The EuroPrevall birth cohort study on food allergy: baseline characteristics of 12,000 newborns and their families from nine European countries

It is unclear why some children develop food allergy. The EuroPrevall birth cohort was established to examine regional differences in the prevalence and risk factors of food allergy in European children using gold-standard diagnostic criteria. The aim of this report was to describe pre-, post-natal and environmental characteristics among the participating countries. In nine countries across four major European climatic regions, mothers and their newborns were enrolled from October 2005 through February 2010. Using standardized questionnaires, we assessed allergic diseases and self-reported food hypersensitivity of parents and siblings, nutrition during pregnancy, nutritional supplements, medications, mode of delivery, socio-demographic data and home environmental exposures. A total of 12,049 babies and their families were recruited. Self-reported adverse reactions to food ever were considerably more common in mothers from Germany (30%), Iceland, United Kingdom, and the Netherlands (all 20-22%) compared with those from Italy (11%), Lithuania, Greece, Poland, and Spain (all 5-8%). Prevalence estimates of parental asthma, allergic rhinitis and eczema were highest in north-west (Iceland, UK), followed by west (Germany, the Netherlands), south (Greece, Italy, Spain) and lowest in central and east Europe (Poland, Lithuania). Over 17% of Spanish and Greek children were exposed to tobacco smoke in utero compared with only 8-11% in other countries. Caesarean section rate was highest in Greece (44%) and lowest in Spain (<3%). We found country-specific differences in antibiotic use, pet ownership, type of flooring and baby's mattress. In the EuroPrevall birth cohort study, the largest study using gold-standard diagnostic criteria for food allergy in children worldwide, we found considerable country-specific baseline differences regarding a wide range of factors that are hypothesized to play a role in the development of food allergy including allergic family history, obstetrical practices, pre- and post-natal environmental exposures.     

Defining “adequate” pathogen reduction performance for transfused blood components

Pathogen reduction of labile blood products offers the opportunity to introduce to the blood banking community the same mechanism of protection that is employed for fractionated or pooled plasma products today—blood components that have been treated with methods to inactivate or reduce the infectivity of a variety of organisms that may contaminate donated blood and thus potentially transmit infection via transfusion. Due to the mechanisms of action, the methods employed in the plasma fractionation environment are not directly applicable to labile blood products. This article examines whether the same criteria of performance required for plasma derivatives (i.e., 6 log/mL reduction by multiple orthogonal methods) should be applied to the treatment of labile components and if not what criteria for performance might be sufficient. In conducting this analysis, we have considered what has been learned in the past several decades regarding the dynamics and infectivity of various pathogens and disease transmission by blood products, the introduction and progressive enhancement of testing methods based on serology and nucleic acid testing, and the performance characteristics for pathogen reduction technologies that are available today.     

Polymer gels for magnetic resonance imaging of radiation dose distributions at normal room atmosphere.

Polymer gels whose NMR and optical properties change when irradiated offer unique advantages for measuring radiation dose distributions. To date, all acrylic polymer gel dosimeters must be manufactured, stored and irradiated in hypoxic conditions which severely limits their use and stability. A new formulation of acrylic dosimeter gel has been developed that responds well in normal atmosphere and which we have named MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper). To produce dosimeter gels, an aqueous solution of gelatin, open to the atmosphere, is mixed with methacrylic acid, copper(II) ions, ascorbic acid and hydroquinone. It is believed that the copper(II) and ascorbic acid form a complex with oxygen which (with radiolysis of water) serves as a free radical source for the initiation of the polymerization of methacrylic acid. At room air the water proton spin relaxation rate R2 in MAGIC gels is proportional to absorbed dose though the precise relationship depends on the composition of the gel and the initiating complex. For example, in the range 0-30 Gy the slope of the response of R2 versus dose at 20 MHz was 0.300, 0.519 and 0.681 s(-1) Gy(-1), respectively, when the concentration of MAA was 3, 6 and 9%. The slopes increased to 0.310, 0.567 and 0.868 s(-1) Gy(-1) at 85 MHz. An important determinant of the sensitivity to detect small dose changes is shown to be the slope-to-intercept ratio of the dose-response curve. These varied from 0.08 to 0.17, comparable to hypoxic gels described earlier. MAGIC gels can be manufactured and used much more easily than the previous formulations and can be imaged by magnetic resonance imaging or optical scanning, and thus they will likely be of considerable interest to radiation physicists.     

Determinants of use and outcomes of invasive coronary procedures in acute coronary syndromes: results from ENACT.

AIMS: To explore the variations in the use of invasive coronary procedures after acute coronary syndromes. METHODS AND RESULTS: In the ENACT registry, use of invasive procedures was analyzed as a function of hospital type, country and patient characteristics among 2768 patients with acute coronary syndromes (731 with ST-segment elevation myocardial infarction (STEMI) within 12h of symptom onset, and 2037 with other acute coronary syndromes). Percutaneous coronary intervention (PCI) was more likely to be performed in teaching than in community hospitals, and in hospitals with, rather than without, catheterization facilities. There were marked country-to-country variations in the use of PCI during the index hospital stay, ranging from 8 to 67% after STEMI (p<0.001) and from 9 to 44% after other acute coronary syndromes (p<0.001). The main independent predictors of the performance of PCI were the country rate of use of PCI and the hospital availability of PCI. For patients with other acute coronary syndromes, the risk of adverse events, assessed by the simplified TIMI-risk score, was not associated with PCI. Logistic regression analysis showed that lack of PCI was an independent predictor of in-hospital mortality (odds ratio (OR): 3.75, p<0.029) after other acute coronary syndromes, but not after STEMI. CONCLUSIONS: The use of PCI after acute coronary syndromes appears related more to local practice and hospital characteristics than to patients' characteristics or risk.     

Opsonization by antigen-specific antibodies as a mechanism of protective immunity induced by Plasmodium falciparum circumsporozoite protein-based vaccine

Recently conducted trials involving the Plasmodium falciparum circumsporozoite (CS) protein-based RTS,S malaria vaccine yielded unprecedented protection against a challenge with infectious sporozoites (spzs). The RTS,S vaccine induced high titres of CS protein-specific antibodies (Abs) in many of the protected volunteers, but the contribution of these Abs to protection remains unknown. Because opsonization by Ab promotes the uptake and destruction of spzs by monocytes and macrophages in both rodent and primate malaria, we asked if the RTS,S-induced Abs have antigen-specific opsonizing activity. Screening plasma from a large number of subjects using spzs was impractical, therefore we developed an alternative assay based on cytofluorometry that allowed the detection of fluoresceinated-Ag-Ab complexes endocytosed by the FcR+ THP-1 human monocyte line. The results showed that plasma samples from RTS,S-immunized subjects contained opsonizing CS protein-specific Abs and the endocytic activity of these Abs in protected subjects was significantly higher than in subjects who were susceptible to infection with spzs. We also demonstrated by electron microscopy that live spzs exposed to RTS,S-immune plasma could be internalized by the THP-1 cells. These results suggest that opsonization by CS protein-specific Abs might be one of the mechanisms that contributes to RTS,S-induced protective immunity.     

Prolonged ingestion of commercial DDT and PCB; effects on progesterone levels and reproduction in the mature female rat

A report linking human polycystic ovary with increased exposure to environmental DDT (Heinrichset al. 1971) prompted the present study comparing effects of PCB and DDT or their combination on reproduction in female rats under more realistic conditions with respect to level (75 and 150 ppm), route of administration (dietary contaminant), and period of exposure (8 and 36 weeks). Evaluation of estrous cycle length, mating frequency, number and size of litters; as well as plasma levels of DDT, PCB, progesterone (P), and 17=hydroxyprogesterone (17=OH-P), permitted comparison of short and long term reproductive changes from ingestion of two levels of DDT and/or PCB.PCB reduced plasma progesterone (p<.01) while plasma 17 OH-P was unchanged by PCB or DDT. High DDT and PCB abolished reproduction. Histologically, distinct ovarian stromal changes accompanied 150 ppm of PCB, while increased numbers of more prominent follicular cysts were evident with 150 ppm of DDT. Although DDT and PCB generally reduced or abolished litter production, no treatment tested significantly altered litter size. Long term chronic ingestion of more realistic levels of technical DDT (85%p,p, 15%o,p-DDT) in these studies did not lead to polycystic ovaries in adult rats comparable to those reported following i.v. administration of pureo,p-DDT to immature rats. Plasma DDT levels above 800 ppb are clearly detrimental to reproduction, while levels below 500 ppb had little effect. Finally, we present the first evidence reported to our knowledge demonstrating that prolonged ingestion of PCB (150 ppm) markedly reduces reproduction (p<.05) accompanied by significantly reduced progesterone in plasma (p<.01) as well as by histologically characteristic ovarian stromal changes not seen with DDT alone.     

Stimulation of hCG and inhibition of hPL in isolated human trophoblast cells in vitro by glycodelin A

The immunosuppressive protein glycodelin A (formerly named PP14) is produced by human decidua and secreted in the maternal circulation. Glycodelin A concentrations in serum have been used as indicators of endometrial function. The purpose of this study was to investigate the effect of glycodelin A on human chorionic gonadotropin (hCG) and human placental lactogen (hPL) release by freshly isolated cytotrophoblasts (in vitro). Cytotrophoblasts have been prepared from human term placenta by the three-step trypsin-DNase dispersion method of villous tissue followed by a percoll gradient centrifugation step. When placed in culture, the isolated mononuclear trophoblasts differentiated into syncytial counterparts within 12-72 h after plating. Trophoblasts were incubated with varying concentrations (60-300 microg/ml) of glycodelin A. Glycodelin A was isolated and purified by chromatographic methods from amnion fluid. Supernatants of the trophoblast cell cultures were assayed for hCG and hPL by immunological methods. The release of hCG is increased in glycodelin A-treated trophoblast cell cultures compared to untreated trophoblast cells. Glycodelin A inhibits the production of hPL in vitro. Differences in Glycodelin A stimulated cells and untreated controls are statistical significant. hCG and hPL are markers for the differentiation process of trophoblast cells to syncytial trophoblasts. The results imply that glycodelin A secreted by decidualised endometrium modulates endocrine function, as well as the differentiation of trophoblasts in culture.     

Emotional perception: correlation of functional MRI and event-related potentials

Dense-array electrocortical and functional hemodynamic measures of human brain activity were collected to assess the relationship between 2 established neural measures of emotional reactivity. Recorded in parallel sessions, the slow-wave late positive potential (LPP) and visual cortical blood oxygen level-dependent (BOLD) signals were both modulated by the rated intensity of picture arousal. The amplitude of the LPP correlated significantly with BOLD intensity in lateral occipital, inferotemporal, and parietal visual areas across picture contents. Estimated strength of modeled regional sources did not correlate significantly with regional BOLD intensity. These data suggest that the enhanced positive slow wave seen over posterior sites during emotional picture processing represents activity in a circuit of visual cortical structures, reflecting a perceptual sensitivity to the motivational relevance of visual scenes.