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

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

Time trends in breast cancer survival: experience in a single centre, 1975-89.

The aim of this retrospective cohort study was to investigate whether survival of patients with breast cancer has changed over the period 1975-89. A total of 2604 women diagnosed as having invasive breast cancer at a clinical oncology unit in London were followed up for between 5 and 20 years. Patients were divided into four groups according to menstrual status (pre or post) and the staging of cancer (operable or inoperable). For each group, survival from diagnosis was compared between three consecutive 5-year cohorts, both with and without adjustments made for relevant prognostic factors. No temporal patterns were found in patients with inoperable cancer, in whom the survival rate was consistently low. Of women with operable cancers, differences were seen only among post-menopausal women, for whom the best survival patterns were seen in patients diagnosed between 1985-89. This is probably due to tamoxifen being commonly prescribed as adjuvant treatment for this cohort of patients. We cannot explain an apparently worse survival in the group of patients presenting in the early 1980s compared with that observed in the late 1970s

Is the biology of breast cancer changing? A study of hormone receptor status 1984-1986 and 1996-1997

Using archived tumours, those from 1984-1986 and 1996-1997 underwent immunohistochemistry for hormone receptors and grade analysis. A significant shift towards more ER-positive and low-grade disease was found; this appears to reflect screening practices, but could still influence survival

The development of the Meaning in Life Index (MILI) and its relationship with personality and religious behaviours and beliefs among UK undergraduate students

The scales available for assessing meaning in life appear to be confounded with several related constructs, including purpose in life, satisfaction with life, and goal-directed behaviour. The Meaning in Life Index (MILI), a new instrument devised as a specific measure of meaning in life, was developed from responses to a pool of 22 items rated by a sample of 501 undergraduate students in Wales. The nine-item scale demonstrated sufficient face validity, internal consistency, and scale reliability to commend the instrument for future use. With respect to personality, the MILI scores were most strongly predicted by neuroticism (negatively), and less strongly by extraversion (positively) and psychoticism (negatively). With respect to several religious behavioural variables, those who attended church at least weekly returned significantly higher MILI scores than those who attended church less frequently. Intrinsic religiosity was the only orientation to be significantly associated with the MILI scale scores, although the magnitude of the association was smaller than anticipated. These results suggest that meaning in life is associated more strongly with individual differences in personality than with specific religious behaviours and attitudes. The implications of these results are discussed in terms of individual's personal values and attitudes that might underlie their experience of a meaning in life

Effectiveness of Writing Groups in Nursing Homes

We examine the effect of participation in an 8-week writing group in six nursing homes. Pretest and posttest assessments of cognitive and affective functional status were administered to 62 participants and 54 control subjects. We asked writing-group participants about previous writing experience and perceived ability to convey feelings, ideas, life experiences, and memories to others. Weekly assessments were conducted on eight group process measures. Findings suggest that participation in writing groups may reduce depression, particularly among residents with higher cognitive ability and greater depression. Significantly more participants than control subjects report an ability to relate feelings and ideas to other residents and staff. Improvement in group process measures is greatest for cognitively impaired participants and those with high physical function scores. There is considerable improve ment in residents for whom writing-group participation frequently is considered inappropriate: those without writing experience, the depressed, and the cognitively impaired.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67030/2/10.1177_073346488900800308.pd