Tussive challenge with ATP and AMP: does it reveal cough hypersensitivity?

Recent studies have demonstrated that blockade of P2X3 adenosine triphosphate (ATP) receptors may profoundly inhibit chronic cough. We have considered whether inhaled ATP produces a tussive response and whether chronic cough patients are hypersensitive to inhaled ATP compared to healthy volunteers. A standardised inhalational cough challenge was performed with ATP and adenosine monophosphate (AMP). 20 healthy volunteers and 20 chronic cough patients were randomised as to the order of challenges. C5 (the concentration of challenge solution causing at least 5 coughs) was compared for ATP and AMP. The study population consisted of 6 male and 14 female volunteers in each group. 2/19 healthy volunteers coughed with AMP, none achieved C5. 8/20 chronic cough patients coughed with AMP, 2 achieved C5. 18/20 healthy volunteers coughed with ATP with 15 achieving C5. 19/19 chronic cough patients coughed with ATP, 18 achieved C5. The chronic cough patients had a greater cough response at lower concentrations of ATP. The greater potency of ATP versus AMP in inhalational challenge suggests that tussive responses are mediated through members of the P2X purinergic receptor family. This acute effect was however not sufficient to explain cough hypersensitivity syndrome.

An Economic Evaluation of Preclinical Testing Strategies Compared to the Compulsory Scrapie Flock Scheme in the Control of Classical Scrapie

Cost-benefit is rarely combined with nonlinear dynamic models when evaluating control options for infectious diseases. The current strategy for scrapie in Great Britain requires that all genetically susceptible livestock in affected flocks be culled (Compulsory Scrapie Flock Scheme or CSFS). However, this results in the removal of many healthy sheep, and a recently developed pre-clinical test for scrapie now offers a strategy based on disease detection. We explore the flock level cost-effectiveness of scrapie control using a deterministic transmission model and industry estimates of costs associated with genotype testing, pre-clinical tests and the value of a sheep culled. Benefit was measured in terms of the reduction in the number of infected sheep sold on, compared to a baseline strategy of doing nothing, using Incremental Cost Effectiveness analysis to compare across strategies. As market data was not available for pre-clinical testing, a threshold analysis was used to set a unit-cost giving equal costs for CSFS and multiple pre-clinical testing (MT, one test each year for three consecutive years). Assuming a 40% within-flock proportion of susceptible genotypes and a test sensitivity of 90%, a single test (ST) was cheaper but less effective than either the CSFS or MT strategies (30 infected-sales-averted over the lifetime of the average epidemic). The MT strategy was slightly less effective than the CSFS and would be a dominated strategy unless preclinical testing was cheaper than the threshold price of £6.28, but may be appropriate for flocks with particularly valuable livestock. Though the ST is not currently recommended, the proportion of susceptible genotypes in the national flock is likely to continue to decrease; this may eventually make it a cost-effective alternative to the MT or CSFS

Supermarkets as a setting to promote health eating : some lessons learnt in Victoria

Issue addressed: Supermarkets are a potential setting in which to deliver nutrition promotion to the community. A pilot project was able to examine the requirements for health authorities to form partnerships with other sectors and opportunities and limitations of using industry- based communication strategies to promote healthy eating messages. Methods: Pre-intervention interviews helped determine communication strategies. Post-intervention interviews were used to assess content and appropriateness of nutrition resources, collaboration between key participants, satisfaction with training and barriers/promoters to implementation. An intercept survey with consumers measured the impact of the intervention. Results: The survey of more than 1,120 women indicated only limited success. 12% of respondents from the intervention supermarkets had watched demonstrations and 20% had noticed the recipe leaflets, with only 5% able to name the promotion. Supermarket owners, representatives from participating food companies and demonstrators were supportive of the concept and content used in the promotion and qualitative analysis provides indicators for similar promotions. Conclusions: Health authorities considering \u27partnerships\u27 with the food/supermarket industry should recognise the diversity of roles and responsibilities of the organisations involved in the supply of food through the retail market and allow for long term planning when working with them. Head office of the supermarket group has a key coordinating role, however, individual supermarkets will be driven by financial returns. So what?: The recognition and trust in the name of health authorities by consumers means that organisations value an association with them.<br /

Association mapping of seed quality traits using the Canadian flax (Linum usitatissimum L.) core collection

KEY MESSAGE: The identification of stable QTL for seed quality traits by association mapping of a diverse panel of linseed accessions establishes the foundation for assisted breeding and future fine mapping in linseed. ABSTRACT: Linseed oil is valued for its food and non-food applications. Modifying its oil content and fatty acid (FA) profiles to meet market needs in a timely manner requires clear understanding of their quantitative trait loci (QTL) architectures, which have received little attention to date. Association mapping is an efficient approach to identify QTL in germplasm collections. In this study, we explored the quantitative nature of seed quality traits including oil content (OIL), palmitic acid, stearic acid, oleic acid, linoleic acid (LIO) linolenic acid (LIN) and iodine value in a flax core collection of 390 accessions assayed with 460 microsatellite markers. The core collection was grown in a modified augmented design at two locations over 3 years and phenotypic data for all seven traits were obtained from all six environments. Significant phenotypic diversity and moderate to high heritability for each trait (0.73–0.99) were observed. Most of the candidate QTL were stable as revealed by multivariate analyses. Nine candidate QTL were identified, varying from one for OIL to three for LIO and LIN. Candidate QTL for LIO and LIN co-localized with QTL previously identified in bi-parental populations and some mapped nearby genes known to be involved in the FA biosynthesis pathway. Fifty-eight percent of the QTL alleles were absent (private) in the Canadian cultivars suggesting that the core collection possesses QTL alleles potentially useful to improve seed quality traits. The candidate QTL identified herein will establish the foundation for future marker-assisted breeding in linseed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00122-014-2264-4) contains supplementary material, which is available to authorized users

Inhibition of insulin-degrading enzyme in human neurons promotes amyloid-β deposition

Alzheimer’s disease (AD) is characterised by the aggregation and deposition of amyloid-β (Aβ) peptides in the human brain. In age-related late-onset AD, deficient degradation and clearance, rather than enhanced production, of Aβ contributes to disease pathology. In the present study, we assessed the contribution of the two key Aβ-degrading zinc metalloproteases, insulin-degrading enzyme (IDE) and neprilysin (NEP), to Aβ degradation in human induced pluripotent stem cell (iPSC)-derived cortical neurons. Using an Aβ fluorescence polarisation assay, inhibition of IDE but not of NEP, blocked the degradation of Aβ by human neurons. When the neurons were grown in a 3D extracellular matrix to visualise Aβ deposition, inhibition of IDE but not NEP, increased the number of Aβ deposits. The resulting Aβ deposits were stained with the conformation-dependent, anti-amyloid antibodies A11 and OC that recognise Aβ aggregates in the human AD brain. Inhibition of the Aβ-forming β-secretase prevented the formation of the IDE-inhibited Aβ deposits. These data indicate that inhibition of IDE in live human neurons grown in a 3D matrix increased the deposition of Aβ derived from the proteolytic cleavage of the amyloid precursor protein. This work has implications for strategies aimed at enhancing IDE activity to promote Aβ degradation in AD

Reviews

The following publications have been reviewed by the mentioned authors;Textile Innovation - reviewed by Helen WilsonTransferring Designs to Textiles - reviewed by Helen WilsonFood Solutions - reviewed by Jonty KinsellaICT Activities for Food Technology - reviewed by Jenny JupeGCSE Food Technology for OCR - reviewed by Karen O'MahonyFocus on Wood Joints - reviewed by Alison HardyDesigning for the future - reviewed by Ian CapewellLearning to Teach Design and Technology in the Secondary School - reviewed by Jenny JupeUnlocking Potential - reviewed by Rowland DyeThe E-learning Revolution - reviewed by Les Porte

Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.

PURPOSE: A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG. METHODS: Healthy BCG-vaccinated volunteers were vaccinated with either 1×10(7) or 1×10(8)PFU of MVA85A. All adverse events were documented and antigen specific T cell responses were measured using an ex vivo IFN-γ ELISPOT assay. Safety and immunogenicity were compared between the 2 dose groups and with a previous trial in which a dose of 5×10(7)PFU MVA85A had been administered. RESULTS: There were no serious adverse events recorded following administration of either 1×10(7) or 1×10(8)PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1×10(8)PFU of MVA85A when compared to either 5×10(7) or 1×10(7)PFU of MVA85A but were mild or moderate in severity and resolved completely within 7 days of immunisation. Antigen specific T cell responses as measured by the IFN-γ ELISPOT were significantly higher following immunisation in adults receiving 1×10(8)PFU compared to the 5×10(7) and 1×10(7) doses. Additionally, a broader range of Ag85A epitopes are detected following 1×10(8)PFU of MVA85A. CONCLUSION: A higher dose of 1×10(8)PFU of MVA85A is well-tolerated, increases the frequency of IFN-γ secreting T cells detected following immunisation and broadens the range of Ag85A epitopes detected