PRegnancy Outcomes after a Maternity Intervention for Stressful EmotionS (PROMISES): study protocol for a randomised controlled trial

Background

There is ample evidence from observational prospective studies that maternal depression or anxiety during pregnancy is a risk factor for adverse psychosocial outcomes in the offspring. However, to date no previous study has demonstrated that treatment of depressive or anxious symptoms in pregnancy actually could prevent psychosocial problems in children. Preventing psychosocial problems in children will eventually bring down the huge public health burden of mental disease. The main objective of this study is to assess the effects of cognitive behavioural therapy in pregnant women with symptoms of anxiety or depression on the child's development as well as behavioural and emotional problems. In addition, we aim to study its effects on the child's development, maternal mental health, and neonatal outcomes, as well as the cost-effectiveness of cognitive behavioural therapy relative to usual care.

Methods/design

We will include 300 women with at least moderate levels of anxiety or depression at the end of the first trimester of pregnancy. By including 300 women we will be able to demonstrate effect sizes of 0.35 or over on the total problems scale of the child behavioural checklist 1.5-5 with alpha 5% and power (1-beta) 80%.Women in the intervention arm are offered 10-14 individual cognitive behavioural therapy sessions, 6-10 sessions during pregnancy and 4-8 sessions after delivery (once a week). Women in the control group receive care as usual.Primary outcome is behavioural/emotional problems at 1.5 years of age as assessed by the total problems scale of the child behaviour checklist 1.5 - 5 years.Secondary outcomes will be mental, psychomotor and behavioural development of the child at age 18 months according to the Bayley scales, maternal anxiety and depression during pregnancy and postpartum, and neonatal outcomes such as birth weight, gestational age and Apgar score, health care consumption and general health status (economic evaluation).

Trial Registration

Netherlands Trial Register (NTR): NTR2242

     

ALG: automated genotype calling of Luminex assays

Single nucleotide polymorphisms (SNPs) are the most commonly used polymorphic markers in genetics studies. Among the different platforms for SNP genotyping, Luminex is one of the less exploited mainly due to the lack of a robust (semi-automated and replicable) freely available genotype calling software. Here we describe a clustering algorithm that provides automated SNP calls for Luminex genotyping assays. We genotyped 3 SNPs in a cohort of 330 childhood leukemia patients, 200 parents of patient and 325 healthy individuals and used the Automated Luminex Genotyping (ALG) algorithm for SNP calling. ALG genotypes were called twice to test for reproducibility and were compared to sequencing data to test for accuracy. Globally, this analysis demonstrates the accuracy (99.6%) of the method, its reproducibility (99.8%) and the low level of no genotyping calls (3.4%). The high efficiency of the method proves that ALG is a suitable alternative to the current commercial software. ALG is semi-automated, and provides numerical measures of confidence for each SNP called, as well as an effective graphical plot. Moreover ALG can be used either through a graphical user interface, requiring no specific informatics knowledge, or through command line with access to the open source code. The ALG software has been implemented in R and is freely available for non-commercial use either at http://alg.sourceforge.net or by request to mathieu.bourgey@umontreal.ca.     

Novel arenavirus sequences in Hylomyscus sp. and Mus (Nannomys) setulosus from Côte d'Ivoire: implications for evolution of arenaviruses in Africa

This study aimed to identify new arenaviruses and gather insights in the evolution of arenaviruses in Africa. During 2003 through 2005, 1,228 small mammals representing 14 different genera were trapped in 9 villages in south, east, and middle west of C?te d'Ivoire. Specimens were screened by pan-Old World arenavirus RT-PCRs targeting S and L RNA segments as well as immunofluorescence assay. Sequences of two novel tentative species of the family Arenaviridae, Menekre and Gbagroube virus, were detected in Hylomyscus sp. and Mus (Nannomys) setulosus, respectively. Arenavirus infection of Mus (Nannomys) setulosus was also demonstrated by serological testing. Lassa virus was not found, although 60% of the captured animals were Mastomys natalensis. Complete S RNA and partial L RNA sequences of the novel viruses were recovered from the rodent specimens and subjected to phylogenetic analysis. Gbagroube virus is a closely related sister taxon of Lassa virus, while Menekre virus clusters with the Ippy/Mobala/Mopeia virus complex. Reconstruction of possible virus-host co-phylogeny scenarios suggests that, within the African continent, signatures of co-evolution might have been obliterated by multiple host-switching events.     

NCS 613, a potent and specific PDE4 inhibitor, displays anti-inflammatory effects on human lung tissues

Chronic inflammation is a hallmark of pulmonary diseases, which leads to lung parenchyma destruction (emphysema) and obstructive bronchiolitis occurring in both chronic obstructive pulmonary disease and asthma. Inflammation is strongly correlated with low intracellular cAMP levels and increase in specific cAMP hydrolyzing activity. The aim of the present study was to investigate the role of the cyclic phosphodiesterase type 4 (PDE4) in human lung and to determine the effects of NCS 613, a new PDE4 inhibitor, on lung inflammation and bronchial hyperresponsiveness. High cAMP-PDE activities were found in the cytosoluble fractions from human lung parenchyma and distal bronchi. PDE4 (rolipram sensitive) represented 40% and 56% of total cAMP-PDE activities in the above-corresponding tissues. Moreover, PDE4A, PDE4B, PDE4C, and PDE4D isoforms were detected in all three subcellular fractions (cytosolic, microsomal, and nuclear) with differential distributions according to specific variants. Pharmacological treatments with NCS 613 significantly decreased PDE4 activity and reduced IκBα degradation in cultured parenchyma, both of which are usually correlated with a lower inflammation status. Moreover, NCS 613 pretreatment potentiated isoproterenol-induced relaxations in human distal bronchi, while reducing TNF-α-induced hyperresponsiveness in cultured bronchi, as assessed in the presence of methacholine, U-46619, or histamine. This reducing effect of NCS 613 on human bronchi hyperresponsiveness triggered by TNF-α was related to a lower expression level of PDE4B and PDE4C, as well as a downregulation of the phosphorylated forms of p38-MAPK, CPI-17, and MYPT-1, which are known to control tone. In conclusion, specific PDE4 inhibitors, such as NCS 613, may represent an alternative and isoform-specific approach toward reducing human lung inflammation and airway overreactivity.     

M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity

Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.     

Hematopoietic miR155 deficiency enhances atherosclerosis and decreases plaque stability in hyperlipidemic mice

microRNA-155 (miR155) is a central regulator of immune responses that is induced by inflammatory mediators. Although miR155 is considered to be a pro-inflammatory microRNA, in vitro reports show anti-inflammatory effects in lipid-loaded cells. In this study we examined the role of miR155 in atherosclerosis in vivo using bone marrow transplantation from miR155 deficient or wildtype mice to hyperlipidemic mice. Hematopoietic deficiency of miR155 enhanced atherosclerotic plaque development and decreased plaque stability, as evidenced by increased myeloid inflammatory cell recruitment to the plaque. The increased inflammatory state was mirrored by a decrease in circulating CD4(+)CD25(+)FoxP3(+) regulatory T cells, and an increase in granulocytes (CD11b(+)Ly6G(+)) in blood of miR155(-/-) transplanted mice. Moreover, we show for the first time a crucial role of miR155 in monocyte subset differentiation, since hematopoietic deficiency of miR155 increases the 'inflammatory' monocyte subset (CD11b(+)Ly6G(-)Ly6C(hi)) and reduces 'resident' monocytes (CD11b(+)Ly6G(-)Ly6C(low)) in the circulation. Furthermore, cytokine production by resident peritoneal macrophages of miR155(-/-) transplanted hyperlipidemic mice was skewed towards a more pro-inflammatory state since anti-inflammatory IL-10 production was reduced. In conclusion, in this hyperlipidemic mouse model miR155 acts as an anti-inflammatory, atheroprotective microRNA. Additionally, besides a known role in lymphoid cell development, we show a crucial role of miR155 in myeloid lineage differentiation.     

Associations of supermarket characteristics with weight status and body fat: a multilevel analysis of individuals within supermarkets (RECORD study)

Purpose

Previous research on the influence of the food environment on weight status has often used impersonal measures of the food environment defined for residential neighborhoods, which ignore whether people actually use the food outlets near their residence. To assess whether supermarkets are relevant contexts for interventions, the present study explored between-residential neighborhood and between-supermarket variations in body mass index (BMI) and waist circumference (WC), and investigated associations between brands and characteristics of supermarkets and BMI or WC, after adjustment for individual and residential neighborhood characteristics.

Methods

Participants in the RECORD Cohort Study (Paris Region, France, 2007–2008) were surveyed on the supermarket (brand and exact location) where they conducted their food shopping. Overall, 7 131 participants shopped in 1 097 different supermarkets. Cross-classified multilevel linear models were estimated for BMI and WC.

Results

Just 11.4% of participants shopped for food primarily within their residential neighborhood. After accounting for participants'' residential neighborhood, people shopping in the same supermarket had a more comparable BMI and WC than participants shopping in different supermarkets. After adjustment for individual and residential neighborhood characteristics, participants shopping in specific supermarket brands, in hard discount supermarkets (especially if they had a low education), and in supermarkets whose catchment area comprised low educated residents had a higher BMI/WC.

Conclusion

A public health strategy to reduce excess weight may be to intervene on specific supermarkets to change food purchasing behavior, as supermarkets are where dietary preferences are materialized into definite purchased foods.