Door-to-balloon delays before primary angioplasty in the Regional Acute Myocardial Infarction Registry of Brittany. An analysis of the Observatoire Régional Breton sur l’Infarctus du myocarde (ORBI)

Minimizing delays to coronary reperfusion is critical in the management of acute myocardial infarction (AMI).

Coping styles as moderating the relationships between terrorist attacks and well‐being outcomes

This study aims to explore use of coping strategies among adolescents and their relationships with well being in the context of ongoing terrorism. Furthermore, we aim to explore to what extent coping styles in addition to exposure variables explain well being of adolescents facing ongoing terror. During September 2003, after three years of ongoing terror attacks, 913 Israeli adolescents aged 12–18 years, completed the following questionnaires during regular class sessions: Demographics, Achenbach's Youth Self Report; Exposure to Terror and Post Traumatic Stress (PTS) questionnaire; Adolescent Coping Scale (ACS) and Brief Symptoms Inventory. Adolescents employed mainly problem solving strategies which mean they have the capacity to cope well in spite of stressful events. Emotional focused coping was associated with PTS and mental health problems. Regression analysis of different exposure and coping variables revealed that exposure, appraisal (subjective exposure) and coping styles explained 26–37% of the variance of different psychological problems. The findings highlight the importance of appraisal (subjective exposure) and coping strategies, for understanding adolescents' mental health outcomes. Moreover, these findings are relevant to the development of prevention/intervention programs that facilitate youth's cognitive and emotional adjustments to ongoing trauma risks and terror threats.

TMEM126A, Encoding a Mitochondrial Protein, Is Mutated in Autosomal-Recessive Nonsyndromic Optic Atrophy

Nonsyndromic autosomal-recessive optic neuropathies are rare conditions of unknown genetic and molecular origin. Using an approach of whole-genome homozygosity mapping and positional cloning, we have identified the first gene, to our knowledge, responsible for this condition, TMEM126A, in a large multiplex inbred Algerian family and subsequently in three other families originating from the Maghreb. TMEM126A is conserved in higher eukaryotes and encodes a transmembrane mitochondrial protein of unknown function, supporting the view that mitochondrial dysfunction may be a hallmark of inherited optic neuropathies including isolated autosomal-recessive forms.

Deficiency of Dol-P-Man Synthase Subunit DPM3 Bridges the Congenital Disorders of Glycosylation with the Dystroglycanopathies

Alpha-dystroglycanopathies such as Walker Warburg syndrome represent an important subgroup of the muscular dystrophies that have been related to defective O-mannosylation of alpha-dystroglycan. In many patients, the underlying genetic etiology remains unsolved. Isolated muscular dystrophy has not been described in the congenital disorders of glycosylation (CDG) caused by N-linked protein glycosylation defects. Here, we present a genetic N-glycosylation disorder with muscular dystrophy in the group of CDG type I. Extensive biochemical investigations revealed a strongly reduced dolichol-phosphate-mannose (Dol-P-Man) synthase activity. Sequencing of the three DPM subunits and complementation of DPM3-deficient CHO2.38 cells showed a pathogenic p.L85S missense mutation in the strongly conserved coiled-coil domain of DPM3 that tethers catalytic DPM1 to the ER membrane. Cotransfection experiments in CHO cells showed a reduced binding capacity of DPM3(L85S) for DPM1. Investigation of the four Dol-P-Man-dependent glycosylation pathways in the ER revealed strongly reduced O-mannosylation of alpha-dystroglycan in a muscle biopsy, thereby explaining the clinical phenotype of muscular dystrophy. This mild Dol-P-Man biosynthesis defect due to DPM3 mutations is a cause for alpha-dystroglycanopathy, thereby bridging the congenital disorders of glycosylation with the dystroglycanopathies.

Allele-Specific Chromatin Remodeling in the ZPBP2/GSDMB/ORMDL3 Locus Associated with the Risk of Asthma and Autoimmune Disease

Common SNPs in the chromosome 17q12-q21 region alter the risk for asthma, type 1 diabetes, primary biliary cirrhosis, and Crohn disease. Previous reports by us and others have linked the disease-associated genetic variants with changes in expression of GSDMB and ORMDL3 transcripts in human lymphoblastoid cell lines (LCLs). The variants also alter regulation of other transcripts, and this domain-wide cis-regulatory effect suggests a mechanism involving long-range chromatin interactions. Here, we further dissect the disease-linked haplotype and identify putative causal DNA variants via a combination of genetic and functional analyses. First, high-throughput resequencing of the region and genotyping of potential candidate variants were performed. Next, additional mapping of allelic expression differences in Yoruba HapMap LCLs allowed us to fine-map the basis of the cis-regulatory differences to a handful of candidate functional variants. Functional assays identified allele-specific differences in nucleosome distribution, an allele-specific association with the insulator protein CTCF, as well as a weak promoter activity for rs12936231. Overall, this study shows a common disease allele linked to changes in CTCF binding and nucleosome occupancy leading to altered domain-wide cis-regulation. Finally, a strong association between asthma and cis-regulatory haplotypes was observed in three independent family-based cohorts (p = 1.78 x 10(-8)). This study demonstrates the requirement of multiple parallel allele-specific tools for the investigation of noncoding disease variants and functional fine-mapping of human disease-associated haplotypes.

67: Outcome prediction in monochorionic diamniotic twin pregancies with discordant amniotic fluid not fulfilling the criteria of TTTS

287: Fetal cerebral blood flow in congenital diaphragmatic hernia

Interactions between nutritional and opioidergic pathways in the control of LH secretion in male sheep

Our aim was to determine the role of opioidergic processes in the effects of nutrition on the secretion of LH pulses in the mature male sheep. In the first of three experiments, adult Merino rams were acclimatised to a maintenance diet and then allocated to one of three dietary groups (n=5): continuation of the maintenance diet (Group M); reduction to half of the maintenance allocation (Group HM); or supplementation of the maintenance diet with lupin grain (Group HD). An initial administration of naloxone (2mg/kg body weight, i.v.) was followed at 40-min intervals by three further administrations (1mg/kg). Blood was sampled every 20 min for 12h before the initial naloxone administration and then for a further 6h. LH pulse frequency after naloxone treatment was significantly higher in Group HD than in Group HM (P<0.05). The second study tested whether the response to naloxone depended on calcium status. We used 22 adult Merino rams in two consecutive experiments, one in which the rams were fed a maintenance diet, and one in which the rams were fed with the maintenance diet plus 1 kg lupin grain for 5 weeks. In both experiments, rams were allocated to groups that received one of the following treatments: (a) 0.02 g/kg calcium borogluconate+0.2mg/kg naloxone hydrochloride (Nal+Ca(2+); n=6); (b) 0.2mg/kg naloxone hydrochloride (Nal; n=6); (c) 0.02 g/kg calcium borogluconate (Ca(2+); n=5); (d) 0.1 ml/kg NaCl 0.9% (Saline; n=5). All treatments were given as a single i.v. administration daily for 5 days. Blood was sampled every 20 min for 24 h during the acclimatization period (Day 0) and on the last day (Day 5) of treatment. In the first study (under maintenance), none of the treatments affected LH pulse frequency. In the second study (the lupin-supplemented rams), LH pulse frequency was significantly increased (P<0.05) by the administration of naloxone+Ca(2+), naloxone alone and Ca(2+) alone. Overall, rams on a low plane of nutrition showed the smallest response to naloxone, suggesting that an opioidergic mechanism is not involved in the suppressive effect of restricted nutrition on the gonadotrophic axis. Rather, because testosterone secretion was increased on the high plane of nutrition, the LH responses to naloxone are better explained by the effects of testosterone on opioidergic mechanisms. Finally, we failed to observe any interaction between opioids and calcium in the control of LH secretion.

Antiviral Activity of Carbohydrate Binding Agents (CBAS) and the Role of DC-SIGN in Dengue Virus and HIV Infection

Classical and effective descriptive complexities of ω-powers

We prove that, for each countable ordinal ξ≥1, there exist some Σξ0-complete ω-powers, and some Πξ0-complete ω-powers, extending previous works on the topological complexity of ω-powers [O. Finkel, Topological properties of omega context free languages, Theoretical Computer Science 262 (1–2) (2001) 669–697; O. Finkel, Borel hierarchy and omega context free languages, Theoretical Computer Science 290 (3) (2003) 1385–1405; O. Finkel, An omega-power of a finitary language which is a borel set of infinite rank, Fundamenta informaticae 62 (3–4) (2004) 333–342; D. Lecomte, Sur les ensembles de phrases infinies constructibles a partir d’un dictionnaire sur un alphabet fini, Séminaire d’Initiation a l’Analyse, 1, année 2001–2002; D. Lecomte, Omega-powers and descriptive set theory, Journal of Symbolic Logic 70 (4) (2005) 1210–1232; J. Duparc, O. Finkel, An ω-Power of a Context-Free Language Which Is Borel Above Δω0, in: S. Bold, B. Löwe, T. Räsch, J. van Benthem (Eds.), in the Proceedings of the international conference foundations of the formal sciences V : Infinite Games, November 26th to 29th, 2004, Bonn, Germany, in: Studies in Logic, vol. 11, College Publications at King’s College, 2007, pp. 109–122]. We prove effective versions of these results; in particular, for each recursive ordinal ξ<ω1CK there exist some recursive sets A⊆2<ω such that A∞∈Πξ0∖Σξ0 (respectively, A∞∈Σξ0∖Πξ0), where Πξ0 and Σξ0 denote classes of the hyperarithmetical hierarchy. To do this, we prove effective versions of a result by Kuratowski, describing a Πξ0 set as the range of a closed subset of the Baire space ωω by a continuous bijection. This leads us to prove closure properties for the pointclasses Σξ0 in arbitrary recursively presented Polish spaces. We apply our existence results to get better computations of the topological complexity of some sets of dictionaries considered in [D. Lecomte, Omega-powers and descriptive set theory, Journal of Symbolic Logic 70 (4) (2005) 1210–1232]