The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure

Background

The primary aim of this study was to test the hypothesis that an orally ingested apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers improves endothelium-dependent brachial artery flow-mediated vasodilatation (FMD) in volunteers with borderline hypertension. The secondary aim of the study was to test whether the investigational product would improve endothelium-independent nitrate-mediated vasodilatation (NMD).

Methods

This was a single centre, repeated-dose, double-blind, placebo-controlled, crossover study in 60 otherwise healthy subjects (26 men, 34 women; aged 40-65 years) with borderline hypertension (blood pressure 130-139/85-89 mmHg) or unmedicated mild hypertension (blood pressure 140-165/90-95 mmHg). The subjects were randomised to receive placebo or the apple polyphenol extract to provide a daily dose of 100 mg epicatechin for 4 weeks, followed by a four to five-week wash-out period, and then 4 weeks intake of the product that they did not receive during the first treatment period. FMD and NMD of the left brachial artery were investigated with ultrasonography at the start and end of both treatment periods, and the per cent increase of the arterial diameter (FMD% and NMD%) was calculated.

Results

With the apple extract treatment, a significant acute improvement was detected in the mean change of maximum FMD% at the first visit 1.16 (p = 0.04, 95% CI: 0.04; 2.28), last visit 1.37 (p = 0.02, 95% CI: 0.22; 2.52) and for both visits combined 1.29 (p < 0.01, 95% CI: 0.40; 2.18). However, such improvement was not statistically significant when apple extract was compared with placebo. The overall long-term effect of apple extract on FMD% was not different from placebo. No statistically significant differences between the apple extract and placebo treatments were observed for endothelium-independent NMD.

Conclusions

A significant acute improvement in maximum FMD% with apple extract administration was found. However, superiority of apple extract over placebo was not statistically significant in our study subjects with borderline hypertension or mild hypertension. The study raised no safety concerns regarding the daily administration of an apple polyphenol extract rich in epicatechin.

Trial registration

The trial is registered at http://clinicaltrials.gov (identifier: NCT01690676). Registered 25th May 2012.

     

Structural and Functional Support by Left Atrial Appendage Transplant to the Left Ventricle after a Myocardial Infarction

The left atrial appendage (LAA) of the adult heart has been shown to contain cardiac and myeloid progenitor cells. The resident myeloid progenitor population expresses an array of pro-regenerative paracrine factors. Cardiac constructs have been shown to inhibit deleterious remodeling of the heart using physical support. Due to these aspects, LAA holds promise as a regenerative transplant. LAAs from adult mT/mG mice were transplanted to the recipient 129X1-SvJ mice simultaneously as myocardial infarction (MI) was performed. A decellularized LAA patch was implanted in the control group. Two weeks after MI, the LAA patch had integrated to the ventricular wall, and migrated cells were seen in the MI area. The cells had two main phenotypes: small F4/80+ cells and large troponin C+ cells. After follow-up at 8 weeks, the LAA patch remained viable, and the functional status of the heart improved. Cardiac echo demonstrated that, after 6 weeks, the mice in the LAA-patch-treated group showed an increasing and statistically significant improvement in cardiac performance when compared to the MI and MI + decellularized patch controls. Physical patch-support (LAA and decellularized LAA patch) had an equal effect on the inhibition of deleterious remodeling, but only the LAA patch inhibited the hypertrophic response. Our study demonstrates that the LAA transplantation has the potential for use as a treatment for myocardial infarction. This method can putatively combine cell therapy (regenerative effect) and physical support (inhibition of deleterious remodeling).     

Sleeping problems and health behaviors as mediators between organizational justice and health.

The aim of this longitudinal cohort study was to investigate whether sleeping problems and health behaviors (smoking, alcohol consumption, and sedentary lifestyle) mediate the association between organizational justice and employee health. Health indicators were minor psychiatric morbidity, as assessed by the General Health Questionnaire (U. Werneke, D. P. Goldberg, 1. Yalcin, & B. T. Ustun, 2000), and poor self-rated health status. The results of logistic regression analysis of data for 416 male and 3,357 female hospital employees working during the 1998-2000 period in 10 Finnish hospitals suggest that sleeping problems are one of the underlying factors causing the adverse health effects of low organizational justice at work. No support for a mediating role of health behaviors between low organizational justice and health problems was obtained. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Oxidative modification of a proline-rich gliadin peptide

Prolamins are proline-rich proteins occurring in cereal grains. Prolamins of wheat, barley and rye, or gluten protein, can cause coeliac disease in individuals not tolerating gluten. Degrading harmful prolamins can reduce their toxicity. A model peptide sequenced in α-gliadin, 33-mer (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF), was chosen for our study. The metal-catalysed oxidation of 33-mer was studied, instead of enzymatic hydrolysis. Peptide 33-mer was treated in several oxidative systems. Iron-catalysed hydrogen peroxide-induced oxidation showed the greatest modification of 33-mer. Carbonyl groups and dityrosine cross-links were readily formed. At best, the immunological activity of 33-mer was reduced to 18% of its initial level after 24 h of oxidation. Oxidative treatment can be further applied for the modification of cereal prolamin proteins, since it appears to be a potential alternative for reduction of coeliac immunological activities in gluten proteins.     

Design and application of a generic clinical decision support system for multiscale data

Medical research and clinical practice are currently being redefined by the constantly increasing amounts of multiscale patient data. New methods are needed to translate them into knowledge that is applicable in healthcare. Multiscale modeling has emerged as a way to describe systems that are the source of experimental data. Usually, a multiscale model is built by combining distinct models of several scales, integrating, e.g., genetic, molecular, structural, and neuropsychological models into a composite representation. We present a novel generic clinical decision support system, which models a patient's disease state statistically from heterogeneous multiscale data. Its goal is to aid in diagnostic work by analyzing all available patient data and highlighting the relevant information to the clinician. The system is evaluated by applying it to several medical datasets and demonstrated by implementing a novel clinical decision support tool for early prediction of Alzheimer's disease.     

Defined-size DNA triple crossover construct for molecular electronics: modification, positioning and conductance properties

We present a novel, defined-size, small and rigid DNA template, a so-called B-A-B complex, based on DNA triple crossover motifs (TX tiles), which can be utilized in molecular scale patterning for nanoelectronics, plasmonics and sensing applications. The feasibility of the designed construct is demonstrated by functionalizing the TX tiles with one biotin-triethylene glycol (TEG) and efficiently decorating them with streptavidin, and furthermore by positioning and anchoring single thiol-modified B-A-B complexes to certain locations on a chip via dielectrophoretic trapping. Finally, we characterize the conductance properties of the non-functionalized construct, first by measuring DC conductivity and second by utilizing AC impedance spectroscopy in order to describe the conductivity mechanism of a single B-A-B complex using a detailed equivalent circuit model. This analysis also reveals further information about the conductivity of DNA structures in general.     

Shear and extensional viscosity of thermally aggregated thermoplastic protein

Novatein is a thermoplastic produced from blood meal and is used in different agricultural applications. Novatein has some unique processing challenges and its rheology was studied using screw-driven capillary rheometry, with a particular focus on sheet extrusion using ethylene glycol, glycerol, propylene glycol (PG), or triethylene glycol (TEG) as plasticizers. The entrance pressure drop contributed up to 44% of the total pressure drop (entrance and capillary pressure drop), but this was significantly reduced by plasticization or increased temperature. Polyol addition led to higher shear viscosities in comparison to no polyol plasticization, most likely due to improved chain mobility resulting in orientation effects. Elongational flow was dominated by primary plasticization of the protein-rich phase and changes in secondary structure, whereas secondary plasticization (phase separation into a polyol-rich phase) played a significant role in the reduction of the shear viscosity. Of the selected plasticizers, PG showed the most efficient plasticization in both shear and elongational flow. When combined with the beneficial secondary structural changes brought about by TEG, the sheet forming ability of Novatein was drastically improved.     

Parental worry about indoor air quality and student symptom reporting in primary schools with or without indoor air quality problems

Poor indoor air quality (IAQ) in schools is related to increased symptom reporting in students. We investigated whether parental worry about school IAQ influences this association. Data came from survey collected from five Finnish primary schools with observed IAQ problems and five control schools. Parents (n = 1868) of primary school students reported worry about IAQ in schools and symptoms of their children. Associations between observed IAQ problems, worry, and five symptom scores (ie, respiratory, lower respiratory, eye, skin, and general symptoms) were analyzed using multivariate logistic regression and mediation analysis. Parents were on average more worried in schools with observed IAQ problems. Observed IAQ problems were strongly associated with increased worry and all symptoms under study (unadjusted ORs ranged between 1.48 [95% CI 1.48‐2.16] and 2.70 [95% CI 1.52‐5.17]). Parental worry was associated with all symptoms (unadjusted ORs ranged between 2.49 [95% CI 1.75‐3.60] and 4.92 [95% CI 2.77‐9.40]). Mediation analyses suggested that parental worry might partially explain the association between observed IAQ problems and symptom reporting (proportion mediated ranged between 67% and 84% for the different symptoms). However, prospective studies are needed to assess causal relationships between observed IAQ problems, worry, and symptom reporting in schools.     

The reliability of component boards studied with different shock impact repetition frequencies

As a result of the ever-shortening time to market of new electronic products there is a clear need to make the currently employed reliability assessment procedures more efficient. However, while trying to achieve these cost savings it is important to pay attention to how much reliability tests can be accelerated without producing misleading lifetime statistics or irrelevant failure modes and mechanisms. Therefore, the primary objective of this work was to clarify the effects of impact repetition frequency on the lifetime and failure mechanisms of electronic component boards. The reliability assessments were conducted with four package types (BGA288, BGA144, QFN72, and μSMD36) with the intention of including different package dimensions and interconnection shapes and sizes in the scope of evaluation. Three shock impact repetition frequencies (0.01 Hz, 0.1 Hz, and 1.6 Hz) were used to study the sensitivity of their lifetime to the time between the shock impacts. The results showed that the impact repetition frequency has a significant effect on the average lifetime of the studied packages: the average number of impacts-to-failure increased with increased impact repetition frequency. A change in the impact repetition frequency did not, however, change the primary failure mode and the failure mechanism. In order to explain this observation, the formation of residual stresses in the solder interconnections from shock impacts and their relaxation during the time between the shock impacts were evaluated by employing FEM, which showed that at room temperature the stress relaxation by creep of solder is significant even at less than 10 s time frame. The effect of the stress relaxation on the lifetime of the component boards was studied experimentally by repeating the impact tests at elevated temperature with the intention of influencing rate of stress relaxation. The results showed that the relaxation of the residual stresses has a significant effect on the component boards shock reliability (at less than 1% risk level). The results presented in this paper indicate that the impact repetition frequency should be taken into account, especially when reliability assessments are being carried out with different testers, since the interval between the shock impacts varies from one test system to another.