Flavonoid intake is associated with lower mortality in the Danish Diet Cancer and Health Cohort

Flavonoids, plant-derived polyphenolic compounds, have been linked with health benefits. However, evidence from observational studies is incomplete; studies on cancer mortality are scarce and moderating effects of lifestyle risk factors for early mortality are unknown. In this prospective cohort study including 56,048 participants of the Danish Diet, Cancer, and Health cohort crosslinked with Danish nationwide registries and followed for 23 years, there are 14,083 deaths. A moderate habitual intake of flavonoids is inversely associated with all-cause, cardiovascular- and cancer-related mortality. This strong association plateaus at intakes of approximately 500 mg/day. Furthermore, the inverse associations between total flavonoid intake and mortality outcomes are stronger and more linear in smokers than in non-smokers, as well as in heavy (\u3e20 g/d) vs. low-moderate (/d) alcohol consumers. These findings highlight the potential to reduce mortality through recommendations to increase intakes of flavonoid-rich foods, particularly in smokers and high alcohol consumers

Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic syndrome: baseline and post intervention effects

<p>Abstract</p> <p>Background</p> <p>Strawberry flavonoids are potent antioxidants and anti-inflammatory agents that have been shown to reduce cardiovascular disease risk factors in prospective cohort studies. Effects of strawberry supplementation on metabolic risk factors have not been studied in obese populations. We tested the hypothesis that freeze-dried strawberry powder (FSP) will lower fasting lipids and biomarkers of oxidative stress and inflammation at four weeks compared to baseline. We also tested the tolerability and safety of FSP in subjects with metabolic syndrome. FSP is a concentrated source of polyphenolic flavonoids, fiber and phytosterols.</p> <p>Methods</p> <p>Females (n = 16) with 3 features of metabolic syndrome (waist circumference >35 inches, triglycerides > 150 mg/dL, fasting glucose > 100 mg/dL and < 126 mg/dL, HDL <50 mg/dL, or blood pressure >130/85 mm Hg) were enrolled in the study. Subjects consumed two cups of the strawberry drink daily for four weeks. Each cup had 25 g FSP blended in water. Fasting blood draws, anthropometrics, dietary analyses, and blood pressure measurements were done at baseline and 4 weeks. Biomarkers of oxidative stress and inflammation were measured using ELISA techniques. Plasma ellagic acid was measured using HPLC-UV techniques.</p> <p>Results</p> <p>Total cholesterol and LDL-cholesterol levels were significantly lower at 4 weeks versus baseline (-5% and -6%, respectively, p < 0.05), as was lipid peroxidation in the form of malondialdehyde and hydroxynonenal (-14%, p < 0.01). Oxidized-LDL showed a decreasing trend at 4 weeks (p = 0.123). No effects were noted on markers of inflammation including C-reactive protein and adiponectin. A significant number of subjects (13/16) showed an increase in plasma ellagic acid at four weeks versus baseline, while no significant differences were noted in dietary intakes at four weeks versus baseline. Thus, short-term supplementation of freeze-dried strawberries appeared to exert hypocholesterolemic effects and decrease lipid peroxidation in women with metabolic syndrome.</p

Twin births, sex of children and maternal risk of ovarian cancer: a cohort study in Norway

In a follow-up of 1 208 001 women aged 20–74 years, no significant association was found between twin births (112 cases) and risk, though those with twin girls had a non-significantly higher risk than those with singleton births; among the latter, those with girls only had a higher risk of endometrioid tumours (incidence rate ratio 1.35; 95% confidence interval 1.03–1.76, based on 475 cases) than women with boys only

The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette Syndrome: How Does It Work?

Tourette Syndrome (TS) is a neuropsychiatric disease characterized by a combination of motor and vocal tics. Deep brain stimulation (DBS), already widely utilized for Parkinson's disease and other movement disorders, is an emerging therapy for select and severe cases of TS that are resistant to medication and behavioral therapy. Over the last two decades, DBS has been used experimentally to manage severe TS cases. The results of case reports and small case series have been variable but in general positive. The reported interventions have, however, been variable, and there remain non-standardized selection criteria, various brain targets, differences in hardware, as well as variability in the programming parameters utilized. DBS centers perform only a handful of TS DBS cases each year, making large-scale outcomes difficult to study and to interpret. These limitations, coupled with the variable effect of surgery, and the overall small numbers of TS patients with DBS worldwide, have delayed regulatory agency approval (e.g., FDA and equivalent agencies around the world). The Tourette Association of America, in response to the worldwide need for a more organized and collaborative effort, launched an international TS DBS registry and database. The main goal of the project has been to share data, uncover best practices, improve outcomes, and to provide critical information to regulatory agencies. The international registry and database has improved the communication and collaboration among TS DBS centers worldwide. In this paper we will review some of the key operation details for the international TS DBS database and registry

Impact of fermentation, drying, roasting and Dutch processing on flavan-3-ol stereochemistry in cacao beans and cocoa ingredients

This paper reports a systematic study of the level of flavan-3-ol monomers during typical processing steps as cacao beans are dried, fermented and roasted and the results of Dutch-processing. Methods have been used that resolve the stereoisomers of epicatechin and catechin. In beans harvested from unripe and ripe cacao pods, we find only (-)-epicatechin and (+)-catechin with (-)-epicatechin being by far the predominant isomer. When beans are fermented there is a large loss of both (-)-epicatechin and (+)-catechin, but also the formation of (-)-catechin. We hypothesize that the heat of fermentation may, in part, be responsible for the formation of this enantiomer. When beans are progressively roasted at conditions described as low, medium and high roast conditions, there is a progressive loss of (-)-epicatechin and (+)-catechin and an increase in (-)-catechin with the higher roast levels. When natural and Dutch-processed cacao powders are analyzed, there is progressive loss of both (-)-epicatechin and (+)-catechin with lesser losses of (-)-catechin. We thus observe that in even lightly Dutch-processed powder, the level of (-)-catechin exceeds the level of (-)-epicatechin. The results indicate that much of the increase in the level of (-)-catechin observed during various processing steps may be the result of heat-related epimerization from (-)-epicatechin. These results are discussed with reference to the reported preferred order of absorption of (-)-epicatechin > (+)-catechin > (-)-catechin. These results are also discussed with respect to the balance that must be struck between the beneficial impact of fermentation and roasting on chocolate flavor and the healthful benefits of chocolate and cocoa powder that result in part from the flavan-3-ol monomers

Age adjustment in ecological studies: using a study on arsenic ingestion and bladder cancer as an example

<p>Abstract</p> <p>Background</p> <p>Despite its limitations, ecological study design is widely applied in epidemiology. In most cases, adjustment for age is necessary, but different methods may lead to different conclusions. To compare three methods of age adjustment, a study on the associations between arsenic in drinking water and incidence of bladder cancer in 243 townships in Taiwan was used as an example.</p> <p>Methods</p> <p>A total of 3068 cases of bladder cancer, including 2276 men and 792 women, were identified during a ten-year study period in the study townships. Three methods were applied to analyze the same data set on the ten-year study period. The first (Direct Method) applied direct standardization to obtain standardized incidence rate and then used it as the dependent variable in the regression analysis. The second (Indirect Method) applied indirect standardization to obtain standardized incidence ratio and then used it as the dependent variable in the regression analysis instead. The third (Variable Method) used proportions of residents in different age groups as a part of the independent variables in the multiple regression models.</p> <p>Results</p> <p>All three methods showed a statistically significant positive association between arsenic exposure above 0.64 mg/L and incidence of bladder cancer in men and women, but different results were observed for the other exposure categories. In addition, the risk estimates obtained by different methods for the same exposure category were all different.</p> <p>Conclusions</p> <p>Using an empirical example, the current study confirmed the argument made by other researchers previously that whereas the three different methods of age adjustment may lead to different conclusions, only the third approach can obtain unbiased estimates of the risks. The third method can also generate estimates of the risk associated with each age group, but the other two are unable to evaluate the effects of age directly.</p

Regioselective synthesis of plant (iso)flavone glycosides in Escherichia coli

The flavonoids genistein, biochanin A, luteolin, quercetin, and kaempferol are plant natural products with potentially useful pharmacological and nutraceutical activities. These natural products usually exist in plants as glycosides, and their glycosylation has a remarkable influence on their pharmacokinetic properties. The glycosyltransferases UGT71G1 and UGT73C8 from Medicago truncatula are excellent reagents for the regioselective glycosylation of (iso)flavonoids in Escherichia coli grown in Terrific broth. Ten to 20 mg/L of either genistein or biochanin A 7-O-glucoside was produced after feeding genistein or biochanin A to E. coli expressing UGT71G1, and similar levels of luteolin 4’-O- and 7-O-glucosides were produced after feeding luteolin to cultures expressing UGT73C8. For the production of kaempferol 3-O-glucoside or quercetin 3-O-glucoside, the Phe148Val or Tyr202Ala mutants of UGT71G1 were employed. Ten to 16 mg/L of either kaempferol 3-O- or quercetin 3-O-glucosides were produced on feeding kaempferol or quercetin to E. coli expressing these enzymes. More than 90% of the glucoside products were released to the medium, facilitating their isolation

Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution

It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution