Endocrine disrupting effects of zearalenone, alpha- and beta-zearalenol at the level of nuclear receptor binding and steroidogenesis.

The mycotoxin zearalenone (ZEN) is a secondary metabolite of fungi which is produced by certain species of the genus Fusarium and can occur in cereals and other plant products. Reporter gene assays incorporating natural steroid receptors and the H295R steroidogenesis assay have been implemented to assess the endocrine disrupting activity of ZEN and its metabolites -zearalenol (-ZOL) and -zearalenol (-ZOL). -ZOL exhibited the strongest estrogenic potency (EC50 0.022 ± 0.001 nM), slightly less potent than 17- estradiol (EC50 0.015 ± 0.002 nM). ZEN was ~70 times less potent than -ZOL and twice as potent as -ZOL. Binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of ZEN, -ZOL or -ZOL. ZEN, -ZOL or -ZOL increased production of progesterone, estradiol, testosterone and cortisol hormones in the H295R steroidogenesis assay, with peak productions at 10 M. At 100 M, cell viability decreased and levels of hormones were significantly reduced except for progesterone. -ZOL increased estradiol concentrations more than -ZOL or ZEN, with a maximum effect at 10 M, with -ZOL (562 ± 59 pg/ml) > -ZOL (494 ± 60 pg/ml) > ZEN (375 ± 43 pg/ml). The results indicate that ZEN and its metabolites can act as potential endocrine disruptors at the level of nuclear receptor signalling and by altering hormone production.

Relative quantification of the proteomeic changes associated with the mycotoxin zearalenone in the H295R steroidogenesis model

Zearalenone (ZEN) is a mycotoxin with endocrine disrupting effects having vast economic implications in e.g. pig farming. Structurally, ZEN resembles 17b-estradiol, and thus is able to bind to estrogen receptors (ER) in target cells. Because of this, it is also classified as a non-steroidal estrogen, a phytoestrogen, a mycoestrogen, and a growth promoter. Quantitative proteomic analysis was undertaken using stable-isotope labeling by amino acids in cell culture (SILAC) upon exposure of the steroidogenesis cell model H295R with ZEN to elucidate its effect on protein regulation. ZEN significantly regulated 21 proteins, including proteins with known endocrine disrupting effects and several oncogenes. In addition, network analysis using Ingenuity Pathway Analysis showed that ZEN affected the oxidative phosphorylation pathway and the mitochondrial dysfunction pathway, both previously reported to be involved in endocrine dysfunction.

Effect of fruit and vegetable intake on oxidative stress and inflammation in COPD: a randomised controlled trial

Epidemiological evidence supports a positive relationship between fruit and vegetable (FV) intake, lung function and chronic obstructive pulmonary disease (COPD). Increasing FV intake may attenuate the oxidative stress and inflammation associated with COPD.

An exploratory randomised controlled trial to examine the effect of increased consumption of FV on oxidative stress and inflammation in moderate-to-severe COPD was conducted. 81 symptomatically stable patients with a habitually low FV intake (two or fewer portions of FV per day) were randomised to the intervention group (five or more portions of FV per day) or the control group (two or fewer portions of FV per day). Each participant received self-selected weekly home deliveries of FV for 12 weeks.

75 participants completed the intervention. There was a significant between-group change in self-reported FV intake and biomarkers of FV intake (zeaxanthin (p=0.034) and ß-cryptoxanthin (p=0.015)), indicating good compliance; post-intervention intakes in intervention and control groups were 6.1 and 1.9 portions of FV per day, respectively. There were no significant changes in biomarkers of airway inflammation (interleukin-8 and myeloperoxidase) and systemic inflammation (C-reactive protein) or airway and systemic oxidative stress (8-isoprostane).

This exploratory study demonstrated that patients with moderate-to-severe COPD were able to comply with an intervention to increase FV intake; however, this had no significant effect on airway or systemic oxidative stress and inflammation.

A new model based approach for the prediction and optimisation of thermal homogeneity in single screw extrusion

In polymer extrusion, delivery of a melt which is homogenous in composition and temperature is important for good product quality. However, the process is inherently prone to temperature fluctuations which are difficult to monitor and control via single point based conventional thermo- couples. In this work, the die melt temperature profile was monitored by a thermocouple mesh and the data obtained was used to generate a model to predict the die melt temperature profile. A novel nonlinear model was then proposed which was demonstrated to be in good agreement with training and unseen data. Furthermore, the proposed model was used to select optimum process settings to achieve the desired average melt temperature across the die while improving the temperature homogeneity. The simulation results indicate a reduction in melt temperature variations of up to 60%.

PROTONATED HCN IN MOLECULAR CLOUDS

Observations of protonated HCN (HCNH+) in a selection of galactic molecular clouds are reported. This species plays a key role in understanding the chemistry of the important high density tracer HCN. HCNH+ has been detected in the nearby cold dust cloud TMC-1 with an ratio relative to HCN of [HCNH+]/[HCN] between 0.015 and 0.26 (preferred value 0.03) and tentatively in DR21(OH) with a ratio of approximately 0.01. This is about 100 times higher than the ratio of protonated carbon monoxide to CO [HCO+]/[CO], but comparable to the [HCS+]/[CS] ratio. Possible explanations of these high abundance ratios are discussed in the light of model calculations.

The effects of ownership, staffing level and organisational justice on nurse commitment, involvement, and satisfaction: A questionnaire study

Background: Elderly care systems have undergone a lot of changes in many European countries, including Finland. Most notably, the number of private for-profit firms has increased. Previous studies suggest that employee well-being and the quality of care might differ according to the ownership type.

Residential consumption of gas and electricity in the U.S.: The role of prices and income

We study the residential demand for electricity and gas, working with nationwide household-level data that cover recent years, namely 1997-2007. Our dataset is a mixed panel/multi-year cross-sections of dwellings/households in the 50 largest metropolitan areas in the United States as of 2008. We estimate static and dynamic models of electricity and gas demand. We find strong household response to energy prices, both in the short and long term. From the static models, we get estimates of the own price elasticity of electricity demand in the -0.860 to -0.667 range, while the own price elasticity of gas demand is -0.693 to -0.566. These results are robust to a variety of checks. Contrary to earlier literature (Metcalf and Hassett, 1999; Reiss and White, 2005), we find no evidence of significantly different elasticities across households with electric and gas heat. The price elasticity of electricity demand declines with income, but the magnitude of this effect is small. These results are in sharp contrast to much of the literature on residential energy consumption in the United States, and with the figures used in current government agency practice. Our results suggest that there might be greater potential for policies which affect energy price than may have been previously appreciated. (C) 2011 Elsevier B.V. All rights reserved.

Hydrothermal synthesis and characterization of ZSM-5 coatings on a molybdenum support and scale-up for application in micro reactors

A procedure has been developed to grow ZSM-5 crystals in situ on a molybdenum (Mo) support. The high heat conductivity (138 W/mK) and high mechanical stability at elevated temperatures of the Mo support allow the application of ZSM-5 coatings in micro reactors for high temperature processes involving large heat effects. The effect of the synthesis mixture composition on ZSM-5 coverage and on the uniformity of the ZSNI-5 coatings was investigated on plates of 10 X 10 mm(2). Ratios of H2O/Si = 50, SUAI = 25, and TPA/Al = 2.0 were found to be optimal for the formation of uniform coatings of 6 g/m(2) at a temperature of 150 degrees C and a synthesis time of 48 h. Scaling up of the synthesis procedure on 72 Mo plates of 40 x 9.8 x 0.1 mm 3 resulted in a uniform coverage of 14.8 +/- 0.4 g/m(2). The low deviation per individual plate (

Effect of alkali on methylene blue (CI Basic Blue 9) and other thiazine dyes

A detailed study of the action of alkali on methylene blue (Cl. Basic Blue 9) and other thiazine dyes was carried out through a combination of UV/visible spectroscopy, thin layer chromatography, mass and NMR spectrometry and computational methods. In 0.1 M aq alkali solution, methylene blue forms a highly coloured, lipophilic species that is mainly Bernthsen's methylene violet i.e. a hydrolysis decomposition product, this being contrary to the report of a red N-hydroxy methylene blue adduct. The nature of the heterocyclic nitrogen atom in C.I. Basic Blue 9 is discussed and it is concluded there is no basis for the proposal of nucleophile addition at this site of the dye. In contrast, other thiazine dyes are deprotonated by alkali to form their neutral, highly coloured, lipophilic conjugate base forms. (C) 2010 Elsevier Ltd. All rights reserved.

Nuclear activation as a high dynamic range diagnostic of laser-plasma interactions

Proton imaging has become a common diagnostic technique for use in laser-plasma research experiments due to their ability to diagnose electric field effects and to resolve small density differences caused through shock effects. These interactions are highly dependent on the use of radiochromic film (RCF) as a detection system for the particle probe, and produces very high-resolution images. However, saturation effects, and in many cases, damage to the film limits the usefulness of this technique for high-flux particle probing. This paper outlines the use of a new technique using contact radiography of (p,n)-generated isotopes in activation samples to produce high dynamic range 2D images with high spatial resolution and extremely high dynamic range, whilst maintaining both energy resolution and absolute flux measurements. (C)007 Elsevier B.V. All rights reserved.

Measurements of the hole boring velocity from Doppler shifted harmonic emission from solid targets

The fast ignitor scheme for inertial confinement fusion requires forward driving of the critical density surface by light pressure (hole boring) to allow energy deposition close to the dense fuel. The recession velocity of the critical density surface has been observed to be nu/c = 0.015 at an irradiance of 1.0 x 10(19) W cm(-2) at a wavelength of 1.05 micron, in quantitative agreement with modeling. (C) 1996 American Institute of Physics.

Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration: One-Year Findings from the IVAN Randomized Trial.

Purpose
To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD).

Design
Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560).

Participants
People >50 years of age with untreated nAMD in the study eye who read =25 letters on the Early Treatment Diabetic Retinopathy Study chart.

Methods
We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review.

Main Outcome Measures
The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs.

Results
Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001).

Conclusions
The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety.

Financial Disclosure(s)
Proprietary or commercial disclosures may be found after the references.

Lycopene intervention reduces inflammation and improves HDL functionality in moderately overweight middle-aged individuals

The management of overweight subjects by interventions aimed at reducing inflammation is highly desirable. To date, observational studies have identified a link between increased dietary antioxidant intake and reduced cardiovascular morbidity. However, direct trial evidence regarding the ability of antioxidants to influence inflammation is lacking. Therefore, this study examined lycopene's ability to lower systemic and high-density lipoprotein (HDL)-associated inflammation in moderately overweight middle-aged subjects. Serum was collected before and after a 12-week intervention from 54 moderately overweight, middle-aged individuals. Subjects were randomised to one of three groups: control diet (