The (cost-)effectiveness of a lifestyle physical activity intervention in addition to a work style intervention on the recovery from neck and upper limb symptoms in computer workers

BACKGROUND: Neck and upper limb symptoms are frequently reported by computer workers. Work style interventions are most commonly used to reduce work-related neck and upper limb symptoms but lifestyle physical activity interventions are becoming more popular to enhance workers health and reduce work-related symptoms. A combined approach targeting work style and lifestyle physical activity seems promising, but little is known on the effectiveness of such combined interventions. METHODS/DESIGN: The RSI@Work study is a randomised controlled trial that aims to assess the added value of a lifestyle physical activity intervention in addition to a work style intervention to reduce neck and upper limb symptoms in computer workers. Computer workers from seven Dutch companies with frequent or long-term neck and upper limb symptoms in the preceding six months and/or the last two weeks are randomised into three groups: (1) work style group, (2) work style and physical activity group, or (3) control group. The work style intervention consists of six group meetings in a six month period that take place at the workplace, during work time, and under the supervision of a specially trained counsellor. The goal of this intervention is to stimulate workplace adjustment and to improve body posture, the number and quality of breaks and coping behaviour with regard to high work demands. In the combined (work style and physical activity) intervention the additional goal is to increase moderate to heavy physical activity. The control group receives usual care. Primary outcome measures are degree of recovery, pain intensity, disability, number of days with neck and upper limb symptoms, and number of months without neck and upper limb symptoms. Outcome measures will be assessed at baseline and six and 12 months after randomisation. Cost-effectiveness of the group meetings will be assessed using an employer's perspective. DISCUSSION: This study will be one of the first to assess the added value of a lifestyle physical activity intervention in addition to a work style intervention in reducing neck and upper limb symptoms of computer workers. The results of the study are expected in 2007

Glucocorticoids promote structural and functional maturation of foetal cardiomyocytes: a role for PGC-1α

Glucocorticoid levels rise dramatically in late gestation to mature foetal organs in readiness for postnatal life. Immature heart function may compromise survival. Cardiomyocyte glucocorticoid receptor (GR) is required for the structural and functional maturation of the foetal heart in vivo, yet the molecular mechanisms are largely unknown. Here we asked if GR activation in foetal cardiomyocytes in vitro elicits similar maturational changes. We show that physiologically relevant glucocorticoid levels improve contractility of primary-mouse-foetal cardiomyocytes, promote Z-disc assembly and the appearance of mature myofibrils, and increase mitochondrial activity. Genes induced in vitro mimic those induced in vivo and include PGC-1α, a critical regulator of cardiac mitochondrial capacity. SiRNA-mediated abrogation of the glucocorticoid induction of PGC-1α in vitro abolished the effect of glucocorticoid on myofibril structure and mitochondrial oxygen consumption. Using RNA sequencing we identified a number of transcriptional regulators, including PGC-1α, induced as primary targets of GR in foetal cardiomyocytes. These data demonstrate that PGC-1α is a key mediator of glucocorticoid-induced maturation of foetal cardiomyocyte structure and identify other candidate transcriptional regulators that may play critical roles in the transition of the foetal to neonatal heart

A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay.

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls (P = 0.0009, OR = 7.2) and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls (P = 0.028, OR = 2.5). Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents (P = 0.037, OR = 6). Probands were more likely to carry an additional large copy-number variant when compared to matched controls (10 of 42 cases, P = 5.7 x 10(-5), OR = 6.6). The clinical features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease

Analyses of ovarian activity reveal repeated evolution of post-reproductive lifespans in toothed whales

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordIn most species the reproductive system ages at the same rate as somatic tissue and individuals continue reproducing until death. However, females of three species – humans, killer whales and short-finned pilot whales – have been shown to display a markedly increased rate of reproductive senescence relative to somatic ageing. In these species, a significant proportion of females live beyond their reproductive lifespan: they have a post-reproductive lifespan. Research into this puzzling life-history strategy is hindered by the difficulties of quantifying the rate of reproductive senescence in wild populations. Here we present a method for measuring the relative rate of reproductive 25 senescence in toothed whales using published physiological data. Of the sixteen species for which 26 data are available (which does not include killer whales), we find that three have a significant post27 reproductive lifespan: short-finned pilot whales, beluga whales and narwhals. Phylogenetic reconstruction suggests that female post-reproductive lifespans have evolved several times independently in toothed whales. Our study is the first evidence of a significant post-reproductive lifespan in beluga whales and narwhals which, when taken together with the evidence for post31 reproductive lifespan in killer whales, doubles the number of non-human mammals known to exhibit post-reproductive lifespans in the wild.Support for this research was provided by a grant from NERC (NE/K01286X/1) awarded to DPC, DWF and MAC