Time-varying risks of infection in patients as they proceed through the phases of 'pre-RA': results from the Scottish Early RA inception cohort.

Unlabelled: ObjectiveRheumatoid arthritis (RA) develops after progressing through sequential 'pre-RA' phases. The mechanisms driving progression from one phase to the next remain poorly understood. This study examined the longitudinal rates of community and hospital infections in patients during sequential stages of pre-RA and early arthritis.

Frailty in people with rheumatoid arthritis: a systematic review of observational studies.

Frailty, an age-related decline in physiological reserve, is an increasingly important concept in the management of chronic diseases. The implications of frailty in people with rheumatoid arthritis are not well understood. We undertook a systematic review to assess prevalence of frailty in people with rheumatoid arthritis, and the relationship between frailty and disease activity or clinical outcomes.

Classification of long-term condition patterns in rheumatoid arthritis and associations with adverse health events: a UK Biobank cohort study.

Purpose: We aimed to classify individuals with RA and ≥2 additional long-term conditions (LTCs) and describe the association between different LTC classes, number of LTCs and adverse health outcomes.

Methods: We used UK Biobank participants who reported RA (n=5,625) and employed latent class analysis (LCA) to create classes of LTC combinations for those with ≥2 additional LTCs. Cox-proportional hazard and negative binomial regression were used to compare the risk of all-cause mortality, major adverse cardiac events (MACE), and number of emergency hospitalisations over an 11-year follow-up across the different LTC classes and in those with RA plus one additional LTC.

Association between risk, duration and cause of hospitalisations in people with rheumatoid arthritis and multimorbidity in the UK Biobank and Scottish Early Rheumatoid Arthritis (SERA) cohorts: Longitudinal observational study.

Objectives: To investigate association between presence of multimorbidity in people with established and early rheumatoid arthritis (RA) and risk, duration and cause of hospitalisations.

Design: Longitudinal observational study.

Setting: UK Biobank, population-based cohort recruited between 2006 and 2010, and the Scottish Early Rheumatoid Arthritis (SERA), inception cohort recruited between 2011 and 2015.

Frailty in rheumatoidrmdopen-2021-002111 arthritis and its relationship with disease activity, hospitalisation and mortality: a longitudinal analysis of the Scottish Early Rheumatoid Arthritis cohort and UK Biobank.

Objective: To assess the prevalence of frailty in rheumatoid arthritis (RA) and its association with baseline and longitudinal disease activity, all-cause mortality and hospitalisation.

Participants: People with RA identified from the Scottish Early Rheumatoid Arthritis (SERA) inception cohort (newly diagnosed, mean age 58.2 years) and UK Biobank (established disease identified using diagnostic codes, mean age 59 years).

The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease.

To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs.

The impact of autoantibodies against citrullinated, carbamylated, and acetylated peptides on radiographic progression in patients with new-onset rheumatoid arthritis: an observational cohort study.

Background: A range of anti-modified protein antibodies (AMPAs) are associated with rheumatoid arthritis. We aimed to assess the relationship between AMPA profiles and radiographic progression in patients with new-onset rheumatoid arthritis.

Methods: In this cohort study, we obtained samples and data from the Scottish Early Rheumatoid Arthritis (SERA) inception cohort and biobank, which recruited patients with new-onset rheumatoid arthritis or undifferentiated arthritis who had at least one swollen joint from 20 hospitals across Scotland.

Tolerance induction in memory CD4 T cells is partial and reversible.

Memory T cells respond rapidly in part because they are less reliant on a heightened levels of costimulatory molecules. This enables rapid control of secondary infecting pathogens but presents challenges to efforts to control or silence memory CD4 T cells, for example in antigen-specific tolerance strategies for autoimmunity. We have examined the transcriptional and functional consequences of reactivating memory CD4 T cells in the absence of an adjuvant.

Unexpected differential metabolic responses of Campylobacter jejuni to the abundant presence of glutamate and fucose.

Introduction: Campylobacter jejuni is the leading cause of foodborne bacterial enteritis in humans, and yet little is known in regard to how genetic diversity and metabolic capabilities among isolates affect their metabolic phenotype and pathogenicity.

Objectives: For instance, the C. jejuni 11168 strain can utilize both L-fucose and L-glutamate as a carbon source, which provides the strain with a competitive advantage in some environments and in this study we set out to assess the metabolic response of C.

PiMP my metabolome: an integrated, web-based tool for LC-MS metabolomics data.

Summary: The Polyomics integrated Metabolomics Pipeline (PiMP) fulfils an unmet need in metabolomics data analysis. PiMP offers automated and user-friendly analysis from mass spectrometry data acquisition to biological interpretation. Our key innovations are the Summary Page, which provides a simple overview of the experiment in the format of a scientific paper, containing the key findings of the experiment along with associated metadata; and the Metabolite Page, which provides a list of each metabolite accompanied by 'evidence cards', which provide a variety of criteria behind metabolite annotation including peak shapes, intensities in different sample groups and database information.

A novel metabolomic approach used for the comparison of planktonic cells and biofilm samples.

Introduction: Bacterial cell characteristics change significantly during differentiation between planktonic and biofilm states. While established methods exist to detect and identify transcriptional and proteomic changes, metabolic fluctuations that distinguish these developmental stages have been less amenable to investigation.

Objectives: The objectives of the study were to develop a robust reproducible sample preparation methodology for high throughput biofilm analysis and to determine differences between Staphylococcus aureus in planktonic and biofilm states.

A comparison of CKD-EPI estimated glomerular filtration rate and measured creatinine clearance in recently admitted critically ill patients with normal plasma creatinine concentrations.

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) has been widely integrated into clinical practice. Although useful in screening for CKD, its' application in critically ill patients with normal plasma creatinine concentrations remains uncertain. The aim of this study was to assess the performance of CKD-EPI eGFR in comparison to creatinine clearance (CLCR) in this setting.

MEROPS: the peptidase database.

Peptidases (proteolytic enzymes or proteases), their substrates and inhibitors are of great relevance to biology, medicine and biotechnology. The MEROPS database (http://merops.sanger.

The MEROPS batch BLAST: a tool to detect peptidases and their non-peptidase homologues in a genome.

Many of the 181 families of peptidases contain homologues that are known to have functions other than peptide bond hydrolysis. Distinguishing an active peptidase from a homologue that is not a peptidase requires specialist knowledge of the important active site residues, because replacement or lack of one of these catalytic residues is an important clue that the homologue in question is unlikely to hydrolyse peptide bonds. Now that the rate at which proteins are characterized is outstripped by the rate that genome sequences are determined, many genes are being incorrectly annotated because only sequence similarity is taken into consideration.

MEROPS: the peptidase database.

Peptidases (proteolytic enzymes) and their natural, protein inhibitors are of great relevance to biology, medicine and biotechnology. The MEROPS database (http://merops.sanger.

Genome of the host-cell transforming parasite Theileria annulata compared with T. parva.

Theileria annulata and T. parva are closely related protozoan parasites that cause lymphoproliferative diseases of cattle. We sequenced the genome of T.

Novel cell-permeable acyloxymethylketone inhibitors of asparaginyl endopeptidase.

Mammalian asparaginyl endopeptidase (AEP) or legumain is a recently identified lysosomal cysteine protease belonging to clan CD. To date it has been shown to be involved in antigen presentation within class II MHC positive cells and in pro-protein processing. Further elucidation of the biological functions of the enzyme will require potent and selective inhibitors and thus we describe here new acyloxymethylketone inhibitors of AEP.