Publications by authors named "Stephen D'Souza"

Maternal infection during pregnancy, leading to maternal immune activation (mIA) and cytokine release, increases the offspring risk of developing a variety of neurodevelopmental disorders (NDDs), including schizophrenia. Animal models have provided evidence to support these mechanistic links, with placental inflammatory responses and dysregulation of placental function implicated. This leads to changes in fetal brain cytokine balance and altered epigenetic regulation of key neurodevelopmental pathways.

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Article Synopsis
  • The study looks at how twins born from assisted reproductive treatments (ART) grow compared to twins conceived naturally (NC) in their early life.
  • Researchers found that ART twins born from frozen embryos grow faster than both naturally conceived twins and those from fresh embryos.
  • The study included over 13,000 twins and measured their growth at different ages, showing some differences in weight and length among the groups.
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Homocysteine is a metabolite generated by methionine cycle metabolism, comprising the demethylated derivative of methionine. Homocysteine can be metabolised by the transsulphuration pathway to cystathionine, which requires vitamin B, or can undergo remethylation to methionine. Homocysteine remethylation to methionine is catalysed by methionine synthase activity which requires vitamin B, regenerating methionine to allow synthesis of the universal methyl donor -adenosylmethionine required for methylation and gene transcription regulation.

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Supplementation with myo-inositol during the periconceptional period of pregnancy may ameliorate the recurrence risk of having a fetus affected by a neural tube defect (NTD; e.g., spina bifida).

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Background: Birth weight and early child growth are important predictors of long-term cardiometabolic disease risk, in line with the Developmental Origins of Health and Disease hypothesis. As human assisted reproductive technologies (ARTs) occur during the sensitive periconceptional window of development, it has recently become a matter of urgency to investigate risk in ART-conceived children.

Methods: We have conducted the first large-scale, national cohort study of early growth in ART children from birth to school age, linking the register of ART, held by the UK's Human Fertilisation and Embryology Authority, to Scottish maternity and child health databases.

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Background: Although exempt, many pregnant Muslim women partake in the daily fast during daylight hours during the month of Ramadan. In other contexts an impoverished diet during pregnancy impacts on birth weight. The aim of this systematic review was to determine whether Ramadan fasting by pregnant women affects perinatal outcomes.

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Purpose: To prospectively analyze technical and clinical outcome of percutaneous thrombectomy aspiration using a vacuum-assisted thrombectomy catheter in acutely thrombosed dialysis arteriovenous fistula (AVF) and/or arteriovenous graft (AVG).

Materials And Methods: From June 2016 to April 2017, 35 patients (average age, 61.8 y; range, 33-81 y) presenting with acute thrombosis of dialysis AVF and/or AVG were prospectively evaluated for mechanical thrombectomy using the Indigo System.

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Methionine demethylation during metabolism generates homocysteine (Hcy) and its remethylation requires folate and cobalamin. Elevated Hcy concentrations are associated with vascular-related complications of pregnancy, including increased vascular stiffness, predictive of clinical vascular disease. Maternal and fetal total Hcy (tHcy) concentrations are positively related, yet the influence of Hcy on fetoplacental vascular function in normal pregnancy has not been examined.

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Elevated maternal plasma concentrations of homocysteine (Hcy) are associated with pregnancy complications and adverse neonatal outcomes. The postulate that we wish to advance here is that placental transport of Hcy, by competing with endogenous amino acids for transporter activity, may account for some of the damaging impacts of Hcy on placental metabolism and function as well as fetal development. In this article, we provide an overview of some recent studies characterising the transport mechanisms for Hcy across the microvillous plasma membrane (MVM) of the syncytiotrophoblast, the transporting epithelium of human placenta.

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Elevated maternal plasma levels of homocysteine (Hcy) are associated with pregnancy complications and adverse neonatal outcomes, suggesting placental transport of Hcy may impact on fetal development. However, such transport mechanisms have not been defined. In this study we characterise Hcy transport mechanisms across the microvillous plasma membrane (MVM) of the syncytiotrophoblast, the transporting epithelium of human placenta.

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Intrauterine growth restriction (IUGR) is associated with reduced activity of placental amino acid transport systems beta and A. Whether this phenotype is maintained in fetal cells outside the placenta is unknown. In IUGR, cord blood tumor necrosis factor (TNF)-alpha concentrations are raised, potentially influencing amino acid transport in fetal cells.

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Congenital abnormalities and impaired development in childhood are attributable to fetal exposure to antiepileptic drugs (AEDs). Pregnancy registries set up to obtain information about the potential risks of fetal exposure to AEDs, in particular major congenital malformations (MCMs), suggest that valproate exposure increases the frequency of congenital malformations more than other AEDs. Furthermore, follow-up studies have drawn attention to cognitive impairments in later childhood after prenatal exposure to valproate.

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During pregnancy, asthma-related alterations in placental function and the maternal immune system, and reduced growth affecting female but not male fetuses have been reported in a study of selected Australian women. The objective of this study was to evaluate the effect of asthma management, declared during pregnancy, on birthweight and neonatal outcome at an inner-city hospital in England. Between June 2001 and December 2003, women at antenatal clinics were questioned about asthma (n = 10 983).

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Maternal smoking during pregnancy inhibits fetal growth, and is a major cause of childhood and adult morbidity, including increased risks of cardiovascular disease and diabetes. However, the use of birthweight as a proxy for future smoking-related morbidity is hindered by its wide variability, suggesting a role for other birthweight-modifying factors. We report here, for the first time, that interactions between specific fetal HLA-DQA1 and DQB1 alleles and maternal smoking can influence birthweight.

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Objectives: To compare lactate uptake in the microvillous plasma membrane (maternal facing [MVM]) in term and preterm placentas in intrauterine growth restriction (IUGR) and appropriate weight for gestational age (AGA) controls, and in the basal plasma membrane (fetal facing [BM]) at term. In addition, we examine the expression of monocarboxylate transporters (MCT1 and MCT4).

Methods: We measured [14C] L-lactate uptakes into vesicles prepared from MVM and BM, stimulated by an inwardly directed H+ gradient.

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The placenta is essential to nutrition before birth. Recent work has shown that a range of clearly defined alterations can be found in the placentas of infants with intrauterine growth restriction (IUGR). In the mouse, a placental specific knockout of a single imprinted gene, encoding IGF-2, results in one pattern of alterations in placenta structure and function which leads to IUGR.

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Objectives: Pregnant women undergoing long-term organ transplant treatment have an increased incidence of delivering infants with intrauterine growth restriction (IUGR). Cyclosporine A is used as an immunosuppressant in such women and indirect evidence suggests that IUGR might result from an effect of cyclosporine A on amino acid transport by the placenta. In this study we tested the hypothesis that the transport of an essential amino acid, taurine, by fetal tissue other than the placenta is modulated by cyclosporine A.

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Background And Aims Of The Study: The study aim was to examine the effect of variation of test frequencies on the duration and kinematics of valve leaflets during opening, and at the fully open position.

Methods: Trileaflet polyurethane heart valves were tested in a Rowan Ash fatigue accelerator at 5, 10 and 15 Hz. Images of the valves were acquired using a high-speed camera and assessed qualitatively during opening and in the fully open position.

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