Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study

Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: −0.4, −0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752.

Climatology and variability of trace gases in extratropical double-tropopause regions from MLS, HIRDLS, and ACE-FTS measurements

Upper tropospheric and lower stratospheric measurements from the Aura Microwave Limb Sounder (MLS), the Aura High Resolution Dynamics Limb Sounder (HIRDLS), and the Atmospheric Chemistry Experiment-Fourier transform spectrometer (ACE-FTS) are used to present the first global climatological comparison of extratropical, nonpolar trace gas distributions in double-tropopause (DT) and single-tropopause (ST) regions. Stratospheric tracers, O3, HNO3, and HCl, have lower mixing ratios ∼2–8 km above the primary (lowermost) tropopause in DT than in ST regions in all seasons, with maximum Northern Hemisphere (NH) differences near 50% in winter and 30% in summer. Southern Hemisphere winter differences are somewhat smaller, but summer differences are similar in the two hemispheres. H2O in DT regions of both hemispheres shows strong negative anomalies in November through February and positive anomalies in July through October, reflecting the strong seasonal cycle in H2O near the tropical tropopause. CO and other tropospheric tracers examined have higher DT than ST values 2–7 km above the primary tropopause, with the largest differences in winter. Large DT-ST differences extend to high NH latitudes in fall and winter, with longitudinal maxima in regions associated with enhanced wave activity and subtropical jet variations. Results for O3 and HNO3 agree closely between MLS and HIRDLS, and differences from ACE-FTS are consistent with its sparse and irregular midlatitude sampling. Consistent signatures in climatological trace gas fields provide strong evidence that transport from the tropical upper troposphere into the layer between double tropopauses is an important pathway for stratosphere-troposphere exchange.

Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial

There is much speculation with regard to the potential cardioprotective benefits of equol, a microbial-derived metabolite of the isoflavone daidzein, which is produced in the large intestine after soy intake in 30% of Western populations. Although cross-sectional and retrospective data support favorable associations between the equol producer (EP) phenotype and cardiometabolic health, few studies have prospectively recruited EPs to confirm this association. The aim was to determine whether the acute vascular benefits of isoflavones differ according to EP phenotype and subsequently investigate the effect of providing commercially produced S-(–)equol to non-EPs. We prospectively recruited male EPs and non-EPs (n = 14/ group) at moderate cardiovascular risk into a double-blind, placebocontrolled crossover study to examine the acute effects of soy isoflavones (80-mg aglycone equivalents) on arterial stiffness [carotid-femoral pulse-wave velocity (cfPWV)], blood pressure, endothelial function (measured by using the EndoPAT 2000; Itamar Medical), and nitric oxide at baseline (0 h) and 6 and 24 h after intake. In a separate assessment, non-EPs consumed 40 mg S-(–)equol with identical vascular measurements performed 2 h after intake. After soy intake, cfPWV significantly improved in EPs at 24 h (cfPWV change from 0 h: isoflavone, 20.2 6 0.2 m/s; placebo, 0.6 6 0.2 m/s; P , 0.01), which was significantly associated with plasma equol concentrations (R = 20.36, P = 0.01). No vascular effects were observed in EPs at 6 h or in non-EPs at any time point. Similarly, no benefit of commercially produced S-(–)equol was observed in non-EPs despite mean plasma equol concentrations reaching 3.2 mmol/L. Acute soy intake improved cfPWV in EPs, equating to an 11–12% reduced risk of cardiovascular disease if sustained. However, a single dose of commercially produced equol had no cardiovascular benefits in non-EPs. These data suggest that the EP phenotype is critical in unlocking the vascular benefits of equol in men, and long-term trials should focus on confirming the implications of EP phenotype on cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01530893. Am J Clin Nutr doi: 10.3945/ajcn.115.125690.

Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial

The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P < 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

Breaking the double-edged sword of effort/trying hard: developmental equilibrium and Longitudinal relations among effort, achievement, and academic self-concept

Ever since the classic research of Nicholls (1976) and others, effort has been recognized as a double-edged sword: whilst it might enhance achievement, it undermines academic self-concept (ASC). However, there has not been a thorough evaluation of the longitudinal reciprocal effects of effort, ASC and achievement,in the context of modern self-concept theory and statistical methodology. Nor have there been developmental equilibrium tests of whether these effects are consistent across the potentially volatile early-to-middle adolescence. Hence, focusing on mathematics, we evaluate reciprocal effects models over the first four years of secondary school, relating effort, achievement (test scores and school grades), ASC, and ASCxEffort interactions for a representative sample of 3,421 German students (Mn age = 11.75 years at Wave 1). ASC, effort and achievement were positively correlated at each wave, and there was a clear pattern of positive reciprocal positive effects among ASC, test scores and school grades—each contributing to the other, after controlling for the prior effects of all others. There was an asymmetrical pattern of effects for effort that is consistent with the double-edged sword premise: prior school grades had positive effects on subsequent effort, but prior effort had non-significant or negative effects on subsequent grades and ASC. However, on the basis of a synergistic application of new theory and methodology, we predicted and found a significant ASC-by-effort interaction, such that prior effort had more positive effects on subsequent ASC and school grades when prior ASC was high—thus providing a key to breaking the double-edged sword.

Bond Strength of Fiber Posts in Different Root Thirds Using Resin Cement

Purpose: The aim of the study was to assess the in vitro bond strength (BS) of glass fiber posts (GF) and carbon fiber posts (CF) in the cervical, middle, and apical thirds of root canals cemented with RelyX-Unicem (RX) and Cement-Post (CP). Materials and Methods: Forty maxillary canines were divided into 4 groups (n = 10) according to the cement and post used: group 1: GF and RX; group 2: CF and RX; group 3: GF and CP; group 4: CF and CP. The push-out test was applied in the cervical, middle and apical thirds of each specimen to assess bond strength of the cement/post complex to the root canal wall. The data obtained were submitted to ANOVA (Bonferroni test, p < 0.05), and fracture analysis was done with SEM. Results: The GF posts presented the best results when cemented with RX and with CF (p < 0.05). RX presented the highest BS values for both GF and CF (p < 0.05). For all the groups, BS was higher in the cervical third, followed by the middle and apical thirds. Fracture analysis showed a predominance of cohesive fracture of posts for RX, and a predominance of adhesive fracture between dentin/cement, and mixed failure mode for CP. Conclusion: GF posts cemented with RX presented the highest BS values in all root thirds.

The effects of lipoic acid and alpha-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial

Antioxidants probably play an important role in the etiology of type 2 diabetes (DM2). This study evaluated the effects of supplementation with lipoic acid (LA) and alpha-tocopherol on the lipid profile and insulin sensitivity of DM2 patients. A randomized, double-blind, placebo-controlled trial involving 102 DM2 patients divided into four groups to receive daily supplementation for 4 months with: 600 mg LA (n = 26); 800 mg alpha-tocopherol (n = 25); 800 mg alpha-tocopherol + 600 mg LA (n = 25); placebo (n = 26). Plasma alpha-tocopherol, lipid profile, glucose, insulin, and the HOMA index were determined before and after supplementation. Differences within and between groups were compared by ANOVA using Bonferroni correction. Student`s t-test was used to compare means of two independent variables. The vitamin E/total cholesterol ratio improved significantly in patients supplemented with vitamin E + LA and vitamin E alone (p <= 0.001). There were improvements of the lipid fractions in the groups receiving LA and vitamin E alone or in combination, and on the HOMA index in the LA group, but not significant. The results suggest that LA and vitamin E supplementation alone or in combination did not affect the lipid profile or insulin sensitivity of DM2 patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Optimizing the nipple-areola sparing mastectomy with double concentric periareolar incision and biodimensional expander-implant reconstruction: Aesthetic and technical refinements

Although the biodimensional anatomical expander-implant system (BEIS) is a reliable technique, little information has been available regarding outcome following nipple-areola sparing mastectomy (NSM). To perform the resection of glandular tissue, while improving the surgical access and maintaining the nipple-areola vascularization we have developed a new approach for NSM based on the double concentric periareolar incision (DCPI). The purpose of this study is to analyze the feasibility, surgical planning and its outcome following NSM. 18 patients underwent NSM reconstructions. Mean time of follow-up was 29 months. The technique was indicated in patients with small/moderate volume breasts. Flap complications were evaluated and information on aesthetic results and patient satisfaction were collected. 83.3% had tumors measuring 2 cm or less (T1) and 72.1% were stage 0 and 1. All patients presented peripherally tumors located (at least 5 cm from the nipple). Skin complications occurred in 11.1%. One patient (5.5%) presented small skin necrosis and a wound dehiscence was observed in one patient (5.5%). The aesthetic result was good/very good in 94.4 percent and the majority of patients were very satisfied/satisfied. No local recurrences were observed. All complications except one were treated by a conservative approach. DCPI-BEIS is a simple and reliable technique for NSM reconstruction. The success depends on patient selection, coordinated planning with the oncologic surgeon and careful intra-operative and post-operative management. (C) 2009 Elsevier Ltd. All rights reserved.

Fracture and fatigue of natural fiber-reinforced cementitious composites

This paper presents the results of an experimental study of resistance-curve behavior and fatigue crack growth in cementitious matrices reinforced with eco-friendly natural fibers obtained from agricultural by-products. The composites include: blast furnace slag cement reinforced with pulped fibers of sisal, banana and bleached eucalyptus pulp, and ordinary Portland cement composites reinforced with bleached eucalyptus pulp. Fracture resistance (R-curve) and fatigue crack growth behavior were studied using single-edge notched bend specimens. The observed stable crack growth behavior was then related to crack/microstructure interactions that were elucidated via scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Fracture mechanics models were used to quantify the observed crack-tip shielding due to crack-bridging. The implications of the results are also discussed for the design of natural fiber-reinforced composite materials for affordable housing. (C) 2009 Elsevier Ltd. All rights reserved.

CHEMICAL EVOLUTION OF THE GALACTIC BULGE: SINGLE AND DOUBLE INFALL MODELS

Recent work, has produced a wealth of data concerning the chemical evolution of the Galactic bulge, both for stars and nebulae. Present theoretical models generally adopt it limited range of such constraints, frequenfly using it single chemical element (usually iron), which is not enough to describe it unambiguously. In this work, we take into account contraints involving,9 Many chemical elements as possible, basically obtained from bulge nebulae and stars. Our main goal is to show that different scenarios can describe, at least partially the abundance distribution and several dishuice-independent correlations for these objects . Three classes of models were developed. The first is it one-zone, single-infall model, the. Second is it one-zone, double-infall model and the third is a multizone, double-infall model. We show that a one-zone model with it single infall episode is able to reproduce some of the observational data, but the best results tire achieved using it multizone, double-infall model.

ON THE DOUBLE NATURED SOLUTIONS OF THE TWO-TEMPERATURE EXTERNAL SOFT PHOTON COMPTONIZED ACCRETION DISKS

We have analyzed pair production in the innermost region of a two-temperature external soft photon Comptonized accretion disk. We have shown that, if the viscosity parameter is greater than a critical value alpha(c), the solution to the disk equation is double valued: one, advection dominated, and the other, radiation dominated. When alpha <= alpha(c), the accretion rate has to satisfy (m) over dot(1) <= (m) over dot <= (m) over dot(c) in order to have two steady-state solutions. It is shown that these critical parameters (m) over dot(1), (m) over dot(c) are functions of r, alpha, and theta(e), and alpha(c) is a function of r and theta(e). Depending on the combination of the parameters, the advection-dominated solution may not be physically consistent. It is also shown that the electronic temperature is maximum at the onset of the thermal instability, from which results this inner region. These solutions are stable against perturbations in the electron temperature and in the density of pairs.