Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis

BACKGROUND: /st> Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor alpha-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-kappaB and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA. OBJECTIVE: /st> To analyse the effect of the 6q23 region on the rate of joint destruction. METHODS: /st> Five single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years. RESULTS: /st> Two polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment. CONCLUSIONS: /st> These data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.Pathophysiology and treatment of rheumatic disease

The effect of exercise training on the course of cardiac troponin T and i levels: Three independent training studies

With the introduction of high-sensitive assays, cardiac troponins became potential biomarkers for risk stratification and prognostic medicine. Observational studies have reported an inverse association between physical activity and basal cardiac troponin levels. However, causality has never been demonstrated. This study investigated whether basal cardiac troponin concentrations are receptive to lifestyle interventions such as exercise training. Basal high-sensitive cardiac troponin T ( cTnT ) and I ( cTnI ) were monitored in two resistance-type exercise training programs ( 12-week ( study 1 ) and 24-week ( study 2 ) ) in older adults ( ≥65 years ). In addition, a retrospective analysis for high sensitive troponin I in a 24-week exercise controlled trial in ( pre )frail older adults was performed ( study 3 ). In total, 91 subjects were included in the final data analyses. There were no significant changes in cardiac troponin levels over time in study 1 and 2 ( study 1: cTnT −0.13 ( −0.33–+0.08 ) ng/L/12-weeks, cTnI −0.10 ( −0.33–+0.12 ) ng/L/12-weeks; study 2: cTnT −1.99 ( −4.79–+0.81 ) ng/L/24-weeks, cTnI −1.59 ( −5.70–+2.51 ) ng/L/24-weeks ). Neither was there a significant interaction between training and the course of cardiac troponin in study 3 ( p = 0.27 ). In conclusion, this study provides no evidence that prolonged resistance-type exercise training can modulate basal cardiac troponin levels

Healthy people with nature in mind

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: The global disease burden resulting from climate change is likely to be substantial and will put further strain on public health systems that are already struggling to cope with demand. An up- stream solution, that of preventing climate change and associated adverse health effects, is a promising approach, which would create win-win-situations where both the environment and human health benefit. One such solution would be to apply methods of behaviour change to prompt pro-environmentalism, which in turn benefits health and wellbeing. DISCUSSION: Based on evidence from the behavioural sciences, we suggest that, like many social behaviours, pro- environmental behaviour can be automatically induced by internal or external stimuli. A potential trigger for such automatic pro-environmental behaviour would be natural environments themselves. Previous research has demonstrated that natural environments evoke specific psychological and physiological reactions, as demonstrated by self-reports, epidemiological studies, brain imaging techniques, and various biomarkers. This suggests that exposure to natural environments could have automatic behavioural effects, potentially in a pro-environmental direction, mediated by physiological reactions. Providing access and fostering exposure to natural environments could then serve as a public health tool, together with other measures, by mitigating climate change and achieving sustainable health in sustainable ecosystems. However, before such actions are implemented basic research is required to elucidate the mechanisms involved, and applied investigations are needed to explore real world impacts and effect magnitudes. As environmental research is still not sufficiently integrated within medical or public health studies there is an urgent need to promote interdisciplinary methods and investigations in this critical field. Health risks posed by anthropogenic climate change are large, unevenly distributed, and unpredictable. To ameliorate negative impacts, pro-environmental behaviours should be fostered. Potentially this could be achieved automatically through exposure to favourable natural environments, with an opportunity for cost-efficient nature-based solutions that provide benefits for both the environment and public health

Potential effects of warmer worms and vectors on onchocerciasis transmission in West Africa

Development times of eggs, larvae and pupae of vectors of onchocerciasis (Simulium spp.) and of Onchocerca volvulus larvae within the adult females of the vectors decrease with increasing temperature. At and above 25C,the parasite could reach its infective stage in less than 7 days when vectors could transmit after only two gonotrophic cycles. After incorporating exponential functions for vector development into a novel blackfly population model, it was predicted that fly numbers in Liberia and Ghana would peak at air temperatures of 29C and 34C, about 3C and 7C above current monthly averages, respectively; parous rates of forest flies (Liberia) would peak at 298C and of savannah flies (Ghana) at 308C. Small temperature increases (less than 28C) might lead to changes in geographical distributions of different vector taxa. When the new model was linked to an existing framework for the population dynamics of onchocerciasis in humans and vectors, transmission rates and worm loads were projected to increase with temperature to at least 338C. By contrast, analyses of field data on forest flies in Liberia and savannah flies in Ghana, in relation to regional climate change predictions, suggested, on the basis of simple regressions, that 13–41% decreases in fly numbers would be expected between the present and before 2040. Further research is needed to reconcile these conflicting conclusions

The Scottish Early Rheumatoid Arthritis (SERA) Study:an inception cohort and biobank

Background: The Scottish Early Rheumatoid Arthritis (SERA) study is an inception cohort of rheumatoid (RA) and undifferentiated arthritis (UA) patients that aims to provide a contemporary description of phenotype and outcome and facilitate discovery of phenotypic and prognostic biomarkers Methods: Demographic and clinical outcome data are collected from newly diagnosed RA/UA patients every 6 months from around Scotland. Health service utilization data is acquired from Information Services Division, NHS National Services Scotland. Plain radiographs of hands and feet are collected at baseline and 12 months. Additional samples of whole blood, plasma, serum and filtered urine are collected at baseline, 6 and 12 months Results: Results are available for 1073 patients; at baseline, 76 % were classified as RA and 24 % as UA. Median time from onset to first review was 163 days (IQR97-323). Methotrexate was first-line DMARD for 75 % patients. Disease activity, functional ability and health-related quality of life improved significantly between baseline and 24 months, however the proportion in any employment fell (51 to 38 %, p = 0.0005). 24 % patients reported symptoms of anxiety and/or depression at baseline. 35/391 (9 %) patients exhibited rapid radiographic progression after 12 months. The SERA Biobank has accrued 60,612 samples Conclusions: In routine care, newly diagnosed RA/UA patients experience significant improvements in disease activity, functional ability and health-related quality of life but have high rates of psychiatric symptoms and declining employment rates. The co-existence of a multi-domain description of phenotype and a comprehensive biobank will facilitate multi-platform translational research to identify predictive markers of phenotype and prognosis

GOALS-JWST: Unveiling Dusty Compact Sources in the Merging Galaxy IIZw096

We have used the Mid-InfraRed Instrument (MIRI) on the James Webb Space Telescope (JWST) to obtain the first spatially resolved, mid-infrared images of IIZw096, a merging luminous infrared galaxy (LIRG) at z = 0.036. Previous observations with the Spitzer Space Telescope suggested that the vast majority of the total IR luminosity (L IR) of the system originated from a small region outside of the two merging nuclei. New observations with JWST/MIRI now allow an accurate measurement of the location and luminosity density of the source that is responsible for the bulk of the IR emission. We estimate that 40%-70% of the IR bolometric luminosity, or 3-5 7 1011 L ⊙, arises from a source no larger than 175 pc in radius, suggesting a luminosity density of at least 3-5 7 1012 L ⊙ kpc−2. In addition, we detect 11 other star-forming sources, five of which were previously unknown. The MIRI F1500W/F560W colors of most of these sources, including the source responsible for the bulk of the far-IR emission, are much redder than the nuclei of local LIRGs. These observations reveal the power of JWST to disentangle the complex regions at the hearts of merging, dusty galaxies

GOALS-JWST: Mid-infrared Spectroscopy of the Nucleus of NGC 7469

We present mid-infrared spectroscopic observations of the nucleus of the nearby Seyfert galaxy NGC 7469 taken with the MIRI instrument on the James Webb Space Telescope (JWST) as part of Directors Discretionary Time Early Release Science program 1328. The high-resolution nuclear spectrum contains 19 emission lines covering a wide range of ionization. The high-ionization lines show broad, blueshifted emission reaching velocities up to 1700 km s−1 and FWHM ranging from ∼500 to 1100 km s−1. The width of the broad emission and the broad-to-narrow line flux ratios correlate with ionization potential. The results suggest a decelerating, stratified, AGN-driven outflow emerging from the nucleus. The estimated mass outflow rate is 1-2 orders of magnitude larger than the current black hole accretion rate needed to power the AGN. Eight pure rotational H2 emission lines are detected with intrinsic widths ranging from FWHM ∼125 to 330 km s−1. We estimate a total mass of warm H2 gas of ∼1.2 7 107 M ⊙ in the central 100 pc. The PAH features are extremely weak in the nuclear spectrum, but a 6.2 μm PAH feature with an equivalent width of ∼0.07 μm and a flux of 2.7 7 10−17 W m−2 is detected. The spectrum is steeply rising in the mid-infrared, with a silicate strength of ∼0.02, significantly smaller than seen in most PG QSOs but comparable to other Seyfert 1s. These early MIRI mid-infrared IFU data highlight the power of JWST to probe the multiphase interstellar media surrounding actively accreting supermassive black holes

GOALS-JWST: NIRCam and MIRI Imaging of the Circumnuclear Starburst Ring in NGC 7469

We present James Webb Space Telescope (JWST) imaging of NGC 7469 with the Near-Infrared Camera and the Mid-InfraRed Instrument. NGC 7469 is a nearby, z = 0.01627, luminous infrared galaxy that hosts both a Seyfert Type-1.5 nucleus and a circumnuclear starburst ring with a radius of ∼0.5 kpc. The new near-infrared (NIR) JWST imaging reveals 66 star-forming regions, 37 of which were not detected by Hubble Space Telescope (HST) observations. Twenty-eight of the 37 sources have very red NIR colors that indicate obscurations up to A v ∼ 7 and a contribution of at least 25% from hot dust emission to the 4.4 μm band. Their NIR colors are also consistent with young (<5 Myr) stellar populations and more than half of them are coincident with the mid-infrared (MIR) emission peaks. These younger, dusty star-forming regions account for ∼6% and ∼17% of the total 1.5 and 4.4 μm luminosity of the starburst ring, respectively. Thanks to JWST, we find a significant number of young dusty sources that were previously unseen due to dust extinction. The newly identified 28 young sources are a significant increase compared to the number of HST-detected young sources (4-5). This makes the total percentage of the young population rise from ∼15% to 48%. These results illustrate the effectiveness of JWST in identifying and characterizing previously hidden star formation in the densest star-forming environments around active galactic nuclei (AGN)