Accuracy of in-utero MRI to detect fetal brain abnormalities and prognosticate developmental outcome : postnatal follow-up of the MERIDIAN cohort

Background In utero MRI (iuMRI) detects fetal brain abnormalities more accurately than ultrasonography and provides additional clinical information in around half of pregnancies. We aimed to study whether postnatal neuroimaging after age 6 months changes the diagnostic accuracy of iuMRI and its ability to predict developmental outcome. Methods Families enrolled in the MERIDIAN study whose child survived to age 3 years were invited to have a case note review and assessment of developmental outcome with the Bayley Scales of Infant and Toddler Development, the Ages and Stages Questionnaire, or both. A paediatric neuroradiologist, masked to the iuMRI results, reviewed the postnatal neuroimaging if the clinical report differed from iuMRI findings. Diagnostic accuracy was recalculated. A paediatric neurologist and neonatologist categorised participants' development as normal, at risk, or abnormal, and the ability of iuMRI and ultrasonography to predict developmental outcome were assessed. Findings 210 participants had case note review, of whom 81 (39%) had additional investigations after age 6 months. The diagnostic accuracy of iuMRI remained higher than ultrasonography (proportion of correct cases was 529 [92%] of 574 vs 387 [67%] of 574; absolute difference 25%, 95% CI 21 to 29; p<0·0001). Developmental outcome data were analysed in 156 participants, and 111 (71%) were categorised as normal or at risk. Of these 111 participants, prognosis was normal or favourable for 56 (51%) using ultrasonography and for 76 (69%) using iuMRI (difference in specificity 18%, 95% CI 7 to 29; p=0·0008). No statistically significant difference was seen in infants with abnormal outcome (difference in sensitivity 4%, 95% CI −10 to 19; p=0·73). Interpretation iuMRI remains the optimal tool to identify fetal brain abnormalities. It is less accurate when used to predict developmental outcome, although better than ultrasonography for identifying children with normal outcome. Further work is needed to determine how the prognostic abilities of iuMRI can be improved. Funding National Institute for Health Research Health Technology Assessment programme

Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammatio

Can Beach Cleans Do More Than Clean-Up Litter? Comparing Beach Cleans to Other Coastal Activities

Coastal visits not only provide psychological benefits but can also contribute to the accumulation of rubbish. Volunteer beach cleans help address this issue, but may only have limited, local impact. Consequently, it is important to study any broader benefits associated with beach cleans. This article examines the well-being and educational value of beach cleans, as well as their impacts on individuals’ behavioral intentions. We conducted an experimental study that allocated students (n = 90) to a beach cleaning, rock pooling, or walking activity. All three coastal activities were associated with positive mood and pro-environmental intentions. Beach cleaning and rock pooling were associated with higher marine awareness. The unique impacts of beach cleaning were that they were rated as most meaningful but linked to lower restorativeness ratings of the environment compared with the other activities. This research highlights the interplay between environment and activities, raising questions for future research on the complexities of person-environment interaction

Prediction of malignant transformation and recurrence of oral epithelial dysplasia using architectural and cytological feature specific prognostic models

Oral epithelial dysplasia (OED) is a precursor state usually preceding oral squamous cell carcinoma (OSCC). Histological grading is the current gold standard for OED prognostication but is subjective and variable with unreliable outcome prediction. We explore if individual OED histological features can be used to develop and evaluate prognostic models for malignant transformation and recurrence prediction. Digitised tissue slides for a cohort of 109 OED cases were reviewed by three expert pathologists, where the prevalence and agreement of architectural and cytological histological features was assessed and association with clinical outcomes analysed using Cox proportional hazards regression and Kaplan–Meier curves. Within the cohort, the most prevalent features were basal cell hyperplasia (72%) and irregular surface keratin (60%), and least common were verrucous surface (26%), loss of epithelial cohesion (30%), lymphocytic band and dyskeratosis (34%). Several features were significant for transformation (p < 0.036) and recurrence (p < 0.015) including bulbous rete pegs, hyperchromatism, loss of epithelial cohesion, loss of stratification, suprabasal mitoses and nuclear pleomorphism. This led us to propose two prognostic scoring systems including a ‘6-point model’ using the six features showing a greater statistical association with transformation and recurrence (bulbous rete pegs, hyperchromatism, loss of epithelial cohesion, loss of stratification, suprabasal mitoses, nuclear pleomorphism) and a ‘two-point model’ using the two features with highest inter-pathologist agreement (loss of epithelial cohesion and bulbous rete pegs). Both the ‘six point’ and ‘two point’ models showed good predictive ability (AUROC ≥ 0.774 for transformation and 0.726 for recurrence) with further improvement when age, gender and histological grade were added. These results demonstrate a correlation between individual OED histological features and prognosis for the first time. The proposed models have the potential to simplify OED grading and aid patient management. Validation on larger multicentre cohorts with prospective analysis is needed to establish their usefulness in clinical practice

MYOD-1 in normal colonic mucosa : role as a putative biomarker?

Background DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. The MYOD-1 gene which is a muscle differentiation gene has been showed to be significantly methylated in colorectal cancer which, is an age related event. However the role of this gene in the colonic mucosa is not understood and whether methylation occurs in subjects without colon cancer. In this study, we have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing. Results We analysed colonic mucosal biopsies in 218 normal individuals and demonstrated that in most individuals promoter hypermethylation was not quantified for MYOD-1. However, promoter hypermethylation increased significantly with age (p < 0.001 using regression analysis) and this was gender independent. We also showed that gene promoter methylation increased positively with an increase in waist to hip (WHR) ratio – the latter is also a known risk factor for colon cancer development. Conclusions Our study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer

Work-related psychological health and psychological type among lead elders within the Newfrontiers network of churches in the United Kingdom

Building on a series of recent studies concerned with assessing work-related psychological health and psychological type among various groups of church leaders, this study reports new data provided by 134 Lead Elders within the Newfrontiers network of churches in the United Kingdom who completed the Francis Psychological Type Scales (FPTS) together with the two scales of the Francis Burnout Inventory (FBI) concerned with emotional exhaustion and satisfaction in ministry. Compared with other groups of church leaders, Lead Elders within the Newfrontiers network of churches reported lower levels of emotional exhaustion and higher levels of satisfaction in ministry. Compared with other groups of church leaders, there was a higher proportion of extraverts among Lead Elders within the Newfrontiers network of churches. There was only a weak association between psychological type and burnout

Imaging muscle as a potential biomarker of denervation in motor neuron disease

Objective To assess clinical, electrophysiological and whole-body muscle MRI measurements of progression in patients with motor neuron disease (MND), as tools for future clinical trials, and to probe pathophysiological mechanisms in vivo. Methods A prospective longitudinal observational clinico-electrophysiological and radiological cohort study was performed. Twenty-nine MND patients and 22 age and gender-matched healthy controls were assessed with clinical measures, electrophysiological motor unit number index (MUNIX) and T2-weighted whole-body muscle MRI, at first clinic presentation and four months later. Between-group differences and associations were assessed using age and gender-adjusted multivariable regression models. Within-subject longitudinal changes were assessed using paired t-tests. Patterns of disease spread were modelled using mixed-effects multivariable regression, assessing associations between muscle relative T2 signal and anatomical adjacency to site of clinical onset. Results MND patients had 30% higher relative T2 muscle signal than controls at baseline (all-regions mean, 95%CI 15%, 45%, p<0.001). Higher T2 signal was associated with greater overall disability (coefficient -0.009, 95%CI -0.017, -0.001, p=0.023), and with clinical weakness and lower MUNIX in multiple individual muscles. Relative T2 signal in bilateral tibialis anterior increased over four months in MND patients (right: 10.2%, 95%CI 2.0%, 18.4%, p=0.017; left: 14.1%, 95%CI 3.4%, 24.9%, p=0.013). Anatomically contiguous disease spread on MRI was not apparent in this model. Conclusions Whole-body muscle MRI offers a new approach to objective assessment of denervation over short timescales in MND, and enables investigation of patterns of disease spread in vivo. Muscles inaccessible to conventional clinical and electrophysiological assessment may be investigated using this methodology