Development of a novel Periconceptual Nutrition Score (PENS) to examine the relationship between maternal dietary quality and fetal growth

Background Maternal nutrition may influence intrauterine fetal development. To date, the relationship between contemporary European dietary guidelines and fetal growth has not been examined. Aims To develop a novel Periconceptual Nutrition Score (PENS) to assess maternal dietary quality in early pregnancy and examine its relationship with fetal growth. Study design Women were recruited conveniently at their first clinic visit and completed a supervised four day retrospective diet history. The PENS was developed using European Food Safety Authority recommended dietary intakes for pregnancy. The relationship between PENS and fetal growth was examined. Subjects Women with a singleton pregnancy. Outcome measures Birthweight, small for gestational age (SGA), neonatal head circumference. Results and conclusions Of the 202 women, the mean age was 32.2 ± 5.0 years and 44.6% were nulliparas. The mean PENS was 9.4 ± 3.1. On multivariable regression, there was a positive relationship between the PENS and birthweight (beta = 45.3, 95%CI 14.8–75.9, P = 0.002) and neonatal head circumference (beta = 0.12, 95%CI 0.01–0.23, P = 0.03). Compared with the lowest PENS quartile, the mean birthweight was increased in the highest quartile (Mean difference 328 g, P = 0.02). The incidence of SGA was 16.4% (n = 10/61) in the lowest PENS quartile compared to 6.5% (n = 9/139) in the top three quartiles (P = 0.03). Thus, higher maternal dietary quality was associated with increased intrauterine fetal growth. The PENS is potentially useful in identifying those women before or during pregnancy who may benefit from dietary interventions that may optimise fetal growth. It may also be useful in tracking maternal dietary quality during pregnancy

Preferences of women for web-based nutritional information in pregnancy

Objectives During pregnancy, women are increasingly turning to web-based resources for information. This study examined the use of web-based nutritional information by women during pregnancy and explored their preferences. Study design Cross-sectional observational study. Methods Women were enrolled at their convenience from a large maternity hospital. Clinical and sociodemographic details were collected and women\u27s use of web-based resources was assessed using a detailed questionnaire. Results Of the 101 women, 41.6% were nulliparous and the mean age was 33.1 years (19–47 years). All women had internet access and only 3% did not own a smartphone. Women derived pregnancy-related nutritional information from a range of online resources, most commonly: What to Expect When You\u27re Expecting (15.1%), Babycenter (12.9%), and Eumom (9.7%). However, 24.7% reported using Google searches. There was minimal use of publically funded or academically supported resources. The features women wanted in a web-based application were recipes (88%), exercise advice (71%), personalized dietary feedback (37%), social features (35%), videos (24%) and cooking demonstrations (23%). Conclusions This survey highlights the risk that pregnant women may get nutritional information from online resources which are not evidence-based. It also identifies features that women want from a web-based nutritional resource

A web-based dietary intervention in early pregnancy and neonatal outcomes: A randomized controlled trial

Background Maternal nutrition is a determinant of pregnancy outcomes. Few studies have evaluated the potential of online nutrition resources to modify behaviour. This randomized controlled trial aimed to determine whether access to a customized evidence-based nutrition website in pregnancy improved neonatal outcomes. Methods Women \u3c18 weeks gestation were recruited at their convenience. The control group received standard care. In addition to standard care, the intervention group received access to an evidence-based nutrition website, customized to the preferences of pregnant women. Results Of the 250 women, there were no differences in characteristics between the two groups. Of the women, 91.0% reported they make a conscious effort currently to eat a healthy diet. However, only 19.6% met dietary requirements for calcium, 13.2% for iron, 2.7% for folate and 2.3% for iodine. The most popular website section was pregnancy nutrition advice but engagement was not sustained. Access to the website was not associated with any improvement in clinical outcomes (P \u3e 0.05). Conclusions We found that provision of a customized website providing nutrition information, did not improve neonatal outcomes. Future studies should explore whether redesign with website interactivity or embedding information on popular digital platforms sustains women’s engagement and modifies dietary behaviour

B cells do not take up bacterial DNA: An essential role for antigen in exposure of DNA to toll-like receptor-9

Murine dendritic cells (DC) and macrophages respond to bacterial CpG DNA through toll-like receptor 9 (TLR9). Although it is frequently assumed that bacterial DNA is a direct stimulus for B cells, published work does not reliably show responses of purified B cells. Here we show that purified splenic B cells did not respond to Escherichia coli DNA with induction of CD86, despite readily responding to single-stranded (ss) phosphodiester CpG oligodeoxynucleotides (ODN). This was due to a combination of weak responses to both long and double-stranded (ds) DNA. B-cell DNA uptake was greatly reduced with increasing DNA length. This contrasts with macrophages where DNA uptake and subsequent responses were enhanced with increasing DNA length. However, when DNA was physically linked to hen egg lysozyme (HEL), HEL-specific B cells showed efficient uptake of DNA, and limited proliferation in response to the HEL-DNA complex. We propose that, in the absence of other signals, B cells have poor uptake and responses to long dsDNA to prevent polyclonal activation. Conversely, when DNA is physically linked to a B-cell receptor (BCR) ligand, its uptake is increased, allowing TLR9-dependent B-cell activation in an antigen-specific manner. We could not generate fragments of E. coli DNA by limited DNaseI digestion that could mimic the stimulatory effect of ss CpG ODN on naive B cells. We suggest that the frequently studied polyclonal B-cell responses to CpG ODN are relevant to therapeutic applications of phosphorothioate-modified CpG-containing ODN, but not to natural responses to foreign or host dsDNA. Immunology and Cell Biology (2011) 89, 517-525; doi:10.1038/icb.2010.112; published online 5 October 201

A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis)

The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals, can also employ a tolerance strategy to maintain good health in the face of on-going infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles, Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and non-immune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other non-genetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein-protein interaction network for the mouse model rodent, Mus musculus, which we validate using our own expression network for M. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2-related genes, Tyrosine-protein kinase BTK and Tyrosine-protein kinase TXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

X-ray Absorption and Reflection in Active Galactic Nuclei

X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote

The Galactic Plane at faint X-ray fluxes - I: Properties and characteristics of the X-ray source population

We investigate the serendipitous X-ray source population revealed in XMM-Newton observations targeted in the Galactic Plane within the region 315<l<45 and |b|<2.5 deg. Our study focuses on a sample of 2204 X-ray sources at intermediate to faint fluxes, which were detected in a total of 116 XMM fields and are listed in the 2XMMi catalogue. We characterise each source as spectrally soft or hard on the basis of whether the bulk of the recorded counts have energies below or above 2 keV and find that the sample divides roughly equally (56%:44%) into these soft and hard categories. The X-ray spectral form underlying the soft sources may be represented as either a power-law continuum with Gamma~2.5 or a thermal spectrum with kT~0.5 keV, with N_H ranging from 10^{20-22} cm^{-2}. For the hard sources, a significantly harder continuum form is likely, i.e., Gamma~1 with N_H=10^{22-24} cm^{-2}. For ~50% of the hard sources, the inferred column density is commensurate with the total Galactic line-of-sight value; many of these sources will be located at significant distances across the Galaxy implying a hard band luminosity L_X>10^{32} erg/s, whereas some will be extragalactic interlopers. >90% of the soft sources have potential NIR (2MASS and/or UKIDSS) counterparts inside their error circles, consistent with the dominant soft X-ray source population being relatively nearby coronally-active stars. These stellar counterparts are generally brighter than J=16, a brightness cutoff which corresponds to the saturation of the X-ray coronal emission at L_X=10^{-3} L_{bol}. In contrast, the success rate in finding likely IR counterparts to the hard X-ray sample is no more than ~15% down to J=16 and ~25% down to J=20, set against a rapidly rising chance coincidence rate. The make-up of the hard X-ray source population, in terms of the known classes of accreting and non-accreting systems, remains uncertain.Comment: 17 pages, 17 figures, accepted for publication in MNRA

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response