Contribution of cod liver oil-related nutrients (vitamins A, D, E and eicosapentaenoic acid and docosahexaenoic acid) to daily nutrient intake and their associations with plasma concentrations in the EPIC-Norfolk cohort

Total nutrient intake (TNI) is intake from food and supplements. This provides an assessment of nutrient adequacy and the prevalence of excessive intake, as well as the response with respect to biomarkers. Cod liver oil (CLO) is the most frequently consumed supplement in the UK, containing nutrients that might have varying influences on health. We calculated TNI for vitamins A, D and E, as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and assessed associations with the respective blood concentrations

Strain Specific Responses in a Microbead Rat Model of Experimental Glaucoma

Purpose: A major challenge in glaucoma research is the lack of reproducible animal models of RGC and optic nerve damage, the characteristic features of this condition. We therefore examined the glaucomatous responses of two different rat strains, the Brown Norway (BN) and Lister Hooded (LH) rats, to high intraocular pressure (IOP) induced by injection of magnetic beads into the anterior chamber. Methods: Magnetic microsphere suspensions (20 µl of 5–20 mg/ml) were injected into the anterior chamber of BN (n = 9) or LH (N = 15) rats. Animals from each strain were divided into three groups, each receiving a different dose of microspheres. IOP was measured over 4 weeks using a rebound tonometer. Retinal ganglion cell (RGC) damage and function were assessed using scotopic electroretinograms (ERGs), retinal flatmounts and optic nerve histology. ANOVA and Student’s t-tests were used to analyse the data. Results: A significant elevation in IOP was observed in BN rats receiving injections of 20 mg (37.18 ± 12.28 mmHg) or 10 mg microspheres/ml (36.95 ± 13.63 mmHg) when compared with controls (19.63 ± 4.29 mmHg) (p < .001) over 2 weeks. This correlated with a significant impairment of RGC function, as determined by scotopic ERG (p < .001), reduction in axon number (p < .05) and lower RGC density (P < .05) in animals receiving 20 mg or 10 mg microspheres/ml as compared with controls. LH rats receiving similar microsphere doses showed reduced scotopic ERG function (p < .001) after 2 weeks. No changes in IOP was seen in this strain, although a reduction in axon density was observed in optic nerve cross-sections (p < .05). Initial changes in IOP and ERG responses observed in BN rats remained unchanged for a duration of 7 weeks. In LH animals, ERG responses were decreased at 1–2 weeks and returned to control levels after 5 weeks. Conclusions: Although this model was easily reproducible in BN rats, the phenotype of injury observed in LH rats was very different from that observed in BN animals. We suggest that differences in the glaucomatous response observed in these two strains may be ascribed to anatomical and physiological differences and merits further investigation

muCool: A novel low-energy muon beam for future precision experiments

Experiments with muons ($\mu^{+}$) and muonium atoms ($\mu^{+}e^{-}$) offer several promising possibilities for testing fundamental symmetries. Examples of such experiments include search for muon electric dipole moment, measurement of muon $g-2$ and experiments with muonium from laser spectroscopy to gravity experiments. These experiments require high quality muon beams with small transverse size and high intensity at low energy. At the Paul Scherrer Institute, Switzerland, we are developing a novel device that reduces the phase space of a standard $\mu^{+}$ beam by a factor of $10^{10}$ with $10^{-3}$ efficiency. The phase space compression is achieved by stopping a standard $\mu^{+}$ beam in a cryogenic helium gas. The stopped $\mu^{+}$ are manipulated into a small spot with complex electric and magnetic fields in combination with gas density gradients. From here, the muons are extracted into the vacuum and into a field-free region. Various aspects of this compression scheme have been demonstrated. In this article the current status will be reported.Comment: 8 pages, 5 figures, TCP 2018 conference proceeding

Mixed-Mode Third-Order Quadrature Oscillator Based on Single MCCFTA

This paper presents a new mixed-mode third-order quadrature oscillator based on new modified current-controlled current follower transconductance amplifier (MCCFTA). The proposed circuit employs one MCCFTA as active element and three grounded capacitors as passive component which is highly suitable for integrated circuit implementation. The condition and frequency of oscillations can be controlled orthogonally and electronically by adjusting the bias currents of the active device. The circuit provides four quadrature current outputs and two quadrature voltage outputs into one single topology, which can be classified as mixed-mode oscillator. In addition, four quadrature current output terminals possess high-impedance level which can be directly connected to next stage without additional buffer circuits. The performance of the proposed structure has been verified through PSPICE simulators using 0.25 µm CMOS process from TSMC and experimental results are also investigated

Comparison of proteomic profiles in the zebrafish retina during experimental degeneration and regeneration

Zebrafish spontaneously regenerate the retina after injury. Although the gene expression profile has been extensively studied in this species during regeneration, this does not reflect protein function. To further understand the regenerative process in the zebrafish, we compared the proteomic profile of the retina during injury and upon regeneration. Using two-dimensional difference gel electrophoresis (2D-DIGE) and label-free quantitative proteomics (quadrupole time of flight LC-MS/MS), we analysed the retina of adult longfin wildtype zebrafish at 0, 3 and 18 days after Ouabain injection. Gene ontology analysis indicates reduced metabolic processing, and increase in fibrin clot formation, with significant upregulation of fibrinogen gamma polypeptide, apolipoproteins A-Ib and A-II, galectin-1, and vitellogenin-6 during degeneration when compared to normal retina. In addition, cytoskeleton and membrane transport proteins were considerably altered during regeneration, with the highest fold upregulation observed for tubulin beta 2 A, histone H2B and brain type fatty acid binding protein. Key proteins identified in this study may play an important role in the regeneration of the zebrafish retina and investigations on the potential regulation of these proteins may lead to the design of protocols to promote endogenous regeneration of the mammalian retina following retinal degenerative disease

Sulfate, Nitrate and Blood Pressure - An EPIC Interaction between Sulfur and Nitrogen

Nitrate (NO3−)-rich foods such as green leafy vegetables are not only part of a healthy diet, but increasingly marketed for primary prevention of cardiovascular disease (CVD) and used as ergogenic aids by competitive athletes. While there is abundant evidence for mild hypotensive effects of nitrate on acute application there is limited data on chronic intake in humans, and results from animal studies suggest no long-term benefit. This is important as nitrate can also promote the formation of nitrosamines. It is therefore classified as ‘probably carcinogenic to humans', although a beneficial effect on CVD risk might compensate for an increased cancer risk. Dietary nitrate requires reduction to nitrite (NO2−) by oral commensal bacteria to contribute to the formation of nitric oxide (NO). The extensive crosstalk between NO and hydrogen sulfide (H2S) related metabolites may further affect nitrate’s bioactivity. Using nitrate and nitrite concentrations of drinking water − the only dietary source continuously monitored for which detailed data exist − in conjunction with data of >14,000 participants of the EPIC-Norfolk study, we found no inverse associations with blood pressure or CVD risk. Instead, we found a strong interaction with sulfate (SO42−). At low sulfate concentrations, nitrate was inversely associated with BP (–4 mmHg in top quintile) whereas this was reversed at higher concentrations (+3 mmHg in top quintile). Our findings have a potentially significant impact for pharmacology, physiology and public health, redirecting our attention from the oral microbiome and mouthwash use to interaction with sulfur-containing dietary constituents. These results also indicate that nitrate bioactivation is more complex than hitherto assumed. The modulation of nitrate bioactivity by sulfate may render dietary lifestyle interventions aimed at increasing nitrate intake ineffective and even reverse potential antihypertensive effects, warranting further investigation.This work was supported by grants from the UK Medical Research Council and Cancer Research UK

Muonium emission into vacuum from mesoporous thin films at cryogenic temperatures

We report on Muonium (Mu) emission into vacuum following {\mu}+ implantation in mesoporous thin SiO2 films. We obtain a yield of Mu into vacuum of (38\pm4)% at 250 K temperature and (20\pm4)% at 100 K for 5 keV {\mu}+ implantation energy. From the implantation energy dependence of the Mu vacuum yield we determine the Mu diffusion constants in these films: D250KMu = (1.6 \pm 0.1) \times 10-4 cm2/s and D100KMu = (4.2\pm0.5)\times10-5 cm2/s. Describing the diffusion process as quantum mechanical tunneling from pore-to-pore, we reproduce the measured temperature dependence T^3/2 of the diffusion constant. We extract a potential barrier of (-0.3 \pm 0.1) eV which is consistent with our computed Mu work-function in SiO2 of [-0.3,-0.9] eV. The high Mu vacuum yield even at low temperatures represents an important step towards next generation Mu spectroscopy experiments.Comment: 5 pages, 5 Figure

Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis

The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway represents a promising therapeutic target to prevent fibrosis. We have tested the effects of new pharmacological inhibitors of MRTF/SRF signalling in a preclinical model of fibrosis. CCG-222740, a novel MRTF/SRF inhibitor, markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC50 of 5 μM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (P < 0.0005) and 33% (P < 0.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum. We conclude that inhibitors of MRTF/SRF-regulated gene transcription such as CCG-222740, potentially represent a new therapeutic strategy to prevent scar tissue formation in the eye and other tissues

Associations between daily sitting time and the combinations of lifestyle risk factors in men

Background: Understanding the reciprocal role that multiple problematic behaviours play in men's health is important for intervention delivery and for reducing the healthcare burden. Data regarding the concurrence of problematic health behaviours is currently limited but offers insights into risk profiles, and should now include total time spent sitting/day. Methods: Self-reported data on lifestyle health behaviours was collected from 232 men aged ≥18 years who engaged in a men's health promotion programme delivered by 16 English Premier League Clubs. Results: Men at risk due to high sitting display multiple concurrent lifestyle risk factors, 88.6% displayed at least two ancillary risk factors and were three times more likely to report ≥2 lifestyle risk factors (OR. =3.13, 95% confidence interval (CI). =1.52-6.42) than those with low sitting risk. Significant differences in the mean number of risk factors reported between those participants in the higher risk (2.43. ±. 0.90) and lower risk (2.13. ±. 0.96) sitting categories were also found (P=0.015). Conclusions: Hard-to-reach men displayed multiple problematic concurrent behaviours, strongly linked to total sitting time. © 2012 WPMH GmbH