921 research outputs found

    A randomised control trial of low glycaemic index carbohydrate diet versus no dietary intervention in the prevention of recurrence of macrosomia

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    <p>Abstract</p> <p>Background</p> <p>Maternal weight and maternal weight gain during pregnancy exert a significant influence on infant birth weight and the incidence of macrosomia. Fetal macrosomia is associated with an increase in both adverse obstetric and neonatal outcome, and also confers a future risk of childhood obesity. Studies have shown that a low glycaemic diet is associated with lower birth weights, however these studies have been small and not randomised <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr></abbrgrp>. Fetal macrosomia recurs in a second pregnancy in one third of women, and maternal weight influences this recurrence risk <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>.</p> <p>Methods/Design</p> <p>We propose a randomised control trial of low glycaemic index carbohydrate diet vs. no dietary intervention in the prevention of recurrence of fetal macrosomia.</p> <p>Secundigravid women whose first baby was macrosomic, defined as a birth weight greater than 4000 g will be recruited at their first antenatal visit.</p> <p>Patients will be randomised into two arms, a control arm which will receive no dietary intervention and a diet arm which will be commenced on a low glycaemic index diet.</p> <p>The primary outcome measure will be the mean birth weight centiles and ponderal indices in each group.</p> <p>Discussion</p> <p>Altering the source of maternal dietary carbohydrate may prove to be valuable in the management of pregnancies where there has been a history of fetal macrosomia. Fetal macrosomia recurs in a second pregnancy in one third of women. This randomised control trial will investigate whether or not a low glycaemic index diet can affect this recurrence risk.</p> <p>Current Controlled Trials Registration Number</p> <p>ISRCTN54392969</p

    The catalytic subunit of the system L1 amino acid transporter (S<i>lc7a5</i>) facilitates nutrient signalling in mouse skeletal muscle

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    The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ∼40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle mass

    Environmental risk assessment of genetically modified plants - concepts and controversies

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    Background and purpose: In Europe, the EU Directive 2001/18/EC lays out the main provisions of environmental risk assessment (ERA) of genetically modified (GM) organisms that are interpreted very differently by different stakeholders. The purpose of this paper is to: (a) describe the current implementation of ERA of GM plants in the EU and its scientific shortcomings, (b) present an improved ERA concept through the integration of a previously developed selection procedure for identification of non-target testing organisms into the ERA framework as laid out in the EU Directive 2001/18/EC and its supplement material (Commission Decision 2002/623/EC), (c) describe the activities to be carried out in each component of the ERA and (d) propose a hierarchical testing scheme. Lastly, we illustrate the outcomes for three different crop case examples. Main features: Implementation of the current ERA concept of GM crops in the EU is based on an interpretation of the EU regulations that focuses almost exclusively on the isolated bacteria-produced novel proteins with little consideration of the whole plant. Therefore, testing procedures for the effect assessment of GM plants on non-target organisms largely follow the ecotoxicological testing strategy developed for pesticides. This presumes that any potential adverse effect of the whole GM plant and the plant-produced novel compound can be extrapolated from testing of the isolated bacteriaproduced novel compound or can be detected in agronomic field trials. This has led to persisting scientific criticism. Results: Based on the EU ERA framework, we present an improved ERA concept that is system oriented with the GM plant at the centre and integrates a procedure for selection of testing organisms that do occur in the receiving environment. We also propose a hierarchical testing scheme from laboratory studies to field trials and we illustrate the outcomes for three different crop case examples. Conclusions and recommendations: Our proposed concept can alleviate a number of deficits identified in the current approach to ERA of GM plants. It allows the ERA to be tailored to the GM plant case and the receiving environment

    The Impact of Official Development Aid on Maternal and Reproductive Health Outcomes: A Systematic Review

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    BACKGROUND: Progress toward meeting Millennium Development Goal 5, which aims to improve maternal and reproductive health outcomes, is behind schedule. This is despite ever increasing volumes of official development aid targeting the goal, calling into question the distribution and efficacy of aid. The 2005 Paris Declaration on Aid Effectiveness represented a global commitment to reform aid practices in order to improve development outcomes, encouraging a shift toward collaborative aid arrangements which support the national plans of aid recipient countries (and discouraging unaligned donor projects). METHODS AND FINDINGS: We conducted a systematic review to summarise the evidence of the impact on MDG 5 outcomes of official development aid delivered in line with Paris aid effectiveness principles and to compare this with the impact of aid in general on MDG 5 outcomes. Searches of electronic databases identified 30 studies reporting aid-funded interventions designed to improve maternal and reproductive health outcomes. Aid interventions appear to be associated with small improvements in the MDG indicators, although it is not clear whether changes are happening because of the manner in which aid is delivered. The data do not allow for a meaningful comparison between Paris style and general aid. The review identified discernible gaps in the evidence base on aid interventions targeting MDG 5, notably on indicators MDG 5.4 (adolescent birth rate) and 5.6 (unmet need for family planning). DISCUSSION: This review presents the first systematic review of the impact of official development aid delivered according to the Paris principles and aid delivered outside this framework on MDG 5 outcomes. Its findings point to major gaps in the evidence base and should be used to inform new approaches and methodologies aimed at measuring the impact of official development aid

    A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

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    Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner
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