Holistic monitoring of freshwater and terrestrial vertebrates by camera trapping and environmental DNA

The anthropogenic impact on the world's ecosystems is severe and the need for non-invasive, cost-effective tools for monitoring and understanding those impacts are therefore urgent. Here, we combine two such methods in a comprehensive multi-year study; camera trapping (CT) and analysis of environmental DNA (eDNA), in river marginal zones of a temperate, wetland Nature Park in Denmark. CT was performed from 2015 to 2019 for a total of 8778 camera trap days and yielded 24,376 animal observations. The CT observations covered 87 taxa, of which 78 were identified to species level, and 73 were wild native species. For eDNA metabarcoding, a total of 114 freshwater samples were collected from eight sites in all four seasons from 2017 to 2018. The eDNA results yielded a total detection of 80 taxa, of which 74 were identified to species level, and 65 were wild native species. While the number of taxa detected with the two methods were comparable, the species overlap was only 20%. In combination, CT and eDNA monitoring thus yielded a total of 115 wild species (20 fishes, 4 amphibians, one snake, 23 mammals, and 67 birds), representing half of the species found via conventional surveys over the last ca. 20 years (83% of fishes, 68% of mammals, 67% of amphibians, 41% of birds, and 20% of reptiles). Our study demonstrates that a holistic approach combining two non-invasive methods, CT, and eDNA metabarcoding, has great potential as a cost-effective biomonitoring tool for vertebrates

Genomewide association study of acute anterior uveitis identifies new susceptibility loci

Acknowledgments The authors thank all participating subjects with AS and healthy individuals who provided the DNA and clinical information necessary for this study. We would like to acknowledge the contributions of Anna Deminger, Sahlgrenska Academy at University of Gothenburg, and Urban Hellman, Umeå University, for their assistance in case recruitment and assessment and handling biological samples Funding Information: The survey was conducted by NatCen and the genomewide scan data were analyzed and deposited by the Wellcome Trust Sanger Institute. Information on how to access the data can be found on the Understanding Society website https: www. understandingsociety.ac.uk/ . We acknowledge and thank the TCRA AS Group for their support in recruiting patients for the study. M.A.B. is funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship, and support for this study was received from a National Health and Medical Research Council (Australia) program Grant (566938) and project Grant (569829), and from the Australian Cancer Research Foundation and Rebecca Cooper Medical Research Foundation. We are also very grateful for the invaluable support received from the National Ankylosing Spondylitis Society (UK) and Spondyloarthritis Association of America in case recruitment. Additional financial and technical support for patient recruitment was provided by the National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit and NIHR Thames Valley Comprehensive Local Research and an unrestricted educational grant from Abbott Laboratories. The authors acknowledge the sharing of data and samples by the BSRBR-AS Register in Aberdeen. Chief Investigator, Prof Gary Macfarlane and Dr Gareth Jones, Deputy Chief Investigator, created the BSRBR-AS study, which was commissioned by the British Society for Rheumatology, funded in part by Abbvie, Pfizer, and UCB. We are grateful to every patient, past and present staff of the BSRBR-AS register team, and to all clinical staff who recruited patients, followed them up and entered data – details here: https://www.abdn.ac.uk/iahs/research/ epidemiology/spondyloarthritis.php#panel1011. Funding was also received from the Swedish Research Council and The Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement. The Irish data was derived from participants in ASRI – The Ankylosing Spondylitis Registry of Ireland, which is funded by unrestricted grants from Abbvie and Pfizer. Funding bodies involved played no role in the study design, performance, or preparation of this manuscript. Funding Information: X.F.H. was funded by the National Natural Science Foundation of China (31771390). The TASC study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants P01-052915, R01-AR046208. Funding was also received from the University of Texas Health Science Center at Houston CTSA grant UL1RR02418, Cedars-Sinai GCRC grant MO1-RR00425, Intramural Research Program, NIAMS/NIH, and Rebecca Cooper Foundation (Australia). This study was funded, in part, by Arthritis Research UK (Grants 19536 and 18797), by the Wellcome Trust (Grant number 076113), and by the Oxford Comprehensive Biomedical Research Centre ankylosing spondylitis chronic disease cohort (Theme Code: A91202). The New Zealand data was derived from participants in the Spondyloarthritis Genetics and the Environment Study (SAGE) and was funded by The Health Research Council, New Zealand. H.X. was funded by the National Natural Science Foundation of China Grant 81020108029 and 30872339. French sample collection was performed by the Groupe Française d’Etude Génétique des Spondylarthrites, coordinated by Professor Maxime Breban, and funded by the Agence Nationale de Recherche GEMISA grant reference ANR-10-MIDI-0002. We acknowledge the Understanding Society: The UK Household Longitudinal Study. This is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council. Publisher Copyright: © 2020 Association for Research in Vision and Ophthalmology Inc.. All rights reserved.Peer reviewedPublisher PD

The variation in free 25-hydroxy vitamin D and vitamin D-binding protein with season and vitamin D status

Purpose: Serum 25-hydroxy vitamin D [25(OH)D] varies greatly with season at northern latitudes. The purpose of this study was to determine if the seasonal variations in serum total 25(OH)D are followed by a concomitant variation in free 25(OH)D or if the variation is damped by alterations in the binding capacity of DBP. Methods: Serum was collected from 540 healthy blood donors (60% men; mean age 41 ± 13 years) during 12 months and analyzed for total 25(OH)D, directly measured free 25(OH)D, vitamin D-binding protein (DBP) and albumin. Calculated free 25(OH)D was estimated. Results: The UV-B radiation during the sampling month was positively correlated with the serum levels of total 25(OH)D (r = 0.355, P < 0.001), directly measured free (r = 0.336, P < 0.001) and calculated free 25(OH)D (r = 0.275, P < 0.001), but not with DBP and albumin. The percentage of free 25(OH)D was higher during the winter months than that during the summer months (0.020 ± 0.005% vs 0.019 ± 0.004%; P = 0.007) and higher in participants with a serum 25(OH)D below 25 nmol/L than that in participants with a serum 25(OH)D above 75 nmol/L (0.031 ± 0.007% vs 0.017 ± 0.003%; P < 0.001). iPTH was correlated with directly measured free 25(OH)D (r = −0.226; P < 0.001), but only weakly with calculated free 25(OH)D (r = −0.095; P = 0.027). Conclusions: Directly measured free serum 25(OH)D was highly correlated with total serum 25(OH)D and followed the same seasonal variation, whereas the serum concentrations of DBP and albumin were stable. The fluctuation in free 25(OH)D was only marginally damped with an increase in the percentage of free 25(OH)D during the winter months and in participants with vitamin D deficiency

Clinical study on osteoporosis in ankylosing spondylitis

ABSTRACT Ankylosing spondylitis (AS) is a disease characterized by chronic inflammation and osteoproliferation in the spine, leading to bony fusion (ankylosis) of the sacroiliacal joints, the growth of bony spurs (syndesmophytes) between the vertebras and impairment of back-mobility. Paradoxically AS patients also have an increased risk of osteoporosis and vertebral fractures. In this cross-sectional study on 210 included AS patients (New York criteria) from West Sweden we found that osteoporosis and vertebral fractures were common but often not diagnosed or treated. Osteoporosis (WHO definition) was found in 21 % and osteopenia in 44 % of patients 50 years or older and bone mineral density (BMD) below expected range for age was found in 5% of patients younger than 50 years. Totally 42 vertebral fractures were diagnosed in 24 patients (12%). Osteoporosis was associated with old age, long disease duration, advanced chronic AS related changes in the spine, impairment of back- mobility, history of coxitis, glucocorticoid use, elevated inflammatory parameters, low BMI and menopause. Vertebral fractures were associated with old age, long disease duration, advanced chronic AS related changes in the spine, impairment of back-mobility, poor self-estimated general health, smoking, menopause and low BMD. The osteoproliferation in AS can cause artifactual increase of lumbar BMD when measured in anteroposterior (AP) projection with dual-energy x-ray absorptiometry (DXA). Lumbar BMD can also be measured in the vertebral bodies using lateral projection. Comparing lateral with AP DXA we found that lateral lumbar DXA was more sensitive in detecting low BMD, less affected by the osteoproliferation in AS and more closely associated with vertebral fractures. Combining AP and lateral lumbar DXA also allows for the estimation of volumetric BMD (vBMD). There is a lack of biomarkers for osteoproliferation and osteoporosis in AS. We analysed serum levels of the following biomarkers for bone metabolism in relation to disease activity, back mobility, osteoproliferation and BMD: Wingless proteins (Wnt-3a, Wnt-5a), Dickkopf-1 (Dkk-1), sclerostin, soluble receptor activator for nuclear factor-κΒ ligand (sRANKL) and osteoprotegerin (OPG). We found that the AS patients in comparison with healthy controls had significantly higher serum levels of Wnt-3a, but lower serum levels of sclerostin and sRANKL. Elevated serum levels of Wnt-3a were associated with osteoproliferation and impairment of back-mobility, independent of age, suggesting that Wnt-3a could be a marker for the osteoproliferative process. High CRP was associated with lower levels of the Wnt inhibitors Dkk-1 and sclerostin. BMD of femoral neck was negatively correlated with Wnt3a and OPG and positively correlated with sRANKL in the univariate analyses, but positively associated with sclerostin after adjusting for age in multiple regression. Osteoproliferation and impairment of back mobility and function were in addition associated with smoking. To study peripheral bone microarchitecture in relation to osteoproliferation, fractures and vBMD of the spine 69 male AS patients were randomized to undergo assessment with High Resolution peripheral Quantitative Computed Tomography (HRpQCT) of the ultra-distal radius and tibia and QCT of the lumbar spine. We found strong correlations between trabecular vBMD in lumbar spine and radius and tibia, indicating coupling of trabecular bone loss in axial and peripheral skeleton. Low lumbar vBMD, vertebral fractures and osteoproliferation were in addition associated with deterioration of the bone microarchitecture of the peripheral skeleton. In lumbar spine decreasing trabecular vBMD was associated with increasing cortical vBMD, suggesting that cortical bone is appositioned as part of the osteoproliferative process meanwhile trabecular bone is lost in the vertebral bodies. AS is closely related to inflammatory bowel disease (IBD) and subclinical intestinal inflammation has been detected in many AS patients. We measured fecal calprotectin, a marker for neutrophil inflammation, to indirectly study the prevalence of gut inflammation in AS. We found elevated levels of fecal calprotectin in 68% of the AS patients, without association with gastrointestinal symptoms. Fecal calprotectin was higher in users of non-steroidal anti-inflammatory drugs (NSAIDs) in a dose dependent manner, but lower in patients treated with methotrexate or TNFα-blockers. No association was found between fecal calprotectin and BMD. ISBN: 978-91-628-8618-

Short-term glucocorticoids reduce risk of chronic NSAID and analgesic use in early methotrexate-treated rheumatoid arthritis patients with favourable prognosis: subanalysis of the CareRA randomised controlled trial

Objective To explore non-steroidal anti-inflammatory drug (NSAID) and analgesic use in early rheumatoid arthritis (eRA) patients with a favourable risk profile initiating methotrexate (MTX) with or without glucocorticoid (GC) bridging.Methods Patients with eRA (≤1 year) and favourable risk profile (no erosions, negative rheumatoid factor and anticitrullinated protein antibodiesor low disease activity) in the 2-year CareRA trial were randomised to MTX 15 mg with a step-down GC scheme (COBRA Slim), or MTX without oral GCs, Tight-Step-Up (TSU). Used analgesics were recorded, including frequency, start/end date and indication. Chronic intake (≥90 consecutive days in trial) of NSAIDs, acetaminophen, opioids including tramadol and antidepressants for the indication of musculoskeletal (MSK) pain was considered. Treatments were compared using χ2 and analysis of variance with Holm’s correction for multiple testing.Results In total, 43 patients were randomised to COBRA Slim and 47 to TSU. At study inclusion, 33/43 (77%) of patients in the COBRA Slim and 32/47 (68%) in the TSU arm had been using analgesics (p=0.5). During the trial, 67 NSAID and analgesics were used for MSK pain in 26/43 (60%) COBRA Slim patients of which 9/43 (21%) daily chronically (DC), while 107 NSAID and analgesics were used in 43/47 (92%) TSU patients, of which 25/47 (53%) DC. The total number of patients on NSAID and analgesics at any time during the study (p&lt;0.01) and chronically (p=0.01) was significantly different between treatment arms. Number of patients on DC NSAIDs was also significantly different (p&lt;0.01) between COBRA Slim 6/43 (14%) and TSU 19/47 (40%).Conclusion In eRA patients considered to have a favourable prognosis, initial oral GC bridging resulted in lower chronic NSAID and analgesic use.Trial registration number NCT01172639

Cardiovascular risk factors in gout, psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis: a cross-sectional survey of patients in Western Sweden

Objectives We aimed to compare traditional (trad) cardiovascular risk factors (CVRFs) among patients with gout, psoriatic arthritis (PsA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) stratified by sex.Methods A survey was sent to patients with gout (n=1589), PsA (n=1200), RA (n=1246) and AS (n=1095). Patients were retrieved from Sahlgrenska University Hospital, the hospitals of Uddevalla and Skövde, and 12 primary care centres in Western Sweden. The prevalence of self-reported trad-CVRFs was compared between diagnoses by age standardisation with the 2018 population of Sweden as the standard population.Results In total, 2896 (56.5%) of 5130 patients responded. Hypertension was the most frequently found comorbidity, reported by 65% of patients with gout, 41% with PsA, 43% with RA and 29% with AS. After age standardisation, women and men with gout had significantly more obesity (body mass index ≥30 kg/m2), hypertension, diabetes, hyperlipidaemia and multiple trad-CVRFs, compared with those with PsA, RA and AS. Obesity was significantly more common in PsA than in RA. In women, obesity, hypertension and multiple trad-CVRFs were more frequently reported in PsA than in RA and AS, whereas similar prevalence of CVRFs and coexistence of multiple trad-CVRFs were found in men with PsA, RA and AS.Conclusions Women and men with gout had the highest prevalence of trad-CVRFs. Differences in occurrence of CVRFs by sex were found in patients with PsA, RA and AS. In women, patients with PsA had higher occurrence of trad-CVRFs than those with RA and AS, whereas in men the distribution of CVRFs was similar in PsA, RA and AS

Physical function and sex differences in radiographic axial spondyloarthritis : a cross-sectional analysis on Bath Ankylosing Spondylitis Functional Index

Background: Physical function is an important determinant of health-related quality of life in radiographic axial spondyloarthritis patients (r-axSpA). To improve the basis of effective healthcare efforts, we aimed to investigate which demographic and disease-related factors that influence Bath Ankylosing Spondylitis Functional Index (BASFI) in r-axSpA patients overall and stratified by sex. Furthermore, we sought to explore differences between sexes regarding separate BASFI questions and also to explore which factors that may contribute to these differences. Methods: This observational cross-sectional study included patients fulfilling the modified New York criteria for Ankylosing Spondylitis. Patients were assessed with 66/68 joint count and Bath Ankylosing Spondylitis Metrology Index (BASMI) measurements. Lateral X-rays were performed for Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP), and BASFI were registered. Multivariable linear regression analyses were used to investigate which factors that associate with BASFI. Results: A total of 353 r-axSpA patients were included, mean age 52.2 ± 12.7 years, 62.3% males. No significant sex difference was seen in BASFI scores (2.7 ± 2.0 in males vs 2.9 ± 2.1 in females). Age, body mass index, ASDAS-CRP, BASMI or mSASSS, fatigue, and tenderness were found to associate independently with BASFI in different models (R 2 0.53–0.63). Investigation of separate BASFI questions revealed that the ability to look over shoulder was worse in males than females (mean 4.43 ± 3.37 vs 3.74 ± 3.06, p = 0.05) and most strongly correlated with mSASSS and BASMI among separate BASFI questions (r = 0.53, p &lt; 0.001; r = 0.62, p &lt; 0.001). The ability to climb stairs was worse in females than males (mean 2.49 ± 2.77 vs 1.54 ± 2.32, p &lt; 0.001). Conclusions: No difference between male and female r-axSpA patients was seen in BASFI despite significant sex differences in BASMI, mSASSS, and CRP levels. Our results underline the impact of fatigue and tenderness on BASFI. The ability to climb stairs without a handrail was scored worse among females compared to males. Furthermore, the ability to look over the shoulder was worse in males than females and closely related to spinal mobility and structural spinal changes

A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis

Background: Knowledge about predictors of new spinal bone formation in patients with ankylosing spondylitis (AS) is limited. AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. Our objectives were to study spinal radiographic progression in patients with AS and investigate predictors of progression overall and by sex. Methods: Swedish patients with AS, age (mean +/- SD) 50 +/- 13 years, were included in a longitudinal study. At baseline and at 5-year follow up, spinal radiographs were graded according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Predictors were assessed by questionnaires, spinal mobility tests and blood samples. Results: Of 204 patients included, 166 (81%) were re-examined and 54% were men. Men had significantly higher mean mSASSS at baseline and higher mean increase in mSASSS than women (1.9 +/- 2.8 vs. 1.2 +/- 3.3; p = 0.005) More men than women developed new syndesmophytes (30% vs. 12%; p = 0.007). Multivariate logistic regression analyses with progression &gt;= 2 mSASSS units over 5 years or development of new syndesmophytes as the dependent variable showed that presence of baseline AS-related spinal radiographic alterations and obesity (OR 3.78, 95% CI 1.3 to 11.2) were independent predictors of spinal radiographic progression in both sexes. High C-reactive protein (CRP) was a significant predictor in men, with only a trend seen in women. Smoking predicted progression in men whereas high Bath Ankylosing Spondylitis Metrology Index (BASMI) and exposure to bisphosphonates during follow up (OR 4.78, 95% CI 1.1 to 20.1) predicted progression in women. Conclusion: This first report on sex-specific predictors of spinal radiographic progression shows that predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men