Effectiveness and cost-effectiveness of early assisted discharge for Chronic Obstructive Pulmonary Disease exacerbations: the design of a randomised controlled trial

Background: Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are the main cause for hospitalisation. These hospitalisations result in a high pressure on hospital beds and high health care costs. Because of the increasing prevalence of COPD this will only become worse. Hospital at home is one of the alternatives that has been proved to be a safe alternative for hospitalisation in COPD. Most schemes are early assisted discharge schemes with specialised respiratory nurses providing care at home. Whether this type of service is cost-effective depends on the setting in which it is delivered and the way in which it is organised. Methods/Design: GO AHEAD (Assessment Of Going Home under Early Assisted Discharge) is a 3-months, randomised controlled, multi-centre clinical trial. Patients admitted to hospital for a COPD exacerbation are either discharged on the fourth day of admission and further treated at home, or receive usual inpatient hospital care. Home treatment is supervised by general nurses. Primary outcome is the effectiveness and cost effectiveness of an early assisted discharge intervention in comparison with usual inpatient hospital care for patients hospitalised with a COPD exacerbation. Secondary outcomes include effects on quality of life, primary informal caregiver burden and patient and primary caregiver satisfaction. Additionally, a discrete choice experiment is performed to provide insight in patient and informal caregiver preferences for different treatment characteristics. Measurements are performed on the first day of admission and 3 days, 7 days, 1 month and 3 months thereafter. Ethical approval has been obtained and the study has been registered. Discussion: This article describes the study protocol of the GO AHEAD study. Early assisted discharge could be an effective and cost-effective method to reduce length of hospital stay in the Netherlands which is beneficial for patients and society. If effectiveness and cost-effectiveness can be proven, implementation in the Dutch health care system should be considered. Trial registration: Netherlands Trial Register NTR1129

Protocol optimization for the mild detemplation of mesoporous silica nanoparticles resulting in enhanced texture and colloidal stability

Porosity development of mesostructured colloidal silica nanoparticles is related to the removal of the organic templates and co-templates which is often carried out by calcination at high temperatures, 500-600 °C. In this study a mild detemplation method based on the oxidative Fenton chemistry has been investigated. The Fenton reaction involves the generation of OH radicals following a redox Fe3+/Fe2+ cycle that is used as catalyst and H2O2 as oxidant source. Improved material properties are anticipated since the Fenton chemistry comprises milder conditions than calcination. However, the general application of this methodology is not straightforward due to limitations in the hydrothermal stability of the particular system under study. The objective of this work is three-fold: 1) reducing the residual Fe in the resulting solid as this can be detrimental for the application of the material, 2) shortening the reaction time by optimizing the reaction temperature to minimize possible particle agglomeration, and finally 3) investigating the structural and textural properties of the resulting material in comparison to the calcined counterparts. It appears that the Fenton detemplation can be optimized by shortening the reaction time significantly at low Fe concentration. The milder conditions of detemplation give rise to enhanced properties in terms of surface area, pore volume, structural preservation, low Fe residue and high degree of surface hydroxylation; the colloidal particles are stable during storage. A relative particle size increase, expressed as 0.11%·h-1, has been determined

Identification of modifiable factors associated with owner-reported equine laminitis in Britain using a web-based cohort study approach

Equine laminitis is a complex disease that manifests as pain and lameness in the feet, often with debilitating consequences. There is a paucity of data that accounts for the multifactorial nature of laminitis and considers time-varying covariates that may be associated with disease development; particularly those that are modifiable and present potential interventions. A previous case-control study identified a number of novel, modifiable factors associated with laminitis which warranted further investigation and corroboration. The aim of this study was to identify factors associated with equine laminitis in horses/ponies in Great Britain (GB) using a prospective, web-based cohort study design, with particular interest in evaluating modifiable factors previously identified in the case-control study

DNA repair endonuclease ERCC1-XPF as a novel therapeutic target to overcome chemoresistance in cancer therapy

The ERCC1–XPF complex is a structure-specific endonuclease essential for the repair of DNA damage by the nucleotide excision repair pathway. It is also involved in other key cellular processes, including DNA interstrand crosslink (ICL) repair and DNA double-strand break (DSB) repair. New evidence has recently emerged, increasing our understanding of its requirement in these additional roles. In this review, we focus on the protein–protein and protein–DNA interactions made by the ERCC1 and XPF proteins and discuss how these coordinate ERCC1–XPF in its various roles. In a number of different cancers, high expression of ERCC1 has been linked to a poor response to platinum-based chemotherapy. We discuss prospects for the development of DNA repair inhibitors that target the activity, stability or protein interactions of the ERCC1–XPF complex as a novel therapeutic strategy to overcome chemoresistance

Loss of Toll-Like Receptor 4 Function Partially Protects against Peripheral and Cardiac Glucose Metabolic Derangements During a Long-Term High-Fat Diet

We would like to acknowledge Matt Priest for excellent technical assistance.Diabetes is a chronic inflammatory disease that carries a high risk of cardiovascular disease. However, the pathophysiological link between these disorders is not well known. We hypothesize that TLR4 signaling mediates high fat diet (HFD)-induced peripheral and cardiac glucose metabolic derangements. Mice with a loss-of-function mutation in TLR4 (C3H/HeJ) and age-matched control (C57BL/6) mice were fed either a high-fat diet or normal diet for 16 weeks. Glucose tolerance and plasma insulin were measured. Protein expression of glucose transporters (GLUT), AKT (phosphorylated and total), and proinflammatory cytokines (IL-6, TNF-α and SOCS-3) were quantified in the heart using Western Blotting. Both groups fed a long-term HFD had increased body weight, blood glucose and insulin levels, as well as impaired glucose tolerance compared to mice fed a normal diet. TLR4-mutant mice were partially protected against long-term HFD-induced insulin resistance. In control mice, feeding a HFD decreased cardiac crude membrane GLUT4 protein content, which was partially rescued in TLR4-mutant mice. TLR4-mutant mice fed a HFD also had increased expression of GLUT8, a novel isoform, compared to mice fed a normal diet. GLUT8 content was positively correlated with SOCS-3 and IL-6 expression in the heart. No significant differences in cytokine expression were observed between groups, suggesting a lack of inflammation in the heart following a HFD. Loss of TLR4 function partially restored a healthy metabolic phenotype, suggesting that TLR4 signaling is a key mechanism in HFD-induced peripheral and cardiac insulin resistance. Our data further suggest that TLR4 exerts its detrimental metabolic effects in the myocardium through a cytokine-independent pathway.Yeshttp://www.plosone.org/static/editorial#pee

Global Chromatin Domain Organization of the Drosophila Genome

In eukaryotes, neighboring genes can be packaged together in specific chromatin structures that ensure their coordinated expression. Examples of such multi-gene chromatin domains are well-documented, but a global view of the chromatin organization of eukaryotic genomes is lacking. To systematically identify multi-gene chromatin domains, we constructed a compendium of genome-scale binding maps for a broad panel of chromatin-associated proteins in Drosophila melanogaster. Next, we computationally analyzed this compendium for evidence of multi-gene chromatin domains using a novel statistical segmentation algorithm. We find that at least 50% of all fly genes are organized into chromatin domains, which often consist of dozens of genes. The domains are characterized by various known and novel combinations of chromatin proteins. The genes in many of the domains are coregulated during development and tend to have similar biological functions. Furthermore, during evolution fewer chromosomal rearrangements occur inside chromatin domains than outside domains. Our results indicate that a substantial portion of the Drosophila genome is packaged into functionally coherent, multi-gene chromatin domains. This has broad mechanistic implications for gene regulation and genome evolution

RNA expression of TLR10 in normal equine tissues

Background: Toll like receptors are one of the major innate immune system pathogen recognition systems. There is little data on the expression of the TLR10 member of this family in the horse. Results: This paper describes the genetic structure of the Equine TLR10 gene and its RNA expression in a range of horse tissues. It describes the phylogenetic analysis of the Equine TLR1,6,10,2 annotations in the horse genome, firmly identifying them in their corresponding gene clades compared to other species and firmly placing the horse gene with other TLR10 genes from odd-toed ungulates. Additional 3’ transcript extensions to that annotated for TLR10 in the horse genome have been identified by analysis of RNAseq data. RNA expression of the equine TLR10 gene was highest in peripheral blood mononucleocytes and lymphoid tissue (lymph nodes and spleen), however some expression was detected in all tissues tested (jejunum, caudal mesenteric lymph nodes, bronchial lymph node, spleen, lung, colon, kidney and liver). Additional data on RNAseq expression of all equine TLR genes (1–4 and 6–10) demonstrate higher expression of TLR4 than other equine TLRs in all tissues. Conclusion: The equine TLR10 gene displays significant homology to other mammalian TLR10 genes and could be reasonably assumed to have similar fuctions. Its RNA level expression is higher in resting state PBMCs in horses than in other tissues

Evaluation of the function and quality of life of patients submitted to girdlestone's resection arthroplasty

OBJECTIVES: To evaluate function and quality of life of patients submitted to Girdlestone's arthroplasty, and to compare outcomes between unilateral Girdlestone's group with the group with contralateral total hip prosthesis. METHODS: Cross-sectional study where 9 patients were evaluated with unilateral Girdlestone's and 3 with Girdlestone's in one hip and contralateral total hip prosthesis. The evaluation consisted in filling in a generic questionnaire on quality of life SF-36 and a specific questionnaire for hip function Harris Hip Score (HHS). The comparison between groups was made by using the Student's t-test and the Fisher's test. RESULTS: The patients of the unilateral Girdlestone's group presented a higher number of SF-36 domains classified as high, although 77.8% of these showed poor results on the HHS. All patients had a leg-length discrepancy and positive Trendelenburg's test, which led to limping gait in 11 of 12 patients evaluated. Of these, only 6 underwent physiotherapy after surgery. CONCLUSION: Girdlestone's postoperative quality of life and function in a Brazilian population still requires further studies, because these outcomes are indicative of study variables' behavior and cannot be regarded as definite.OBJETIVOS: Avaliar a função e a qualidade de vida dos pacientes pós-artroplastia de Girdlestone e comparar os resultados entre os grupos Girdlestone unilateral e o grupo com prótese total de quadril contralateral. MÉTODOS: estudo transversal no qual foram avaliados 9 pacientes com Girdlestone unilateral e 3 com Girdlestone em um quadril e prótese total no quadril contralateral. A avaliação constitui-se em aplicar o questionário genérico de qualidade de vida SF-36 e um questionário funcional específico para o quadril, Harris Hip Score (HHS). A comparação dos grupos foi realizada usando-se o teste t- Student e o teste de Fisher. RESULTADOS: Os pacientes do grupo Girdlestone unilateral apresentaram maior quantidade de domínios do SF-36 classificados como elevados, embora 77,8% destes tenham obtido resultados ruins no HHS. Todos os pacientes apresentaram o teste de Trendelenburg positivo e discrepância de membros, o que levou à marcha claudicante em 11 dos 12 pacientes avaliados. Destes, apenas 6 submeteram-se a fisioterapia pós-operatória. CONCLUSÃO: A qualidade de vida e a função pós-operatória de Girdlestone, na população brasileira, ainda necessita ser mais pesquisada, pois estes resultados são indicações do comportamento das variáveis de estudo e não podem ser consideradas encerradas.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Ortopedia e TraumatologiaUNIFESP-EPM DOTUNIFESP, EPM, Depto. de Ortopedia e TraumatologiaUNIFESP, EPM DOTSciEL