DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with Ulcerative Colitis (UC)

Introduction: Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and none assessing its relationship with lifestyle exposures. Aims & Methods: To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor - 1) and N-33 (tumour suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) whilst gene specific methylation was quantified using the COBRA method. Results: The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs 5.9%; p = 0.015 and 66% vs 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected. Conclusions: For the first time, we have shown increased methylation in the promoter regions of the putative tumour suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggests that, inactivation through methylation of the putative tumour suppressor genes N-33 and ESR-1, may not be associated with colorectal carcinogenesis in UC

The rate of brain abnormalities on in utero MRI studies in fetuses with normal ultrasound examinations of the brain and calculation of indicators of diagnostic performance

AIM To estimate the rate of unexpected brain abnormalities detected by in utero magnetic resonance imaging (iuMRI) in fetuses without abnormalities at ultrasonography (USS). MATERIALS AND METHODS A prospective cohort study of pregnant women whose fetus had no structural brain (or body) abnormalities recognised on antenatal ultrasonography. Women were recruited from 12 centres across the UK and underwent iuMRI at 18 gestational weeks or more in the [blinded for review]. The imaging studies were reviewed by an experienced neuroradiologist. The positive and negative predictive values of both USS and iuMRI have been calculated by combining the results of this study with the results from the main [blinded for review] study. RESULTS One hundred and ninety-eight pregnant women were recruited and underwent iuMRI of 205 fetuses. Brain abnormalities were shown on iuMRI in two fetuses that were not recognised on USS (one case of a focal cortical abnormality and one case of mild ventriculomegaly). The negative predictive value for USS was 99.5% and 100% for iuMRI. CONCLUSIONS To the authors' knowledge, this is the first study comparing USS and iuMRI in low-risk pregnancies. USS has a comparatively high rule-out for fetal brain abnormalities and should remain the screening tool of choice

Is It Complicated? Validity of Personality Interactions for Predicting Performance

Research on personality within the organizational sciences and for employee selection typically focuses on main effects, as opposed to interactive effects between personality variables. Large, multi-organizational datasets involving two different measures of personality were examined to test theoretically driven trait by trait interactions in predicting job performance. Interactive effects of Agreeableness and Conscientiousness, Agreeableness and Extraversion, Extraversion and Conscientiousness, and Emotional Stability and Conscientiousness were hypothesized as predicting overall job performance. However, these hypothesized effects were generally not supported. Implications for personality assessment are discussed

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

A rapid review indicated higher recruitment rates in treatment trials than in prevention trials

Objectives To test the hypothesis that the percentage of patients screened that randomize differs between prevention and therapy trials. Study Design and Setting Rapid review of randomized controlled trials (RCTs) identified through published systematic reviews in August 2013. Individually randomized, parallel group controlled RCTs were eligible if they evaluated metformin monotherapy or exercise for the prevention or treatment of type 2 diabetes. Numbers of patients screened and randomized were extracted by a single reviewer. Percentages were calculated for each study for those randomized: as a function of those approached, screened, and eligible. Percentages (95% confidence intervals) from each individual study were weighted according to the denominator and pooled rates calculated. Statistical heterogeneity was assessed using I2. Results The percentage of those screened who subsequently randomized was 6.2% (6.0%, 6.4%; 3 studies, I2 = 100.0%) for metformin prevention trials; 50.7% (49.9%, 51.4%; 21 studies, I2 = 99.6%) for metformin treatment trials; 4.8% (4.7%, 4.8%; 14 studies, I2 = 99.9%) for exercise prevention trials; and 43.3% (42.6%, 43.9%; 28 studies, I2 = 99.8%) for exercise treatment trials. Conclusion This study provides qualified support for the hypothesis that prevention trials recruit a smaller proportion of those screened than treatment trials. Statistical heterogeneity associated with pooled estimates and other study limitations is discussed. Keywords Prevention; Treatment; RCTs; Recruitment rates; Exercise; Screening failures; Consent rates; Eligibilit

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

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

Should we perform in utero MRI on a fetus at increased risk of a brain abnormality if ultrasonography is normal or shows non-specific findings?

There are a number of reasons why a pregnant woman might be considered to have an increased risk of carrying a fetus with a brain abnormality, but they fall broadly into two groups. First, there may be a relevant family history usually, but not always, when a fetus/child from a previous pregnancy has a developmental brain abnormality and a clinical geneticist judges that there is a risk of recurrence. Second, there may be findings in their current pregnancy that increases the risk of the fetus either having a developmental brain abnormality or accruing acquired brain pathology. Antenatal ultrasonography remains the mainstay of fetal screening and anomaly scanning, but there is now persuasive evidence that in utero magnetic resonance imaging should have an important supporting role. This is important, as more accurate and more certain diagnoses are central to providing parents with accurate information about the likely clinical outcome. In pregnancies at increased risk of brain abnormalities, it is also important to provide the best quality information that the fetal brain is normal to provide reassurance to parents. In this paper, we review the proposition that in utero magnetic resonance imaging should be used in pregnancies at increased risk of brain abnormalities, even if the consultant-led ultrasound examination is normal or showed non-specific findings only

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

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