MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR

Background Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method. Method We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR. Results When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods) had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06). One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods. Conclusion In our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method

Associations between general self-efficacy and health-related quality of life among 12-13-year-old school children: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>While research on school children's health has mainly focused on risk factors and illness, few studies have examined aspects of health promotion. Thus, this study focuses on health promotional factors including general self-efficacy (GSE) and health-related quality of life (HRQOL). GSE refers to a global confidence in coping ability across a wide range of demanding situations, and is related to health. The purpose of this study was to examine associations between GSE and HRQOL, and associations between HRQOL and socio-demographic characteristics. Knowledge of these associations in healthy school children is currently lacking.</p> <p>Methods</p> <p>During 2006 and 2007, 279 school children in the seventh grade across eastern Norway completed a survey assessing their GSE and HRQOL. The children were from schools that had been randomly selected using cluster sampling. T-tests were computed to compare mean subscale values between HRQOL and socio-demographic variables. Single and multiple regression analyses were performed to explore associations among GSE, HRQOL and socio-demographic variables.</p> <p>Results</p> <p>Regression analyses showed a significant relationship between increasing degrees of GSE and increasing degrees of HRQOL. In analyses adjusted for socio-demographic variables, boys scored higher than girls on self-esteem. School children from single-parent families had lower scores on HRQOL than those from two-parent families, and children who had relocated within the last five years had lower scores on HRQOL than those who had not relocated.</p> <p>Conclusion</p> <p>The strong relationship between GSE and HRQOL indicates that GSE might be a resource for increasing the HRQOL for school children.</p

Cognitive factors predicting intentions to search for health information: an application of the theory of planned behaviour

Peoples' ability to obtain health information is a precondition for their effective participation in decision making about health. However, there is limited evidence describing which cognitive factors can predict the intention of people to search for health information. To test the utility of a questionnaire in predicting intentions to search for health information, and to identify important predictors associated with this intention such that these could be targeted in an Intervention. A questionnaire was developed based on the Theory of Planned Behaviour and tested on both a mixed population sample (n=30) and a sample of parents (n = 45). The questionnaire was explored by testing for internal consistency, calculating inter-correlations between theoretically-related constructs, and by using multiple regression analysis. The reliability and validity of the questionnaire were found to be satisfactory and consistent across the two samples. The questionnaires' direct measures prediction of intention was high and accounted for 47% and 55% of the variance in behavioural intentions. Attitudes and perceived behavioural control were identified as important predictors to intention for search for health information. The questionnaire may be a useful tool for understanding and evaluating behavioural intentions and beliefs related to searches for health informatio

Important periods of weight development in childhood: a population-based longitudinal study

Background: Identifying important ages for the development of overweight is essential for optimizing preventive efforts. The purpose of the study was to explore early growth characteristics in children who become overweight or obese at the age of 8 years to identify important ages for the onset of overweight and obesity. Methods: Data from the Norwegian Child Growth Study in 2010 (N = 3172) were linked with repeated measurements from health records beginning at birth. Weight and height were used to derive the body mass index (BMI) in kg/m2. The BMI standard deviation score (SDS) for each participant was estimated at specific target ages, using a piecewise linear mixed effect model. Results: At 8 years of age, 20.4% of the children were overweight or obese. Already at birth, overweight children had a significantly higher mean BMI SDS than normal weight 8-year-olds (p < .001) and this difference increased in consecutive age groups in infancy and childhood. A relatively large increase in BMI during the first 9 months was identified as important for being overweight at 8 years. BMI SDS at birth was associated with overweight at 8 years of age (OR, 1.8; 1.6–2.0), and with obesity (OR, 1.8; 1.4–2.3). The Odds Ratios for the BMI SDS and change in BMI SDS further increased up to 1 year of age became very high from 2 years of age onwards. Conclusions: A high birth weight and an increasing BMI SDS during the first 9 months and high BMI from 2 years of age proved important landmarks for the onset of being overweight at 8 years of age. The risks of being overweight at 8 years appear to start very early. Interventions to prevent children becoming overweight should not only start at a very early age but also include the prenatal stage

The Time Course of Markers of Neutrophil Extracellular Traps in Patients Undergoing Revascularisation for Acute Myocardial Infarction or Stable Angina Pectoris

Background and Aims. Neutrophil extracellular traps (NETs) have been identified in acute myocardial infarction. We assessed the time profile and association with infarct size for NETs markers in ST-elevation myocardial infarction (STEMI) and stable angina pectoris (AP). Methods. In 20 patients with STEMI and 10 with AP undergoing percutaneous coronary intervention (PCI), blood samples were collected before PCI (only AP group) and after 3 and 12 hours, days 1, 3, 5, 7, and 14 for measurement of NETs markers. Results. Double-stranded deoxyribonucleic acid (dsDNA) and nucleosome levels were higher in STEMI than AP until day 3 and 12 hours ( &lt; 0.03, all). DsDNA declined after day 5 in both groups ( &lt; 0.04, all), while nucleosomes declined until day 3 only in the AP group ( &lt; 0.05, all). DsDNA correlated with peak troponin T and creatine kinase MB (CKMB) at day 5 ( = 0.48, = 0.03, both) and with MRI-measured infarct size at days 5 and 7 ( = 0.61, = 0.01 and = 0.52, = 0.04, resp.), while nucleosomes correlated with infarct size at day 5 ( = 0.58, = 0.02). Conclusions. High levels of NETs markers were observed in STEMI shortly after revascularisation and were partly associated with infarct size. The decline thereafter in both groups indicates a role for NETs in both acute and chronic atherothrombosis

The Time Course of Markers of Neutrophil Extracellular Traps in Patients Undergoing Revascularisation for Acute Myocardial Infarction or Stable Angina Pectoris

Background and Aims. Neutrophil extracellular traps (NETs) have been identified in acute myocardial infarction. We assessed the time profile and association with infarct size for NETs markers in ST-elevation myocardial infarction (STEMI) and stable angina pectoris (AP). Methods. In 20 patients with STEMI and 10 with AP undergoing percutaneous coronary intervention (PCI), blood samples were collected before PCI (only AP group) and after 3 and 12 hours, days 1, 3, 5, 7, and 14 for measurement of NETs markers. Results. Double-stranded deoxyribonucleic acid (dsDNA) and nucleosome levels were higher in STEMI than AP until day 3 and 12 hours (p<0.03, all). DsDNA declined after day 5 in both groups (p<0.04, all), while nucleosomes declined until day 3 only in the AP group (p<0.05, all). DsDNA correlated with peak troponin T and creatine kinase MB (CKMB) at day 5 (r=0.48, p=0.03, both) and with MRI-measured infarct size at days 5 and 7 (r=0.61, p=0.01 and r=0.52, p=0.04, resp.), while nucleosomes correlated with infarct size at day 5 (r=0.58, p=0.02). Conclusions. High levels of NETs markers were observed in STEMI shortly after revascularisation and were partly associated with infarct size. The decline thereafter in both groups indicates a role for NETs in both acute and chronic atherothrombosis

The Time Profile of Pentraxin 3 in Patients with Acute ST-Elevation Myocardial Infarction and Stable Angina Pectoris Undergoing Percutaneous Coronary Intervention

Background. High levels of Pentraxin 3 (PTX3) are reported in acute myocardial infarction (AMI). Aim. To investigate circulating levels and gene expression of PTX3 in patients with AMI and stable angina pectoris (AP) undergoing PCI. Methods. Ten patients with AP and 20 patients with AMI were included. Blood samples were drawn before PCI in the AP group and after 3 and 12 hours and days 1, 3, 5, 7, and 14 in both groups. Results. Circulating PTX3 levels were higher in AMI compared to AP at 3 and 12 hours (P<0.001 and P=0.003). Within the AMI group, reduction from 3 hours to all later time points was observed (all P≤0.001). Within the AP group, increase from baseline to 3 hours (P=0.022), followed by reductions thereafter (all P<0.05), was observed. PTX3 mRNA increased in the AMI group from 3 hours to days 7 and 14 in a relative manner of 62% and 73%, while a relative reduction from baseline to 3 and 12 hours of 29% and 37% was seen in the AP group. Conclusion. High circulating PTX3 levels shortly after PCI in AMI indicate that AMI itself influences PTX3 levels. PTX3 mRNA might be in response to fluctuations in circulating levels

Gestational diabetes mellitus among Nordic Caucasian women: Prevalence and risk factors according to WHO and simplified IADPSG criteria

Background. Gestational diabetes mellitus (GDM) is associated with both maternal and offspring adverse effects. The World Health Organization (WHO) has recently adopted novel GDM criteria. The aim of this study was to evaluate the former WHO and a simplified version of the new International Association for Diabetes in Pregnancy Study Group (IADPSG) criteria as to prevalence of and risk factors for GDM in a Nordic Caucasian population. Methods. A 75 g oral glucose tolerance test was performed in 687 women at 18-22 and 32-36 pregnancy weeks. GDM was defined according to the WHO criteria as fasting plasma glucose >= 7.0 mmol/L and/or 2-hour plasma glucose >= 7.8 mmol/L and by a simplified version of the IADPSG criteria as either fasting glucose >= 5.1 mmol/L and/or 2-h plasma glucose >= 8.5 mmol/L. One-hour glucose values were not available and were thus not included in the diagnosis of GDM by IADPSG. Prevalence of GDM during pregnancy and risk factors for GDM at 18-22 weeks were studied in retrospect according to each of the two criteria. Results. The total prevalence of GDM during pregnancy was 6.1% (42/687) for the WHO criteria and 7.4% (51/687) for the simplified IADPSG criteria. High maternal age and short stature were independently associated with WHO GDM. Maternal age, fasting insulin and no regular exercise at 18-22 pregnancy weeks associated with simplified IADPSG GDM. Conclusions. Simplified IADPSG criteria moderately increase GDM prevalence compared with the WHO criteria. Risk factors for GDM differ with the diagnostic criteria used