Collecting saliva samples for DNA extraction from children and parents: findings from a pilot study using lay interviewers in the UK

In recent years there has been a substantial increase in the collection of biological data on social surveys. Biological data has hitherto been primarily collected by medically trained personnel in a clinic or laboratory setting or using specialist nurse interviewers in a home-visit setting. However, improvements in technology and the development of minimally or non- invasive data collection methods have made it increasingly feasible to collect bio-measures in a home setting using non-medically trained lay interviewers. In the field of genetic research, it has become increasingly common to collect DNA from saliva samples. This paper provides an account of a pilot study investigating the feasibility of collecting saliva samples for DNA extraction from mothers, fathers and children aged around 11 years old using lay interviewers on the UK Millennium Cohort Study. The pilot study was carried out in 2011 in five areas of the UK with one interviewer in each area. 45 families took part in the pilot and saliva samples were obtained from 73 per cent of mothers, 76 per cent of fathers and 74 per cent of children. We demonstrate that it is indeed viable to collect saliva samples for DNA extraction from children and parents using lay interviewers in a home setting, and provide practical suggestions about how the data collection process could be improved in order to achieve higher response rates and improved specimen quality. Our findings are relevant to other surveys planning to incorporate saliva sample collection for DNA extraction, particularly for those involving lay interviewers in a home setting

Frequency of <i>KLK3 </i>gene deletions in the general population

Background One of the kallikrein genes ( KLK3) encodes prostate-specific antigen, a key biomarker for prostate cancer. A number of factors, both genetic and non-genetic, determine variation of serum prostate-specific antigen concentrations in the population. We have recently found three KLK3 deletions in individuals with very low prostate-specific antigen concentrations, suggesting a link between abnormally reduced KLK3 expression and deletions of KLK3. Here, we aim to determine the frequency of kallikrein gene 3 deletions in the general population. Methods The frequency of KLK3 deletions in the general population was estimated from the 1958 Birth Cohort sample ( n = 3815) using amplification ratiometry control system. In silico analyses using PennCNV were carried out in the same cohort and in NBS-WTCCC2 in order to provide an independent estimation of the frequency of KLK3 deletions in the general population. Results Amplification ratiometry control system results from the 1958 cohort indicated a frequency of KLK3 deletions of 0.81% (3.98% following a less stringent calling criterion). From in silico analyses, we found that potential deletions harbouring the KLK3 gene occurred at rates of 2.13% (1958 Cohort, n = 2867) and 0.99% (NBS-WTCCC2, n = 2737), respectively. These results are in good agreement with our in vitro experiments. All deletions found were in heterozygosis. Conclusions We conclude that a number of individuals from the general population present KLK3 deletions in heterozygosis. Further studies are required in order to know if interpretation of low serum prostate-specific antigen concentrations in individuals with KLK3 deletions may offer false-negative assurances with consequences for prostate cancer screening, diagnosis and monitoring. </jats:sec

The long-term impact of folic acid in pregnancy on offspring DNA methylation : follow-up of the Aberdeen folic acid supplementation trial (AFAST)

Funding This work was supported by the NIHR Bristol Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. R.C.R., G.C.S., N.K., T.G., G.D.S. and C.L.R. work in a unit that receives funds from the University of Bristol and the UK Medical Research Council (MC_UU_12013/1, MC_UU_12013/2 and MC_UU_12013/8). This work was also supported by CRUK (grant number C18281/A19169) and the ESRC (grant number ES/N000498/1). C.M.T. is supported by a Wellcome Trust Career Re-entry Fellowship (grant number 104077/Z/14/Z).Peer reviewedPublisher PD

Immersive virtual reality in a northern Queensland haemodialysis unit: Study protocol for a cross-over randomised controlled feasibility trial (ACTRN12621000732886)

Introduction: Despite being a life-preserving medical treatment, the demands of haemodialysis are a significant impost on individuals, posing considerable burdens on their work, vocational activities and involvement with family and community. This manuscript describes the protocol for a cross-over randomised controlled feasibility trial that will explore the impact of an immersive virtual reality (VR) experience for patients attending a northern Queensland Australia haemodialysis service and provide information to inform a future multi-centre randomised controlled trial (RCT). Methods: Participants in the trial will be patients who undergo haemodialysis three times/week at one of two dialysis units. During the 4-week intervention period (12 haemodialysis sessions), participants will be provided a headset with vision representative of the natural environment, and with audio. The 4-week control period will comprise usual activities, such as watching television, reading and sleeping. Outcomes will be measured by participants’: attendance at scheduled dialysis sessions; adherence to lifestyle modifications; wellbeing, anxiety and depression; acceptability and usability of VR; and adverse events such as nausea. The feasibility and acceptability of the intervention from the clinicians’ perspectives will also be explored. Discussion: To our knowledge this is the first RCT in Australia investigating the impact of an immersive VR experience for patients receiving haemodialysis.Trial registration: ACTRN12621000732886

Distinct DNA methylation profiles in subtypes of orofacial cleft

Abstract Background Epigenetic data could help identify risk factors for orofacial clefts, either by revealing a causal role for epigenetic mechanisms in causing clefts or by capturing information about causal genetic or environmental factors. Given the evidence that different subtypes of orofacial cleft have distinct aetiologies, we explored whether children with different cleft subtypes showed distinct epigenetic profiles. Methods In whole-blood samples from 150 children from the Cleft Collective cohort study, we measured DNA methylation at over 450,000 sites on the genome. We then carried out epigenome-wide association studies (EWAS) to test the association between methylation at each site and cleft subtype (cleft lip only (CLO) n = 50; cleft palate only (CPO) n = 50; cleft lip and palate (CLP) n = 50). We also compared methylation in the blood to methylation in the lip or palate tissue using genome-wide data from the same 150 children and conducted an EWAS of CLO compared to CLP in lip tissue. Results We found four genomic regions in blood differentially methylated in CLO compared to CLP, 17 in CPO compared to CLP and 294 in CPO compared to CLO. Several regions mapped to genes that have previously been implicated in the development of orofacial clefts (for example, TBX1, COL11A2, HOXA2, PDGFRA), and over 250 associations were novel. Methylation in blood correlated with that in lip/palate at some regions. There were 14 regions differentially methylated in the lip tissue from children with CLO and CLP, with one region (near KIAA0415) showing up in both the blood and lip EWAS. Conclusions Our finding of distinct methylation profiles in different orofacial cleft (OFC) subtypes represents a promising first step in exploring the potential role of epigenetic modifications in the aetiology of OFCs and/or as clinically useful biomarkers of OFC subtypes

Digital consultations for weight management in the NHS: A qualitative evaluation

© 2023 The Authors. Published by Elsevier. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.orcp.2023.03.003Receiving digital healthcare consultations for weight management, in place of in-person appointments, has proliferated in recent years, accelerated by the COVID-19 pandemic. The objective of the present study was to investigate patients’ experiences of digital weight management services (DWMS) provided by the National Health Service (NHS). Particular emphasis was placed on examining the perceived benefits and limitations of DWMS so as to identify potential means of improving provision. Sixteen patients (eight male; eight female) accessing digital consultations at one of two West Midlands (UK) NHS trusts, participated in semi-structured interviews. Interviews were transcribed verbatim and analysed via thematic analysis. We identified three overarching themes and associated sub-themes that reflect the perceived benefits and limitations of service provision as identified by patients. These were technology acceptability (sub-themes ‘challenges’, ‘requirements/facilitators’, and ‘beneficial features’); treatment acceptability (sub-themes ‘treatment features’, ‘patient attributes’, and ‘practitioner skills’); and treatment efficacy (sub-themes ‘treatment features’, ‘patient attributes’, and ‘practitioner skills’). Themes identified in this study have informed recommendations intended to enhance acceptability of DWMS technology and treatment, potentially encouraging engagement and increasing treatment efficacy. Limitations of the present study and recommendations for further research are also presented.This work was supported by the Association for the Study of Obesity (grant reference: 2104) and the University of Wolverhampton.Published versio

Remote and digital interventions for weight management in the NHS: A qualitative evaluation & service delivery applications

Poster presented at British Obesity & Metabolic Surgery Society Annual Scientific Meeting, 6th-7th June 2023, Birmingham

Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems

BACKGROUND: Conduct problems (CP) and attention deficit hyperactivity disorder (ADHD) are often comorbid and have each been linked to ‘unhealthy diet’. Early‐life diet also associates with DNA methylation of the insulin‐like growth factor 2 gene (IGF2), involved in fetal and neural development. We investigated the degree to which prenatal high‐fat and ‐sugar diet might relate to ADHD symptoms via IGF2 DNA methylation for early‐onset persistent (EOP) versus low CP youth. METHODS: Participants were 164 youth with EOP (n = 83) versus low (n = 81) CP drawn from the Avon Longitudinal Study of Parents and Children. We assessed if the interrelationships between high‐fat and ‐sugar diet (prenatal, postnatal), IGF2 methylation (birth and age 7, collected from blood), and ADHD symptoms (age 7–13) differed for EOP versus low CP youth. RESULTS: Prenatal ‘unhealthy diet’ was positively associated with IGF2 methylation at birth for both the EOP and low CP youth. For EOP only: (a) higher IGF2 methylation predicted ADHD symptoms; and (b) prenatal ‘unhealthy diet’ was associated with higher ADHD symptoms indirectly via higher IGF2 methylation. CONCLUSIONS: Preventing ‘unhealthy diet’ in pregnancy might reduce the risk of ADHD symptoms in EOP youth via lower offspring IGF2 methylation

Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems

textabstractBackground: Conduct problems (CP) and attention deficit hyperactivity disorder (ADHD) are often comorbid and have each been linked to 'unhealthy diet'. Early-life diet also associates with DNA methylation of the insulin-like growth factor 2 gene (IGF2), involved in fetal and neural development. We investigated the degree to which prenatal high-fat and -sugar diet might relate to ADHD symptoms via IGF2 DNA methylation for early-onset persistent (EOP) versus low CP youth. Methods: Participants were 164 youth with EOP (n = 83) versus low (n = 81) CP drawn from the Avon Longitudinal Study of Parents and Children. We assessed if the interrelationships between high-fat and -sugar diet (prenatal, postnatal), IGF2 methylation (birth and age 7, collected from blood), and ADHD symptoms (age 7-13) differed for EOP versus low CP youth. Results: Prenatal 'unhealthy diet' was positively associated with IGF2 methylation at birth for both the EOP and low CP youth. For EOP only: (a) higher IGF2 methylation predicted ADHD symptoms; and (b) prenatal 'unhealthy diet' was associated with higher ADHD symptoms indirectly via higher IGF2 methylation. Conclusions: Preventing 'unhealthy diet' in pregnancy might reduce the risk of ADHD symptoms in EOP youth via lower offspring IGF2 methylation

Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems

Background: Conduct problems (CP) and attention deficit hyperactivity disorder (ADHD) are often comorbid and have each been linked to 'unhealthy diet'. Early-life diet also associates with DNA methylation of the insulin-like growth factor 2 gene (IGF2), involved in fetal and neural development. We investigated the degree to which prenatal high-fat and -sugar diet might relate to ADHD symptoms via IGF2 DNA methylation for early-onset persistent (EOP) versus low CP youth. Methods: Participants were 164 youth with EOP (n = 83) versus low (n = 81) CP drawn from the Avon Longitudinal Study of Parents and Children. We assessed if the interrelationships between high-fat and -sugar diet (prenatal, postnatal), IGF2 methylation (birth and age 7, collected from blood), and ADHD symptoms (age 7-13) differed for EOP versus low CP youth. Results: Prenatal 'unhealthy diet' was positively associated with IGF2 methylation at birth for both the EOP and low CP youth. For EOP only: (a) higher IGF2 methylation predicted ADHD symptoms; and (b) prenatal 'unhealthy diet' was associated with higher ADHD symptoms indirectly via higher IGF2 methylation. Conclusions: Preventing 'unhealthy diet' in pregnancy might reduce the risk of ADHD symptoms in EOP youth via lower offspring IGF2 methylation