Risks associated with endotoxins in feed additives produced by fermentation

Acknowledgements We thank Jordi Tarrés Call, who recorded the discussions and offered advice about procedures, and Nicole Reisinger and Gerd Schatzmayr, who provided valuable information about endotoxins in animal feeds. The Rowett Institute of Nutrition and Health is funded by the Rural and Environment Science and Analytical Services Division (RESAS) of the Scottish Government.Peer reviewedPublisher PD

Can electronic monitoring with a digital smart spacer support personalised medication adherence and inhaler technique education in patients with asthma?:Protocol of the randomised controlled OUTERSPACE trial

INTRODUCTION: Medication adherence and inhaler technique in patients with asthma remain suboptimal. A digital, smart spacer may support personalised adherence and inhaler technique education. The aim of this study is to assess the feasibility of undertaking a definitive randomised controlled trial of personalised, smart spacer data-driven education and explore clinical benefits. METHODS AND ANALYSIS: We present the design of the multicentre, randomised controlled OUtcomes following Tailored Education and Retraining: Studying Performance and AdherenCE feasibility trial of 2 months. Patients will be recruited from four Dutch general practices. At t=-1, patients with asthma ≥18 years using inhaled corticosteroids±long-acting beta-agonists±short-acting beta-agonists administered with a pressurised-metered-dose-inhaler and spacer (n=40) will use a smart spacer for 1 month. The rechargeable CE-marked smart spacer (Aerochamber Plus with Flow Vu) includes a sensor that monitors adherence and inhalation technique to prescribed dosing regimen of both maintenance and reliever inhalers. After 1 month (t=0), patients are 1:1 randomised into two groups: control group (usual care) versus intervention group (personalised education). At t=-1, t=0 and t=1 month, the Asthma Control Questionnaire (ACQ), Work Productivity and Activity Impairment (WPAI) questionnaire and Test of Adherence to Inhalers (TAI) are administered and fractional exhaled nitric oxide (FeNO) is assessed. At t=0 and t=1, spirometry is performed. At t=1, usability and satisfaction will be analysed using the System Usability Scale and interviews with patients and healthcare providers. Primary outcome is the overall feasibility of a definitive trial assessed by patient recruitment speed, participation and drop-out rate. Secondary outcomes are patient and healthcare provider satisfaction and exploratory clinical outcomes are adherence, inhaler technique, TAI score, FeNO, lung function, ACQ and WPAI. ETHICS AND DISSEMINATION: Ethical approval was obtained from the RTPO in Leeuwarden, Netherlands (number: NL78361.099.21). Patients will provide written informed consent. Study findings will be disseminated through conferences and peer-reviewed scientific and professional journals. TRIAL REGISTRATION NUMBER: NL9637

Electronic monitoring with a digital smart spacer to support personalized inhaler use education in patients with asthma:The randomized controlled OUTERSPACE trial

BACKGROUND: Poor adherence to inhaled medication has been associated with poor outcomes. Smart spacers can monitor inhaler use and technique, yet their feasibility in adults with asthma and their potential benefits are unknown.OBJECTIVE: Assessing the feasibility of undertaking a definitive randomized controlled trial (RCT) of smart spacer-based inhaler education and explore potential clinical benefits in adults with asthma.METHODS: Two-month randomized controlled feasibility OUtcomes following Tailored Education and Retraining: Studying Performance and AdherenCE (OUTERSPACE) trial comparing personalized smart spacer-based inhaler education versus usual care. Patients were recruited in four Dutch primary care centres. Outcomes were feasibility (inclusion speed, patient acceptance), medication adherence, inhaler technique, clinical effects (lung function, ACQ, FeNO) and usability (System Usability Scale [SUS]).RESULTS: 42 patients were randomized and all completed the study. The feasibility of performing a larger trial focusing on asthma patient education using a smart spacer was demonstrated with all patients included in four months and a participation rate of 86%. In the intervention group, inhalation errors per day decreased by 26.2% while in the usual care group inhalation errors increased by 14.6% (p = 0.021). Adherence decreased slightly in the intervention group as opposed to improvement in the control group (difference 12%, p = 0.028). No changes in lung function, ACQ or FeNO were observed. Usability was deemed high (SUS patients 71, nurses 89).CONCLUSION: This RCT showed that smart spacer-driven education in patients with asthma is feasible and in this short-term study reduced inhaler errors. Longer-term and larger studies are required to assess clinical effects.</p

Digital spacer data driven COPD inhaler adherence education:The OUTERSPACE proof-of-concept study

Pressurized metered dose inhalers are recommended to be used in combination with spacers, yet inhaler technique and adherence are poor. A novel digital "smart" spacer can record spacer use and technique errors and could facilitate personalized education. In this proof-of-concept study, we assessed the usability of the digital spacer and explored its effects on inhaler technique, adherence, long-term systemic drug exposure and clinical outcomes in COPD. Usability was deemed high. One month after personalized digital spacer inhaler education, the mean number of errors per patient per day decreased with 36%, from 6.40 errors/day to 4.07 errors/day (p = 0.038). Drug exposure was confirmed by bioanalytical scalp hair analysis of formoterol. No significant change in clinical outcomes was observed. This study demonstrates the digital spacer's potential value in inhaler education, but larger, longer-term studies are required

Calcium flashes orchestrate the wound inflammatory response through DUOX activation and hydrogen peroxide release

A crucial early wound response is the recruitment of inflammatory cells drawn by danger cues released by the damaged tissue. Hydrogen peroxide (H2O2) has recently been identified as the earliest wound attractant in Drosophila embryos and zebrafish larvae. The H2O2 signal is generated by activation of an NADPH oxidase, DUOX, and as a consequence, the first inflammatory cells are recruited to the wound within minutes. To date, nothing is known about how wounding activates DUOX. Here, we show that laser wounding of the Drosophila embryo epidermis triggers an instantaneous calcium flash, which travels as a wave via gap junctions several cell rows back from the wound edge. Blocking this calcium flash inhibits H2O2 release at the wound site and leads to a reduction in the number of immune cells migrating to the wound. We suggest that the wound-induced calcium flash activates DUOX via an EF hand calcium-binding motif and thus triggers the production of the attractant damage cue H2O2. Therefore, calcium represents the earliest signal in the wound inflammatory response

Mapping Peptidergic Cells in Drosophila: Where DIMM Fits In

The bHLH transcription factor DIMMED has been associated with the differentiation of peptidergic cells in Drosophila. However, whether all Drosophila peptidergic cells express DIMM, and the extent to which all DIMM cells are peptidergic, have not been determined. To address these issues, we have mapped DIMM expression in the central nervous system (CNS) and periphery in the late larval stage Drosophila. At 100 hr after egg-laying, DIMM immunosignals are largely congruent with a dimm-promoter reporter (c929-GAL4) and they present a stereotyped pattern of 306 CNS cells and 52 peripheral cells. We assigned positional values for all DIMM CNS cells with respect to reference gene expression patterns, or to patterns of secondary neuroblast lineages. We could assign provisional peptide identities to 68% of DIMM-expressing CNS cells (207/306) and to 73% of DIMM-expressing peripheral cells (38/52) using a panel of 24 markers for Drosophila neuropeptide genes. Furthermore, we found that DIMM co-expression was a prevalent feature within single neuropeptide marker expression patterns. Of the 24 CNS neuropeptide gene patterns we studied, six patterns are >90% DIMM-positive, while 16 of 22 patterns are >40% DIMM-positive. Thus most or all DIMM cells in Drosophila appear to be peptidergic, and many but not all peptidergic cells express DIMM. The co-incidence of DIMM-expression among peptidergic cells is best explained by a hypothesis that DIMM promotes a specific neurosecretory phenotype we term LEAP. LEAP denotes Large cells that display Episodic release of Amidated Peptides