Smoking cessation intervention during pregnancy in a Polish urban community – what is the target population?

The aim of this project was to evaluate the effect of intensive individual anti-smoking counselling among pregnant women from a Polish urban community with a large representation of socially underprivileged women. The study was conducted between 1 December 2000 and 31 December 2001. Out of 204 women who were asked to take part in a midwives-assisted program of educational counselling to stop smoking, 152 (74.5%) agreed to participate. The intervention program included four visits of a midwife trained in smoking cessation techniques to the home of a smoking pregnant woman. The control group were 145 pregnant women who on the first visit to a maternity unit received only a standard written information on the health risk from maternal smoking to the foetus. The percentage of pregnant women who quitted smoking during the project was 46.1% in the intervention group and 23.4% among the controls (p < 0.001). After combining the intervention group with the women who refused to participate in the project, the rate of quitting was 36.3%, still significantly higher than in controls (p = 0.01). The strongest influence of the intervention was found among women smoking more than 5 cigarettes/day. Women covered by the intervention programme, who reported smoking in previous pregnancies, were found to quit smoking to a much higher extent than the controls with a similar background. Such pattern was also observed for women whose husbands were smokers. The benefits of the intervention, especially for the socially underprivileged women, seem to result from an increased proportion of subjects who undertook a quitting attempt, rather than the effectiveness of these attempts. In the intervention group, among the subjects who did not manage to quit smoking during pregnancy, the number of women who at least slightly reduced their smoking rate was twice as high as in the controls

A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis

Funding: The study was supported by the European Cooperation in Science and Technology, who provided funds for publication. KMG is supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre and by the European Union's Seventh Framework Programme (FP7/2007-2013), projects Early Nutrition and ODIN under grant agreement numbers 289346 and 613977.Peer reviewedPublisher PD

Helicobacter pylori Outer Membrane Protein 18 ( Hp1125 ) Induces Dendritic Cell Maturation and Function

Background.  Dendritic cells (DCs) are potent antigen-presenting cells that initiate T-cell responses. A robust adaptive Th1 immune response is crucial to an adaptive (Th2) immune response necessary for vaccine-induced protective immunity against Helicobacter pylori. It has been shown that several outer membrane proteins (Omps) induce a robust antibody response. However, it is also known that the antibodies generated are not protective. Moreover there is great variation in the recognition of high molecular weight H. pylori proteins by sera from infected patients. In contrast to the high molecular weight proteins, serologic responses to small molecular weight proteins provide assessment of current infection with H. pylori and also of its eradication. Aim.  The goal of the study was to analyze the activation of the immune response by a specific low molecular weight Omp that is universally expressed by all H. pylori strains. Therefore, we studied interaction of H. pylori Omp18 with DCs. Methods.  Activation of murine bone marrow-derived DCs and production of cytokines by Omp18 was assessed by fluorescence-activated cell sorter (FACS) for costimulatory markers and ELISA, respectively. The ability of Omp18 stimulated DCs to induce lymphocyte proliferation was measured in a mixed leukocyte reaction. Results.  Omp18 induced higher expression of the B7 (CD80 and CD86) costimulatory molecule after 18 hours indicating processing and presentation of the antigen on the surface by bone marrow-derived DCs. The maturing DCs also secreted significant levels of IL-12, but was 4-fold less than that stimulated by whole bacteria. Omp18-primed DCs induced proliferation and release of IFNγ by syngeneic splenocytes. Conclusion.  We concluded that Omp18 is capable of activating DCs initiating a Th1 immune response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73882/1/j.1523-5378.2005.00350.x.pd

Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

Consequential considerations when mapping tRNA fragments

We examine several of the choices that went into the design of tDRmapper, a recently reported tool for identifying transfer RNA (tRNA) fragments in deep sequencing data, evaluate them in the context of currently available knowledge, and discuss their potential impact on the output that the tool generates

A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis

Background Maternal smoking during pregnancy is linked to reduced birth weight but the gestation at onset of this relationship is not certain. We present a systematic review of the literature describing associations between maternal smoking during pregnancy and ultrasound measurements of fetal size, together with an accompanying meta-analysis. Methods Studies were selected from electronic databases (OVID, EMBASE and Google Scholar) that examined associations between maternal smoking or smoke exposure and antenatal fetal ultrasound measurements. Outcome measures were first, second or third trimester fetal measurements. Results There were 284 abstracts identified, 16 papers were included in the review and the metaanalysis included data from eight populations. Maternal smoking was associated with reduced second trimester head size (mean reduction 0.09 standard deviation (SD) [95% CI 0.01, 0.16]) and femur length (0.06 [0.01, 0.10]) and reduced third trimester head size (0.18SD [0.13, 0.23]), femur length (0.27 SD [0.21, 0.32]) and estimated fetal weight (0.18 SD [0.11, 0.24]). Higher maternal cigarette consumption was associated with a lower z score for head size in the second (mean difference 0.09 SD [0, 0.19]) and third (0.15 SD [0.03, 0.26]) trimesters compared to lower consumption. Fetal measurements were not reduced for those whose mothers quit before or after becoming pregnant compared to mothers who had never smoked. Conclusions Maternal smoking during pregnancy is associated with reduced fetal measurements after the first trimester, particularly reduced head size and femur length. These effects may be attenuated if mothers quit or reduce cigarette consumption during pregnancy

Dissociable dopaminergic and pavlovian influences in goal-trackers and sign-trackers on a model of compulsive checking in OCD

Abstract: Rationale: Checking is a functional behaviour that provides information to guide behaviour. However, in obsessive-compulsive disorder (OCD), checking may escalate to dysfunctional levels. The processes underpinning the transition from functional to dysfunctional checking are unclear but may be associated with individual differences that support the development of maladaptive behaviour. We examined one such predisposition, sign-tracking to a pavlovian conditioned stimulus, which we previously found associated with dysfunctional checking. How sign-tracking interacts with another treatment with emerging translational validity for OCD-like checking, chronic administration of the dopamine D2 receptor agonist quinpirole, is unknown. Objectives: We tested how functional and dysfunctional checking in the rat observing response task (ORT) was affected by chronic quinpirole administration in non-autoshaped controls and autoshaped animals classified as sign-trackers or goal-trackers. Methods: Sign-trackers or goal-trackers were trained on the ORT before the effects of chronic quinpirole administration on checking were assessed. Subsequently, the effects on checking of different behavioural challenges, including reward omission and the use of unpredictable reinforcement schedules, were tested. Results: Prior autoshaping increased checking. Sign-trackers and goal-trackers responded differently to quinpirole sensitization, reward omission and reinforcement uncertainty. Sign-trackers showed greater elevations in dysfunctional checking, particularly during uncertainty. By contrast, goal-trackers predominantly increased functional checking responses, possibly in response to reduced discrimination accuracy in the absence of cues signalling which lever was currently active. Conclusions: The results are discussed in terms of how pavlovian associations influence behaviour that becomes compulsive in OCD and how this may be dependent on striatal dopamine D2 receptors

Stem cell function and stress response are controlled by protein synthesis.

Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis. Mechanistically, we show that inhibition of post-transcriptional cytosine-5 methylation locks tumour-initiating cells in this distinct translational inhibition programme. Paradoxically, this inhibition renders stem cells hypersensitive to cytotoxic stress, as tumour regeneration after treatment with 5-fluorouracil is blocked. Thus, stem cells must revoke translation inhibition pathways to regenerate a tissue or tumour.This work was funded by Cancer Research UK (CR-UK), Worldwide Cancer Research, the Medical Research Council (MRC), the European Research Council (ERC), and EMBO. Research in Michaela Frye's laboratory is supported by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Cambridge Stem Cell Institute.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1828