PPARGC1A sequence variation and cardiovascular risk-factor levels: a study of the main genetic effects and gene x environment interactions in children from the European Youth Heart Study.

AIMS/HYPOTHESIS: The PPARGC1A gene coactivates multiple nuclear transcription factors involved in cellular energy metabolism and vascular stasis. In the present study, we genotyped 35 tagging polymorphisms to capture all common PPARGC1A nucleotide sequence variations and tested for association with metabolic and cardiovascular traits in 2,101 Danish and Estonian boys and girls from the European Youth Heart Study, a multicentre school-based cross-sectional cohort study. METHODS: Fasting plasma glucose concentrations, anthropometric variables and blood pressure were measured. Habitual physical activity and aerobic fitness were objectively assessed using uniaxial accelerometry and a maximal aerobic exercise stress test on a bicycle ergometer, respectively. RESULTS: In adjusted models, nominally significant associations were observed for BMI (rs10018239, p = 0.039), waist circumference (rs7656250, p = 0.012; rs8192678 [Gly482Ser], p = 0.015; rs3755863, p = 0.02; rs10018239, beta = -0.01 cm per minor allele copy, p = 0.043), systolic blood pressure (rs2970869, p = 0.018) and fasting glucose concentrations (rs11724368, p = 0.045). Stronger associations were observed for aerobic fitness (rs7656250, p = 0.005; rs13117172, p = 0.008) and fasting glucose concentrations (rs7657071, p = 0.002). None remained significant after correcting for the number of statistical comparisons. We proceeded by testing for gene x physical activity interactions for the polymorphisms that showed nominal evidence of association in the main effect models. None of these tests was statistically significant. CONCLUSIONS/INTERPRETATION: Variants at PPARGC1A may influence several metabolic traits in this European paediatric cohort. However, variation at PPARGC1A is unlikely to have a major impact on cardiovascular or metabolic health in these children.

Targeting stem cell niches and trafficking for cardiovascular therapy.

Regenerative cardiovascular medicine is the frontline of 21st-century health care. Cell therapy trials using bone marrow progenitor cells documented that the approach is feasible, safe and potentially beneficial in patients with ischemic disease. However, cardiovascular prevention and rehabilitation strategies should aim to conserve the pristine healing capacity of a healthy organism as well as reactivate it under disease conditions. This requires an increased understanding of stem cell microenvironment and trafficking mechanisms. Engagement and disengagement of stem cells of the osteoblastic niche is a dynamic process, finely tuned to allow low amounts of cells move out of the bone marrow and into the circulation on a regular basis. The balance is altered under stress situations, like tissue injury or ischemia, leading to remarkably increased cell egression. Individual populations of circulating progenitor cells could give rise to mature tissue cells (e.g. endothelial cells or cardiomyocytes), while the majority may differentiate to leukocytes, affecting the environment of homing sites in a paracrine way, e.g. promoting endothelial survival, proliferation and function, as well as attenuating or enhancing inflammation. This review focuses on the dynamics of the stem cell niche in healthy and disease conditions and on therapeutic means to direct stem cell/progenitor cell mobilization and recruitment into improved tissue repair.

Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes

AIM: 25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated with major clinical outcomes, with a suggestion that individual risk may vary according to common genetic differences in the vitamin D receptor (VDR) gene. Hence, we tested for the interactions between two previously studied VDR polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes in a large population-based study. METHODS: Interactions between two previously studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on metabolic and cardiovascular disease-related outcomes such as obesity- (body mass index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and diastolic blood pressure), lipid- (high- and low-density lipoprotein, triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen, insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated haemoglobin) related markers were examined in the 1958 British Birth cohort (n up to 5160). Interactions between each SNP and 25OHD concentrations were assessed using linear regression and the likelihood ratio test. RESULTS: After Bonferroni correction, none of the interactions reached statistical significance except for the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist-hip ratio (WHR) (P=0.03). For every 1nmol/L higher 25OHD concentrations, the association with WHR was stronger among those with two major alleles (-4.0%, P=6.26e-24) compared to those with either one or no major alleles (-2.3%, P≤8.201e-07, for both) of the VDR SNP rs2239179. CONCLUSION: We found no evidence for VDR polymorphisms acting as major modifiers of the association between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR SNP rs2239179 and 25OHD on WHR warrants further confirmation.

Flavonoid-rich fruits and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease – FLAVURS: a randomized controlled trial

BACKGROUND: Observed associations between increased fruit and vegetable (F&V) consumption, particularly those F&Vs that are rich in flavonoids, and vascular health improvements require confirmation in adequately powered randomized controlled trials. OBJECTIVE: This study was designed to measure the dose-response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual F&V intakes and vascular function and other cardiovascular disease (CVD) risk indicators. DESIGN: A single-blind, dose-dependent, parallel randomized controlled dietary intervention study was conducted. Male and female low-F&V consumers who had a ≥1.5-fold increased risk of CVD (n = 174) were randomly assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every 6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO), vascular function, and inflammation were determined at baseline and at 6, 12, and 18 wk. RESULTS: In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with +2 portions/d (at 6 wk) and reduced C-reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion molecule (P = 0.0468) with +4 portions/d (at 12 wk). HF F&Vs increased plasma NO (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO (P = 0.0299) in the control group. CONCLUSION: These data support recommendations to increase F&V intake to ≥6 portions daily, with additional benefit from F&Vs that are rich in flavonoids, particularly in men with an increased risk of CVD. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

Development of a food-exchange model to replace saturated fat with MUFAS and n-6 PUFAS in adults at moderate cardiovascular risk

The recommendation to reduce saturated fatty acid (SFA) consumption to ≤10% of total energy (%TE) is a key public health target aimed at lowering cardiovascular disease (CVD) risk. Replacement of SFA with unsaturated fats may provide greater benefit than replacement with carbohydrates, yet the optimal type of fat is unclear. The aim was to develop a flexible food-exchange model to investigate the effects of substituting SFAs with monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on CVD risk factors. In this parallel study, UK adults aged 21-60 y with moderate CVD risk (50% greater than the population mean) were identified using a risk assessment tool (n = 195; 56% females). Three 16-wk isoenergetic diets of specific fatty acid (FA) composition (%TE SFA:%TE MUFA:%TE n-6 PUFA) were designed using spreads, oils, dairy products, and snacks as follows: 1) SFA-rich diet (17:11:4; n = 65); 2) MUFA-rich diet (9:19:4; n = 64); and 3) n-6 PUFA-rich diet (9:13:10; n = 66). Each diet provided 36%TE total fat. Dietary targets were broadly met for all intervention groups, reaching 17.6 ± 0.4%TE SFA, 18.5 ± 0.3%TE MUFA, and 10.4 ± 0.3%TE n-6 PUFA in the respective diets, with significant overall diet effects for the changes in SFA, MUFA, and n-6 PUFA between groups (P < 0.001). There were no differences in the changes of total fat, protein, carbohydrate, and alcohol intake or anthropometric measures between groups. Plasma phospholipid FA composition showed changes from baseline in the proportions of total SFA, MUFA, and n-6 PUFA for each diet group, with significant overall diet effects for total SFA and MUFA between groups (P < 0.001). In conclusion, successful implementation of the food-exchange model broadly achieved the dietary target intakes for the exchange of SFA with MUFA or n-6 PUFA with minimal disruption to the overall diet in a free-living population. This trial was registered at clinicaltrials.gov as NCT01478958.

Dairy and cardiovascular health: friend or foe?

Cardiovascular disease (CVD) prevalence at a global level is predicted to increase substantially over the next decade due to the increasing ageing population and incidence of obesity. Hence, there is an urgent requirement to focus on modifiable contributors to CVD risk, including a high dietary intake of saturated fatty acids (SFA). As an important source of SFA in the UK diet, milk and dairy products are often targeted for SFA reduction. The current paper acknowledges that milk is a complex food and that simply focusing on the link between SFA and CVD risk overlooks the other beneficial nutrients of dairy foods. The body of existing prospective evidence exploring the impact of milk and dairy consumption on risk factors for CVD is reviewed. The current paper highlights that high milk consumption may be beneficial to cardiovascular health, while illustrating that the evidence is less clear for cheese and butter intake. The option of manipulating the fatty acid profile of ruminant milk is discussed as a potential dietary strategy for lowering SFA intake at a population level. The review highlights that there is a necessity to perform more well-controlled human intervention-based research that provides a more holistic evaluation of fat-reduced and fat-modified dairy consumption on CVD risk factors including vascular function, arterial stiffness, postprandial lipaemia and markers of inflammation. Additionally, further research is required to investigate the impact of different dairy products and the effect of the specific food matrix on CVD development.

Long-term drift of the coronal source magnetic flux and the total solar irradiance

We test the method of Lockwood et al. [1999] for deriving the coronal source flux from the geomagnetic aa index and show it to be accurate to within 12% for annual means and 4.5% for averages over a sunspot cycle. Using data from four solar constant monitors during 1981-1995, we find a linear relationship between this magnetic flux and the total solar irradiance. From this correlation, we show that the 131% rise in the mean coronal source field over the interval 1901-1995 corresponds to a rise in the average total solar irradiance of {\Delta}I = 1.65 +/- 0.23 Wm^{-2}.

Auroral bright spot sequence near 1400 MLT: Coordinated optical and ion drift observations

Optical observations of a dayside auroral brightening sequence, by means of all-sky TV cameras and meridian scanning photometers, have been combined with EISCAT ion drift observations within the same invariant latitude-MLT sector. The observations were made during a January 1989 campaign by utilizing the high F region ion densities during the maximum phase of the solar cycle. The characteristic intermittent optical events, covering ∼300 km in east-west extent, move eastward (antisunward) along the poleward boundary of the persistent background aurora at velocities of ∼1.5 km s−1 and are associated with ion flows which swing from eastward to westward, with a subsequent return to eastward, during the interval of a few minutes when there is enhanced auroral emission within the radar field of view. The breakup of discrete auroral forms occurs at the reversal (negative potential) that forms between eastward plasma flow, maximizing near the persistent arc poleward boundary, and strong transient westward flow to the south. The reported events, covering a 35 min interval around 1400 MLT, are embedded within a longer period of similar auroral activity between 0830 (1200 MLT) and 1300 UT (1600 MLT). These observations are discussed in relation to recent models of boundary layer plasma dynamics and the associated magnetosphere-ionosphere coupling. The ionospheric events may correspond to large-scale wave like motions of the low-latitude boundary layer (LLBL)/plasma sheet (PS) boundary. On the basis of this interpretation the observed spot size, speed and repetition period (∼10 min) give a wavelength (the distance between spots) of ∼900 km in the present case. The events can also be explained as ionospheric signatures of newly opened flux tubes associated with reconnection bursts at the magnetopause near 1400 MLT. We also discuss these data in relation to random, patchy reconnection (as has recently been invoked to explain the presence of the sheathlike plasma on closed field lines in the LLBL). In view of the lack of IMF data, and the existing uncertainty on the location of the open-closed field line boundary relative to the optical events, an unambiguous discrimination between the different alternatives is not easily obtained.

Orange juice–derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease

Background: Epidemiological data suggest inverse associations between citrus flavanone intake and cardiovascular disease (CVD) risk. However, insufficient randomized controlled trial (RCT) data limit our understanding of mechanisms by which flavanones and their metabolites potentially reduce cardiovascular (CV) risk factors. Objective: We examined the effects of orange juice or a dose-matched hesperidin supplement on plasma concentrations of established and novel flavanone metabolites and their effects on CV risk biomarkers in men at moderate CVD risk. Methods: In an acute, randomized, placebo-controlled crossover trial, 16 fasted participants (aged 51-69 y) received orange juice or a hesperidin supplement (both providing 320 mg hesperidin) or control (all matched for sugar and vitamin C content). At baseline and 5 h post-intake, endothelial function (primary outcome), further CV risk biomarkers (i.e. blood pressure, arterial stiffness, cardiac autonomic function, platelet activation and NADPH oxidase gene expression) and plasma flavanone metabolites were assessed. Prior to each intervention, a diet low in flavonoids, nitrate/nitrite, alcohol and caffeine was followed and a standardized low-flavonoid evening meal was consumed. Results: Orange juice intake significantly elevated mean (± SEM) plasma concentrations of 8 flavanone (1.75 ± 0.35 µmol/L, P < 0.0001) and 15 phenolic metabolites (13.27 ± 2.22 µmol/L, P < 0.0001) compared with control at 5 h post-consumption. Despite increased plasma flavanone and phenolic metabolite concentrations, CV risk biomarkers were unaltered. Following hesperidin supplement intake, flavanone metabolites were not different to control, suggesting altered absorption/metabolism compared with the orange juice matrix. Conclusions: Following single-dose flavanone intake within orange juice, we detected circulating flavanone and phenolic metabolites collectively reaching a concentration of 15.20 ± 2.15 µmol/L but observed no effect on CV risk biomarkers. Longer-duration RCTs are required to further examine the previous associations between higher flavanone intakes and improved cardiovascular health and to ascertain the relative importance of food matrix and flavanone-derived phenolic metabolites.

Apples and cardiovascular health: is the gut microbiota a core consideration?

There is now considerable scientific evidence that a diet rich in fruits and vegetables can improve human health and protect against chronic diseases. However, it is not clear whether different fruits and vegetables have distinct beneficial effects. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fiber. A major proportion of the bioactive components in apples, including the high molecular weight polyphenols, escape absorption in the upper gastrointestinal tract and reach the large intestine relatively intact. There, they can be converted by the colonic microbiota to bioavailable and biologically active compounds with systemic effects, in addition to modulating microbial composition. Epidemiological studies have identified associations between frequent apple consumption and reduced risk of chronic diseases such as cardiovascular disease. Human and animal intervention studies demonstrate beneficial effects on lipid metabolism, vascular function and inflammation but only a few studies have attempted to link these mechanistically with the gut microbiota. This review will focus on the reciprocal interaction between apple components and the gut microbiota, the potential link to cardiovascular health and the possible mechanisms of action.

Fast adaptive real-time classification for data streams with concept drift

An important application of Big Data Analytics is the real-time analysis of streaming data. Streaming data imposes unique challenges to data mining algorithms, such as concept drifts, the need to analyse the data on the fly due to unbounded data streams and scalable algorithms due to potentially high throughput of data. Real-time classification algorithms that are adaptive to concept drifts and fast exist, however, most approaches are not naturally parallel and are thus limited in their scalability. This paper presents work on the Micro-Cluster Nearest Neighbour (MC-NN) classifier. MC-NN is based on an adaptive statistical data summary based on Micro-Clusters. MC-NN is very fast and adaptive to concept drift whilst maintaining the parallel properties of the base KNN classifier. Also MC-NN is competitive compared with existing data stream classifiers in terms of accuracy and speed.

Three dimensional analysis of cardiovascular development in mouse embryos using X-ray microcomputed tomography

Micro-computed tomography (μCT) has been successfully used to study the cardiovascular system of mouse embryos in situ. With the use of barium as a suitable contrast agent, blood vessels have been imaged and analysed quantitatively such as blood volume and vessel sizes on embryos of ages 14.5 to 16.5 days old. The advantage of using this imaging modality is that it has provided three dimensional information whilst leaving samples intact for further study.

Drift from the use of handheld knapsack pesticide sprayers in Boyacá (Colombian Andes)

Offsite pesticide losses in tropical mountainous regions have been little studied. One example is measuring pesticide drift soil deposition, which can support pesticide risk assessment for surface water, soil, bystanders, off target plants and fauna. This is considered a serious gap, given the evidence of pesticide-related poisoning in those regions. Empirical data of drift deposition of a pesticide surrogate, Uranine tracer, within one of the highest potato producing regions in Colombia, characterized by small plots and mountain orography, is presented. High drift values encountered in our study reflect the actual spray conditions using handled knapsack sprayers. Comparison between measured and predicted drift values using three existing empirical equations showed important underestimation. However, after their optimization based on measured drift information, the equations showed a strong predictive power for this study area and the study conditions. The most suitable curve to assess mean relative drift was the IMAG calculator after optimization.

Plenary Lecture 2: Milk and dairy produce and CVD: new perspectives on dairy and cardiovascular health

Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity worldwide. One of the key dietary recommendations for CVD prevention is reduction of saturated fat intake. Yet despite milk and dairy foods contributing on average 27 % of saturated fat intake in the UK diet, evidence from prospective cohort studies does not support a detrimental effect of milk and dairy foods on risk of CVD. This paper provides a brief overview of the role of milk and dairy products in the diets of UK adults, and will summarise the evidence in relation to the effects of milk and dairy consumption on CVD risk factors and mortality. The majority of prospective studies and meta-analyses examining the relationship between milk and dairy product consumption and risk of CVD show that milk and dairy products, excluding butter, are not associated with detrimental effects on CVD mortality or risk biomarkers, that include serum LDL cholesterol. In addition, there is increasing evidence that milk and dairy products are associated with lower blood pressure and arterial stiffness. These apparent benefits of milk and dairy foods have been attributed to their unique nutritional composition, and suggest that the elimination of milk and dairy may not be the optimum strategy for CVD risk reduction.