Coordinated and tailored work rehabilitation: a randomized controlled trial with economic evaluation undertaken with workers on sick leave due to musculoskeletal disorders

Introduction In Denmark, the magnitude and impact of work disability on the individual worker and society has prompted the development of a new "coordinated and tailored work rehabilitation" (CTWR) approach. The aim of this study was to compare the effects of CTWR with conventional case management (CCM) on return-to-work of workers on sick leave due to musculoskeletal disorders (MSDs). Methods The study was a randomized controlled trial with economic evaluation undertaken with workers on sick leave for 4-12 weeks due to MSDs. CTWR consists of a work disability screening by an interdisciplinary team followed by the collaborative development of a RTW plan. The primary outcome variable was registered cumulative sickness absence hours during 12 months follow-up. Secondary outcomes were work status as well as pain intensity and functional disability, measured at baseline, 3 and 12 months follow-up. The economic evaluation (intervention costs, productivity loss, and health care utilization costs) was based on administrative data derived from national registries. Results For the time intervals 0-6 months, 6-12 months, and the entire follow-up period, the number of sickness absence hours was significantly lower in the CTWR group as compared to the control group. The total costs saved in CTWR participants compared to controls were estimated at US $1,366 per person at 6 months follow-up and US$ 10,666 per person at 12 months follow-up. Conclusions Workers on sick leave for 4-12 weeks due to MSD who underwent "CTWR" by an interdisciplinary team had fewer sickness absence hours than controls. The economic evaluation showed that-in terms of productivity loss-CTWR seems to be cost saving for the society

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Declining incidence of malaria imported into the UK from West Africa

BACKGROUND: Two thirds of all falciparum malaria cases reported in the United Kingdom (UK) are acquired in West Africa (WA). To ensure recommendations and guidelines for malaria prophylaxis in travellers to West Africa correlate to the risk of infection, a study was undertaken to examine recent trends and predict future patterns of imported malaria acquired by UK residents visiting West Africa and West African visitors to the UK between 1993 and 2006. METHODS AND RESULTS: Using passenger numbers and malaria surveillance reports, the data revealed a 2.3-fold increase in travel to West Africa with a five-fold increase in travelers visiting friends and relatives (VFR). Malaria incidence fell through the study period, the greatest decline noted in VFR with a fall from 196 cases/1,000 person-years to 52 cases/1,000 person-years, 9.8% per year p < 0.0001. The risk for travellers from the UK visiting for other reasons declined 2.7 fold, at an annual decrease of 7.0%, with the incidence in West African visitors to the UK falling by 2.3 fold, a rate of 7.9% annually. DISCUSSION: The reduction in incidence among all three groups of travellers may be explained by several factors; changing chemoprophylaxis usage and/or increased travel in urban areas where malaria risk has declined over the past decade, or widespread reduction in malaria transmission in West Africa. CONCLUSION: With the reduction in malaria incidence seen in both visitors to and from West Africa, the most rational explanation for these findings is a fall in malaria transmission in West Africa, which may require a change in chemoprophylaxis policy for UK travelers over the next 5-10 years

Prediction of potential drug targets based on simple sequence properties

<p>Abstract</p> <p>Background</p> <p>During the past decades, research and development in drug discovery have attracted much attention and efforts. However, only 324 drug targets are known for clinical drugs up to now. Identifying potential drug targets is the first step in the process of modern drug discovery for developing novel therapeutic agents. Therefore, the identification and validation of new and effective drug targets are of great value for drug discovery in both academia and pharmaceutical industry. If a protein can be predicted in advance for its potential application as a drug target, the drug discovery process targeting this protein will be greatly speeded up. In the current study, based on the properties of known drug targets, we have developed a sequence-based drug target prediction method for fast identification of novel drug targets.</p> <p>Results</p> <p>Based on simple physicochemical properties extracted from protein sequences of known drug targets, several support vector machine models have been constructed in this study. The best model can distinguish currently known drug targets from non drug targets at an accuracy of 84%. Using this model, potential protein drug targets of human origin from Swiss-Prot were predicted, some of which have already attracted much attention as potential drug targets in pharmaceutical research.</p> <p>Conclusion</p> <p>We have developed a drug target prediction method based solely on protein sequence information without the knowledge of family/domain annotation, or the protein 3D structure. This method can be applied in novel drug target identification and validation, as well as genome scale drug target predictions.</p

Origin and History of Mitochondrial DNA Lineages in Domestic Horses

Domestic horses represent a genetic paradox: although they have the greatest number of maternal lineages (mtDNA) of all domestic species, their paternal lineages are extremely homogeneous on the Y-chromosome. In order to address their huge mtDNA variation and the origin and history of maternal lineages in domestic horses, we analyzed 1961 partial d-loop sequences from 207 ancient remains and 1754 modern horses. The sample set ranged from Alaska and North East Siberia to the Iberian Peninsula and from the Late Pleistocene to modern times. We found a panmictic Late Pleistocene horse population ranging from Alaska to the Pyrenees. Later, during the Early Holocene and the Copper Age, more or less separated sub-populations are indicated for the Eurasian steppe region and Iberia. Our data suggest multiple domestications and introgressions of females especially during the Iron Age. Although all Eurasian regions contributed to the genetic pedigree of modern breeds, most haplotypes had their roots in Eastern Europe and Siberia. We found 87 ancient haplotypes (Pleistocene to Mediaeval Times); 56 of these haplotypes were also observed in domestic horses, although thus far only 39 haplotypes have been confirmed to survive in modern breeds. Thus, at least seventeen haplotypes of early domestic horses have become extinct during the last 5,500 years. It is concluded that the large diversity of mtDNA lineages is not a product of animal breeding but, in fact, represents ancestral variability

A prospective multi-center cohort study of acute non-displaced fractures of the scaphoid: operative versus non-operative treatment [NCT00205985]

BACKGROUND: Acute scaphoid fractures are common in active adults and do lead to reasonable time lost to work. One important goal of treatment is early return to work or sport. On this background, the adequate treatment of non-displaced acute scaphoid fractures is still under discussion. The aim of this study is to compare time to return to previous activity level comparing surgical versus non-surgical treatment of non-displaced acute scaphoid fractures. METHODS/DESIGN: The study is designed as a non-randomized multiple center cohort study including 12 sites in Germany and Austria. The inclusion period is planned to be 12 months with a follow up of 6 months. Allocation to operative or non-operative treatment is choosen by the patient together with his treating surgeon. The primary outcome is time to return to previous activity level adapted for loading of the wrist in daily life as measured by a newly developed questionnaire (PLDL-wrist). Factors identified a priori to be associated with the outcome, e.g., poverty status, age, education, smoking status, gender, and occupation, are measured to ensure adequate control for their potential confounding effects. DISCUSSION: The rationale and the design of a multiple center cohort study are presented. As it is not considered feasible to randomize patients in this study, potential confounding effects need to be controlled adequately

PEG-Albumin Plasma Expansion Increases Expression of MCP-1 Evidencing Increased Circulatory Wall Shear Stress: An Experimental Study

Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS), decreasing endothelial nitric oxide (NO) production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb) causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic. An acute 40% hemodilution/exchange-transfusion protocol was used to compare 4% PEG-Alb to Ringer’s lactate, Dextran 70 kDa and 6% Hetastarch (670 kDa) in unanesthetized CD-1 mice. Serum cytokine analysis showed that PEG-Alb elevates monocyte chemotactic protein-1 (MCP-1), a member of a small inducible gene family, as well as expression of MIP-1α, and MIP-2. MCP-1 is specific to increased WSS. Given the direct link between increased WSS and production of NO, the beneficial resuscitation effects due to PEG-Alb plasma expansion appear to be due to increased WSS through increased perfusion and blood flow rather than blood viscosity

Differential requirements for Tousled-like kinases 1 and 2 in mammalian development

The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type. To begin to address this, we have generated Tlk1- and Tlk2-deficient mice. We found that while TLK1 was dispensable for murine viability, TLK2 loss led to late embryonic lethality because of placental failure. TLK2 was required for normal trophoblast differentiation and the phosphorylation of ASF1 was reduced in placentas lacking TLK2. Conditional bypass of the placental phenotype allowed the generation of apparently healthy Tlk2-deficient mice, while only the depletion of both TLK1 and TLK2 led to extensive genomic instability, indicating that both activities contribute to genome maintenance. Our data identifies a specific role for TLK2 in placental function during mammalian development and suggests that TLK1 and TLK2 have largely redundant roles in genome maintenance