migratory and anchorage independent growth capacity of these cells. Pharmacological inhibition of CaMKII decreases MDA-MB-231 migration and invasion. Furthermore, we demonstrate that overexpression of T286D, but not WT or T286V-CaMKII, leads to phosphorylation of FAK, STAT5a, and Akt. These results demonstrate a novel function for phosphorylation of CaMKII at T286 in the control of breast cancer metastasis, offering a promising target for the development of therapeutics to prevent breast cancer metastasis.

Our preliminary findings indicate potential for resveratrol treatment to reduce chronic pain in age-related osteoarthritis. Resveratrol consumption may also boost perceptions of well-being in postmenopausal women. Further investigation to elucidate underlying mechanisms is warranted.