The Development of Principles for Patient and Public Involvement (PPI) in Preclinical Spinal Cord Research: A Modified Delphi Study.

INTRODUCTION: There is currently limited guidance for researchers on Patient and Public Involvement (PPI) for preclinical spinal cord research, leading to uncertainty about design and implementation. This study aimed to develop evidence-informed principles to support preclinical spinal cord researchers to incorporate PPI into their research. METHODS: This study used a modified Delphi method with the aim of establishing consensus on a set of principles for PPI in spinal cord research. Thirty-eight stakeholders including researchers, clinicians and people living with spinal cord injury took part in the expert panel. Participants were asked to rate their agreement with a series of statements relating to PPI in preclinical spinal cord research over two rounds. As part of Round 2, they were also asked to rate statements as essential or desirable. RESULTS: Thirty-eight statements were included in Round 1, after which five statements were amended and two additional statements were added. After Round 2, consensus (> 75% agreement) was reached for a total of 27 principles, with 13 rated as essential and 14 rated as desirable. The principles with highest agreement related to diversity in representation among PPI contributors, clarity of the purpose of PPI and effective communication. CONCLUSION: This research developed a previously unavailable set of evidence-informed principles to inform PPI in preclinical spinal cord research. These principles provide guidance for researchers seeking to conduct PPI in preclinical spinal cord research and may also inform PPI in other preclinical disciplines. PATIENT AND PUBLIC INVOLVEMENT STATEMENT: This study was conducted as part of a project aiming to develop PPI in preclinical spinal cord injury research associated with an ongoing research collaboration funded by the Irish Rugby Football Union Charitable Trust (IRFU CT) and the Science Foundation Ireland Centre for Advanced Materials and BioEngineering Research (SFI AMBER), with research conducted by the Tissue Engineering Research Group (TERG) at the RCSI University of Medicine and Health Sciences. The project aims to develop an advanced biomaterials platform for spinal cord repair and includes a PPI Advisory Panel comprising researchers, clinicians and seriously injured rugby players to oversee the work of the project. PPI is included in this study through the involvement of members of the PPI Advisory Panel in the conceptualisation of this research, review of findings, identification of key points for discussion and preparation of the study manuscript as co-authors.

The role of Patient and public involvement (PPI) in pre-clinical spinal cord research: An interview study.

BACKGROUND: Patient and public involvement in research (PPI) has many benefits including increasing relevance and impact. While using PPI in clinical research is now an established practice, the involvement of patients and the public in pre-clinical research, which takes place in a laboratory setting, has been less frequently described and presents specific challenges. This study aimed to explore the perspectives of seriously injured rugby players' who live with a spinal cord injury on PPI in pre-clinical research. METHODS: Semi-structured interviews were conducted via telephone with 11 seriously injured rugby players living with spinal cord injury on the island of Ireland. A purposive sampling approach was used to identify participants. Selected individuals were invited to take part via gatekeeper in a charitable organisation that supports seriously injured rugby players. Interviews were transcribed verbatim and analysed thematically. FINDINGS: Six themes were identified during analysis: 'appreciating potential benefits of PPI despite limited knowledge', 'the informed perspectives of people living with spinal cord injury can improve pre-clinical research relevance', 'making pre-clinical research more accessible reduces the potential for misunderstandings to occur', 'barriers to involvement include disinterest, accessibility issues, and fear of losing hope if results are negative', 'personal contact and dialogue helps people feel valued in pre-clinical research, and 'PPI can facilitate effective dissemination of pre-clinical research as desired by people living with spinal cord injury.' CONCLUSION: People affected by spinal cord injury in this study desire further involvement in pre-clinical spinal cord injury research through dialogue and contact with researchers. Sharing experiences of spinal cord injury can form the basis of PPI for pre-clinical spinal cord injury research.

Applying Patient and Public Involvement in preclinical research: A co-created scoping review.

BACKGROUND: Patient and Public Involvement (PPI) in research aims to improve the quality, relevance and appropriateness of research. PPI has an established role in clinical research where there is evidence of benefit, and where policymakers and funders place continued emphasis on its inclusion. However, for preclinical research, PPI has not yet achieved the same level of integration. As more researchers, including our team, aim to include PPI in preclinical research, the development of an evidence-based approach is important. Therefore, this scoping review aimed to identify and map studies where PPI has been used in preclinical research and develop principles that can be applied in other projects. METHODS: A scoping review was conducted to search the literature in Medline (PubMed), EMBASE, CINAHL, PsycInfo and Web of Science Core Collection to identify applied examples of preclinical PPI. Two independent reviewers conducted study selection and data extraction separately. Data were extracted relating to PPI in terms of (i) rationale and aims, (ii) approach used, (iii) benefits and challenges, (iv) impact and evaluation and (v) learning opportunities for preclinical PPI. Findings were reviewed collaboratively by PPI contributors and the research team to identify principles that could be applied to other projects. RESULTS: Nine studies were included in the final review with the majority of included studies reporting PPI to improve the relevance of their research, using approaches such as PPI advisory panels and workshops. Researchers report several benefits and challenges, although evidence of formal evaluation is limited. CONCLUSION: Although currently there are few examples of preclinical research studies reporting empirical PPI activity, their findings may support those aiming to use PPI in preclinical research. Through collaborative analysis of the scoping review findings, several principles were developed that may be useful for other preclinical researchers. PATIENT OR PUBLIC CONTRIBUTION: This study was conducted as part of a broader project aiming to develop an evidence base for preclinical PPI that draws on a 5-year preclinical research programme focused on the development of advanced biomaterials for spinal cord repair as a case study. A PPI Advisory Panel comprising seriously injured rugby players, clinicians, preclinical researchers and PPI facilitators collaborated as co-authors on the conceptualization, execution and writing of this review, including refining the findings into the set of principles reported here.

Patient and Public Involvement (PPI) in preclinical research: A scoping review protocol.

Introduction: Patient and public involvement (PPI) aims to improve the quality, relevance, and appropriateness of research and ensure that it meets the needs and expectations of those affected by particular conditions to the greatest possible degree. The evidence base for the positive impact of PPI on clinical research continues to grow, but the role of PPI in preclinical research (an umbrella term encompassing 'basic', 'fundamental', 'translational' or 'lab-based' research) remains limited. As funding bodies and policymakers continue to increase emphasis on the relevance of PPI to preclinical research, it is timely to map the PPI literature to support preclinical researchers involving the public, patients, or other service users in their research. Therefore, the aim of this scoping review is to explore the literature on patient and public involvement in preclinical research from any discipline. Methods: This scoping review will search the literature in Medline (PubMed), Embase, CINAHL, PsycINFO, Web of Science Core Collection, Scopus, and OpenGrey.net to explore the application of PPI in preclinical research. This review will follow the Joanna Briggs Institute (JBI) guidelines for scoping reviews. It will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Two reviewers will independently review articles for inclusion in the final review. Data extraction will be guided by the research questions. The PPI advisory panel will then collaboratively identify themes in the extracted data. Discussion: This scoping review will provide a map of current evidence surrounding preclinical PPI, and identify the body of literature on this topic, which has not been comprehensively reviewed to date. Findings will inform ongoing work of the research team, support the work of other preclinical researchers aiming to include PPI in their own research, and identify knowledge and practice gaps. Areas for future research will be identified.

Structural and positional studies of the antimicrobial peptide brevinin-1BYa in membrane-mimetic environments.

Brevinin-1BYa (FLPILASLAAKFGPKLFCLVTKKC), first isolated from skin secretions of the foothill yellow-legged frog Rana boylii, shows broad-spectrum activity, being particularly effective against opportunistic yeast pathogens. The structure of brevinin-1BYa was investigated in various solution and membrane-mimicking environments by proton nuclear magnetic resonance (1 H-NMR) spectroscopy and molecular modelling. The peptide does not possess a secondary structure in aqueous solution. In a 33% 2,2,2-trifluoroethanol (TFE-d3 )-H2 O solvent mixture, as well as in membrane-mimicking sodium dodecyl sulfate and dodecylphosphocholine micelles, the peptide's structure is characterised by a flexible helix-hinge-helix motif, with the hinge located at the Gly13 /Pro14 residues, and the two α-helices extending from Pro3 to Phe12 and from Pro14 to Thr21 . Positional studies involving the peptide in sodium dodecyl sulfate and dodecylphosphocholine micelles using 5-doxyl-labelled stearic acid and manganese chloride paramagnetic probes show that the peptide's helical segments lie parallel to the micellar surface, with the residues on the hydrophobic face of the amphipathic helices facing towards the micelle core and the hydrophilic residues pointing outwards, suggesting that the peptide exerts its biological activity by a non-pore-forming mechanism.

Insights into conformation and membrane interactions of the acyclic and dicarba-bridged brevinin-1BYa antimicrobial peptides.

Brevinin-1BYa is a 24-amino acid residue host-defense peptide, first isolated from skin secretions of the foothill yellow-legged frog Rana boylii. The peptide is of interest, as it shows broad-spectrum antimicrobial activity, and is particularly effective against opportunistic yeast pathogens. Its potential for clinical use, however, is hindered by its latent haemolytic activity. The structures of two analogues, the less haemolytic [C18S,C24S]brevinin-1BYa and the more potent cis-dicarba-brevinin-1BYa, were investigated in various solution and membrane-mimicking environments by [Formula: see text] spectroscopy and molecular modelling techniques. Neither peptide possesses a secondary structure in aqueous solution. In both the membrane-mimicking sodium dodecyl sulphate micelles and 33% 2,2,2-trifluoroethanol ([Formula: see text] solvent mixture, the peptides' structures are characterised by two [Formula: see text]-helices connected by a flexible hinge located at the [Formula: see text] residues. With the aid of molecular dynamics simulations and paramagnetic probes, it was determined that the peptides' helical segments lie parallel to the micellar surface, with their hydrophobic residues facing towards the micelle core and the hydrophilic residues pointing outwards, suggesting that both peptides exert their biological activity by a non-pore-forming mechanism. Unlike that of the dicarba analogue, the C-terminus of the acyclic peptide is only weakly associated with the micellar surface and is in direct contact with the surrounding aqueous solvent.

Conformational and membrane interaction studies of the antimicrobial peptide alyteserin-1c and its analogue [E4K]alyteserin-1c.

Alyteserin-1c (GLKEIFKAGLGSLVKGIAAHVAS.NH(2)), first isolated from skin secretions of the midwife toad Alytes obstetricans, shows selective growth-inhibitory activity against Gram-negative bacteria. The structures of alyteserin-1c and its more potent and less haemolytic analogue [E4K]alyteserin-1c were investigated in various solution and membrane mimicking environments by proton NMR spectroscopy and molecular modelling. In aqueous solution, the peptide displays a lack of secondary structure but, in a 2,2,2-trifluoroethanol (TFE-d(3))-H(2)O solvent mixture, the structure is characterised by an extended alpha helix between residues Leu(2) and Val(21). Solution structural studies in the membrane mimicking environments, sodium dodecyl sulphate (SDS), dodecylphosphocholine (DPC), and 1,2-dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC) micelles, indicate that these peptides display an alpha helical structure between residues Lys(3) and Val(21). Positional studies of the peptides in SDS, DPC and DHPC media show that the N-terminal and central residues lie inside the micelle while C-terminal residues beyond Ala(19) do not interact with the micelles.