Setting international standards for patient and parent involvement and engagement in childhood, adolescent and young adult cancer research: A report from a European Collaborative Workshop

BACKGROUND: Patient and Public Involvement and Engagement (PPIE) in research, advocates for research conducted ‘with’ not ‘for’ the affected population. In paediatric oncology research, the parents of children, adolescents and young adults affected by cancer are represented by the term ‘public’ in the acronym PPIE. Patients (those with cancer and cancer survivors) are also passionate advocates who drive forward the research priorities of children, adolescents and young adults throughout the entire research process. AIMS: A workshop was held at an international professional meeting in 2019 with the aim to define Patient and Parent Involvement and Engagement (PPIE); capture PPIE activities on a European level; and to explore the role of PPIE in non-interventional research. A proposed framework for a European PPIE strategy for childhood, adolescent and young adult cancers was also discussed. METHODS: The 60-minute workshop was attended by health care professionals, researchers, scientists, parents, survivors and charity/support organisations. A presentation to define PPIE, including the difference in terminology for PPIE in the context of childhood, adolescent, and young adult cancers was discussed. Best practice examples from the United Kingdom (UK) helped to demonstrate the positive impact of PPIE in paediatric oncology research. Three breakout groups then explored themes relating to PPIE, namely PPIE priorities, PPIE mapping for Europe, and PPIE in non-interventional research and data-linkage. RESULTS: Disparity in PPIE activities across Europe was evident, with ambiguity surrounding terminology and expected roles for PPIE representatives in paediatric oncology research. A lack of PPIE activity in Eastern Europe correlated with a lack of availability for clinical trials and poorer survival rates for paediatric oncology patients. There was unanimous support for PPIE embedded research in all areas, including in non-interventional studies. CONCLUSION: A European-level definition of PPIE for paediatric oncology research is needed. Further exploration into the role and responsibilities of patients, parents, and professionals when undertaking PPIE related activities is also recommended. Best practice examples from the UK, France, Germany, The Netherlands and Belgium demonstrated a preliminary evidence base from which a European PPIE strategy framework can be designed, inclusive of the patient and parent voice

Actinomyces spp. gene expression in root caries lesions

Background: studies of the distribution of Actinomyces spp. on carious and non-carious root surfaces have not been able to confirm the association of these bacteria with root caries, although they were extensively implicated as a prime suspect in root caries. Objective: the aim of this study was to observe the gene expression of Actinomyces spp. in the microbiota of root surfaces with and without caries. Design: the oral biofilms from exposed sound root surface (SRS; n=10) and active root caries (RC; n=30) samples were collected. The total bacterial RNA was extracted and the mRNA was isolated. Samples with low RNA concentration were pooled, yielding a final sample size of SRS=10 and RC=9. cDNA libraries were prepared and sequenced on the Illumina Hi-Seq2500. Sequence reads were mapped to eight Actinomyces genomes. Count data were normalized using DESeq2 to analyse differential gene expression applying the Benjamini-Hochberg correction (FDR0.05), except for Actinomyces OT178 (p=0.001) and A. gerencseriae (p=0.004), which had higher read count in the SRS. Genes that code for stress proteins (clp, dnaK and groEL), enzymes of glycolysis pathways (including, enolase and phosphoenolpyruvate carboxykinase), adhesion (Type-2 fimbrial and collagen-binding protein) and cell growth (EF-Tu) were highly, but not differentially (p>0.001) expressed in both groups. Genes with the most significant up-regulation in RC were those coding for hypothetical proteins and uracil DNA glycosylase (p=2.61E-17). The gene with the most significant up-regulation in SRS was a peptide ABC transporter substrate-binding protein (log2FC= -6.00, FDR= 2.37E-05). Conclusion: there were similar levels of Actinomyces gene expression in both sound and carious root biofilms. These bacteria can be commensal in root surface sites, but may be cariogenic due to survival mechanisms allowing them to exist in acid environment and metabolize sugars saving energy

The metatranscriptomes of root caries and sound root surface biofilms

There is limited knowledge of bacterial metabolism in root caries lesions. The aim of this study was to describe the bacterial metatranscriptomes associated with root caries and sound root surfaces using an RNA-seq analysis approach. The biofilms from exposed root surfaces were sampled from caries-free volunteers (n=10), and from the infected dentine of volunteers with root caries (n=30). Total bacterial RNA was extracted; cDNA libraries were prepared and sequenced on the Illumina Hi-Seq2500. The function and composition of the metabolically active microbiota were investigated using: a) MG-RAST, and b) denovo assembly of the read data and mapping to contigs. Differential gene expression analysis was done using the R package DESeq2 (padj <10−3). Transcripts with the highest expression levels were those coding for membrane transport systems, ribosomal proteins, enolase and glycolytic pathways in both groups. Differential analysis indicated that genes coding for the OmpA domain protein and metalloprotease domain protein were over-expressed in the caries samples (log2FoldChange = –12.2; padj= 3.5 × 10−13), whereas genes in the samples from healthy sites over-expressed pilus biosynthesis protein, thiamine diphosphokinase and transporter protein (log2FoldChange = 16.5; padj = 2.2 × 10−21). Metatranscriptomic analyses show unique gene expression profiles in sound root surface and carious biofilms

The subgingival microbiomes in periodontitis and health of individuals with rheumatoid arthritis and at risk of developing rheumatoid arthritis

Serum anti-citrullinated protein antibodies (ACPAs), present in 70% of people with rheumatoid arthritis (RA), can be detected ≤10years before the onset of clinical disease. RA and periodontitis are epidemiologically associated and we have reported a high incidence of periodontitis in people who are ACPA+ and at risk of RA. Periodontal bacteria may contribute by multiple routes to the generation of RA-autoantibodies. This study aims to characterise the subgingival microbiomes from periodontitis and health in individuals with/without RA and at risk of RA. Forty-five ACPA+ no RA (RA-at-risk; RAR), 31 healthy controls (HC) and 30 ACPA+ RA patients (RA) underwent a periodontal examination. DNA from subgingival plaque from healthy and deep pocket sites were paired-end sequenced using the Illumina HiSeq3000 and data analysed using MG-RAST + DESeq. Metagenomes in RA samples had high proportions of Actinobacteria; RAR microbiomes contained higher proportions of Bacteroidetes than HC. The relative abundance of P. gingivalis was high in periodontitis and RAR; Aggregatibacter actinomycetemcomitans was detected with similar frequency in each group. Other bacteria implicated in periodontitis and/or autoantibody generation (Filifactor alocis, Prevotella spp, Leptotrichia spp.) were detected. Analyses are on-going to elucidate the diversity and functional potential of the subgingival microbiome associated with RA

The rise of dentine hypersensitivity and tooth wear in an ageing population

Our understanding of the aetiology of dentine hypersensitivity (DH) has changed dramatically over the past few decades. It is no longer an enigma, but other problems exist. The prevalence of DH in the world and in particular in the UK is increasing, predominately due to increases in tooth wear and the erosive dietary intake in the younger population. DH is increasingly reported in all age groups and is shown to provide clinical indication of an active erosive tooth wear. As the population ages and possibly retain teeth for longer, the likelihood of tooth wear and DH could increase. This paper describes the prevalence, aetiology, diagnosis and management of DH in relation to tooth wear, which work together through a surface phenomenon. The aim is to raise awareness of the conditions and to help inform a prevention strategy in an ageing population, which starts from younger age groups to reduce disease into older age