Association of season of birth with DNA methylation and allergic disease.

BACKGROUND: Season of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy. METHODS: In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n = 367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation method examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third-generation cohort newborns. RESULTS: Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome-wide association study. In validation, significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season-associated methylation was enriched among networks relating to development, the cell cycle and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season-associated methylation was largely absent in newborns, suggesting it arises post-natally. CONCLUSIONS: This study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, although other mechanisms are also likely to be involved.

Changing prevalence of wheeze, rhinitis and allergic sensitisation in late childhood: findings from 2 Isle of Wight birth cohorts 12 years apart.

BACKGROUND: While the prevalence of asthma in children is decreasing or remaining the same, time trends in the prevalence of rhinitis in children are not known. Understanding sensitisation trends may help inform about trends in asthma and rhinitis prevalence. OBJECTIVE: To assess time trends of wheeze, rhinitis and aero-allergen sensitisation prevalence at 10 years of age, we compared two birth cohorts established 12 years apart. To gain insight into differences in disease prevalence, we assessed association of family history, early life exposures and sensitisation with wheeze and rhinitis in each cohort. METHODS: The IoW (Isle of Wight) and FAIR (Food Allergy and Intolerance Research) unselected birth cohorts were established in 1989 and 2001 respectively in IoW. Identical ISAAC questionnaire and skin prick test data were collected and compared at 10 years of age. RESULTS: Over the 12-year period from 2001 to 2012, prevalence of lifetime wheeze, current wheeze and those ever treated for asthma decreased by 15.9% (45.5 vs. 29.6, P < 0.001), 3.9% (18.9 vs. 15, P = 0.020) and 8.2% (31.7 vs. 23.5, P = 0.001), respectively. Conversely, current rhinitis and lifetime rhinitis prevalence increased by 5.5% (22.6 vs. 28.1, P = 0.004) and 13% (18.6 vs. 31.7, P < 0.001), respectively. Atopic status remained stable; however, house dust mite (HDM) sensitisation decreased by 5.6% (19.2 vs. 13.6, P = 0.004) and grass sensitisation increased by 3.5% (12.9 vs. 16.4, P = 0.054). Male sex, parental history of asthma and HDM sensitisation were significantly associated with lifetime wheeze in both cohorts, while maternal smoking during pregnancy was a significant risk factor only in the earlier IoW cohort. Parental history of rhinitis and grass sensitisation was significantly associated with lifetime rhinitis in both cohorts, while HDM sensitisation was significant only for the IoW cohort. CONCLUSION: Contrasting changes were noted with falling wheeze and HDM sensitisation but rising rhinitis and grass sensitisation prevalence. Changing prevalence of aero-allergen sensitisations may explain the different time trends observed in these cohorts.

Intravenous lipid emulsion - rescued at LAST.

The accidental overdose of local anaesthetics may prove fatal. The commonly used amide local anaesthetics have varying adverse effects on the myocardium and beyond a certain dose all are capable of causing death. Local anaesthetics are the most frequently used drugs in dentistry and although uncommon, local anaesthetic systemic toxicity (LAST) accounts for a high proportion of mortalities in the dental office, with local anaesthetic-induced cardiac arrest particularly resistant to standard resuscitation methods. Over the last decade there has been convincing evidence of using intravenous lipid emulsions as a rescue in local anaesthetic - cardiotoxicity and anaesthetic organisations over the globe have developed guidelines on the use of this drug. Despite this, however, awareness among practitioners appears to be lacking. All who use local anaesthetics in their practice should have an appreciation of patients at high risk of toxicity, early symptoms and signs of toxicity, preventative measures when using these drugs and the initial management of systemic toxicity with intravenous lipid emulsion. In this review we intend to discuss the pharmacology and pathophysiology of local anaesthetic toxicity, and the rationale for intravenous lipid emulsion therapy.

Intestinal atresia: an end-to-end linear anastomotic technique.

In a series of 19 neonates with small-bowel atresia, 16 were treated by end-to-end linear anastomosis (ELA) without resection and 3 by resection anastomosis (RA). Seven atresias were jejunal, 11 were ileal, and 1 jejunoileal; 3 cases were type II, 12 type IIIa, 3 type IIIb, and 1 type IV. There were 4 deaths, 1 after ELA and 3 after RA. The overall mortality decreased from 68 to 20.80% and for linear anastomosis to 6.25% presumably, because the intestinal contents are propelled along the lumen in a linear fashion and not at an angle as in end-to-back anastomosis, avoiding shearing of the suture line. The additional plicating sutures reduce the radius and increase the propelling force. We recommend this technique because it is based on sound principles of physics and preserves the entire available length of intestine.