Effects on musculoskeletal pain, work ability and sickness absence in a 1-year randomised controlled trial among cleaners

<p>Abstract</p> <p>Background</p> <p>Only a few workplace initiatives among cleaners have been reported, even though they constitute a job group in great need of health promotion. The purpose of this trial was to evaluate the effect of either physical coordination training or cognitive behavioural training on musculoskeletal pain, work ability and sickness absence among cleaners.</p> <p>Methods</p> <p>A cluster-randomised controlled trial was conducted among 294 female cleaners allocated to either physical coordination training (PCT), cognitive behavioural training (CBTr) or a reference group (REF). Questionnaires about musculoskeletal pain and work ability were completed at baseline and after one year's intervention. Sickness absence data were obtained from the managers' records. Analyses were performed according to the intention-to-treat-principle (ITT).</p> <p>Results</p> <p>No overall reduction in musculoskeletal pain, work ability or sickness absence from either PCT or CBTr compared with REF was found in conservative ITT analyses. However, explorative analyses revealed a treatment effect for musculoskeletal pain of the PCT. People with chronic neck/shoulder pain at baseline were more frequently non-chronic at follow-up after PCT compared with REF (p = 0.05).</p> <p>Conclusions</p> <p>The PCT intervention appeared effective for reducing chronic neck/shoulder pain among the female cleaners. It is recommended that future interventions among similar high-risk job groups focus on the implementation aspects of the interventions to maximise outcomes more distal from the intervention such as work ability and sickness absence.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN96241850">ISRCTN96241850</a></p

Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane

Rif1 is involved in telomere homeostasis, DNA replication timing, and DNA double-strand break (DSB) repair pathway choice from yeast to human. The molecular mechanisms that enable Rif1 to fulfill its diverse roles remain to be determined. Here, we demonstrate that Rif1 is S-acylated within its conserved N-terminal domain at cysteine residues C466 and C473 by the DHHC family palmitoyl acyltransferase Pfa4. Rif1 S-acylation facilitates the accumulation of Rif1 at DSBs, the attenuation of DNA end-resection, and DSB repair by non-homologous end-joining (NHEJ). These findings identify S-acylation as a posttranslational modification regulating DNA repair. S-acylated Rif1 mounts a localized DNA-damage response proximal to the inner nuclear membrane, revealing a mechanism of compartmentalized DSB repair pathway choice by sequestration of a fatty acylated repair factor at the inner nuclear membrane

Maximum in the Middle: Nonlinear Response of Microbial Plankton to Ultraviolet Radiation and Phosphorus

The responses of heterotrophic microbial food webs (HMFW) to the joint action of abiotic stressors related to global change have been studied in an oligotrophic high-mountain lake. A 2×5 factorial design field experiment performed with large mesocosms for >2 months was used to quantify the dynamics of the entire HMFW (bacteria, heterotrophic nanoflagellates, ciliates, and viruses) after an experimental P-enrichment gradient which approximated or surpassed current atmospheric P pulses in the presence vs. absence of ultraviolet radiation. HMFW underwent a mid-term (<20 days) acute development following a noticeable unimodal response to P enrichment, which peaked at intermediate P-enrichment levels and, unexpectedly, was more accentuated under ultraviolet radiation. However, after depletion of dissolved inorganic P, the HMFW collapsed and was outcompeted by a low-diversity autotrophic compartment, which constrained the development of HMFW and caused a significant loss of functional biodiversity. The dynamics and relationships among variables, and the response patterns found, suggest the importance of biotic interactions (predation/parasitism and competition) in restricting HMFW development, in contrast to the role of abiotic factors as main drivers of autotrophic compartment. The response of HMFW may contribute to ecosystem resilience by favoring the maintenance of the peculiar paths of energy and nutrient-mobilization in these pristine ecosystems, which are vulnerable to threats by the joint action of abiotic stressors related to global change.This research was supported by Junta de Andalucía (Excelencia P07-CVI-02598 to PC, and P09-RNM-5376 to JMMS), the Spanish Ministries of Medio Ambiente, Rural y Marino (PN2009/067 to PC) and Ciencia e Innovación (GLC2008-01127/BOS and CGL2011-23681 to PC), the ERC Advanced Grant project number 250254 “MINOS” (to GB), and two Spanish government grants (to JADM and FJB)

Therapeutic potential for phenytoin : targeting Nav1.5 sodium channels to reduce migration and invasion in metastatic breast cancer

Voltage-gated Na(+) channels (VGSCs) are heteromeric membrane protein complexes containing pore-forming α subunits and smaller, non-pore-forming β subunits. VGSCs are classically expressed in excitable cells, including neurons and muscle cells, where they mediate action potential firing, neurite outgrowth, pathfinding, and migration. VGSCs are also expressed in metastatic cells from a number of cancers. The Na(v)1.5 α subunit (encoded by SCN5A) is expressed in breast cancer (BCa) cell lines, where it enhances migration and invasion. We studied the expression of SCN5A in BCa array data, and tested the effect of the VGSC-blocking anticonvulsant phenytoin (5,5-diphenylhydantoin) on Na(+) current, migration, and invasion in BCa cells. SCN5A was up-regulated in BCa samples in several datasets, and was more highly expressed in samples from patients who had a recurrence, metastasis, or died within 5 years. SCN5A was also overexpressed as an outlier in a subset of samples, and associated with increased odds of developing metastasis. Phenytoin inhibited transient and persistent Na(+) current recorded from strongly metastatic MDA-MB-231 cells, and this effect was more potent at depolarized holding voltages. It may thus be an effective VGSC-blocking drug in cancer cells, which typically have depolarized membrane potentials. At a concentration within the therapeutic range used to treat epilepsy, phenytoin significantly inhibited the migration and invasion of MDA-MB-231 cells, but had no effect on weakly metastatic MCF-7 cells, which do not express Na(+) currents. We conclude that phenytoin suppresses Na(+) current in VGSC-expressing metastatic BCa cells, thus inhibiting VGSC-dependent migration and invasion. Together, our data support the hypothesis that SCN5A is up-regulated in BCa, favoring an invasive/metastatic phenotype. We therefore propose that repurposing existing VGSC-blocking therapeutic drugs should be further investigated as a potential new strategy to improve patient outcomes in metastatic BCa