L’évolution des enfants difficiles

Dans cet article, les auteurs relatent une recherche faite, dans le cadre du projet Concordia Longitudinal Risk Project, sur l'ajustement des enfants socialement atypiques durant l'adolescence. Plus précisément, ils tentent de répondre à la question suivante: Quels comportements de l'enfant et quelles tangentes de son développement mènent à des problèmes psychologiques majeurs à l'adolescence et à l'âge adulte? Après une analyse complexe de divers facteurs, leurs résultats indiquent que les enfants perçus comme agressifs, repliés sur eux-mêmes ou souvent agressifs et repliés sur eux-mêmes par leur camarades, sont susceptibles d'avoir des problèmes à l'adolescence. Ils explicitent ensuite selon ces trois groupes les difficultés de chacun.In this article, the authors discuss a study carried out during a Concordia Longitudinal Risk Project that deals with the adjustment of socially atypical children in their adolescent years. More precisely, they try to answer the following question : What child behaviors and which tangents of their development lead to major psychological problems as an adolescent and as an adult? After a complex analysis of various factors, their results indicate that children perceived as aggressive, keeping to themselves or often aggressive and keeping to themselves because of peer pressure, are liable to have problems in their adolescent years. The authors then elaborate on the difficulties experienced by each of these three groups

Inflammatory pathways in the mechanism of parturition

Increasing evidence suggests that parturition is an inflammatory process. In this brief overview, inflammatory events occurring in association with parturition, and the mechanism by which they may contribute to labour and delivery will be discussed. Mention will be made of how this information may be of use in regulating the timing and the onset of parturition

De l’agressivité à la maternité. Étude longitudinale sur 30 ans auprès de filles agressives devenues mères : trajectoires de leur agressivité durant l’enfance, indicateurs de leurs caractéristiques parentales et développement de leurs enfants

L’agressivité chez les filles tend à ne pas se manifester de la même façon que chez les garçons ; de plus, elle suit une trajectoire longitudinale particulière. Les filles agressives envers leurs pairs ne se caractérisent pas tant par leurs manifestations de délinquance et de criminalité ; elles s’orientent plutôt vers une trajectoire de troubles sociaux et de santé mentale qui, à terme, compromet leur avenir scolaire, social et professionnel, de même que leur état de santé physique. Les compétences parentales des filles agressives, de même que le fonctionnement de leur famille, peuvent aussi être affectées ; dans ce cas, c’est la socialisation, la santé et le développement de toute une nouvelle génération d’enfants qui sont menacés. La Concordia Longitudinal Risk Project (Enquête longitudinale sur les risques, Université Concordia) suit un échantillon intergénérationnel de 1 770 sujets vivant à Montréal, dont un sous-échantillon de plus de 200 filles dites très agressives, et le compare avec un échantillon de garçons agressifs et un groupe témoin composé d’enfants des deux sexes. Les participants sont suivis de l’enfance à l’âge adulte sur une période de 30 ans. Le présent article décrit les trajectoires à long terme des filles agressives et les conséquences de cette agressivité sur une large variété d’éléments psychosociaux et de santé comme la maternité et la transmission des risques à la prochaine génération. Plus particulièrement, nous souhaitons : (1) établir les trajectoires des filles qui mènent de l’agressivité dans l’enfance au développement négatif à l’âge adulte, (2) établir les indicateurs de santé et les facteurs physiologiques connexes qui comportent des risques pour les filles agressives et leurs enfants et (3) évaluer comment l’agressivité à l’enfance se répercute sur le rôle maternel et le développement de la prochaine génération. Enfin, les retombées de nos conclusions seront discutées.Childhood aggression in girls may take different forms and follow different longitudinal trajectories from those typical of aggressive boys. Even when overt delinquency and criminality are avoided, girls who are aggressive towards their peers may follow a life course involving continuing social and mental health problems. From a longterm perspective, academic, social, health, and occupational achievement are likely to be negatively affected. Family functioning and parenting abilities may also be compromised, placing the offspring of these girls, a subsequent generation, at risk for social, health, and developmental problems. The Concordia Longitudinal Risk Project, which follows an intergenerational sample of 1770 inner-city Montrealers, includes a sub-sample of over 200 highly aggressive girls, with comparison groups of aggressive boys and normative children of both genders. Participants have been followed over a 30-year period, from childhood into adulthood. The present paper describes the long-term trajectories and sequelae of girlhood aggression in the context of a broad range of negative psychosocial and health outcomes, including parenting and the inter generational transfer of risk to offspring. More specifically, (1) trajectories by which childhood aggression places girls at risk for negative developmental outcomes are outlined, (2) health behaviours and physiological correlates that signify risk to aggressive girls and their offspring are delineated, and (3) pathways through which girlhood aggression influences parenting and offspring development are elucidated. Implications of these findings are discussed

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Transcription analysis of the myometrium of labouring and non-labouring women

An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in non-labouring and labouring gestational tissues is necessary to help bridge these gaps in our knowledge. In this work, gene expression in 48 (22 labouring, 26 non-labouring) lower-segment myometrial samples collected at Caesarean section were analysed using Illumina HT-12 v4.0 BeadChips. Normalised data were compared between labouring and non-labouring groups using traditional statistical methods and a novel network graph approach. We sought technical validation with quantitative real-time PCR, and biological replication through inverse variance-weighted meta-analysis with published microarray data. We have extended the list of genes suggested to be associated with labour: Compared to non-labouring samples, labouring samples showed apparent higher expression at 960 probes (949 genes) and apparent lower expression at 801 probes (789 genes) (absolute fold change ≥1.2, rank product percentage of false positive value (RP-PFP) <0.05). Although half of the women in the labouring group had received pharmaceutical treatment to induce or augment labour, sensitivity analysis suggested that this did not confound our results. In agreement with previous studies, functional analysis suggested that labour was characterised by an increase in the expression of inflammatory genes and network analysis suggested a strong neutrophil signature. Our analysis also suggested that labour is characterised by a decrease in the expression of muscle-specific processes, which has not been explicitly discussed previously. We validated these findings through the first formal meta-analysis of raw data from previous experiments and we hypothesise that this represents a change in the composition of myometrial tissue at labour. Further work will be necessary to reveal whether these results are solely due to leukocyte infiltration into the myometrium as a mechanism initiating labour, or in addition whether they also represent gene changes in the myocytes themselves. We have made all our data available at www.ebi.ac.uk/arrayexpress/ (accession number E-MTAB-3136) to facilitate progression of this work

The Role of Toll-Like Receptors (TLR-2 and-4) and Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) in Human Term and Preterm Labor

Objective. To define the role of Toll-like receptors (TLR-2, TLR-4) and triggering receptor expressed on myeloid cells-1 (TREM-1) in pregnant human myometrium. Study Design. Expression of TLR-2 and -4 mRNA and protein and TREM-1 mRNA was quantified in human myometrial samples. Subsequently, we investigated the effect of medroxyprogesterone acetate (MPA) as a functional inhibitor of the TLR agonist lipopolysaccharide (LPS). Results. Messenger RNA expression of TLR-2 and -4 was significantly higher in myometrium at term compared with preterm (P = .009 and .016, respectively). Toll-like receptor-2 protein expression was significantly higher during labor (P = .002) compared with nonlaboring samples. Triggering receptor expressed on myeloid cells-1 mRNA expression was increased in both myometrium and cervix after labor at term (P &lt; .05). Medroxyprogesterone acetate significantly suppressed LPS-induced production of interleukin 1b (IL-1b), IL-6, and IL-8 in vitro (P &lt; .05). Conclusion. Toll-like receptors 2and 4 and TREM-1 are expressed in human myometrium and may play a role in the mechanism of labor at term, and their functional effects are inhibited by MPA

Neighbourhood disadvantage and behavioural problems during childhood and the risk of cardiovascular disease risk factors and events from a prospective cohort

Both low socioeconomic status (SES) and behavioural problems in childhood are associated with cardiovascular disease (CVD) in adulthood, but their combined effects on CVD are unknown. Study objectives were to investigate the effect of neighbourhood level SES and behavioural problems during childhood on the development of CVD risk factors and events during adulthood. Participants were from a longitudinal cohort (n=3792, baseline: 6–13years of age) of Montreal children, followed from 1976 to 2010. SES was a composite measure of neighbourhood income, employment, education, and single-parent households separately assessed from census micro data sets in 1976, 2001, and 2006. Behavioural problems were assessed based on sex-specific peer assessments. CVD events were from medical records. Sex-stratified multivariable Cox regression models adjusted for age, frequency of medical visits, and parental history of CVD. Males from disadvantaged neighbourhoods during childhood were 2.06 (95% CI: 1.09–3.90, p=0.03) and 2.51 (95% CI: 1.49–4.22, p=0.0005) times more likely to develop a CVD risk factor or an event, respectively, than males not from disadvantaged neighbourhoods. Aggressive males were also 50% more likely to develop a CVD risk factor or event. Females from disadvantaged neighbourhoods during childhood were 1.85 (95% CI: 1.33–2.59, p=0.0003) times more likely to develop a CVD risk factor. Future studies should aim to disentangle the interpersonal from the socioeconomic effects on CVD incidence. Keywords: Neighbourhood disadvantage, Cardiovascular risk, Prospective cohort, Socioeconomic status, Longitudina