Clinical utility of g-cimp and idh1 status as dual prognostic markers in glioblastoma

The glioma CpG island methylator phenotype (G-CIMP) has been shown to be highly correlated with prognosis andwas noted to be highly concordant with IDH1mutation in malignant glioma in the limited number of samples analyzed. To better understand the relationship of G-CIMP with IDH1 mutation status and patient outcome, we examined G-CIMP status in detail in a larger retrospective series of glioblastomas as well as tumor samples from the RTOG 0525 clinical trial. Sampleswere tested for 6 CIMPmarkers andwere correlated with patient outcomes. In the retrospective tumor set (n ¼ 301),we found 3 distinct survival groups based on the number of CIMP markers: 0-1 (CIMP-negative), 2-4 (CIMP-intermediate), and 5 or greater (CIMP-positive) with median survivals 13.8, 20.1, and 90.6 months, respectively. This finding was validated in the RTOG 0525 samples (median survivals 15.0, 20.3, and 37.0 months). Among 787 cases with both IDH and CIMP data, 617 were CIMP-negative, 136 were CIMP-intermediate, and 34 were CIMP-positive. Seven hundred forty-four were wild type for IDH1 mutation, and 43 were mutant. CIMP and IDH status were positively correlated but outliers were found. Among the 610 CIMP-negative tumors, there were 7 IDH-mutant tumors, which showed no difference in outcome. Similarly, among the 34 CIMP-positive tumors, there were 21 IDH-mutant cases, which also showed no difference in outcome. However, among the CIMP-intermediate cases, there were 15 IDH-mutant cases with significantly (p ¼ 0.0003) improved outcome (medians not reached vs. 18.5 months, 2 year survival 87% vs. 32%). Multivariate analysis showed that both IDH1 mutation status and CIMP status were independent predictors of outcome. These findings suggest the clinical utility of refining the CIMP status into negative, intermediate, and positive groups and the finding that both IDH1 and CIMPstatus are important molecular markers in GBM.

Epidemiology of inflammatory bowel disease: Is there a shift towards onset at a younger age?

OBJECTIVES: Increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) are reported. To determine whether this observation is a consequence of a shift towards onset at a younger age, we analysed retrospective data from patients enrolled in the Swiss IBD Cohort Study (SIBDCS). PATIENTS AND METHODS: The SIBDCS is a disease-based cohort in Switzerland, which collects retrospective and prospective data on a large sample of patients with inflammatory bowel disease (IBD). Patients, diagnosed from 1980, were stratified according to diagnosis of CD and UC. Age at disease onset (age at first symptoms and age at diagnosis) was analysed in relation to calendar year of disease onset. Data were extracted from physician and patient questionnaires. Linear regressions of age at disease onset by calendar year of disease onset adjusted by sex, country of birth, and education were performed. RESULTS: Adjusted regression coefficients for CD and UC were significantly positive, that is, age at disease onset has increased with time. Male sex was associated with an increase in age at disease onset, and birth in Switzerland with a decrease. These associations were statistically significant. CONCLUSIONS: The results from the SIBDCS do not support the hypothesis that disease onset of both CD and UC occur today at a younger age. On the contrary, our results show that there is a significant trend for age at disease onset occurring at an older age today as compared with recent decades. We conclude that the observation of increasing numbers of paediatric and adolescent patients with IBD is not caused by a trend towards disease onset at a younger age, but that this may rather be a consequence of the overall increasing incidence of these conditions.

Gender differences in paediatric patients of the swiss inflammatory bowel disease cohort study.

PURPOSE: Gender differences in paediatric patients with inflammatory bowel disease (IBD) are frequently reported as a secondary outcome and the results are divergent. To assess gender differences by analysing data collected within the Swiss IBD cohort study database since 2008, related to children with IBD, using the Montreal classification for a systematic approach. METHODS: Data on gender, age, anthropometrics, disease location at diagnosis, disease behaviour, and therapy of 196 patients, 105 with Crohn's disease (CD) and 91 with ulcerative or indeterminate colitis (UC/IC) were retrieved and analysed. RESULTS: THE CRUDE GENDER RATIO (MALE : female) of patients with CD diagnosed at <10 years of age was 2.57, the adjusted ratio was 2.42, and in patients with UC/IC it was 0.68 and 0.64 respectively. The non-adjusted gender ratio of patients diagnosed at ≥10 years was 1.58 for CD and 0.88 for UC/IC. Boys with UC/IC diagnosed <10 years of age had a longer diagnostic delay, and in girls diagnosed with UC/IC >10 years a more important use of azathioprine was observed. No other gender difference was found after analysis of age, disease location and behaviour at diagnosis, duration of disease, familial occurrence of IBD, prevalence of extra-intestinal manifestations, complications, and requirement for surgery. CONCLUSION: CD in children <10 years affects predominantly boys with a sex ratio of 2.57; the impact of sex-hormones on the development of CD in pre-pubertal male patients should be investigated.

Pseudotumeur inflammatoire de la caroncule [Inflammatory pseudotumor of the caruncle].

A 6-year-old girl exhibited a recent caruncular tumor which was increasing in size. It was removed after a CT scan had showed a both medial and superficial mass. Fortunately, histological tests only found inflammatory cells attesting that the mass was due to an inflammation of this area. Inflammation is one of the different processes that may increase the size of the caruncle, but sometimes, only histopathology can provide conclusive evidence.

Contrasting the form and use of reformulation markers

This paper deals with the form and use of reformulation markers in research papers written in English, Spanish and Catalan. Considering the form and frequency of themarkers, English papers tends to prefer simple fixed markers and includes less reformulators than Spanish and Catalan. On the contrary, formal Catalan and Spanish papers include more markers, some of which are complex and allow for some structural variability. As for use, reformulation markers establish dynamic relationships between portions of discourse which can be identified in our corpus with expansion, reduction, and permutation. The analysis of the corpus shows that English authors usually reformulate to add more information to the concept (expansion), whereas Catalan and Spanish authors reduce the contents or the implicatures of the previous formulation more frequently than English.

Exhaled breath condensate (EBC) as a matrix for nanoparticle exposure and health effect evaluation : final scientific report

The aim of this pilot project was to evaluate the feasibility of assessing the deposited particle dose in the lungs by applying the dynamic light scattering-based methodology in exhaled breath condensateur (EBC). In parallel, we developed and validated two analytical methods allowing the determination of inflammatory (hydrogen peroxide - H2O2) and lipoperoxidation (malondialdehyde - MDA) biomarkers in exhaled breath condensate. Finally, these methods were used to assess the particle dose and consecutive inflammatory effect in healthy nonsmoker subjects exposed to environmental tobacco smoke in controlled situations was done.

Association of education and receiving social transfers with allostatic load in the Swiss population-based CoLaus study.

BACKGROUND: Allostatic load reflects cumulative exposure to stressors throughout lifetime and has been associated with several adverse health outcomes. It is hypothesized that people with low socioeconomic status (SES) are exposed to higher chronic stress and have therefore greater levels of allostatic load. OBJECTIVE: To assess the association of receiving social transfers and low education with allostatic load. METHODS: We included 3589 participants (1812 women) aged over 35years and under retirement age from the population-based CoLaus study (Lausanne, Switzerland, 2003-2006). We computed an allostatic load index aggregating cardiovascular, metabolic, dyslipidemic and inflammatory markers. A novel index additionally including markers of oxidative stress was also examined. RESULTS: Men with low vs. high SES were more likely to have higher levels of allostatic load (odds ratio (OR)=1.93/2.34 for social transfers/education, 95%CI from 1.45 to 4.17). The same patterns were observed among women. Associations persisted after controlling for health behaviors and marital status. CONCLUSIONS: Low education and receiving social transfers independently and cumulatively predict high allostatic load and dysregulation of several homeostatic systems in a Swiss population-based study. Participants with low SES are at higher risk of oxidative stress, which may justify its inclusion as a separate component of allostatic load.

Prevalence of inflammatory bowel disease in the canton of Vaud (Switzerland) : a population-based cohort study

Abstract : Background and aims: Because of the changing epidemiology of Inflammatory Bowel Diseases (IBD), we set out to characterize the population-based prevalence of Crohn's Disease (CD) and Ulcerative Colitis (UC) in a defined population of Switzerland. Methods: Adult IBD patients were identified by across-matched review of histological, hospital and gastroenterologist files throughout a geographical defined population (Canton of Vaud). Demographic factors statistically significantly associated with prevalence were evaluated using a stepwise Poisson regression analysis. Results were compared to IBD prevalence rates in other population-based studies and time trends were performed, based on a systematic literature review. Results: Age and sex-adjusted prevalence rates were 205.7 IBD (100.7 CD and 105.0 UC) cases per 10,5 inhabitants. Among 1016 IBD patients (519 CD and 497 UC), females outnumbered males in CD (p<0.001), but males were more represented in elderly UC patients (p=0.008). Thus, being a mate was statistically associated with UC (Relative Risk (RR) 1.25; p=0.013), whereas being a female was associated with CD (RR 1.27; p=0.007). Living in an urban zone was associated with both CD and UC (RR 1.49; p<0.001, 1.63; p<0.001, respectively). From 1960 to 2005, increases in UC and CD prevalences of 2.4% (95%CI, 2.1%-2.8%; p<0.001) and 3.6% (95%CI, 3.1%-4.1%; p<0.001) per annum were found in industrialised countries. Résumé de synthèse : 1. Introduction : Étant donné l'évolution constante des donnés épidémiologiques sur les maladies inflammatoires chroniques de l'intestin (MICI), nous avons recherché à caractériser la prévalence de la maladie de Crohn (MC) et de la colite ulcéreuse (CU) dans une population définie de la Suisse. 2. Méthodes : Nous avons identifiés, dans une population délimitée au Canton de Vaud, les patients adultes atteints de maladies inflammatoires de l'intestin en regroupant les données histologiques et médicales disponibles à l'hôpital et au cabinet du gastroentérologue. Pour nos analyses, nous avons utilisé la méthode de la régression de Poisson afin d'identifier les facteurs démographiques significativement liés avec la prévalence. Ensuite, nos résultats ont été comparés aux valeurs de prévalence des MICI issues d'autres études de population (revue systématique de la littérature) afin de dégager les tendances de leur évolution au cours du temps. 3. Résultats : La prévalence des MICI pondérée selon l'âge et le sexe était de 205.7 cas (100.7 MC et 105.0 CU) pour 10,5 habitants. Parmi les 1016 patients identifiés (519 MC et 497 CU), les femmes étaient plus représentées que les hommes dans la MC (P<0.0001), alors que la proportion d'hommes dépassait celle des femmes chez les patients âgés atteints de CU (p=0.008). Par conséquent, le fait d'être un homme était statistiquement associé à la CU (Risque relatif (RR) 1.25, p=0.013), et celui d'être une femme était associé à la MC (RR 1.27 ; p=0.007). L'étude a également montré qu'habiter en zone urbaine était significativement associé avec les deux types de MICI (RR (MC) 1.49; p<0.001, (CU) 1.63; p<0.001). Enfin, il a été mis en évidence dans les pays industrialisés, entre 1960 et 2005, une augmentation annuelle des taux de prévalences de 2.4% (95% IC, 2.1 %-2.8% ; p<0.001) pour la MC et de 3.6% (95% IC, 3.1 %-4.1 % ; p<0.001) pour la CU. 4. Conclusion : L'extrapolation de nos données au niveau Suisse fournit une estimation de 12 000 cas de MICI pour le pays soit 1 cas pour 500 habitants. Notre étude contribue également à démontrer une augmentation de la prévalence des MICI en Europe.

Topographical body fat distribution links to amino acid and lipid metabolism in healthy non-obese women.

Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2)) under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

Forensic identification of urine samples: a comparison between nuclear and mitochondrial DNA markers.

Urine samples from 20 male volunteers of European Caucasian origin were stored at 4 degrees C over a 4-month period in order to compare the identification potential of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) markers. The amount of nDNA recovered from urines dramatically declined over time. Consequently, nDNA likelihood ratios (LRs) greater than 1,000 were obtained for 100, 70 and 55% of the urines analysed after 6, 60 and 120 days, respectively. For the mtDNA, HVI and HVII sequences were obtained for all samples tested, whatever the period considered. Nevertheless, the highest mtDNA LR of 435 was relatively low compared to its nDNA equivalent. Indeed, LRs obtained with only three nDNA loci could easily exceed this value and are quite easier to obtain. Overall, the joint use of nDNA and mtDNA markers enabled the 20 urine samples to be identified, even after the 4-month period.

The course of inflammatory bowel disease during pregnancy and postpartum: a prospective European ECCO-EpiCom Study of 209 pregnant women.

BACKGROUND: The impact of pregnancy on the course of IBD is still controversial. AIM: To investigate the impact of pregnancy on IBD and to search for factors with potential impact on remission. METHODS: Pregnant IBD women from 12 European countries were enrolled between January 2003 and December 2006 and compared at conception (1:1) with nonpregnant IBD women. Data on disease course were prospectively collected at each trimester during pregnancy and in the postpartum (6 months) using a standardised questionnaire. RESULTS: A total of 209 pregnant IBD women were included: 92 with Crohn's disease (CD; median age 31 years, range 17-40) and 117 with ulcerative colitis (UC; median age 32 years, range 19-42). No statistically significant difference in disease course during pregnancy and postpartum was observed between pregnant and nonpregnant CD women. Longer disease duration in CD and immunosuppressive therapy were found to be risk factors for activity during pregnancy. Pregnant UC women were more likely than nonpregnant UC women to relapse both during pregnancy (RR 2.19; 95% CI: 1.25-3.97, 0.004) and postpartum (RR 6.22; 95% CI: 2.05-79.3, P = 0.0004). During pregnancy, relapse was mainly observed in the first (RR 8.80; 95% CI 2.05-79.3, P < 0.0004) and the second trimester (RR 2.84, 95% CI 1.2-7.45, P = 0.0098). CONCLUSIONS: Pregnant women with Crohn's disease had a similar disease course both during pregnancy and after delivery as the nonpregnant women. In contrast, pregnant women with ulcerative colitis were at higher risk of relapse during pregnancy and in the postpartum than nonpregnant ulcerative colitis women.

The Toarcian in the Subbetic basin (southern Spain): Bio-events (ammonite and calcareous nannofossils) and carbon-isotope stratigraphy

A detailed carbon-isotope stratigraphic study for the uppermost Pliensbachian lowermost Aalenian interval in the Median Subbetic palaeogeographic domain (External zones of the Betic Cordillera, southern Spain) has been carried out. During the Early Jurassic, the Median Subbetic, which represents a typical basin of the Hispanic Corridor connecting the Tethys and the Eastern Pacific, was located in the westernmost Tethys. The analyzed sections encompass the entire Toarcian stage as represented in the southern Iberian palaeomargin. Rocks are mainly rhythmic sequences of grey marls and marly limestones containing a rich ammonite fauna, nannofossils, and benthic foraminifers-all these provide an accurate biostratigraphic control. The lower and upper Toarcian boundaries are well represented in some of these sections and therefore represent optimal sites to link the carbon-isotope curves to ammonite zones, and to nannofossil events. delta C-13 values of bulk carbonates from the different localities of the Subbetic basin have similar variations from the uppermost Pliensbachian to the lowermost Aalenian, suggesting changes in the original DIC carbon isotope composition along the Hispanic corridor. The transition from Pliensbachian to Toarcian is marked by increasing delta C-13 values from similar to 12 to 2.0 parts per thousand, interrupted in the Serpentinum Zone by a negative shift concomitant with the Toarcian oceanic anoxic event (T-OAE), with the major ammonite extinction event of the Toarcian, and an important turnover of calcareous nannoplankton. The negative shift observed in the Serpentinum Zone confirms the global perturbation of the carbon cycling documented along the Tethys and the palaeo-Pacific in organic material and in marine carbonates. However, the amplitude of the negative excursion (similar to - 1.5 parts per thousand) is not compatible with an isotopic homogeneous seawater DIC and/or CO2 atmospheric reservoirs. The interval from the middle to the top of the Toarcian delta C-13 shows relatively constant values, minor ammonite turnovers, and is associated with increasing diversity of calcareous nannoplankton. (c) 2012 Elsevier B.V. All rights reserved.

Development of neuronal markers in aggregating fetal rat telencephalon cells cultured in the presence of triiodothyronine.

The concentrations of the general neuronal markers D2-protein (N-CAM), D3-protein and neuron specific enolase (NSE) in reaggregating cultures of fetal rat telencephalon cells were affected by the presence of 30 nM triiodothyronine in the defined culture medium. The extent of normal developmental changes were enhanced by triiodothyronine, as demonstrated by crossed immunoelectrophoresis. From 13 to 19 days in culture, the concentration of D2-protein decreased, and the concentrations of both D3-protein and NSE increased. Nerve growth factor (NGF) was without effect on the development of these general neuronal markers. However, as shown previously both triiodothyronine and NGF increased the activity of choline acetyltransferase, a marker for cholinergic neurons. The results suggest an enhanced overall differentiation of several types of telencephalon neurons in the presence of triiodothyronine, and a specific stimulation of cholinergic telencephalon neurons by NGF.