Critical Lower-Limb Ischemia and Arterial Thrombosis Following Intraarticular Corticosteroid Injection of the Knee.

ABSTRACT: We present a case of acute lower-limb arterial thrombosis following intra-articular steroid injection into the knee of a previously fit and active 41-year-old man. Symptoms of acute limb ischemia developed within 24 hours of treatment. Objective assessment with ultrasound arterial duplex and CT angiogram of the lower limb confirmed acute thrombosis of the popliteal artery in the treated leg. Although there is documented evidence of the association between steroid therapy and venous thromboembolic phenomena, there are no cases of arterial thrombosis in the literature. The temporal series of events that we report strongly suggest an association between the corticosteroid injection and the acute thrombotic event, the mechanism of which remains unclear. The patient underwent successful revascularization. It is important to document and disseminate this seemingly rare complication of a commonly associated procedure to increase awareness, invoke caution, and invite others to share similar cases.

Assessing the Impact of Developments in Genetic Testing on Insurers' Risk Exposure.

Predictive genetic testing provides individuals with information about their future risk of developing health conditions. Theoretically, predictive genetic tests could have positive or negative impacts on the insurance industry. If genetic test results stimulate actions to reduce health risks, they may reduce costs to insurers. If disclosed to insurers, such information may allow them to better understand individual- and population-level risks and make insurance more affordable. However, if individuals who know they are at high genetic risk of becoming ill or dying are more likely to apply for insurance than those not at high risk, this may lead to an unanticipated increase in claims. It may be exacerbated if people at low genetic risk are less likely to apply for insurance compared to the general population. If this happened on a large scale it could make the insurance market unsustainable. Determining whether a genetic test could affect the insurance industry is complex and needs to be evaluated on a per-test basis. The Cambridge Centre for Health Services Research, a collaboration between RAND Europe and the University of Cambridge, developed a framework for evaluating the potential impacts on the UK insurance industry arising from predictive genetic tests. It considers the characteristics of genetic tests and behavioural aspects that influence their uptake. It is intended to provide a transparent approach for evaluating whether a specific condition for which a test is available could impact the insurance industry, currently or in the future, and understanding the key factors that influence this.

Correction: Howe et al. "Effects of Long Chain Omega-3 Polyunsaturated Fatty Acids on Brain Function in Mildly Hypertensive Older Adults" Nutrients 2018, 10, 1413.

The authors wish to make a correction to the published version of their paper [...].

Effects of Long Chain Omega-3 Polyunsaturated Fatty Acids on Brain Function in Mildly Hypertensive Older Adults.

Purported benefits of long chain omega-3 polyunsaturated fatty acid (LCn-3PUFA) for brain function may be attributable, at least in part, to improved cerebral perfusion. A pilot randomised controlled trial was undertaken to investigate effects of taking a DHA-rich fish oil supplement for 20 weeks on cerebrovascular function, mood and cognitive performance. Borderline hypertensives aged 40⁻85 years with low habitual LCn-3PUFA intake took four capsules/day of EPAX (1600 mg DHA + 400 mg EPA) or placebo (corn oil). Cerebrovascular function was assessed at baseline and after 20 weeks in 38 completers (19 on each supplement) using transcranial Doppler ultrasound of blood flow in the middle cerebral artery at rest and whilst performing a battery of cognitive tasks (neurovascular coupling). The primary outcome, cerebrovascular responsiveness (CVR) to hypercapnia, increased 26% (p = 0.024) in women; there was no change in men. In contrast, neurovascular coupling increased significantly (p = 0.01 for the overall response) in men only; the latter correlated with an increase of EPA in erythrocytes (r = 0.616, p = 0.002). There was no associated improvement of mood or cognition in either men or women. These preliminary observations indicate that LCn-3PUFA supplementation has the potential to enhance blood flow in the brain in response to both hypercapnic and cognitive stimuli. Future studies should examine differential effects of EPA and DHA and take account of the gender differences in responsiveness to supplementation.

Resveratrol supplementation reduces pain experience by postmenopausal women.

OBJECTIVE: Pain is a common complaint among postmenopausal women. It has been postulated that vascular dysfunction caused by estrogen decline at menopause plays a key role in the initiation and progression of degradative joint disease, namely age-related osteoarthritis. We evaluated whether supplementation with resveratrol, a phytoestrogen, could improve aspects of well-being such as chronic pain that is commonly experienced by postmenopausal women. METHODS: A 14-week randomized, double-blind, placebo-controlled intervention with trans-resveratrol (75 mg, twice daily) was conducted in 80 healthy postmenopausal women. Aspects of well-being, including pain, menopausal symptoms, sleep quality, depressive symptoms, mood states, and quality of life were assessed by Short form-36 at baseline and at the end of treatment. Rating scales were averaged to provide a composite score representing overall well-being. Cerebral vasodilator responsiveness to hypercapnia was also assessed as a surrogate marker for cerebrovascular function. RESULTS: Compared with placebo treatment, there was a significant reduction in pain and an improvement in total well-being after resveratrol supplementation. Both benefits, including measures of quality of life, correlated with improvements in cerebrovascular function. CONCLUSIONS: 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.

Effects of Resveratrol on Cognitive Performance, Mood and Cerebrovascular Function in Post-Menopausal Women; A 14-Week Randomised Placebo-Controlled Intervention Trial.

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.

Phosphorylation of calcium/calmodulin-stimulated protein kinase II at T286 enhances invasion and migration of human breast cancer cells.

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.

Clinical Evaluation of Effects of Chronic Resveratrol Supplementation on Cerebrovascular Function, Cognition, Mood, Physical Function and General Well-Being in Postmenopausal Women-Rationale and Study Design.

BACKGROUND: This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at least partly due to loss of beneficial effects of estrogen on the cerebrovasculature. We hypothesise that resveratrol, a phytoestrogen, may counteract this risk by enhancing cerebrovascular function and improving regional blood flow in response to cognitive demands. A clinical trial was designed to test this hypothesis. METHOD: Healthy postmenopausal women were recruited to participate in a randomised, double-blind, placebo-controlled (parallel comparison) dietary intervention trial to evaluate the effects of resveratrol supplementation (75 mg twice daily) on cognition, cerebrovascular responsiveness to cognitive tasks and overall well-being. They performed the following tests at baseline and after 14 weeks of supplementation: Rey Auditory Verbal Learning Test, Cambridge Semantic Memory Battery, the Double Span and the Trail Making Task. Cerebrovascular function was assessed simultaneously by monitoring blood flow velocity in the middle cerebral arteries using transcranial Doppler ultrasound. CONCLUSION: This trial provides a model approach to demonstrate that, by optimising circulatory function in the brain, resveratrol and other vasoactive nutrients may enhance mood and cognition and ameliorate the risk of developing dementia in postmenopausal women and other at-risk populations.

Poor cerebrovascular function is an early marker of cognitive decline in healthy postmenopausal women.

INTRODUCTION: Impairment of cerebrovascular function becomes evident after menopause. No study has yet explored relationships between deficits in cerebrovascular function, cognitive performance, and mood in postmenopausal women. METHOD: Cerebrovascular function was assessed in 80 healthy postmenopausal women by monitoring blood flow velocity (BFV) in the middle and posterior cerebral arteries using transcranial Doppler ultrasound at rest, following a hypercapnic challenge, and during performance of a cognitive test battery; the latter assessed domains of memory and executive functions. Various measures of mood (i.e., Profile of Mood States and Center for Epidemiological Studies Depression Scale) were also assessed. RESULTS: Cerebral artery elasticity and BFV responsiveness to cognitive tests (neurovascular coupling) correlated with cognitive performance but not with depressive symptoms or mood states. Mood deficits were related to poor cognitive performance. CONCLUSION: These results highlight the importance of adequate cerebral perfusion for optimized cognitive function in healthy postmenopausal women. Preventative strategies to attenuate accelerated cognitive decline should also consider restoring cerebrovascular function.