Guy's and St Thomas' NHS Foundation Trust

About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Abstract: Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology.

Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations.

Abstract: Background: Filaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy Household peanut consumption is associated with peanut allergy, and peanut allergen in household dust correlates with household peanut consumption Objective: We sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds Methods: Exposuretopeanutantigenindustwithinthefirstyearof life was measured in a population-based birth cohort Peanut sensitization and peanut allergy (defined by using oral food challengesorcomponent-resolveddiagnostics[CRD])wereassessed at 8 and 11 years Genotyping was performed for 6 FLG mutations Results: After adjustment for infantile atopic dermatitis and preceding egg skin prick test (SPT) sensitization, we found a strong and significant interaction between natural log (ln [loge]) peanutdustlevelsandFLGmutationsonpeanutsensitizationand peanut allergy Among children with FLG mutations, for each ln unit increase in the house dust peanut protein level, there was a morethan6-foldincreasedoddsofpeanutSPTsensitization,CRD sensitization, or both in children at ages 8 years, 11 years, or both and a greater than 3-fold increased odds of peanut allergy compared with odds seen in children with wild-type FLG There was no significant effect of exposure in children without FLG mutations In children carrying an FLG mutation, the threshold level for peanut SPT sensitization was 092 mg of peanut protein per gram (95% CI, 070-122 mg/g), that for CRD sensitization was 103 mg/g (95% CI, 090-182 mg/g), and that for peanut allergy was 117 mg/g (95% CI, 001-16383 mg/g) Conclusion: Early-life environmental peanut exposure is associated with an increased risk of peanut sensitization and allergy in children who carry an FLG mutation These data support the hypothesis that peanut allergy develops throughtranscutaneoussensitizationinchildrenwithanimpaired skin barrier (J Allergy Clin Immunol 2014;134:867-75)

Mephedrone use and associated adverse effects in school and college/university students before the UK legislation change.

Abstract: Background: Mephedrone is a synthetic cathinone that is commonly used as a recreational drug among those who attend nightclubs. There have been increasing reports of toxicity associated with its use and it was controlled as a Class B drug under the Misuse of Drugs Act (1971) in the UK on 16 April 2010. There has been a suggestion from media reports that mephedrone use is common in children/students but there is no data on the prevalence of its use among the general population. The aim of this study was to determine the prevalence and frequency of use of mephedrone among school and college/university aged individuals and to collect data on the sources of mephedrone and acute harm related to its use. Methods: Data was collected using a questionnaire survey in schools, colleges and universities in the Tayside area of Scotland, UK in February 2010. Results: A total of 1006 individuals completed the survey [501 (49.8%) males and 505 (50.2%) females], of whom 349 classified their educational institute as a school and 657 as a college/university. Among them 205 (20.3%) reported previous use of mephedrone; 23.4% reported using only using mephedrone on one occasion previously, although 4.4% reported daily use. A total of 56% of those who had used mephedrone, reported at least one unwanted effect associated with its use. A total of 17.6% of users reported ‘addiction or dependence’ symptoms associated with their mephedrone use. A total of 48.8% of users sourced mephedrone from street level dealers, 10.7% from the Internet. Conclusions: We have shown in this study that the use of mephedrone among school and college/university students is common and that users found it easy to obtain. There was a high prevalence of unwanted effects associated with its use. Further work is needed to determine the impact of the recent changes in the UK legislation relating to mephedrone and other related cathinones and whether this has been effective in reducing the prevalence of mephedrone use.