Adapting an evidence-based, home cardiac rehabilitation programme for people with heart failure and their caregivers to the Danish context: DK:REACH-HF study.

AIMS: Adapting interventions with an existing evidence base offers a more efficient approach than development of a new intervention. The aim of this study was to describe the process of adapting a home-based cardiac rehabilitation (CR) programme (REACH-HF) intervention originally developed in the United Kingdom for people with heart failure (HF) to the Danish health system - the 'DK:REACH-HF' programme. METHODS AND RESULTS: We followed methodological framework for the conduct and reporting of studies adapting interventions, utilizing documentary analysis, qualitative interviews, stakeholder consultations, and mapping of the Danish policy context. Our study found broad support for the REACH-HF intervention as an alternative to existing centre-based CR. We also identified three key areas of adaptation for the Danish context. First, reduce the word-count of the intervention's resources by linking to existing publicly available CR materials. Second, whilst retaining REACH-HF core components, adapt its content and delivery to reflect differences between Denmark and United Kingdom. Thirdly, to develop a digital version of the intervention. CONCLUSION: Using an evidence-based approach, we successfully adapted the REACH-HF intervention to the context of the Danish healthcare setting, maintaining core components of the original intervention, and developing both a paper based and digital version of the programme material. To inform scaled national implementation of the DK:REACH-HF programme, we seek to undertake a pilot study to test the adapted intervention materials feasibility and acceptability to healthcare practitioners, patients, and their caregivers and confirm the positive impact on the outcomes of HF patients and caregivers.

Content validation of the HeartRunner questionnaire to volunteer responders dispatched to out-of-hospital cardiac arrests: A qualitative study.

Aim: To increase survival after out-of-hospital cardiac arrest (OHCA) in Denmark, volunteer responders are activated through a smartphone application (HeartRunner app) to quickly locate an automated external defibrillator (AED) and assist with cardiopulmonary resuscitation (CPR). All dispatched volunteer responders who have been activated by the app receive a follow-up questionnaire to evaluate their participation in the programme. The content of the questionnaire has never been thoroughly evaluated. We therefore aimed to validate the content of the questionnaire. Methods: Content validity was evaluated qualitatively. It was based on individual interviews with three experts, along with three focus group interviews and five individual interviews using cognitive interview technique, with a total of 19 volunteer responders. The interviews were also used to inform refinements of the questionnaire to reach improvements in content validity. Results: The initial questionnaire consisted of 23 items. After the content validation process, the questionnaire consisted of 32 items; with the addition of 9 new items. Specifically, some original items were merged into one item or divided into separate items. Moreover, we revised the order of items, some sentences were rephrased or reworded, an introduction and headlines to different sections were added, and skip logic were incorporated to hide non-relevant items. Conclusion: Our findings support the importance of validating questionnaires to ensure accuracy of survey instruments. Validation led to modifications of the questionnaire, and we propose a new version of the HeartRunner questionnaire. Our findings support the content validity of the final HeartRunner questionnaire. The questionnaire may allow the collection of quality data to evaluate and improve volunteer responder programmes.

The PSY Peptide Family-Expression, Modification and Physiological Implications.

Small post-translationally modified peptides are gaining increasing attention as important signaling molecules in plant development. In the family of plant peptides containing tyrosine sulfation (PSYs), only PSY1 has been characterized at the mature level as an 18-amino-acid peptide, carrying one sulfated tyrosine, and involved in cell elongation. This review presents seven additional homologs in Arabidopsis all sharing high conservation in the active peptide domain, and it shows that PSY peptides are found in all higher plants and mosses. It is proposed that all eight PSY homologs are post-translationally modified to carry a sulfated tyrosine and that subtilisin-like subtilases (SBTs) are involved in the processing of PSY propeptides. The PSY peptides show differential expression patterns indicating that they serve several distinct functions in plant development. PSY peptides seem to be at least partly regulated at the transcriptional level, as their expression is greatly influenced by developmental factors. Finally, a model including a receptor in addition to PSY1R is proposed.

Evidence for multiple receptors mediating RALF-triggered Ca2+ signaling and proton pump inhibition.

Acidification of the apoplastic space facilitates cell wall loosening and is therefore a key step in cell expansion. PSY1 is a growth-promoting secreted tyrosine-sulfated glycopeptide whose receptor directly phosphorylates and activates the plasma membrane H+ -ATPase, which results in acidification and initiates cellular expansion. Although the mechanism is not clear, the Rapid Alkalinization Factor (RALF) family of small, secreted peptides inhibits the plasma membrane H+ -ATPase, leading to alkalinization of the apoplastic space and reduced growth. Here we show that treating Arabidopsis thaliana roots with PSY1 induced the transcription of genes encoding the RALF peptides RALF33 and RALFL36. A rapid burst of intracellular Ca2+ preceded apoplastic alkalinization in roots triggered by RALFs, with peptide-specific signatures. Ca2+ channel blockers abolished RALF-induced alkalinization, indicating that the Ca2+ signal is an obligatory part of the response and that it precedes alkalinization. As expected, fer mutants deficient in the RALF receptor FERONIA did not respond to RALF33. However, we detected both Ca2+ and H+ signatures in fer mutants upon treatment with RALFL36. Our results suggest that different RALF peptides induce extracellular alkalinization by distinct mechanisms that may involve different receptors.

Activation of the LRR Receptor-Like Kinase PSY1R Requires Transphosphorylation of Residues in the Activation Loop.

PSY1R is a leucine-rich repeat (LRR) receptor-like kinase (RLK) previously shown to act as receptor for the plant peptide hormone PSY1 (peptide containing sulfated tyrosine 1) and to regulate cell expansion. PSY1R phosphorylates and thereby regulates the activity of plasma membrane-localized H+-ATPases. While this mechanism has been studied in detail, little is known about how PSY1R itself is activated. Here we studied the activation mechanism of PSY1R. We show that full-length PSY1R interacts with members of the SERK co-receptor family in planta. We identified seven in vitro autophosphorylation sites on serine and threonine residues within the kinase domain of PSY1R using mass spectrometry. We furthermore show that PSY1R autophosphorylation occurs in trans and that the initial transphosphorylation takes place within the activation loop at residues Ser951, Thr959, and Thr963. While Thr959 and Thr963 are conserved among other related plant LRR RLKs, Ser951 is unique to PSY1R. Based on homology modeling we propose that phosphorylation of Ser951 stabilize the inactive conformation of PSY1R.

Receptor kinase-mediated control of primary active proton pumping at the plasma membrane.

Acidification of the cell wall space outside the plasma membrane is required for plant growth and is the result of proton extrusion by the plasma membrane-localized H+-ATPases. Here we show that the major plasma membrane proton pumps in Arabidopsis, AHA1 and AHA2, interact directly in vitro and in planta with PSY1R, a receptor kinase of the plasma membrane that serves as a receptor for the peptide growth hormone PSY1. The intracellular protein kinase domain of PSY1R phosphorylates AHA2/AHA1 at Thr-881, situated in the autoinhibitory region I of the C-terminal domain. When expressed in a yeast heterologous expression system, the introduction of a negative charge at this position caused pump activation. Application of PSY1 to plant seedlings induced rapid in planta phosphorylation at Thr-881, concomitant with an instantaneous increase in proton efflux from roots. The direct interaction between AHA2 and PSY1R observed might provide a general paradigm for regulation of plasma membrane proton transport by receptor kinases.

Interaction of barley powdery mildew effector candidate CSEP0055 with the defence protein PR17c.

A large number of effector candidates have been identified recently in powdery mildew fungi. However, their roles and how they perform their functions remain unresolved. In this study, we made use of host-induced gene silencing and confirmed that the secreted barley powdery mildew effector candidate, CSEP0055, contributes to the aggressiveness of the fungus. This result suggests that CSEP0055 is involved in the suppression of plant defence. A yeast two-hybrid screen indicated that CSEP0055 interacts with members of the barley pathogenesis-related protein families, PR1 and PR17. Interaction with PR17c was confirmed by bimolecular fluorescence complementation analyses. Down-regulation and over-expression of PR17c in epidermal cells of barley confirmed that this protein is important for penetration resistance against the powdery mildew fungus. In line with this, PR17c was found to be apoplastic, localizing to the papillae formed in response to this fungus. The CSEP0055 transcript did not start to accumulate until 24 h after inoculation. This suggests that this gene is expressed too late to influence primary penetration events, but rather sustains the fungus at sites of secondary penetration, where PR17c appears to be able to accumulate.