Fatty acid profile in cord blood of neonates born to optimally controlled gestational diabetes mellitus

OBJECTIVE: To evaluate the fatty acid profile of cord blood phospholipids (PL), cholesteryl esters (CE), triglycerides (TG) and non-esterified fatty acids (NEFA) in neonates born to mothers with gestational diabetes mellitus (GDM) compared to non-diabetic mothers. METHODS: The offspring of 30 pregnant women (15 non-diabetic controls, 15 with diet- or insulin-controlled GDM) were recruited before delivery. Cord blood was collected. After lipid extraction, PL, CE, TG and NEFA were separated by thin layer chromatography and analysed by gas chromatography. RESULTS: In GDM vs. control mothers, maternal glycated haemoglobin (A1C, mean±SD) was not different between groups: 5.3±0.5% vs. 5.3±0.3% (p=0.757), respectively. Cord plasma fatty acids were not different in TG, CE and NEFA between GDM and non-diabetic mothers. However, in PL, levels of palmitate, palmitoleate, oleate, vaccinate and di-homo-gamma-linolenate were significantly lower, with a trend for lower arachidonate (p=0.078), in neonates born to GDM mothers compared to controls. CONCLUSION: In contrast to other studies on cord blood docosahexaenoic acid (DHA) levels in GDM mothers, we did not found lower levels of DHA in cord PL, CE, TG or NEFA in neonates born to GDM compared to non-diabetic mothers

Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animal model

AbstractObjectiveAbnormal uterine contraction patterns were recently demonstrated in uterine strips from pregnant women treated with Levothyroxine (T4). These abnormalities were correlated with an increased risk of C-section delivery and associated surgical complications. To date, no study has investigated whether uterine contractility is modified by hypothyroidism or T4 treatment. Herein, we analyze the physiological role of T4 on uterine contractions.Study designFemale non-pregnant Sprague–Dawley rats (N = 22) were used and divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low T4 doses (20 μg/kg/day) and 4) with high T4 doses (100 μg/kg/day). Hypothyroidism was induced by an iodine-deficient diet. Isometric tension measurements were performed in vitro on myometrium tissues in isolated organ baths. Contractile activity parameters were quantified (amplitude, duration, frequency and area under the curve) using pharmacological tools to assess their effect.ResultsScreening of thyroid function confirmed a hypothyroid state for all rats under iodine-free diet to which T4 was subsequently administered to counterbalance hypothyroidism. Results demonstrate that hypothyroidism significantly decreased contractile duration (−17%) and increased contractile frequency (+26%), while high doses of T4 increased duration (+200%) and decreased frequency (−51%). These results thus mimic the pattern of abnormal contractions previously observed in uterine tissue from T4-treated hypothyroid pregnant women.ConclusionOur data suggest that changes in myometrial reactivity are induced by T4 treatment. Thus, in conjunction with our previous observations on human myometrial strips, management of hypothyroidism should be improved to reduce the rate of C-sections in this group of patients

Effects of caffeine and/or nasal CPAP treatment on laryngeal chemoreflexes in preterm lambs

Current knowledge suggests that laryngeal chemoreflexes (LCR) are involved in the occurrence of certain neonatal apneas/bradycardias, especially in the preterm newborn. While caffeine and/or nasal continuous positive airway pressure (nCPAP) are the most frequent options used for treating apneas in preterm newborns, their effects on LCR-related apneas/bradycardias are virtually unknown. The aim of the present study was to test the hypothesis that caffeine and/or nCPAP decreases LCR-related cardiorespiratory inhibition in a preterm ovine model. Seven preterm lambs were born vaginally on gestational day 133 (normal gestation: 147 days) after intramuscular injections of betamethasone and mifepristone. Five days after birth, a chronic surgical instrumentation was performed to record states of alertness, electrocardiogram, systemic arterial pressure, and electromyographic activity of a laryngeal constrictor muscle, as well as to insert a transcutaneous supraglottal catheter. LCR were induced in quiet sleep under four conditions: 1) control (without caffeine or nCPAP); 2) nCPAP (5 cmH2O, without caffeine); 3) caffeine (10 mg/kg infused intravenously for 30 min, without nCPAP); and 4) nCPAP + caffeine. Our results showed that nCPAP consistently blunted LCR-related cardiorespiratory inhibition vs. control condition, contrary to caffeine whose overall effect was nonsignificant. In addition, nCPAP condition was characterized by a more consistent and rapid arousal after HCl injection. No significant differences were observed between all tested conditions with regard to swallowing and cough. It is concluded that nCPAP should be further assessed for its usefulness in treating neonatal apneas linked to LCR

In Utero Exposure to Persistent Organic Pollutants and Childhood Lipid Levels

Animal studies have shown that developmental exposures to polybrominated diphenyl ethers (PBDE) permanently affect blood/liver balance of lipids. No human study has evaluated associations between in utero exposures to persistent organic pollutants (POPs) and later life lipid metabolism. In this pilot, maternal plasma levels of PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) and polychlorinated biphenyls (PCB-138, PCB-153, and PCB-180) were determined at delivery in participants of GESTation and Environment (GESTE) cohort. Total cholesterol (TCh), triglycerides (TG), low- and high-density lipoproteins (LDL-C and HDL-C), total lipids (TL), and PBDEs were determined in serum of 147 children at ages 6–7. General linear regression was used to estimate the relationship between maternal POPs and child lipid levels with adjustment for potential confounders, and adjustment for childhood POPs. In utero BDE-99 was associated with lower childhood levels of TG (p = 0.003), and non-significantly with HDL-C (p = 0.06) and TL (p = 0.07). Maternal PCB-138 was associated with lower childhood levels of TG (p = 0.04), LDL-C (p = 0.04), and TL (p = 0.02). Our data indicate that in utero exposures to POPs may be associated with long lasting decrease in circulating lipids in children, suggesting increased lipid accumulation in the liver, a mechanism involved in NAFLD development, consistent with previously reported animal data

3D Cohort Study : The Integrated Research Network in Perinatology of Quebec and Eastern Ontario

Background: The 3D Cohort Study (Design, Develop, Discover) was established to help bridge knowledge gaps about the links between various adverse exposures during pregnancy with birth outcomes and later health outcomes in children. Methods: Pregnant women and their partners were recruited during the first trimester from nine sites in Quebec and followed along with their children through to 2 years of age. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, mental health and life style, medical history, psychosocial measures, diet, infant growth, and neurodevelopment. Information on the delivery and newborn outcomes were abstracted from medical charts. Biological specimens were collected from mothers during each trimester, fathers (once during the pregnancy), and infants (at delivery and 2 years of age) for storage in a biological specimen bank. Results: Of the 9864 women screened, 6348 met the eligibility criteria and 2366 women participated in the study (37% of eligible women). Among women in the 3D cohort, 1721 of their partners (1704 biological fathers) agreed to participate (73%). Two thousand two hundred and nineteen participants had a live singleton birth (94%). Prenatal blood and urine samples as well as vaginal secretions were collected for ≥98% of participants, cord blood for 81% of livebirths, and placental tissue for 89% of livebirths. Conclusions: The 3D Cohort Study combines a rich bank of multiple biological specimens with extensive clinical, life style, and psychosocial data. This data set is a valuable resource for studying the developmental etiology of birth and early childhood neurodevelopmental outcomes

Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk.

BACKGROUND: We have followed-up on the recent genome-wide association (GWA) of the clusterin gene (CLU) with increased risk for Alzheimer disease (AD), by performing an unbiased resequencing of all CLU coding exons and regulatory regions in an extended Flanders-Belgian cohort of Caucasian AD patients and control individuals (n = 1930). Moreover, we have replicated genetic findings by targeted resequencing in independent Caucasian cohorts of French (n = 2182) and Canadian (n = 573) origin and by performing meta-analysis combining our data with previous genetic CLU screenings. RESULTS: In the Flanders-Belgian cohort, we identified significant clustering in exons 5-8 of rare genetic variations leading to non-synonymous substitutions and a 9-bp insertion/deletion affecting the CLU β-chain (p = 0.02). Replicating this observation by targeted resequencing of CLU exons 5-8 in 2 independent Caucasian cohorts of French and Canadian origin identified identical as well as novel non-synonymous substitutions and small insertion/deletions. A meta-analysis, combining the datasets of the 3 cohorts with published CLU sequencing data, confirmed that rare coding variations in the CLU β-chain were significantly enriched in AD patients (OR(MH) = 1.96 [95% CI = 1.18-3.25]; p = 0.009). Single nucleotide polymorphisms (SNPs) association analysis indicated the common AD risk association (GWA SNP rs11136000, p = 0.013) in the 3 combined datasets could not be explained by the presence of the rare coding variations we identified. Further, high-density SNP mapping in the CLU locus mapped the common association signal to a more 5' CLU region. CONCLUSIONS: We identified a new genetic risk association of AD with rare coding CLU variations that is independent of the 5' common association signal identified in the GWA studies. At this stage the role of these coding variations and their likely effect on the β-chain domain and CLU protein functioning remains unclear and requires further studies.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

QUARITE (quality of care, risk management and technology in obstetrics): a cluster-randomized trial of a multifaceted intervention to improve emergency obstetric care in Senegal and Mali

<p>Abstract</p> <p>Background</p> <p>Maternal and perinatal mortality are major problems for which progress in sub-Saharan Africa has been inadequate, even though childbirth services are available, even in the poorest countries. Reducing them is the aim of two of the main Millennium Development Goals. Many initiatives have been undertaken to remedy this situation, such as the Advances in Labour and Risk Management (ALARM) International Program, whose purpose is to improve the quality of obstetric services in low-income countries. However, few interventions have been evaluated, in this context, using rigorous methods for analyzing effectiveness in terms of health outcomes. The objective of this trial is to evaluate the effectiveness of the ALARM International Program (AIP) in reducing maternal mortality in referral hospitals in Senegal and Mali. Secondary goals include evaluation of the relationships between effectiveness and resource availability, service organization, medical practices, and satisfaction among health personnel.</p> <p>Methods/Design</p> <p>This is an international, multi-centre, controlled cluster-randomized trial of a complex intervention. The intervention is based on the concept of evidence-based practice and on a combination of two approaches aimed at improving the performance of health personnel: 1) Educational outreach visits; and 2) the implementation of facility-based maternal death reviews.</p> <p>The unit of intervention is the public health facility equipped with a functional operating room. On the basis of consent provided by hospital authorities, 46 centres out of 49 eligible were selected in Mali and Senegal. Using randomization stratified by country and by level of care, 23 centres will be allocated to the intervention group and 23 to the control group. The intervention will last two years. It will be preceded by a pre-intervention one-year period for baseline data collection. A continuous clinical data collection system has been set up in all participating centres. This, along with the inventory of resources and the satisfaction surveys administered to the health personnel, will allow us to measure results before, during, and after the intervention. The overall rate of maternal mortality measured in hospitals during the post-intervention period (Year 4) is the primary outcome. The evaluation will also include cost-effectiveness.</p> <p>Trial Registration</p> <p>The QUARITE trial is registered on the Current Controlled Trials website under the number ISRCTN46950658 <url>http://www.controlled-trials.com/</url>.</p

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

Amyloid-beta 42 (A beta 42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for A beta 42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple A beta 42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.Peer reviewe