Association between peripheral activated naive and double negative 2 B-cell subsets and clinical parameters in lupus nephritis patients.

Altered composition of B-cell compartments is a known feature in patients with systemic lupus erythematosus (SLE). However, deep characterisation of B-cell subsets and their relation to clinical manifestations and disease activity in patients is limited. In this study, we analysed peripheral B-cell subsets phenotype in SLE (n = 35) and healthy controls (HCs, n = 15) by spectral flow cytometry.

Arthritis progressors have a decreased frequency of circulating autoreactive T cells during the at-risk phase of rheumatoid arthritis.

Objectives: The aim of this study was to combine deep T cell phenotyping with assessment of citrulline-reactive CD4+T cells in the pre-rheumatoid arthritis (RA) phase.

Methods: 20 anti-CCP2 positive individuals () presenting musculoskeletal complaints without clinical or ultrasound signs of synovitis; 10 arthritis progressors and 10 matched non-arthritis progressors were included. Longitudinal samples (1-3 time points) of peripheral blood mononuclear cells were assessed using HLA-class II tetramers with 12 different citrullinated candidate autoantigens combined in a >20-colour spectral flow cytometry panel.

Impaired Periodontitis-Induced Cytokine Production by Peripheral Blood Monocytes and Myeloid Dendritic Cells in Patients with Rheumatoid Arthritis: A Case-Control Study.

: Immune cells from rheumatoid arthritis (RA) patients display a reduced in vitro response to (), which may have functional immune consequences. The aim of this study was to characterize, by flow cytometry, the frequency/activity of monocytes and naturally occurring myeloid dendritic cells (mDCs) in peripheral blood samples from patients with periodontitis and patients with periodontitis and RA. : The relative frequency of monocytes and mDCs in the whole blood, the frequency of these cells producing TNFα or IL-6 and the protein expression levels for each cytokine, before and after stimulation with lipopolysaccharide (LPS) from plus interferon-γ (IFN-γ), were assessed by flow cytometry, in peripheral blood samples from 10 healthy individuals (HEALTHY), 10 patients with periodontitis (PERIO) and 17 patients with periodontitis and RA (PERIO+RA).

The impact of periodontitis and periodontal treatment on rheumatoid arthritis outcomes: an exploratory clinical trial.

Objective: Studies suggest rheumatoid arthritis (RA) patients could benefit from periodontal treatment. However, published data are inconsistent, and there is a need for better-controlled research. Our study aims to address these limitations.

Exhaled Nitric Oxide Reflects the Immune Reactions of the Airways in Early Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included.

Sex-specific assumptions and their importance in models of sexual selection.

Sexual selection is a field coloured by tension and contrasting views. One contested claim is the causal link from the definition of the sexes (anisogamy) to divergent selection on the sexes. Does theory truly engage with this claim? We survey the extent to which theory makes sex-specific assumptions and engages with anisogamy, and discuss these issues in a broader context.

Anti-Citrullinated Protein Antibody Reactivity towards Neutrophil-Derived Antigens: Clonal Diversity and Inter-Individual Variation.

Background: Why the adaptive immune system turns against citrullinated antigens in rheumatoid arthritis (RA) and whether anti-citrullinated protein antibodies (ACPAs) contribute to pathogenesis are questions that have triggered intense research, but still are not fully answered. Neutrophils may be crucial in this context, both as sources of citrullinated antigens and also as targets of ACPAs. To better understand how ACPAs and neutrophils contribute to RA, we studied the reactivity of a broad spectrum of RA patient-derived ACPA clones to activated or resting neutrophils, and we also compared neutrophil binding using polyclonal ACPAs from different patients.

The Demographic Costs of Sexually Antagonistic Selection in Partially Selfing Populations.

AbstractWhen selection differs between the sexes, genes expressed by both males and females can experience sexually antagonistic (SA) selection, where beneficial alleles for one sex are deleterious for the other. Classic population genetics theory has been fundamental to understanding how and when SA genetic variation can be maintained by balancing selection, but these models have rarely considered the demographic consequences of coexisting alleles with deleterious fitness effects in each sex. In this article, we develop a stage-structured Mendelian matrix model and jointly analyze the evolutionary and demographic consequences of SA selection in obligately outcrossing (i.

Antibodies to a Citrullinated Epitope Are Increased in Early Rheumatoid Arthritis, and Can Be Produced by Gingival Tissue B Cells: Implications for a Bacterial Origin in RA Etiology.

Based on the epidemiological link between periodontitis and rheumatoid arthritis (RA), and the unique feature of the periodontal bacterium to citrullinate proteins, it has been suggested that production of anti-citrullinated protein antibodies (ACPA), which are present in a majority of RA patients, may be triggered in the gum mucosa. To address this hypothesis, we investigated the antibody response to a citrullinated peptide in relation to the autoimmune ACPA response in early RA, and examined citrulline-reactivity in monoclonal antibodies derived from human gingival B cells. Antibodies to a citrullinated peptide derived from (denoted CPP3) and human citrullinated peptides were analyzed by multiplex array in 2,807 RA patients and 372 controls; associations with RA risk factors and clinical features were examined.

Antibodies to Are Increased in Patients with Severe Periodontitis, and Associate with Presence of Specific Autoantibodies and Myocardial Infarction.

There is accumulating data suggesting that periodontitis is associated with increased risk of systemic and autoimmune diseases, including cardiovascular disease, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and there is an unmet need to identify these individuals early. With the periodontal bacteria () as one of the key drivers of periodontitis, we set out to investigate whether antibodies to virulence factor arginine gingipain (Rgp) could serve as a biomarker for periodontitis patients at increased risk of autoimmunity and systemic disease. We measured serum anti-Rgp IgG in three study populations: PAROKRANK (779 individuals with myocardial infarction (MI); 719 controls), where 557 had periodontitis, and 312 were positive for autoantibodies associated with RA/SLE; the PerioGene North pilot (41 periodontitis; 39 controls); and an SLE case/control study (101 SLE; 100 controls).

Selection in two-sex stage-structured populations: Genetics, demography, and polymorphism.

The outcome of natural selection depends on the demographic processes of birth, death, and development. Here, we derive conditions for protected polymorphism in a population characterized by age- or stage-dependent demography with two sexes. We do so using a novel two-sex matrix population model including basic Mendelian genetics (one locus, two alleles, random mating).

Stage-Structured Evolutionary Demography: Linking Life Histories, Population Genetics, and Ecological Dynamics.

Demographic processes and ecological interactions are central to understanding evolution and vice versa. We present a novel framework that combines basic Mendelian genetics with the powerful demographic approach of matrix population models. The ecological components of the model may be stage classified or age classified, linear or nonlinear, time invariant or time varying, and deterministic or stochastic.

Age × stage-classified demographic analysis: a comprehensive approach.

This paper presents a comprehensive theory for the demographic analysis of populations in which individuals are classified by both age and stage. The earliest demographic models were age classified. Ecologists adopted methods developed by human demographers and used life tables to quantify survivorship and fertility of cohorts and the growth rates and structures of populations.

Demography when history matters: construction and analysis of second-order matrix population models.

History matters when individual prior conditions contain important information about the fate of individuals. We present a general framework for demographic models which incorporates the effects of history on population dynamics. The framework incorporates prior condition into the -state variable and includes an algorithm for constructing the population projection matrix from information on current state dynamics as a function of prior condition.

The effectiveness of mediolateral episiotomy in preventing obstetric anal sphincter injuries during operative vaginal delivery: a ten-year analysis of a national registry.

Introduction And Hypothesis: Obstetric anal sphincter injuries (OASIS) are associated with an increased risk of faecal incontinence after vaginal delivery. The aim of this retrospective population-based cohort study was to assess whether mediolateral episiotomy is associated with a reduction in the rate of OASIS during operative vaginal delivery.

Methods: We used data from the Dutch Perinatal Registry (Perined) that includes records of almost all births between 2000 and 2010 in The Netherlands.

Limiting disproportionate disaccommodation in design for human variability.

In the design of artefacts, tasks and environments for human use, the body dimensions of the target population are a critical element in spatial optimisation of the design. This study examines how the choices designers make affect the ability of different user groups to safely and effectively interact with a designed artefact. Due to the variability in body size and shape across different demographic groups, heterogeneous user populations are unlikely to experience uniform levels of performance.

Birth in an ordinary instant.

Our daily lives are a series of ordinary moments and unnoticed thresholds-times that define us in ways we often do not give much attention. While we consider childbirth to be one of life's extra-ordinary events, the hours of labor and birth need not be dramatic (or traumatic) ones. I describe a quiet, well-supported birth in the Netherlands that is cause for celebration of the beauty of an ordinary instant that can define and enrich the human experience.

Childbirth education in the 21st century: an immodest proposal.

Childbirth education was an important social movement in the 20th century but has lost its way in recent years. We describe the reasons for the dwindling importance of childbirth education and offer a proposal for reform that will align childbirth education with the needs of today's birthing mothers. Our plan will create "Centers for the Childbearing Year" (CCBYs) and a new model of childbirth educator, which we call the "birth coach.