DYRK1a inhibitor mediated rescue of Drosophila models of Alzheimer’s disease-Down Syndrome phenotypes

Alzheimer’s disease (AD) is the most common neurodegenerative disease which is becoming increasingly prevalent due to ageing populations resulting in huge social, economic, and health costs to the community. Despite the pathological processing of genes such as Amyloid Precursor Protein (APP) into Amyloid-β and Microtubule Associated Protein Tau (MAPT) gene, into hyperphosphorylated Tau tangles being known for decades, there remains no treatments to halt disease progression. One population with increased risk of AD are people with Down syndrome (DS), who have a 90% lifetime incidence of AD, due to trisomy of human chromosome 21 (HSA21) resulting in three copies of APP and other AD-associated genes, such as DYRK1A (Dual specificity tyrosine-phosphorylation-regulated kinase 1A) overexpression. This suggests that blocking DYRK1A might have therapeutic potential. However, it is still not clear to what extent DYRK1A overexpression by itself leads to AD-like phenotypes and how these compare to Tau and Amyloid-β mediated pathology. Likewise, it is still not known how effective a DYRK1A antagonist may be at preventing or improving any Tau, Amyloid-β and DYRK1a mediated phenotype. To address these outstanding questions, we characterised Drosophila models with targeted overexpression of human Tau, human Amyloid-β or the fly orthologue of DYRK1A, called minibrain (mnb). We found targeted overexpression of these AD-associated genes caused degeneration of photoreceptor neurons, shortened lifespan, as well as causing loss of locomotor performance, sleep, and memory. Treatment with the experimental DYRK1A inhibitor PST-001 decreased pathological phosphorylation of human Tau [at serine (S) 262]. PST-001 reduced degeneration caused by human Tau, Amyloid-β or mnb lengthening lifespan as well as improving locomotion, sleep and memory loss caused by expression of these AD and DS genes. This demonstrated PST-001 effectiveness as a potential new therapeutic targeting AD and DS pathology

Informing the design of a national screening and treatment programme for chronic viral hepatitis in primary care: qualitative study of at-risk immigrant communities and healthcare professionals

n Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThis paper presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-1209-10038).

Does trust in health care influence the use of complementary and alternative medicine by chronically ill people?

BACKGROUND: People's trust in health care and health care professionals is essential for the effectiveness of health care, especially for chronically ill people, since chronic diseases are by definition (partly) incurable. Therefore, it may be understandable that chronically ill people turn to complementary and alternative medicine (CAM), often in addition to regular care. Chronically ill people use CAM two to five times more often than non-chronically ill people. The trust of chronically ill people in health care and health care professionals and the relationship of this with CAM use have not been reported until now. In this study, we examine the influence of chronically ill people's trust in health care and health care professionals on CAM use. METHODS: The present sample comprises respondents of the 'Panel of Patients with Chronic Diseases' (PPCD). Patients (≥25 years) were selected by GPs. A total of 1,625 chronically ill people were included. Trust and CAM use was measured by a written questionnaire. Statistical analyses were t tests for independent samples, Chi-square and one-way analysis of variance, and logistic regression analysis. RESULTS: Chronically ill people have a relatively low level of trust in future health care. They trust certified alternative practitioners less than regular health care professionals, and non-certified alternative practitioners less still. The less trust patients have in future health care, the more they will be inclined to use CAM, when controlling for socio-demographic and disease characteristics. CONCLUSION: Trust in future health care is a significant predictor of CAM use. Chronically ill people's use of CAM may increase in the near future. Health policy makers should, therefore, be alert to the quality of practising alternative practitioners, for example by insisting on professional certification. Equally, good quality may increase people's trust in public health care

Constraining sub-seismic deep-water stratal elements with electrofacies analysis; A case study from the Upper Cretaceous of the Måløy Slope, offshore Norway

Electrofacies represent rock facies identified from wireline-log measurements, and allow extrapolation of petrophysical characteristics away from stratigraphic intervals that are calibrated to core. This approach has been employed to reduce uncertainty in the identification of the sub-seismic depositional elements in the late Cenomanian-Coniacian succession of the northern Måløy Slope, offshore Norway. Core logging permits identification of eleven distinct sedimentary facies that are grouped into four facies associations: FA A-turbidite sandstones, FA B-heterolithic siltstones and sandstones, FA C-debrites and FA D-slide and slump deposits. Each facies association is defined by a distinct combination of petrophysical characteristics, including porosity, density, gamma-ray, sonic and resistivity. Using neural network analysis, electrofacies are calibrated with sedimentary facies, thereby allowing us to map their thickness and stacking patterns within the studied deep-water succession. We demonstrate that this approach is particularly useful where the presence of glauconite makes the distinction between sandstone- from shale-rich units difficult using gamma-ray logs alone. Our results indicate that the succession of interest is dominated by debris flows and slide and slump deposits, which are commonly poorly imaged on seismic reflection datasets in the northern North Sea. The methodology presented here can aid the correlation of deep-water stratal elements at production and exploration scales in stratigraphic successions that have undergone similar burial histories.Furthermore, this method may help in the identification of mass flow deposits that are present in Upper Cretaceous deep-water systems of the North Sea

Asylum seekers' expectations of and trust in general practice: a qualitative study

<b>Background</b> The UK has substantial minority populations of short-term and long-term migrants from countries with various types of healthcare systems.<p></p> <b>Aim</b> This study explored how migrants' previous knowledge and experience of health care influences their current expectations of health care in a system relying on clinical generalists performing a gatekeeping role.<p></p> <b>Design of study</b> Two qualitative methods.<p></p> <b>Setting</b> Glasgow, UK.<p></p> <b>Method</b> Focus groups or semi-structured interviews were conducted with 52 asylum seekers. Analyses identified several areas where previous experience affected current expectations. An overview of health systems in each country of origin was established by combining responders' accounts with World Health Organization statistics.<p></p> <b>Results</b> Asylum seekers had previous experience of a diverse range of healthcare systems, most of which were characterised by a lack of GPs and direct access to hospital-based specialists. For some responders, war or internal conflict resulted in a complete breakdown of healthcare systems. Responders' accounts also highlighted the difficulties that marginalised groups had in accessing health care. Although asylum seekers were generally pleased with the care they received from the NHS, there were areas where they experienced difficulties: confidence in their GP and access to hospital-based specialists and medication. These difficulties encountered might be explained by previous experience.<p></p> <b>Conclusion</b> GPs and other healthcare professionals need to be aware that experience of different systems of care can have an impact on individuals' expectations in a GP-led system. If these are not acknowledged and addressed, a lack of confidence and trust in the GP may undermine the effectiveness of the clinical consultation