Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope and risk of future rheumatoid arthritis: a nested case–control study

Introduction: The aim of this study was to characterize anti-citrullinated peptide antibody (ACPA) serostatus in pre-clinical rheumatoid arthritis (RA) with and without Human Leukocyte Antigen-Shared Epitope (HLA-SE) alleles. Methods: We identified 192 women in the Nurses’ Health Study cohorts with blood samples obtained 4 months to 17 years prior to medical record-confirmed RA diagnosis. Three controls were selected matched on age, cohort, menopausal status and post-menopausal hormone use. Reactivities to 18 ACPAs were measured using a custom BioPlex platform. We used conditional logistic regression to calculate the relative risk (RR) of RA for any ACPA-positive and peptide-specific ACPA-positive and examined RRs by time between blood draw and RA onset. Measures of multiplicative and additive interaction between any ACPA-positive and HLA-SE were calculated. Results: All ACPAs by peptide groups were significantly associated with RA risk, RRs ranged from 4.7 to 11.7. The association between ACPA and RA varied over time with the strongest association in those with blood draw less than 5 years before onset (RR 17.0 [95% CI 5.8 to 53.7]) and no association 10 or more years prior to onset (RR 1.4 [95% CI 0.5 to 4.3]). Individuals with both HLA-SE and any ACPA-positive had the highest risk of RA. HLA-SE-positive RA cases showed reactivity to more ACPA types than HLA-SE negative (χ2 test for trend, P = 0.01). Conclusions: There is increasing ACPA reactivity up to 10 years before RA onset with the strongest association within 5 years of RA onset. The magnitude of the response to ACPAs, in combination with the presence of HLA-SE, is most important for identifying those individuals with the highest risk of RA

Most Remarkable Move

Reflections on working with a young woman in a therapeutic way over an extended period of time

The Rebel Jesus and Trauma Therapy with the Divine Child Within

Reflections on the connection between the archetypal aspects of Jesus’ birth story and the therapeutic work the author engages in. It expands its reflections on these insights with implications for individuals, communities, and societies

As Her Pastor

A poem by a pastoral counselor

Immunohistochemical, morphological and ultrastructural resemblance between dendritic cells and folliculo-stellate cells in normal human and rat anterior pituitaries

Immunolabeling of cryo-sections of human anterior pituitaries obtained at autopsy, and of cryo-sections of freshly prepared rat anterior pituitaries, with a panel of monoclonal antibodies against markers of the monocyte/dendritic cell/macrophage lineage, reveals in both species a characteristic pattern of immunopositive cells, among which many cells with dendritic phenotype are found. Cells characterized by marker expression of MHC-class II determinants and a dendritic morphology are present in both human and rat anterior pituitary. Markers characteristic of dendritic cells such as the L25 antigen and the OX62 antigen were present in anterior pituitaries from human and rat respectively. The population of MHC-class II expressing dendritic cells of the rat anterior pituitary is compared at the ultrastructural level with the folliculo-stellate cell population, which cell type has been previously characterized by its distinctive ultrastructure and immunopositivity for the S100 protein. Using immune-electron microscopy of rat anterior pituitaries fixed with periodate-lysine-paraformaldehyde, we were able to distinguish non-granulated cells expressing MHC-class II determinants, whereas no MHC-class II expression was found in the granulated endocrine cells. Using double immunolabeling of cryo-sections of these rat AP with 25 nm and 15 nm gold labels, we demonstrated an overlap between the populations of MHC-class II-expressing and S100 protein-expressing cells. Furthermore, MHC-class II-expressing and S100-positive cells showed ultrastructural characteristics that have been previously ascribed to folliculo-stellate cells. At the light microscopical level in the rat AP, a proportion of 10 to 20% of the S100-positive cells was found immunopositive for the MHC-class II marker OX6. In the hu

Experimenteele psychologische onderzoekingen bij normalen en geesteszieken

Eerst in het midden der vorige eeuw werd het experiment in de psychologie ingevoerd. Fechner riep toen de psychophysica in het leven, waarddor getracht werd de verhouding tusschen psychische en phisische processen te leeren kennen. Men begon toen naar methoden te zoeken, die ons in staat zouden stellen de verschillende psychische functies in maat en getal uit te drukken; door deze, de intensiteit aangegeven getallen, zouden dan onderling vergelijkbare waarden gekregen worden. Zie: Inleidin

Integrating modelling of biodiversity composition and ecosystem function

There is increasing reliance on ecological models to improve our understanding of how ecological systems work, to project likely outcomes under alternative global change scenarios and to help develop robust management strategies. Two common types of spatiotemporally explicit ecological models are those focussed on biodiversity composition and those focussed on ecosystem function. These modelling disciplines are largely practiced separately, with separate literature, despite growing evidence that natural systems are shaped by the interaction of composition and function. Here we call for the development of new modelling approaches that integrate composition and function, accounting for the important interactions between these two dimensions, particularly under rapid global change. We examine existing modelling approaches that have begun to combine elements of composition and function, identifying their potential contribution to fully integrated modelling approaches. The development and application of integrated models of composition and function face a number of important challenges, including biological data limitations, system knowledge and computational constraints. We suggest a range of promising avenues that could help researchers overcome these challenges, including the use of virtual species, macroecological relationships and hybrid correlative-mechanistic modelling. Explicitly accounting for the interactions between composition and function within integrated modelling approaches has the potential to improve our understanding of ecological systems, provide more accurate predictions of their future states and transform their management

Epidemiology of Chronic Pain in Ukraine: Findings from the World Mental Health Survey

Chronic pain can pose a serious challenge in everyday life for many individuals globally, especially in developing countries, but studies explicitly exploring risk factors of chronic pain beyond demographic characteristics using survey data have been scarce. To address this problem, this study analyzed World Health Organization data on chronic pain in Ukraine to explore demographic, psychological, and treatment perception-related risk factors to chronic pain. We replicated previous reports of older age, female sex, married status, inadequate financial resources, and comorbidity of other physical conditions as significant demographic risk factors for chronic pain diagnosis but not necessarily for severe pain. We also found evidence for psychological risk factors and treatment perceptions as significant predictors for chronic pain diagnosis and its severity. These results provide a first step in examining beyond demographic risk factors for chronic pain diagnosis and severity and, instead, assessing potential psychological risk factors

Assessing Hazard Vulnerability, Habitat Conservation, and Restoration for the Enhancement ofmainland China’s Coastal Resilience

Worldwide, humans are facing high risks from natural hazards, especially in coastal regions with high population densities. Rising sea levels due to global warming are making coastal communities’ infrastructure vulnerable to natural disasters. The present study aims to provide a coupling approach of vulnerability and resilience through restoration and conservation of lost or degraded coastal natural habitats to reclamation under different climate change scenarios. The integrated valuation of ecosystems and tradeoffs model is used to assess the current and future vulnerability of coastal communities. The model employed is based on seven different biogeophysical variables to calculate a natural hazard index and to highlight the criticality of the restoration of natural habitats. The results show that roughly 25% of the coastline and more than 5 million residents are in highly vulnerable coastal areas of mainland China, and these numbers are expected to double by 2100. Our study suggests that restoration and conservation in recently reclaimed areas have the potential to reduce this vulnerability by 45%. Hence, natural habitats have proved to be a great defense against coastal hazards and should be prioritized in coastal planning and development. The findings confirm that natural habitats are critical for coastal resilience and can act as a recovery force of coastal functionality loss. Therefore, we recommend that the Chinese government prioritizes restoration (where possible) and conservation of the remaining habitats for the sake of coastal resilience to prevent natural hazards from escalating into disasters. Plain Language Summary: Coastal populations are especially at risk from sea-level rise (SLR), induced storm surges, and other natural hazards. Therefore, it becomes essential to analyze the current and future vulnerabilities of coastal regions to natural hazards. Furthermore, it is desirable for the policy and the decision making to propose the suitable approaches for the resilience enhancement. This paper analyzes the current and future vulnerability of mainland China’s coast to the SLR-induced natural hazards using a natural hazard index incorporating a coupled approach to vulnerability and resilience. The results show that the restoration of lost mangroves (where possible) and conservation of remaining coastal natural habitats can reduce the future coastal vulnerability by 45%. This study confirms that natural habitats are significant for coastal resilience and the governments should prioritize them for the sake of coastal resilience to mitigate the impacts of natural hazards. Includes supplemental material