Chronic low back pain among French healthcare workers and prognostic factors of return to work (RTW): a non-randomized controlled trial

BACKGROUND: Many factors influence the return to work of workers with chronic low back pain (CLBP). They have been said to vary according to socio-professional group. This study first aimed to compare prognostic factors influencing the return to work of CLBP healthcare workers (HCWs) and other workers (non-HCWs) after rehabilitation coupled with an occupational intervention. The second objective was to improve the evolution of indicators such as clinical examination, psychosocial impact and pain impact. METHODS: Between 2007 and 2012, a cohort of 217 CLBP workers (54.8 %-women; mean age = 41.3 ± 9.5 years, 118 non-HCWs; 99 HCWs mainly from the public sector) was included in an ambulatory rehabilitation program (standard physiotherapy or intensive network physiotherapy) coupled with an occupational intervention. Workers completed a questionnaire and had a clinical examination at baseline and after 24 months\u27 follow up. Physical, social and occupational data was collected at the same time. Statistical analyses were performed to evaluate prognostic factors for return to work and compare the two worker populations. RESULTS: There was no difference between groups for the rate of OP (occupational physician) intervention or type of physiotherapy. 77.3 % of workers returned to work after 2 years following inclusion. To be an HCW (OR 0.1; 95 % CI [0.03-0.34]), to have less than 112 sick- leave days (OR 1.00; 95 % CI [0.93-1.00]), a small fingertip-floor distance (OR 0.96; 95 % CI [0.93-0.99]), a low anxiety/depression score (OR 0.97; 95 % CI [0.95-1.00]), a low impact of CLBP on daily life (OR 0.96; 95 % CI [0.93-1.00]), and on quality of life (OR 0.98; 95 % CI [0.95-1.00]) at baseline were statistically associated with return to work after 2 years of follow up. Only the profession (workplace) was statistically associated with return to work after 2 years of follow up using multivariate analysis. CONCLUSION: To our knowledge, this is the first cohort study concerning predictive factors of RTW among CLBP workers after 2 years of follow up. Interventions in the work environment did not seem to predict job retention significantly. But only 50 % of the employees in both groups (HCW and non-HCW) had one intervention at their workplace after 2 years. This study underlined the fact that the type of physiotherapy with a well-trained physiotherapist used to take care of CLBP could not impact on the RTW forecast. To develop these initial results, it might be interesting to study the comparison between private and public sectors and to randomize the physiotherapeutic intervention

Psychosocial factors associated with change in pain and disability outcomes in chronic low back pain patients treated by physiotherapist: a systematic review

Background: Almost 80% of people have low back pain at least once in their life. Clinical guidelines emphasize the use of conservative physiotherapy and the importance of staying active. While the psychological factors predicting poor recovery following surgical intervention are understood, the psychosocial factors associated with poor outcomes following physiotherapy have yet to be identified. Methods: Electronic searches of PubMed, Medline, CINAHL, PsycINFO and EBSCO were conducted using terms relating to psychosocial factors, chronic low back pain, disability and physiotherapy. Papers examining the relationship between psychosocial factors and pain and disability outcomes following physiotherapy were included. Two reviewers selected, appraised and extracted studies independently. Results: In total, 10 observational studies were identified that suggested an association between fear of movement, depression, self-efficacy and catastrophizing in modifying pain and disability outcomes following physiotherapy. Discussion: Although limited by methodological shortcomings of included studies, and heterogeneity of physiotherapy interventions and measures of disability and psychosocial outcomes, the findings are consistent with other research in the context of back pain and physiotherapy, which suggest an association between psychosocial factors, including fear of movement, catastrophizing and self-efficacy and pain and disability outcomes in chronic low back pain patients treated by physiotherapist. However, a direct relationship cannot be concluded from this study. Conclusion: Findings suggest an association between psychosocial factors, including fear of movement, catastrophizing and self-efficacy and pain and disability outcomes in chronic low back pain patients treated by physiotherapist, which warrants further study

An mRNA decapping mutant deficient in P body assembly limits mRNA stabilization in response to osmotic stress

Yeast is exposed to changing environmental conditions and must adapt its genetic program to provide a homeostatic intracellular environment. An important stress for yeast in the wild is high osmolarity. A key response to this stress is increased mRNA stability primarily by the inhibition of deadenylation. We previously demonstrated that mutations in decapping activators (edc3∆ lsm4∆C), which result in defects in P body assembly, can destabilize mRNA under unstressed conditions. We wished to examine whether mRNA would be destabilized in the edc3∆ lsm4∆C mutant as compared to the wild-type in response to osmotic stress, when P bodies are intense and numerous. Our results show that the edc3∆ lsm4∆C mutant limits the mRNA stability in response to osmotic stress, while the magnitude of stabilization was similar as compared to the wild-type. The reduced mRNA stability in the edc3∆ lsm4∆C mutant was correlated with a shorter PGK1 poly(A) tail. Similarly, the MFA2 mRNA was more rapidly deadenylated as well as significantly stabilized in the ccr4∆ deadenylation mutant in the edc3∆ lsm4∆C background. These results suggest a role for these decapping factors in stabilizing mRNA and may implicate P bodies as sites of reduced mRNA degradation

Post-Transcriptional Trafficking and Regulation of Neuronal Gene Expression

Intracellular messenger RNA (mRNA) traffic and translation must be highly regulated, both temporally and spatially, within eukaryotic cells to support the complex functional partitioning. This capacity is essential in neurons because it provides a mechanism for rapid input-restricted activity-dependent protein synthesis in individual dendritic spines. While this feature is thought to be important for synaptic plasticity, the structures and mechanisms that support this capability are largely unknown. Certainly specialized RNA binding proteins and binding elements in the 3′ untranslated region (UTR) of translationally regulated mRNA are important, but the subtlety and complexity of this system suggests that an intermediate “specificity” component is also involved. Small non-coding microRNA (miRNA) are essential for CNS development and may fulfill this role by acting as the guide strand for mediating complex patterns of post-transcriptional regulation. In this review we examine post-synaptic gene regulation, mRNA trafficking and the emerging role of post-transcriptional gene silencing in synaptic plasticity

Downregulation of the AU-Rich RNA-Binding Protein ZFP36 in Chronic HBV Patients: Implications for Anti-Inflammatory Therapy

Inflammation caused by chronic hepatitis B virus (HBV) infection is associated with the development of cirrhosis and hepatocellular carcinoma; however, the mechanisms by which HBV infection induces inflammation and inflammatory cytokine production remain largely unknown. We analyzed the gene expression patterns of lymphocytes from chronic HBV-infected patients and found that the expression of ZFP36, an AU-rich element (ARE)-binding protein, was dramatically reduced in CD4+ and CD8+ T lymphocytes from chronic HBV patients. ZFP36 expression was also reduced in CD14+ monocytes and in total PBMCs from chronic HBV patients. To investigate the functional consequences of reduced ZFP36 expression, we knocked down ZFP36 in PBMCs from healthy donors using siRNA. siRNA-mediated silencing of ZFP36 resulted in dramatically increased expression of multiple inflammatory cytokines, most of which were also increased in the plasma of chronic HBV patients. Furthermore, we found that IL-8 and RANTES induced ZFP36 downregulation, and this effect was mediated through protein kinase C. Importantly, we found that HBsAg stimulated PBMCs to express IL-8 and RANTES, resulting in decreased ZFP36 expression. Our results suggest that an inflammatory feedback loop involving HBsAg, ZFP36, and inflammatory cytokines may play a critical role in the pathogenesis of chronic HBV and further indicate that ZFP36 may be an important target for anti-inflammatory therapy during chronic HBV infection

Epigenetic mechanisms in virus-induced tumorigenesis

About 15–20% of human cancers worldwide have viral etiology. Emerging data clearly indicate that several human DNA and RNA viruses, such as human papillomavirus, Epstein–Barr virus, Kaposi’s sarcoma-associated herpesvirus, hepatitis B virus, hepatitis C virus, and human T-cell lymphotropic virus, contribute to cancer development. Human tumor-associated viruses have evolved multiple molecular mechanisms to disrupt specific cellular pathways to facilitate aberrant replication. Although oncogenic viruses belong to different families, their strategies in human cancer development show many similarities and involve viral-encoded oncoproteins targeting the key cellular proteins that regulate cell growth. Recent studies show that virus and host interactions also occur at the epigenetic level. In this review, we summarize the published information related to the interactions between viral proteins and epigenetic machinery which lead to alterations in the epigenetic landscape of the cell contributing to carcinogenesis

The Circadian Deadenylase Nocturnin Is Necessary for Stabilization of the iNOS mRNA in Mice

Nocturnin is a member of the CCR4 deadenylase family, and its expression is under circadian control with peak levels at night. Because it can remove poly(A) tails from mRNAs, it is presumed to play a role in post-transcriptional control of circadian gene expression, but its target mRNAs are not known. Here we demonstrate that Nocturnin expression is acutely induced by the endotoxin lipopolysaccharide (LPS). Mouse embryo fibroblasts (MEFs) lacking Nocturnin exhibit normal patterns of acute induction of TNFα and iNOS mRNAs during the first three hours following LPS treatment, but by 24 hours, while TNFα mRNA levels are indistinguishable from WT cells, iNOS message is significantly reduced 20-fold. Accordingly, analysis of the stability of the mRNAs showed that loss of Nocturnin causes a significant decrease in the half-life of the iNOS mRNA (t1/2 = 3.3 hours in Nocturnin knockout MEFs vs. 12.4 hours in wild type MEFs), while having no effect on the TNFα message. Furthermore, mice lacking Nocturnin lose the normal nighttime peak of hepatic iNOS mRNA, and have improved survival following LPS injection. These data suggest that Nocturnin has a novel stabilizing activity that plays an important role in the circadian response to inflammatory signals

Membrane-association of mRNA decapping factors is independent of stress in budding yeast

Recent evidence has suggested that the degradation of mRNA occurs on translating ribosomes or alternatively within RNA granules called P bodies, which are aggregates whose core constituents are mRNA decay proteins and RNA. In this study, we examined the mRNA decapping proteins, Dcp1, Dcp2, and Dhh1, using subcellular fractionation. We found that decapping factors co-sediment in the polysome fraction of a sucrose gradient and do not alter their behaviour with stress, inhibition of translation or inhibition of the P body formation. Importantly, their localisation to the polysome fraction is independent of the RNA, suggesting that these factors may be constitutively localised to the polysome. Conversely, polysomal and post-polysomal sedimentation of the decapping proteins was abolished with the addition of a detergent, which shifts the factors to the non-translating RNP fraction and is consistent with membrane association. Using a membrane flotation assay, we observed the mRNA decapping factors in the lower density fractions at the buoyant density of membrane-associated proteins. These observations provide further evidence that mRNA decapping factors interact with subcellular membranes, and we suggest a model in which the mRNA decapping factors interact with membranes to facilitate regulation of mRNA degradation