Circulating and Synovial Pentraxin-3 (PTX3) Expression Levels Correlate With Rheumatoid Arthritis Severity and Tissue Infiltration Independently of Conventional Treatments Response

International audienceAims To determine the relationship between PTX3 systemic and synovial levels and the clinical features of rheumatoid arthritis (RA) in a cohort of early, treatment naïve patients and to explore the relevance of PTX3 expression in predicting response to conventional-synthetic (cs) Disease-Modifying-Anti-Rheumatic-Drugs (DMARDs) treatment. Methods PTX3 expression was analyzed in 119 baseline serum samples from early naïve RA patients, 95 paired samples obtained 6-months following the initiation of cs-DMARDs treatment and 43 healthy donors. RNA-sequencing analysis and immunohistochemistry for PTX3 were performed on a subpopulation of 79 and 58 synovial samples, respectively, to assess PTX3 gene and protein expression. Immunofluorescence staining was performed to characterize PTX3 expressing cells within the synovium. Results Circulating levels of PTX3 were significantly higher in early RA compared to healthy donors and correlated with disease activity at baseline and with the degree of structural damages at 12-months. Six-months after commencing cs-DMARDs, a high level of PTX3, proportional to the baseline value, was still detectable in the serum of patients, regardless of their response status. RNA-seq analysis confirmed that synovial transcript levels of PTX3 correlated with disease activity and the presence of mediators of inflammation, tissue remodeling and bone destruction at baseline. PTX3 expression in the synovium was strongly linked to the degree of immune cell infiltration, the presence of ectopic lymphoid structures and seropositivity for autoantibodies. Accordingly, PTX3 was found to be expressed by numerous synovial cell types such as plasma cells, fibroblasts, vascular and lymphatic endothelial cells, macrophages, and neutrophils. The percentage of PTX3-positive synovial cells, although significantly reduced at 6-months post-treatment as a result of global decreased cellularity, was similar in cs-DMARDs responders and non-responders. Conclusion This study demonstrates that, early in the disease and prior to treatment modification, the level of circulating PTX3 is a reliable marker of RA activity and predicts a high degree of structural damages at 12-months. In the joint, PTX3 associates with immune cell infiltration and the presence of ectopic lymphoid structures. High synovial and peripheral blood levels of PTX3 are associated with chronic inflammation characteristic of RA. Additional studies to determine the mechanistic link are required

Thermal niche evolution and geographical range expansion in a species complex of western Mediterranean diving beetles

[Background] Species thermal requirements are one of the principal determinants of their ecology and biogeography, although our understanding of the interplay between these factors is limited by the paucity of integrative empirical studies. Here we use empirically collected thermal tolerance data in combination with molecular phylogenetics/phylogeography and ecological niche modelling to study the evolution of a clade of three western Mediterranean diving beetles, the Agabus brunneus complex.[Results] The preferred mitochondrial DNA topology recovered A. ramblae (North Africa, east Iberia and Balearic islands) as paraphyletic, with A. brunneus (widespread in the southwestern Mediterranean) and A. rufulus (Corsica and Sardinia) nested within it, with an estimated origin between 0.60-0.25 Ma. All three species were, however, recovered as monophyletic using nuclear DNA markers. A Bayesian skyline plot suggested demographic expansion in the clade at the onset of the last glacial cycle. The species thermal tolerances differ significantly, with A. brunneus able to tolerate lower temperatures than the other taxa. The climatic niche of the three species also differs, with A. ramblae occupying more arid and seasonal areas, with a higher minimum temperature in the coldest month. The estimated potential distribution for both A. brunneus and A. ramblae was most restricted in the last interglacial, becoming increasingly wider through the last glacial and the Holocene.[Conclusions] The A. brunneus complex diversified in the late Pleistocene, most likely in south Iberia after colonization from Morocco. Insular forms did not differentiate substantially in morphology or ecology, but A. brunneus evolved a wider tolerance to cold, which appeared to have facilitated its geographic expansion. Both A. brunneus and A. ramblae expanded their ranges during the last glacial, although they have not occupied areas beyond their LGM potential distribution except for isolated populations of A. brunneus in France and England. On the islands and possibly Tunisia secondary contact between A. brunneus and A. ramblae or A. rufulus has resulted in introgression. Our work highlights the complex dynamics of speciation and range expansions within southern areas during the last glacial cycle, and points to the often neglected role of North Africa as a source of European biodiversity.This work was supported by an FPI grant to AH-G and projects CGL2007-61665 and CGL2010-15755 from the Spanish government to IR. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Synovial tissue signatures enhance clinical classification and prognostic/treatment response algorithms in early inflammatory arthritis and predict requirement for subsequent biological therapy: results from the pathobiology of early arthritis cohort (PEAC)

Funding for PEAC MRC: Grant code 36661. Funding Infrastructure support to EMR, Arthritis Research UK Experimental Treatment Centre: Grant code 20022

Women's Experiences and Views about Costs of Seeking Malaria Chemoprevention and other Antenatal Services: A Qualitative Study from two Districts in Rural Tanzania.

The Tanzanian government recommends women who attend antenatal care (ANC) clinics to accept receiving intermittent preventive treatment against malaria during pregnancy (IPTp) and vouchers for insecticide-treated nets (ITNs) at subsidized prices. Little emphasis has been paid to investigate the ability of pregnant women to access and effectively utilize these services. To describe the experience and perceptions of pregnant women about costs and cost barriers for accessing ANC services with emphasis on IPTp in rural Tanzania. Qualitative data were collected in the districts of Mufindi in Iringa Region and Mkuranga in Coast Region through 1) focus group discussions (FGDs) with pregnant women and mothers to infants and 2) exit-interviews with pregnant women identified at ANC clinics. Data were analyzed manually using qualitative content analysis methodology. FGD participants and interview respondents identified the following key limiting factors for women's use of ANC services: 1) costs in terms of money and time associated with accessing ANC clinics, 2) the presence of more or less official user-fees for some services within the ANC package, and 3) service providers' application of fines, penalties and blame when failing to adhere to service schedules. Interestingly, the time associated with travelling long distances to ANC clinics and ITN retailers and with waiting for services at clinic-level was a major factor of discouragement in the health seeking behaviour of pregnant women because it seriously affected their domestic responsibilities. A variety of resource-related factors were shown to affect the health seeking behaviour of pregnant women in rural Tanzania. Thus, accessibility to ANC services was hampered by direct and indirect costs, travel distances and waiting time. Strengthening of user-fee exemption practices and bringing services closer to the users, for example by promoting community-directed control of selected public health services, including IPTp, are urgently needed measures for increasing equity in health services in Tanzania

Author correction : a global database for metacommunity ecology, integrating species, traits, environment and space

Correction to: Scientific Data https://doi.org/10.1038/s41597-019-0344-7, published online 08 January 202

Genotoxic Effects in Swimmers Exposed to Disinfection By-products in Indoor Swimming Pools

37 páginas, 1 figura, 4 tablas.-- PDF con material suplementario.[BACKGROUND]: Exposure to disinfection by-products (DBPs) in drinking water has been associated with cancer risk. A recent study found an increased bladder cancer risk among subjects attending swimming pools relative to those not attending.[OBJECTIVES]: To evaluate whether swimming in pools is associated with biomarkers of genotoxicity.[METHODS]: We collected blood, urine, and exhaled air samples from 49 non-smoking adult volunteers before and after they swam for 40 min in an indoor chlorinated pool. We estimated associations between the concentrations of four trihalomethanes in exhaled breath and changes in the following biomarkers: micronuclei and DNA damage (comet assay) in peripheral blood lymphocytes before and 1 h after swimming, urine mutagenicity (Ames assay) before and 2 h after swimming, and micronuclei in exfoliated urothelial cells before and 2 weeks after swimming. We also estimated associations and interactions with polymorphisms in genes related to DNA repair or DBP metabolism.[RESULTS]: After swimming, the total concentration of the four trihalomethanes in exhaled breath was seven times higher than before swimming. The change in the frequency of micronucleated lymphocytes after swimming increased in association with exhaled concentrations of the brominated trihalomethanes (p = 0.03 for CHCl2Br, p = 0.05 for CHClBr2, p = 0.01 for CHBr3) but not chloroform. Swimming was not associated with DNA damage detectable by the comet assay. Urine mutagenicity increased significantly after swimming in association with the concentration of exhaled CHBr3 (p = 0.004). No significant associations with changes in micronucleated urothelial cells were observed.[CONCLUSIONS]: Our findings support potential genotoxic effects of exposure to DBPs from swimming pools. The positive health effects gained by swimming could be increased by reducing the potential health risks of pool water.Research supported by Plan Nacional Grant SAF2005-07643-C03-01/02/03, Spain and FIS CP06/00341, Spain. CM Villanueva supported by the ISCIII (CP06/00341), Spain, L Font-Ribera by a predoctoral fellowship (FI06/00651), Spain, and D Liviac by a postgraduate fellowship UAB (PIF409-009), Barcelona.Peer reviewe

Author correction : a global database for metacommunity ecology, integrating species, traits, environment and space

Correction to: Scientific Data https://doi.org/10.1038/s41597-019-0344-7, published online 08 January 202

What’s in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water

38 páginas, 2 figuras, 4 tablas.-- PDF con material suplementario.[BACKGROUND]: Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in the water and related that to mutagenicity.[OBJECTIVES]: We performed a comprehensive identification of DBPs and disinfectant species in waters from public swimming pools in Barcelona, Catalonia, Spain, that disinfect with either chlorine or bromine, and we determined the mutagenicity of the waters to compare to the analytical results.[METHODS]: We used gas chromatography (GC)/mass spectrometry (MS) to measure THMs in water and GC with electron capture detection (ECD) for air, low and high resolution GC/MS to comprehensively identify DBPs, photometry to measure disinfectant species (free chlorine, monochloroamine, dichloramine, and trichloramine) in the waters, and an ion chromatography method to measure trichloramine in air. We assessed mutagenicity in the Salmonella mutagenicity assay.[RESULTS]: We identified more than 100 DBPs, including many nitrogen-containing DBPs that were likely formed from nitrogen-containing precursors from human inputs, such as urine, sweat, and skin cells. Many DBPs were new and have not been reported previously in either swimming pool or drinking waters. Bromoform levels were greater in the brominated vs. chlorinated pool waters, but many brominated DBPs were also identified in the chlorinated waters. The pool waters were mutagenic at levels similar to that of drinking water (~1200 revertants/L-eq in strain TA100 –S9 mix).[CONCLUSIONS]: This study identified many new DBPs not identified previously in swimming pool or drinking water and found that swimming pool waters are as mutagenic as typical drinking waters.This research was supported by EPA’s intramural research program and the Spanish grants SAF2005-07643-C03-01 (Plan Nacional) and CP06/00341 (Fondo de Investigación Sanitaria). CMV and LFR have, respectively, a contract and a predoctoral fellowship by the Instituto de Salud Carlos III (CP06/00341, FI06/00651). CL acknowledges a grant from the Agreement between Santander-Central Hispano and CSIC.Peer reviewe

Loss of flight promotes beetle diversification

The evolution of flight is a key innovation that may enable the extreme diversification of insects. Nonetheless, many species-rich, winged insect groups contain flightless lineages. The loss of flight may promote allopatric differentiation due to limited dispersal power and may result in a high speciation rate in the flightless lineage. Here we show that loss of flight accelerates allopatric speciation using carrion beetles (Coleoptera: Silphidae). We demonstrate that flightless species retain higher genetic differentiation among populations and comprise a higher number of genetically distinct lineages than flight-capable species, and that the speciation rate with the flightless state is twice that with the flight-capable state. Moreover, a meta-analysis of 51 beetle species from 15 families reveals higher genetic differentiation among populations in flightless compared with flight-capable species. In beetles, which represent almost one-fourth of all described species, repeated evolution of flightlessness may have contributed to their steady diversification since the Mesozoic era