599 research outputs found

    A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)

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    Rationale Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5–<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three nonadjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20 000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39 800/QALY. Conclusions Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective

    Siglec-F-dependent negative regulation of allergen-induced eosinophilia depends critically on the experimental model

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    Siglec-8 and siglec-F are paralogous membrane proteins expressed on human and murine eosinophils respectively. They bind similar sialylated and sulphated glycans and mediate eosinophil apoptosis when cross-linked with antibodies or glycan ligands. In models of allergic eosinophilic airway inflammation, siglec-F was shown previously to be important for negatively regulating eosinophilia. It was proposed that this was due to siglec-F-dependent apoptosis, triggered via engagement with ligands that are upregulated on bronchial epithelium. Our aim was to further investigate the functions of siglec-F by comparing two commonly used models of ovalbumin-induced airway inflammation that differ in the dose and route of administration of ovalbumin. In confirmation of published results, siglec-F-deficient mice had enhanced lung tissue eosinophilia in response to intranasal ovalbumin delivered every other day. However, following aerosolised ovalbumin delivered daily, there was no influence of siglec-F deficiency on lung eosinophilia. Expression of siglec-F ligands in lung tissues was similar in both models of allergen induced inflammation. These data demonstrate that siglec-F-dependent regulation of eosinophilia is subtle and depends critically on the model used. The findings also indicate that mechanisms other than ligand-induced apoptosis may be important in siglec-F-dependent suppression of eosinophilia

    Intersection of inflammation and herbal medicine in the treatment of osteoarthritis

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    Herbal remedies and dietary supplements have become an important area of research and clinical practice in orthopaedics and rheumatology. Understanding the risks and benefits of using herbal medicines in the treatment of arthritis, rheumatic diseases, and musculoskeletal complaints is a key priority of physicians and their patients. This review discusses the latest advances in the use of herbal medicines for treating osteoarthritis (OA) by focusing on the most significant trends and developments. This paper sets the scene by providing a brief introduction to ethnopharmacology, Ayurvedic medicine, and nutrigenomics before discussing the scientific and mechanistic rationale for targeting inflammatory signalling pathways in OA by use of herbal medicines. Special attention is drawn to the conceptual and practical difficulties associated with translating data from in-vitro experiments to in-vivo studies. Issues relating to the low bioavailability of active ingredients in herbal medicines are discussed, as also is the need for large-scale, randomized clinical trial

    RIPCAL: a tool for alignment-based analysis of repeat-induced point mutations in fungal genomic sequences

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    Background Repeat-induced point mutation (RIP) is a fungal-specific genome defence mechanism that alters the sequences of repetitive DNA, thereby inactivating coding genes. Repeated DNA sequences align between mating and meiosis and both sequences undergo C:G to T:A transitions. In most fungi these transitions preferentially affect CpA di-nucleotides thus altering the frequency of certain di-nucleotides in the affected sequences. The majority of previously published in silico analyses were limited to the comparison of ratios of pre- and post-RIP di-nucleotides in putatively RIP-affected sequences – so-called RIP indices. The analysis of RIP is significantly more informative when comparing sequence alignments of repeated sequences. There is, however, a dearth of bioinformatics tools available to the fungal research community for alignment-based RIP analysis of repeat families. Results We present RIPCAL http://www.sourceforge.net/projects/ripcal, a software tool for the automated analysis of RIP in fungal genomic DNA repeats, which performs both RIP index and alignment-based analyses. We demonstrate the ability of RIPCAL to detect RIP within known RIP-affected sequences of Neurospora crassa and other fungi. We also predict and delineate the presence of RIP in the genome of Stagonospora nodorum – a Dothideomycete pathogen of wheat. We show that RIP has affected different members of the S. nodorum rDNA tandem repeat to different extents depending on their genomic contexts. Conclusion The RIPCAL alignment-based method has considerable advantages over RIP indices for the analysis of whole genomes. We demonstrate its application to the recently published genome assembly of S. nodorum
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