Analysis of epigenetic changes in survivors of preterm birth reveals the effect of gestational age and evidence for a long term legacy

BACKGROUND: Preterm birth confers a high risk of adverse long term health outcomes for survivors, yet the underlying molecular mechanisms are unclear. We hypothesized that effects of preterm birth can be mediated through measurable epigenomic changes throughout development. We therefore used a longitudinal birth cohort to measure the epigenetic mark of DNA methylation at birth and 18 years comparing survivors of extremely preterm birth with infants born at term. METHODS: Using 12 extreme preterm birth cases and 12 matched, term controls, we extracted DNA from archived neonatal blood spots and blood collected in a similar way at 18 years of age. DNA methylation was measured at 347,789 autosomal locations throughout the genome using Infinium HM450 arrays. Representative methylation differences were confirmed by Sequenom MassArray EpiTYPER. RESULTS: At birth we found 1,555 sites with significant differences in methylation between term and preterm babies. At 18 years of age, these differences had largely resolved, suggesting that DNA methylation differences at birth are mainly driven by factors relating to gestational age, such as cell composition and/or maturity. Using matched longitudinal samples, we found evidence for an epigenetic legacy associated with preterm birth, identifying persistent methylation differences at ten genomic loci. Longitudinal comparisons of DNA methylation at birth and 18 years uncovered a significant overlap between sites that were differentially-methylated at birth and those that changed with age. However, we note that overlapping sites may either differ in the same (300/1,555) or opposite (431/1,555) direction during gestation and aging respectively. CONCLUSIONS: We present evidence for widespread methylation differences between extreme preterm and term infants at birth that are largely resolved by 18 years of age. These results are consistent with methylation changes associated with blood cell development, cellular composition, immune induction and age at these time points. Finally, we identified ten probes significantly associated with preterm individuals and with greater than 5% methylation discordance at birth and 18 years that may reflect a long term epigenetic legacy of preterm birth

Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace (Review)

Backgroun

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Capacity for absorption and relaxation during electromyograph biofeedback and no-feedback conditions

Examined the relation between absorption capacity and relaxation during EMG biofeedback and no-feedback (instructions only) conditions. 16 high absorption and 16 low absorption female undergraduates underwent a biofeedback and a no-feedback session with the order of conditions counterbalanced. For high absorption Ss in the 1st session, EMG reductions were greater during no-feedback than during biofeedback, although the performance of biofeedback Ss improved in the 2nd session. For low absorption Ss, no differences in EMG reductions were apparent across experimental conditions. Postexperimental self-report data demonstrated differences between absorption groups in Ss' state of arousal and quality of consciousness. It is concluded that for Ss with high capacity for absorbed attention, experimental conditions that allow for a withdrawal from the external environment are most conducive to relaxation, whereas for Ss with limited capacity for absorbed attention, conditions such as biofeedback that place an attentional demand on Ss may be preferable. (31 ref) (PsycINFO Database Record (c) 2006 APA, all rights reserved)

5β-Dihydroprogesterone and steroid 5β-reductase decrease in association with human parturition at term

The role of progesterone withdrawal in human parturition continues to provoke controversy. One possible mechanism by which functional progesterone withdrawal may be achieved is by a decrease in the circulating concentration of its bioactive metabolites. The progesterone metabolite 5 beta-dihydroprogesterone (5 beta DHP) has been shown to be a potent tocolytic in vitro. We quantified plasma concentrations of 5 beta DHP in association with the onset of spontaneous labour in women at term and steroid 5 beta-reductase mRNA expression in placenta, myometrium, chorion and amnion in relation to parturition, using real time RT-PCR. Serial blood samples were obtained from patients late in pregnancy, before term labour, during term labour and within the first 24 h postpartum. Following organic solvent extraction, steroids including 5 beta DHP were separated by high-performance liquid chromatography ( HPLC) and then quantified by radioimmunoassay (RIA). 5 beta DHP concentration decreased two-fold ( P = 0.00001, n = 25) from 0.317 +/- 0.039 nmol/ml to 0.178 +/- 0.017nmol/ml in association with active labour. Tissue 5 beta-reductase mRNA-relative abundance was determined in placenta, myometrium, chorion and amnion obtained from labouring and non-labouring women. In placenta and myometrium, relative expression decreased significantly in association with labour, by about two-fold and 10-fold, respectively. These data are consistent with a possible role for 5 beta DHP in the onset of spontaneous human labour. Further studies exploring this hitherto unrecognized endocrinological pathway are indicated

Clinical Application of Quantitative Foetal Fibronectin for the Prediction of Preterm Birth in Symptomatic Women

Aim: To evaluate the clinical application of the new Hologic quantitative foetal fibronectin (qfFN) bedside test for the prediction of spontaneous preterm birth (sPTB) in patients with symptoms suggestive of spontaneous threatened preterm labour (sPTL). Methods: A prospective observational study with 154 pregnant women presenting signs and symptoms of sPTL was conducted. These women were subjected to a qfFN test between 22 and 35 weeks of gestation For each cut-off threshold, the ability to predict sPTB at within 14 days of conducting the test and 200 ng/mL produced a 50.0% PPVthus, qfFN added enhanced discrimination between high- and low-risk patients. The overall rate of sPTB (< 37) was 13.3% (16/120), which increased progressively with increasing levels of fFN, with rates of 9.8% (8/81), 11.5% (3/26), 14.2% (1/7), 50% (3/6) within the 4 categories (fFN 0-9, 10-49, 50-200, 200+) respectively. Conclusions: The use of the qfFN testing in symptomatic patients allowed for more accurate identification of women at risk of sPTB and thus more directed management. (C) 2017 S. Karger AG, BaselUniv Melbourne, Royal Womens Hosp, Dept Perinatal Med, Parkville, Vic, AustraliaUniv Melbourne, Royal Womens Hosp, Dept Obstet & Gynaecol, Parkville, Vic, AustraliaMonash Univ, Dept Obstet & Gynaecol, Clayton, Vic, AustraliaMonash Ultrasound Women, Clayton, Vic, AustraliaUniv Fed Sao Paulo, Paulista Sch Med, Dept Obstet, Sao Paulo, BrazilUniv Fed Sao Paulo, Paulista Sch Med, Dept Obstet, Sao Paulo, BrazilWeb of Scienc

Identification of biochemical biomarkers associated with premature cervical shortening in high-risk, asymptomatic pregnant women: a retrospective data analysis

Reliably predicting spontaneous preterm birth remains challenging, therefore it persists as a major contributor to perinatal morbidity and mortality. The use of biomarkers to predict premature cervical shortening, a recognised risk factor for spontaneous preterm birth, is yet to be fully explored in current literature. This study evaluates seven cervicovaginal biochemical biomarkers as possible predictors of premature cervical shortening. Asymptomatic, high-risk women (n = 131) presenting to a specialised preterm birth prevention clinic were analysed through a retrospective data analysis. Cervicovaginal biochemical biomarker concentrations were obtained, and the shortest cervical length measurement, up to 28 weeks’ gestation, was recorded. Associations between biomarker concentration and cervical length were then analysed. Of the seven biochemical biomarkers, Interleukin-1 Receptor Antagonist and Extracellular Matrix Protein-1 had statistically significant relationships with cervical shortening below 25 mm. Further investigation is required to validate these findings and any downstream clinical utility, with intentions to improve perinatal outcomes.IMPACT STATEMENT What is already known on this subject? Preterm birth is a major cause of perinatal morbidity and mortality. A woman’s risk of delivering preterm is currently stratified using historical risk factors, mid-gestation cervical length, and biochemical biomarkers such as foetal fibronectin. What do the results of this study add? In a cohort of high-risk, asymptomatic pregnant women, two cervicovaginal biochemical biomarkers, Interleukin-1 Receptor Antagonist and Extracellular Matrix Protein-1, displayed associations with premature cervical shortening. What are the implications of these findings for clinical practice and/or further research? Further investigation into the possible clinical utility of these biochemical biomarkers is warranted, with a view to improving preterm birth prediction and antenatal resource utilisation, thereby reducing the burden of preterm birth and its sequelae in a cost-effective manner

Objets en procès : après la dématérialisation de l'art = Objects In Progress : After the Dematerialisation of Art

"In the 1970s, talking about the « dematerialisation of art » meant taking stock of the transformations effected in art by « conceptual » approaches. This book lays out the problem of dematerialisation in a fresh way. What is going on with the materiality of works that are deployed in space, as installations, or play out over time, such as performance art ? The various essays brought together here are less attuned to the absence of objects than to the questioning of their character as works of art. Looming on the horizon of late-twentieth-century art, the notion of the object is worth exploring by rethinking its materiality in terms of how space and time put it to the test" -- p [4] of cover