No abstract

The analysis of a lymphoblastoid cell line (5106), derived from a rare individual of normal intelligence with an unmethylated full mutation of the FMR1 gene, allowed us to reconstruct the chain of molecular events leading to the FMR1 inactivation and to fragile X syndrome. We found that lack of DNA methylation of the entire promoter region, including the expanded CGG repeat, correlates with methylation of lysine 4 residue on the N-tail of histone H3 (H3-K4), as in normal controls. Normal levels of FMR1 mRNA were detected by real-time fluorescent RT-PCR (0.8-1.4 times compared with a control sample), but mRNA translation was less efficient (-40%), as judged by polysome profiling, resulting in reduced levels of FMRP protein (approximately 30% of a normal control). These results underline once more that CGG repeat amplification per se does not prevent FMR1 transcription and FMRP production in the absence of DNA methylation. Surprisingly, we found by chromatin immunoprecipitation that cell line 5106 has deacetylated histones H3 and H4 as well as methylated lysine 9 on histone H3 (H3-K9), like fragile X cell lines, in both the promoter and exon 1. This indicates that these two epigenetic marks (i.e. histone deacetylation and H3-K9 methylation) can be established in the absence of DNA methylation and do not interfere with active gene transcription, contrary to expectation. Our results also suggest that the molecular pathways regulating DNA and H3-K4 methylation are independent from those regulating histone acetylation and H3-K9 methylation.

BackgroundAging of the workforce is a growing problem. As workers age, their physical, physiological and psychosocial capabilities change. Keeping older workers healthy and productive is a key goal of European labor policy and health promotion is a key to achieve this result. Previous studies about workplace health promotion (WHP) programs are usually focused on the entire workforce or to a specific topic. Within the framework of the EU-CHAFEA ProHealth65+ project, this paper aims to systematically review the literature on WHP interventions specifically targeted to older workers (OWs).MethodsThis systematic review was conducted by making a comprehensive search of MEDLINE, ISI Web of Science, SCOPUS, The Cochrane Library, CINAHL and PsychINFO databases. Search terms included ageing (and synonyms), worker (and synonyms), intervention (and synonyms), and health (and synonyms). The search was limited to papers in English or Italian published between January, 1st 2000 and May, 31st 2015. Relevant references in the selected articles were also analyzed.ResultsOf the 299 articles initially identified as relating to the topic, 18 articles met the inclusion criteria. The type, methods and outcome of interventions in the WHP programs retrieved were heterogenous, as was the definition of the age at which a worker is considered to be ‘older’. Most of the available studies had been conducted on small samples for a limited period of time.ConclusionOur review shows that, although this issue is of great importance, studies addressing WHP actions for OWs are few and generally of poor quality. Current evidence fails to show that WHP programs improve the work ability, productivity or job retention of older workers. In addition, there is limited evidence that WHP programs are effective in improving lifestyles and concur to maintain the health and well-being of older workers. There is a need for future WHP programs to be well-designed so that the effectiveness and cost-benefit of workplace interventions can be properly investigated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-016-1518-z) contains supplementary material, which is available to authorized users.

Topical application of tranexamic acid into the pericardial cavity after cardiopulmonary bypass in patients undergoing primary coronary bypass operations significantly reduces postoperative bleeding. Further studies must be carried out to clarify whether a more pronounced effect on both bleeding and blood products requirement might be seen in procedures with a higher risk of bleeding.