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Background/AimThe association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption.MethodsBetween 2002–2004, 1772 men and 1931 women aged 54–79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 − 5 g/d), low (> 5 to  ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women,  > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude.ResultsAdjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[− 0.17(95%CI − 0.32; − 0.02)], and Bif-IMTmean[− 0.07(95%CI − 0.13; − 0.01)] at baseline and decreasing C-IMTmean[− 0.006 (95%CI − 0.011; − 0.000)], Bif-IMTmean[− 0.016(95%CI − 0.027; − 0.005)], ICA-IMTmean[− 0.009(95% − 0.016; − 0.002)] and ICA-IMTmax[− 0.016(95%: − 0.032; − 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT.ConclusionIn this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.

The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–maxβ = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.

Background and aims: In neonates the gastrointestinal tract is exposed to food and bacterial antigens at a time when the gut mucosal immune system has not developed the ability to induce oral tolerance. This increases the risk for an inappropriate immune response to oral antigens. Transforming growth factor β (TGF-β) is an immunoregulatory cytokine present in high concentration in maternal milk. Interleukin 18 (IL-18) is a cytokine that mediates early immune events, and drives T cell development. We assessed the role of TGF-β in mediating mucosal immune development and specifically the effect on endogenous IL-18. Methods: Rat pups were randomly assigned to the following groups, naturally suckled, maternal milk via cannula, and formula fed with and without physiological levels of TGF-β2. A comparison of the immune response profile was then carried out. Cytokine profiles, dendritic cell, intestinal mast cell, and eosinophil numbers were assessed. Results: We show that feeding formula deficient in TGF-β2 resulted in accumulated IL-18 protein release from intestinal epithelial cells and IL-18 mRNA up regulation. A proinflammatory cytokine profile resulted in the gut, along with increased numbers of activated dendritic cells, eosinophils, and mast cells. Supplementation of the formula with TGF-β2 down regulated the proinflammatory cytokine mRNA as well as the number of activated lymphocytes, eosinophils, mast cells, CD80, and CD86 positive dendritic cells. Conclusion: The data suggests an important role for maternal milk, in regulating immune responses after exposure to food antigens, which might otherwise induce deleterious immune responses in the intestine of suckling neonates. This regulation is potentially mediated by milk TGF-β2, as well as endogenous IL-18.

A unique model of formula feeding in the neonatal rat was utilized to investigate the effects of an enterally delivered artificial milk formula on clinically relevant immunological and biological characteristics in the gut, compared to naturally reared pups. Hooded Wistar rat pups were randomly allocated to two treatment groups: formula-fed (FF) or naturally suckled (NS). A flexible silastic intra-gastric cannula was surgically implanted into the FF pups, through which an artificial rat milk supplement was continuously delivered from day 4 to day 10 of life. Rat pups were sacrificed at 10 days of age. Body weight, small intestinal weight, mucosal CD8⁺ cell numbers, and ileal lactase activity in FF animals were significantly decreased compared to their NS counterparts (P < 0.05). Numbers of eosinophils, mucosal mast cells, CD4⁺ T-cells, ileal villus height and gastric emptying times were significantly increased in FF pups (P < 0.05). We have developed a new rat model of artificial feeding which possesses important immunological and biological similarities to the premature human infant.

Maternal milk cytokines have an important role in regulating the immune response after exposure to food antigens that which might otherwise induce deleterious immune responses in the intestine of suckling neonates. Maternal milk cytokines are involved in maintenance of normal gut homeostasis until the gut has matured to produce its own immunoregulatory cytokines. In the absence of maternal milk cytokines (i.e. formula feeding) the potential for immune activation to oral antigens would be increased.

We present a conceptual design for an experiment to measure the neutron lifetime (~886 s) with an accuracy of 10(-4). The lifetime will be measured by observing the decay rate of a sample of ultracold neutrons (UCN) confined in vacuum in a magnetic trap. The UCN collaboration at Los Alamos National Laboratory has developed a prototype UCN source that is expected to produce a bottled UCN density of more than 100/cm(3) [1]. The availability of such an intense source makes it possible to approach the measurement of the neutron lifetime in a new way. We argue below that it is possible to measure the neutron lifetime to 10(-4) in a vacuum magnetic trap. The measurement involves no new technology beyond the expected UCN density. If even higher densities are available, the experiment can be made better and/or less expensive. We present the design and methodology for the measurement. The slow loss of neutrons that have stable orbits, but are not energetically trapped would produce a systematic uncertainty in the measurement. We discuss a new approach, chaotic cleaning, to the elimination of quasi-neutrons from the trap by breaking the rotational symmetry of the quadrupole trap. The neutron orbits take on a chaotic character and mode mixing causes the neutrons on the quasi-bound orbits to leave the trap.

Transforming growth factor‐β (TGF‐β) is present at high concentrations in maternal milk. In milk TGF‐β2 is the predominant isoform. For function TGF‐β2 requires TβRIII to facilitate efficient binding to the TGF‐β receptor types I and II signalling complex. We have shown that TGF‐β receptor types I (TβRI), II (TβRII) and III (TβRIII) are coexpressed in the suckling rat intestine. Immunostaining for TβRIII was also observed in the intestinal lumen prior to weaning. TβRIII (or betaglycan) has been reported in serum, cell culture medium and extracellular matrix. To determine whether a soluble form of TβRIII is present in milk, the rat milk aqueous phase was analysed by slot‐blot and Western blot. Soluble TβRIII was detected in milk throughout lactation. Western blot analysis of rat milk revealed a high molecular weight band of glycosylated protein of >200 kDa, with a core protein of approximately 110–120 kDa that comigrated with recombinant TβRIII. Immunoabsorption of soluble TβRIII (sTβRIII) from milk resulted in partial depletion of active TGF‐β from milk, suggesting that the receptor may interact with ligand in milk. In addition rat pups suckled on mother's milk demonstrated an enhanced labelling of TβRIII in the gut, as compared with pups fed on a rat milk substitute (RMS). These findings suggest that milk sTβRIII is functional, and may modulate milk‐derived TGF‐β function in the developing intestine.

Background Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled trial (RCT). We aimed to compare clinical and immunological outcomes after baked egg (BE) consumption in young BE tolerant egg allergic children. Methods In a double blind RCT, BE tolerant egg allergic children consumed 10 g BE (1.3 g protein) 2 to 3 times per week for 6 months (n = 21 intervention group) or similar egg free baked goods (n = 22 control group) while maintaining an otherwise egg free diet. The final assessment was a raw egg oral food challenge (OFC) 1 month after ceasing the intervention product. Egg specific IgE and IgG4 were assessed at baseline and 7 months. Results After the intervention there was no difference in raw egg tolerance between groups, (23.5% (4/17) intervention group and 33.3% (6/18) control group). This was independent of age and amount of BE consumed (aOR 0.50 CI 0.11–2.40 p = 0.39). Both groups demonstrated decreased egg specific serum IgE titres and decreased whole egg specific IgE/IgG4 ratios. Discussion We conducted this trial because inclusion of baked egg protein in the diet of egg allergic children appears to move children towards a more tolerant immune profile. Strengths of our study include design of the blinded intervention, the consistent dosing protocol and the regular monitoring of symptoms and intake. However, the study was limited by small sample size resulting in insufficient power to show statistically significant results. Conclusion Our study suggests that short term, regular consumption of BE by BE tolerant 1 to 5 year old children with IgE mediated raw egg allergy may not induce, accelerate or slow development of tolerance to raw egg in this selected population. Trials with larger sample sizes are required to further test this hypothesis. Trial Registration The trial was registered on 7th February 2012 with the Australian New Zealand Clinical Trials Registry (ACTRN 12612000173897).

In this article we describe the photon detection readout electronics for the nEDM@SNS experiment. The chosen \"photon counting\" architecture, which utilizes high-efficiency silicon photomultipliers (SiPMs) and is appropriate for low-light applications, allows the use of a relatively high SiPM operating voltage. This maximizes photon detection efficiency and minimizes gain/efficiency voltage-dependence while eliminating optical cross-talk.