Connectivity Mapping (ssCMap) To Predict A20 Inducing Drugs: Anti-inflammatory Action In Cystic Fibrosis

Cystic Fibrosis (CF) lung disease is characterised by a chronic and exaggerated inflammation in the airways. Despite recent developments to therapeutically overcome the underlying functional defect in CFTR (cystic fibrosis transmembrane conductance regulator), there is still an unmet need to also normalise the inflammatory response. The prolonged and heightened inflammatory response in CF is in part mediated by a lack of intrinsic downregulation of the pro-inflammatory NF-kB pathway. We have previously identified reduced expression of the NF-kB down-regulator A20 in CF as a key target to normalise the inflammatory response. Here we have used publically available gene array expression data together with sscMap (statistically significant connections’map)to successfully predict drugs already licensed for the use in humans to induce A20 mRNA and protein expression and thereby reduce inflammation. The effect of the predicted drugs on A20 and NFkB (p65) expression (mRNA) as well as pro-inflammatory cytokine release (IL-8) in the presence and absence of bacterial LPS was shown in bronchial epithelial cells lines (16HBE14o-, CFBE41o-) and in primary nasal epithelial cells (PNECs) from patients with CF (Phe508del homozygous) and non-CF controls. Additionally, the specificity of the drug action on A20 was confirmed using cell lines with TNFAIP3 (A20) knockdown (siRNA). We also show that the A20 inducing effect of ikarugamycin and quercetin is lower in CF derived airway epithelial cells than in non-CF cells.

Creating New Design-Build-Test Experiences as Outputs of Undergraduate Design-Build-Test Projects

This paper describes a methodology of using individual engineering undergraduate student projects as a means of effectively and efficiently developing new Design-Build-Test (DBT) learning experiences and challenges.
A key aspect of the rationale for this approach is that it benefits all parties. The student undertaking the individual project gets an authentic experience of producing a functional artefact, which has been the result of a design process that addresses conception, design, implementation and operation. The supervising faculty member benefits from live prototyping of new curriculum content and resources with a student who is at a similar level of knowledge and experience as the intended end users of the DBT outputs. The multiple students who ultimately undertake the DBT experiences / challenges benefit from the enhanced nature of a learning experience which has been “road tested” and optimised.
To demonstrate the methodology the paper will describe a case study example of an individual project completed in 2015. This resulted in a DBT design challenge with a theme of designing a catapult for throwing table tennis balls, the device being made from components laser cut from medium density fibreboard (MDF). Further three different modes of operation will be described which use the same resource materials but operate over different timescales and with different learning outcomes, from an icebreaker exercise focused on developing team dynamics through to full DBT where students get an opportunity to experience the full impact of their design decisions by competing against other students with a catapult they have designed and built themselves.

Withdrawal of Antidementia Drugs in Older People: Who, When and How?

The evidence base to guide withdrawal of antidementia medications in older people with dementia is limited; while some randomised controlled studies have considered discontinuation of cholinesterase inhibitors, no such studies examining discontinuation of the N-Methyl-D-aspartate receptor antagonist memantine have been conducted to date. The purpose of this opinion article was to summarise the existing evidence on withdrawal of cholinesterase inhibitors and memantine, to highlight the key considerations for clinicians when making these prescribing decisions and to offer guidance as to when and how treatment might be discontinued. Until the evidence-base is enhanced by the findings of large scale randomised controlled discontinuation trials of ChEIs and memantine which use multiple, clinically relevant cognitive, functional and behavioural outcome measures, clinicians’ prescribing decisions involve balancing the risks of discontinuation with side-effects and costs of continued treatment. Such decisions must be highly individualised and patient-centred.

Prescribing of Psychoactive Drugs for Older People in Nursing Homes: An Analysis of Treatment Culture

Background There is increasing interest in how culture may affect the quality of healthcare services, and previous research has shown that ‘treatment culture’—of which there are three categories (resident centred, ambiguous and traditional)—in a nursing home may influence prescribing of psychoactive medications. Objective The objective of this study was to explore and understand treatment culture in prescribing of psychoactive medications for older people with dementia in nursing homes. Method Six nursing homes—two from each treatment culture category—participated in this study. Qualitative data were collected through semi-structured interviews with nursing home staff and general practitioners (GPs), which sought to determine participants’ views on prescribing and administration of psychoactive medication, and their understanding of treatment culture and its potential influence on prescribing of psychoactive drugs. Following verbatim transcription, the data were analysed and themes were identified, facilitated by NVivo and discussion within the research team. Results Interviews took place with five managers, seven nurses, 13 care assistants and two GPs. Four themes emerged: the characteristics of the setting, the characteristics of the individual, relationships and decision making. The characteristics of the setting were exemplified by views of the setting, daily routines and staff training. The characteristics of the individual were demonstrated by views on the personhood of residents and staff attitudes. Relationships varied between staff within and outside the home. These relationships appeared to influence decision making about prescribing of medications. The data analysis found that each home exhibited traits that were indicative of its respective assigned treatment culture. Conclusion Nursing home treatment culture appeared to be influenced by four main themes. Modification of these factors may lead to a shift in culture towards a more flexible, resident-centred culture and a reduction in prescribing and use of psychoactive medication. 

An exploration of men’s experiences of undergoing active surveillance for favourable-risk prostate cancer: A mixed methods study protocol

Background
Prostate cancer is one of the most common male cancers worldwide. Active Surveillance (AS) has been developed to allow men with lower risk disease to postpone or avoid the adverse side effects associated with curative treatments until the disease progresses. Despite the medical benefits of AS, it is reported that living with untreated cancer can create a significant emotional burden for patients.

Methods/design
The aim of this study is to gain insight into the experiences of men eligible to undergo AS for favourable-risk PCa.

This study has a mixed-methods sequential explanatory design consisting of two phases: quantitative followed by qualitative. Phase 1 has a multiple point, prospective, longitudinal exploratory design. Ninety men diagnosed with favourable-risk prostate cancer will be assessed immediately post-diagnosis (baseline) and followed over a period of 12 months, in intervals of 3 month. Ninety age-matched men with no cancer diagnosis will also be recruited using peer nomination and followed up in the same 3 month intervals. Following completion of Phase 1, 10–15 AS participants who have reported both the best and worst psychological functioning will be invited to participate in semi-structured qualitative interviews. Phase 2 will facilitate further exploration of the quantitative results and obtain a richer understanding of participants’ personal interpretations of their illness and psychological wellbeing.

Discussion
To our knowledge, this is the first study to utilise early baseline measures; include a healthy comparison group; calculate sample size through power calculations; and use a mixed methods approach to gain a deeper more holistic insight into the experiences of men diagnosed with favourable-risk prostate cancer.