Monitoring changes in submarine canyon coral habitats - Leg 1 (MoCha_SCan)

This survey focused on the maiden deployment of a number of novel, ROV-adapted lander systems in the Porcupine Bank Canyon (PBC) coral habitats, NE Atlantic. Cold water corals (CWCs) flourish on the Irish-Atlantic margin between 600 and 100 m water depth, where they form a number of structural habitat types (coral reefs, mounds and gardens). Recent research shows that deep water habitats, including CWC habitats on the Irish margin, may be impacted by recent environmental change. The main objectives of this survey are: a) to deploy 8 new lander systems within a range of coral habitats throughout the PBC; b) to complete mapping coverage within the PBC; c) to sample the coral, sediment and ambient watermass around the lander sites and; d) to sample particulate organic matter around key coral habitats. Data recorded via landers from each habitat will allow to determine the controls on habitat variability. Furthermore, this data can be used as a baseline to which later deployments at this site will be used to compare against. Completed canyon coverage will feed into a number of multiscale mapping projects including the H2020 project â Integrated Assessment of Atlantic Marine Ecosystems in Space & Timeâ (iATLANTIC) and the SFI-, GSI- and MI-funded â Mapping, Modelling and Monitoring Key Processes and Controls on Cold Water Coral Habitats in Submarine Canyonsâ (MMMonKey_Pro) programme. Video data will be used to characterise key coral habitat within the canyon and subsequesntly, HD DEMâ s will be generated as a central dataset for the multiscale projects listed above

HLA-B*27 is associated with CNO in a European cohort

Abstract Objectives To determine the influence of HLA-B27 positivity on risk of developing chronic nonbacterial osteomyelitis (CNO). Methods HLA-B*27 genotype was assessed in 3 European CNO populations and compared with local control populations (572 cases, 33,256 controls). Regional or whole-body MRI was performed at diagnosis and follow-up in all cases which reduces the risk of disease misclassification. Genotyping was performed using either next generation DNA sequencing or PCR based molecular typing. Statistical analysis used Fisher’s exact test with Bonferroni correction and a fixed effects model for meta-analysis of odds ratios. Results HLA-B*27 frequency was higher in all 3 populations compared with local controls (combined odds ratio (OR) = 2.2, p-value = 3 × 10–11). This association was much stronger in male compared with female cases (OR = 1.99, corrected p-value = 0.015). However, the HLA-B*27 status was not statistically significantly associated with co-occurrence of psoriasis, arthritis or inflammatory bowel disease. Conclusion Carriage of HLA-B*27 is associated with greater risk of developing CNO, particularly in male cases

Incidence of chronic recurrent multifocal osteomyelitis in children and adolescents in the UK and Republic of Ireland.

OBJECTIVES: Chronic Recurrent Multifocal Osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis (CNO), is a rare autoinflammatory condition affecting the bones in children and teenagers. The actual incidence of CRMO remains uncertain. The objective of this study is to identify the incidence of CRMO in children and young people under the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). We also aim to delineate the demographics, clinical presentation, investigations, initial management and healthcare needs for children and adolescents with CRMO. METHODS: We conducted monthly surveys among all paediatric consultants and paediatric orthopaedic surgeons to identify patients newly diagnosed with CRMO between October 2020 and November 2022. A standardised questionnaire was sent to reporting clinicians to collect further information. RESULTS: Over the surveillance period, 288 patients were reported, among which, 165 confirmed and 20 probable cases were included in the analysis. The highest incidences were among 8-10 year-olds. A two-to-one female-to-male difference in incidence was observed, and male patients were more likely to present with multifocal disease. A negative correlation was observed between reporting clavicular and leg pain. Investigation-wise, 80.0% of patients were reported to have undergone whole-body MRI and 51.1% had bone biopsies. The most common initial treatments were NSAIDs (93.9%) and bisphosphonates (44.8%). CONCLUSION: This study estimates an average annual CRMO incidence of 0.65 cases per 100 000 children and adolescents in the UK and ROI. These findings establish a crucial baseline for ongoing research and improvement in the care of individuals with CRMO

A novel RELA truncating mutation in familial Behçet’s Disease-like mucocutaneous ulcerative condition

Objectives Monogenic Behçet’s Disease (BD)‐like conditions are increasingly recognised and to date predominantly involve loss‐of‐function variants in TNFAIP3. The objective of this study was to identify genetic and pathobiological mechanisms associated with a BD‐like mucocutaneous ulcerative syndrome and neuromyelitis optica (NMO) occurring in a three‐generation Irish family (n=5 cases; n=5 familial controls). Methods Whole exome sequencing was used to identify potential pathogenic variants in affected family members and determine segregation between affected and unaffected individuals. Relative RELA expression in peripheral blood mononuclear cells was compared by western blot. Human epithelial and RelA‐/‐ mouse fibroblast experimental systems were used to determine the molecular impact of the RELA truncation in response to TNF. NF‐κB signalling, transcriptional activation, apoptosis and cytokine production was compared between wild‐type and truncated RELA in experimental systems and patient samples. Results A heterozygous cytosine deletion at position c.1459 in RELA was detected in affected members. This mutation results in a frameshift p.His487ThrfsTer7, producing a truncated protein disrupting two transactivation domains. The truncated RELA protein lacks a full transactivation domain. The RELA protein variants were expressed at equal levels in peripheral mononuclear cells. RelA‐/‐ mouse embryonic fibroblast (MEF) cells expressing recombinant human RELAp.His487ThrfsTer7 were compared to those expressing RELAWT, however there was no difference in RELA nuclear translocation. In RelA‐/‐ MEF expression of RELAp.His487ThrfsTer7 resulted in 1.98‐fold higher ratio of cleaved caspase‐3/caspase‐3 induced by TNF (p=0.036) compared to RELAWT. Conclusions Our data support RELA loss‐of‐function mutations as causing BD‐like autoinflammation and NMO via impaired NF‐κB signalling and increased apoptosis

Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: A double-blind randomised controlled trial

Background: Lowserum vitamin D levels are associated with susceptibility to, and severity of, multiple sclerosis. High dose vitamin D has been proposed as a potential immunomodulator in multiple sclerosis. Objectives: We performed a single centre, investigator-led, exploratory, double-blind, randomised, placebo controlled, trial of vitamin D3 in clinically isolated syndrome and healthy control participants to assess its immunological effects. Secondary end-points included clinical and magnetic resonance imaging outcomes and safety. Methods: Clinically isolated syndrome patients and healthy control participants were randomised to: placebo, 5000 IU or 10,000 IU vitamin D3/day (Vigantol oil). Study duration was 24 weeks. Results: The trial did not meet its primary end point, with no difference in the frequency of proinflammatory CD4þ T cells (interleukin (IL)-17þ/interferon (IFN)-gþ) seen. A higher level of disease freedom (67% versus 50%) was seen in those with serum 1,25 (OH) vitamin D levels>100 nmol/l but this did not reach significance. High dose vitamin D3 was well tolerated with no safety signal. Conclusions: High dose vitamin D3 over 24 weeks was well tolerated but without immunological, magnetic resonance imaging or clinical evidence of benefit. The hypothesised therapeutic effects in clinically isolated syndrome or multiple sclerosis patients may require longer periods of administration or may only be seen in patients treated with vitamin D3 as an adjunct to established disease modifying therapies