Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection

Background Candidalysin is a cytolytic peptide toxin secreted by Candida albicans hyphae and has significantly advanced our understanding of fungal pathogenesis. Candidalysin is critical for mucosal C albicans infections and is known to activate epithelial cells to induce downstream innate immune responses that are associated with protection or immunopathology during oral or vaginal infections. Furthermore, candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. However, the role of candidalysin in driving systemic infections is unknown. Methods In this study, using candidalysin-producing and candidalysin-deficient C albicans strains, we show that candidalysin activates mitogen-activated protein kinase (MAPK) signaling and chemokine secretion in endothelial cells in vitro. Results Candidalysin induces immune activation and neutrophil recruitment in vivo, and it promotes mortality in zebrafish and murine models of systemic fungal infection. Conclusions The data demonstrate a key role for candidalysin in neutrophil recruitment and fungal virulence during disseminated systemic C albicans infections

Rheumatoid factor isotype switch and somatic mutation variants within rheumatoid arthritis synovium

The presence of clonally-related B-lymphocyte aggregates within synovial lining tisue of rheumatoid arthritis (RA) patients suggests a germinal centre-like reaction, which may hold implications for disease pathogenesis and the causes of chronic inflammation. We studied 250 rheumatoid factor (RF) heavy-chain sequences cloned from the synovium of three patients with RA, to determine whether they undergo both somatic mutation and isotype switching consistent with this hypothesis. Size analysis of immunoglobulin heavy-chain cDNAs from synovial RF+ B cells revealed oligoclonal RF+ populations and identically-sized VH-D-JH transcripts of different immunoglobulin isotypes. Sequencing of individual inserts selected from cloned immunoglobulin heavy-chain cDNAs demonstrated a clonal relationship between immunoglobulin M (IgM) RF and IgA RF, suggesting that this isotype switch occurred in synovium. Furthermore, most somatic mutations were found to have occurred after this isotype switch. This finding suggests that the RA synovial microenvironment sustains somatic mutation and isotype switching in RF-specific B lymphocytes akin to secondary lymphoid organs

The global epidemiology of RSV in the community and hospitalized care: findings from 15 countries.

Background Respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infections. To optimize control strategies, a better understanding of the global epidemiology of RSV is critical. To this end, we initiated the Global Epidemiology of RSV in Hospitalized and Community care study (GERi). Methods Focal points from 44 countries were approached to join GERi and share detailed RSV surveillance data. Countries completed a questionnaire on the characteristics of their surveillance system. Results Fifteen countries provided granular surveillance data and information on their surveillance system. A median of 1,641 (IQR:552 – 2,415) RSV cases per season were reported from 2000 and 2020. The majority (55%) of RSV cases occurred in the <1-year-olds, with 8% of cases reported in those aged ≥65 years. Hospitalized cases were younger than those in community care. We found no age difference between RSV subtypes and no clear pattern of dominant subtypes. Conclusions The high number of cases in the <1 year-olds indicates a need to focus prevention efforts in this group. The minimal differences between RSV subtypes and their co-circulation implies prevention needs to target both subtypes. Importantly, there appears to be a lack of RSV surveillance data in the elderly

Inequality and welfare evaluation of heterogeneous income distributions

This paper establishes the principles that should govern the welfare and inequality analysis of heterogeneous income distributions. Two basic criteria – the ‘equity preference’ condition and the ‘compensation principle’ – are shown to be fundamentally incompatible. The paper favours the latter, thereby vindicating the traditional method of dealing with heterogeneous samples. However, inequality and welfare comparisons will usually be well defined only if equivalent incomes are obtained using constant scale factors; and researchers will need to distinguish clearly between inequality of nominal incomes and inequality of living standards. Furthermore, household observations must always be weighted according to family size. Copyright Kluwer Academic Publishers 2004income distributions, inequality, living standards, needs,