PATIENT AND PUBLIC INVOLVEMENT IN EARLY AWARENESS AND ALERT ACTIVITIES: AN EXAMPLE FROM THE UNITED KINGDOM.

OBJECTIVES: The aim of this study is to report on the experiences, benefits, and challenges of patient and public involvement and engagement (PPIE) from a publicly funded early awareness and alert (EAA) system in the United Kingdom. METHODS: Using email, telephone, a Web site portal, Twitter and focus groups, patients and the public were involved and engaged in the recognized stages of an EAA system: identification, filtration, prioritization, early assessment, and dissemination. RESULTS: Approaches for PPIE were successfully integrated into all aspects of the National Institute for Health Research Horizon Scanning Research and Intelligence Centre's EAA system. Input into identification activities was not as beneficial as involvement in prioritization and early assessment. Patients gave useful insight into the Centre's Web site and engaging patients using Twitter has enabled the Centre to disseminate outputs to a wider audience. CONCLUSIONS: EAA systems should consider involving and engaging with patients and the public in identification, prioritization, and assessment of emerging health technologies where practicable. Further research is required to examine the value and impact of PPIE in EAA activities and in the early development of health technologies.

Diagnosing Alzheimer's disease: are we any nearer to useful biomarker-based, non-invasive tests?

BACKGROUND: Alzheimer's disease (AD) accounts for 60-80% of cases of dementia and causes significant morbidity in patients and carers, and expense for health and social services. There is a need for a validated, non-invasive and cheap test to diagnose early AD, as diagnosis may enable prompt treatment and service planning. AIM: To identify emerging biomarker-based tests for the early diagnosis of AD which could be available for use in primary or generalist care in the near future. DESIGN: Horizon scanning review. METHODS: We searched online sources to identify emerging non-invasive, biomarker-based tests. Tests were included if they used blood, saliva or urine; and there was evidence of use in trials in patients with AD. For tests licensed for use in clinical or research settings we requested information from the developer on the intended place of use and plans for availability in Europe. RESULTS: We identified 6 biomarker-based tests of which 5 are available for research or clinical use. The closest to market were AclarusDX™ (ExonHit Therapeutics) a gene signature test, and INNO-BIA plasma Aß forms assay (Innogenetics N.V.) which may be CE marked for clinical use in 2015. We found no evidence of clinical utility or cost. CONCLUSION: Although biomarker-based tests are nearing clinical availability and may have a future role to help target AD-specific treatment and guide prognosis, they are not yet ready for trials of clinical utility in primary care.

Overexpression of nPKC theta is inhibitory for agrin-induced nicotinic acetylcholine receptor clustering in C2C12 myotubes.

Protein kinase C (PKC) activity has been implicated in nicotinic acetylcholine receptor (nAChR) cluster disruption but the specific PKC isoforms involved have not been identified. We first tested whether phorbol esters, which activate PKCs, regulate agrin-induced nAChR clustering in C(2)C(12) cells. We found that extended phorbol ester treatment (6 hr) increased nAChR clustering by two-fold. This increase correlated in time with downregulation of PKCs, as indicated by the disappearance of cPKC alpha, suggesting that the presence of PKCs is inhibitory for maximal nAChR clustering. To address the question whether nPKC theta, a specific PKC isoform restricted in expression to skeletal muscle and localized to neuromuscular junctions, regulates agrin-induced nAChR cluster formation we overexpressed an nPKC theta -green fluorescent protein (GFP) fusion protein in C(2)C(12) myotubes. The number of nAChR clusters was significantly reduced in nPKC theta-GFP compared to GFP overexpressing myotubes at less-than-maximal clustering concentrations of agrin. These data indicate that nPKC theta activity inhibits nAChR cluster formation. To examine whether nPKC theta activation by phorbol esters regulates agrin-induced nAChR clustering, we treated overexpressing myotubes overnight with maximal agrin concentrations followed by phorbol esters for 1 hr. Phorbol ester treatment reduced preexisting nAChR cluster numbers in nPKC theta-GFP compared to GFP-overexpressing myotubes, suggesting that stimulating nPKC theta activity disrupts nAChR clusters in the presence of maximal clustering concentrations of agrin. Together these findings, that nPKC theta activity inhibits agrin-induced nAChR cluster formation and disrupts preexisting agrin-induced nAChR clusters, suggest that nPKC theta activity is inhibitory for agrin function.

Neurotrophin-3 and TrkC are expressed in the outflow tract of the developing chicken heart.

Transcripts encoding trkC and full-length (catalytic) TrkC receptors were detected in the outflow tract of the chicken heart during early development (stage 17; embryonic day [E] 2.5) before the start of septation. Expression of trkC mRNA persisted through early septation (stage 25, E4.5-E5) but was no longer evident by the end of septation (stage 34, E8). Neurotrophin-3 (NT-3) mRNA was also shown to be present in the outflow tract throughout cardiac development. Quail-chick chimeras were used to confirm that cardiac neural crest cells were not present in the outflow tract at stage 17 (E2.5). Our results show that NT-3 interacts with cells in the outflow tract that are not of neural crest origin. This finding indicates that, in addition to effects on neural crest cells, NT-3 may be important for cardiac development due to its interaction with cells in the outflow tract such as those arising from the secondary heart field.