Childhood adversity as a risk for cancer: findings from the 1958 British birth cohort study.

International audienceBACKGROUND: To analyse whether Adverse Childhood Experiences (ACE) are associated with an increased risk of cancer. METHODS: The National child development study (NCDS) is a prospective birth cohort study with data collected over 50 years. The NCDS included all live births during one week in 1958 (n = 18558) in Great Britain. Self-reported cancer incidence was based on 444 participants reporting having had cancer at some point and 5694 reporting never having cancer. ACE was measured using reports of: 1) child in care, 2) physical neglect, 3) child's or family's contact with the prison service, 4) parental separation due to divorce, death or other, 5) family experience of mental illness & 6) family experience of substance abuse. The resulting variable had three categories, no ACEs/ one ACE/ 2 + ACEs and was used to test for a relationship with cancer. Information on socioeconomic characteristics, pregnancy and birth were extracted as potential confounders. Information on adult health behaviours, socioeconomic environment, psychological state and age at first pregnancy were added to the models. Multivariate models were run using multiply-imputed data to account for missing data in the cohort. RESULTS: The odds of having a cancer before 50y among women increased twofold for those who had 2+ ACEs versus those with no ACEs, after adjusting for adult factors and early life confounders (OR: 2.1, 95%CI: 1.42-3.21, p < 0.001). CONCLUSION: These findings suggest that cancer risk may be influenced by exposure to stressful conditions and events early on in life. This is potentially important in furthering our understanding of cancer aetiology, and consequently in redirecting scientific research and developing appropriate prevention policies

Recent expansion of the oriental shrimp Palaemon macrodactylus (Crustacea: Decapoda) on the western coasts of France

The invasive oriental shrimp Palaemon macrodactylus Rathbun, 1902 has considerably extended its distribution in transitional waters along the Atlantic and Channel coasts of France during the period 2007-2010. The most probable method of a primary introduction of this species is ballast waters, but passive transport by water currents is also a possible mechanism of colonization (secondary introductions). Palaemon macrodactylus is a powerful invader of transitional waters and these new populations should be monitored in the future to assess any consequences to native species

Mcl-1 is essential for the survival of plasma cells

The long-term survival of plasma cells is entirely dependent on signals derived from their environment. These extrinsic factors presumably induce and sustain the expression of antiapoptotic proteins of the Bcl-2 family. It is uncertain whether there is specificity among Bcl-2 family members in the survival of plasma cells and whether their expression is linked to specific extrinsic factors. We found here that deletion of the gene encoding the antiapoptotic protein Mcl-1 in plasma cells resulted in rapid depletion of this population in vivo. Furthermore, we found that the receptor BCMA was needed to establish high expression of Mcl-1 in bone marrow but not spleen plasma cells and that establishing this survival pathway preceded the component of plasma cell differentiation that depends on the transcriptional repressor Blimp-1. Our results identify a critical role for Mcl-1 in the maintenance of plasma cell

Harnessing the Vnn1 pantetheinase pathway boosts short chain fatty acids production and mucosal protection in colitis

Objective In the management of patients with IBD, there is a need to identify prognostic markers and druggable biological pathways to improve mucosal repair and probe the efficacy of tumour necrosis factor alpha biologics. Vnn1 is a pantetheinase that degrades pantetheine to pantothenate (vitamin B 5 , a precursor of coenzyme A (CoA) biosynthesis) and cysteamine. Vnn1 is overexpressed by inflamed colonocytes. We investigated its contribution to the tolerance of the intestinal mucosa to colitis-induced injury. Design We performed an RNA sequencing study on colon biopsy samples from patients with IBD stratified according to clinical severity and modalities of treatment. We generated the VIVA mouse transgenic model, which specifically overexpresses Vnn1 on intestinal epithelial cells and explored its susceptibility to colitis. We developed a pharmacological mimicry of Vnn1 overexpression by administration of Vnn1 derivatives. Results VNN1 overexpression on colonocytes correlates with IBD severity. VIVA mice are resistant to experimentally induced colitis. The pantetheinase activity of Vnn1 is cytoprotective in colon: it enhances CoA regeneration and metabolic adaptation of colonocytes; it favours microbiota-dependent production of short chain fatty acids and mostly butyrate, shown to regulate mucosal energetics and to be reduced in patients with IBD. This prohealing phenotype is recapitulated by treating control mice with the substrate (pantethine) or the products of pantetheinase activity prior to induction of colitis. In severe IBD, the protection conferred by the high induction of VNN1 might be compromised because its enzymatic activity may be limited by lack of available substrates. In addition, we identify the elevation of indoxyl sulfate in urine as a biomarker of Vnn1 overexpression, also detected in patients with IBD. Conclusion The induction of Vnn1/VNN1 during colitis in mouse and human is a compensatory mechanism to reinforce the mucosal barrier. Therefore, enhancement of vitamin B 5-driven metabolism should improve mucosal healing and might increase the efficacy of antiinflammatory therapy