The Foetal Origins of Allergy and Potential Nutritional Interventions to Prevent Disease

The first nine months from conception to birth involves greater changes than at any other time in life, affecting organogenesis, endocrine, metabolic and immune programming. It has led to the concept that the “first 1000 days” from conception to the second birthday are critical in establishing long term health or susceptibility to disease. Immune ontogeny is predominantly complete within that time and is influenced by the maternal genome, health, diet and environment pre-conception and during pregnancy and lactation. Components of the immunological protection of the pregnancy is the generation of Th-2 and T-regulatory cytokines with the consequence that neonatal adaptive responses are also biased towards Th-2 (allergy promoting) and T-regulatory (tolerance promoting) responses. Normally after birth Th-1 activity increases while Th-2 down-regulates and the evolving normal human microbiome likely plays a key role. This in turn will have been affected by maternal health, diet, exposure to antibiotics, mode of delivery, and breast or cow milk formula feeding. Complex gene/environment interactions affect outcomes. Many individual nutrients affect immune mechanisms and variations in levels have been associated with susceptibility to allergic disease. However, intervention trials employing single nutrient supplementation to prevent allergic disease have not achieved the expected outcomes suggested by observational studies. Investigation of overall dietary practices including fresh fruit and vegetables, fish, olive oil, lower meat intake and home cooked foods as seen in the Mediterranean and other healthy diets have been associated with reduced prevalence of allergic disease. This suggests that the “soup” of overall nutrition is more important than individual nutrients and requires further investigation both during pregnancy and after the infant has been weaned. Amongst all the potential factors affecting allergy outcomes, modification of maternal and infant nutrition and the microbiome are easier to employ than changing other aspects of the environment but require large controlled trials before recommending changes to current practice

Genotype moderates the impact of food additives on hyperactive behavior in children

Introduction: The claim of a relationship between artificial food color and additive (AFCs) intake and behavior is highly contentious. We have shown in a previous population-based trial with 3yo children adverse effects of food additives on parentally-rated hyperactive behaviour (Bateman et al, 2004). The possible role of genetic polymorphisms in moderating this adverse effect has not been previously examined. Methods A randomised, double blind, placebo-controlled, within subject crossover food challenge was used for 144, 8 to 9 year old children and 153, 3 year old children. Following baseline assessment children were placed on a diet eliminating food additives and a benzoate preservative for 6 weeks during which time they were challenged for weekly periods with either a placebo mix or a drink containing sodium benzoate (45mg daily) and one of two mixes of AFCs.: Results: The T939C and Thr105Ile polymorphisms of the histamine N-methyltransferase gene (HNMT) moderated the adverse effect s of AFCs but the polymorphisms in catecholamine genes COMT Val108Met and ADRA2A C1291G did not. These findings point to a possible role for histamine in mediating the effects of food additives and help to explain why there has been inconsistency between previous studies. Conclusions: Genes influencing a range of neurotransmitter systems and their interplay with environmental factors, such as diet, need to be examined to understand genetic influences on hyperactivity.<br/

1RXS J232953.9+062814: A Dwarf Nova with a 64-minute Orbital Period and a Conspicuous Secondary Star

We present spectroscopy and time-series photometry of the newly discovered dwarf nova 1RXS J232953.9+062814. Photometry in superoutburst reveals a superhump with a period of 66.06(6) minutes. The low state spectrum shows Balmer and HeI emission on a blue continuum, and in addition shows a rich absorption spectrum of type K4 +- 2. The absorption velocity is modulated sinusoidally at P_orb = 64.176(5) min, with semi-amplitude K = 348(4) km/s. The low-state light curve is double-humped at this period, and phased as expected for ellipsoidal variations. The absorption strength does not vary appreciably around the orbit. The orbital period is shorter than any other cataclysmic variable save for a handful of helium-star systems and V485 Centauri (59 minutes). The secondary is much hotter than main sequence stars of similar mass, but is well-matched by helium-enriched models, indicating that the secondary evolved from a more massive progenitor. A preliminary calculation in which a 1.2 solar-mass star begins mass transfer near the end of H burning matches this system's characteristics remarkably well.Comment: accepted to Astrophysical Journal Letters; 14 pages, 3 eps figures + 1 jpg greyscale figur

An Evaluation of the Sensitivity of Subjects with Peanut Allergy to Very Low Doses of Peanut Protein: A Randomized, Double-Blind, Placebo-Controlled Food Challenge Study

The minimum dose of food protein to which subjects with food allergy have reacted in double-blind, placebo-controlled food challenges is between 50 and 100 mg. However, subjects with peanut allergy often report severe reactions after minimal contact with peanuts, even through intact skin. Objective: We sought to determine whether adults previously proven by challenge to be allergic to peanut react to very low doses of peanut protein. Methods: We used a randomized, double-blind, placebo-controlled food challenge of 14 subjects allergic to peanuts with doses of peanut ranging from 10 μg to 50 mg, administered in the form of a commercially available peanut flour. Results: One subject had a systemic reaction to 5 mg of peanut protein, and two subjects had mild objective reactions to 2 mg and 50 mg of peanut protein, respectively. Five subjects had mild subjective reactions (1 to 5 mg and 4 to 50 mg). All subjects with convincing objective reactions had short-lived subjective reactions to preceding doses, as low as 100 μg in two cases. Five subjects did not react to any dose up to 50 mg. Conclusion: Even in a group of well-characterized, highly sensitive subjects with peanut allergy, the threshold dose of peanut protein varies. As little as 100 μg of peanut protein provokes symptoms in some subjects with peanut allergy

Photonic band structure of highly deformable, self-assembling systems

We calculate the photonic band structure at normal incidence of highly deformable, self-assembling systems - cholesteric elastomers subjected to external stress. Cholesterics display brilliant reflection and lasing owing to gaps in their photonic band structure. The band structure of cholesteric elastomers varies sensitively with strain, showing new gaps opening up and shifting in frequency. A novel prediction of a total band gap is made, and is expected to occur in the vicinity of the previously observed de Vries bandgap, which is only for one polarisation

Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial

   Objective To determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma. &lt;br&gt; &lt;br&gt;Design Randomised, double-blind, placebo-controlled, parallel-group trial. &lt;br&gt; &lt;br&gt;Setting Nineteen European asthma clinics. &lt;br&gt; &lt;br&gt;Participants 312 patients aged 7-70 with inadequately controlled persistent atopic asthma. &lt;br&gt; &lt;br&gt;Main outcome measure Proportion of patients with an increase of &amp;gt;= 0.5 points in asthma quality of life score after 1 year of treatment. &lt;br&gt; &lt;br&gt;Results TLA devices were successfully installed in the bedrooms of 282 (90%) patients included in the primary efficacy analysis. There was a difference in treatment response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%) groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02).(3) In patients aged &amp;gt;= 12, on whom the study was powered, the difference in response rate was similar-active 106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7, p=0.059). There was a difference between groups in fractional exhaled nitric oxide change of -7.1 ppb (-13.6 to -0.7, p=0.03). Active treatment was associated with less increase in cat-specific IgE than placebo. There was no difference in adverse event rates between treatment groups. &lt;br&gt; &lt;br&gt;Conclusion Inhalant exposure reduction with TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. TLA may be a treatment option for patients with inadequately controlled persistent atopic asthma.funding agencies|Airsonett AB||National Institute for Health Research||National Institute for Health Research Biomedical Research Centre||MRC||Asthma UK Centre in Allergic Mechanisms of Asthma||</p

Recommendations for Competency in Allergy Training for Undergraduates Qualifying as Medical Practitioners: A Position Paper of the World Allergy Organization

The global increased prevalence of allergy is such that between 20-30% of the world's population now suffers from some form of allergic disease, with considerable and continuing increases in prevalence over the last three decades [1]. Although the specialty of allergy is practiced and recognized in most developed countries, even some developed countries lack adequate resources to manage the local burden of allergic disease. In many developing countries there are few or no allergy specialists due to either the prevailing healthcare infrastructure, to socio-economic reasons, and/or to the lack of recognition of allergy as a clinical specialty. There is often minimal or no inclusion of allergy education/training in the undergraduate medical curriculum, and this shortfall must be addressed if the increasing burden of allergic diseases is to be managed. The majority of patients with common allergic diseases around the world are treated by primary care physicians, and not by trained specialists. However, a lack of appropriate education and training in allergy at the undergraduate level leaves many medical graduates with low baseline knowledge and skills in the science and practice of allergy. In addition, because it is a relatively new discipline, education and training in allergy in medical schools has lagged behind scientific and clinical developments in this field, and there are few allergy specialists available to teach this multidisciplinary subject. This phenomenon is described by the World Health Organization as the knowledge/practice gap. Unless allergy training is included as an essential part of undergraduate medical education at the clinical level, many physicians will qualify with inadequate competency to manage the diagnosis and treatment of allergic diseases at the primary care level. Thus, a cycle of lack of basic knowledge about the most common allergic diseases, lack of recognition of allergic disease at the clinical level, and inadequate knowledge and skills in the diagnosis and treatment of allergic diseases will be perpetuated. To help break this cycle the World Allergy Organization (WAO) presents broad guidelines for the curriculum of education and training of medical students in the immune mechanisms of allergic responses, and the commonest manifestations of clinical allergy. Inclusion of these educational guidelines into curriculum development will provide medical graduates with the basic knowledge required to recognize and treat common allergic diseases during postgraduate training or as a general practitioner (care level 1), and the knowledge of when to refer the more complex problems to appropriate organ-based or allergy specialists (care levels 2 and 3) [2]. These guidelines outline optimal curriculum content, and are offered for consideration and modification to meet local needs and healthcare provision structures. Although certain immunodeficiency states may accompany allergies or may need to be considered in the differential diagnosis of allergic diseases, this document is not intended to provide a comprehensive guideline on the teaching of immune deficiencies to medical students