Structural damage in rheumatoid arthritis assessed by musculoskeletal ultrasound: A systematic literature review by the Structural Joint Damage Task Force of the OMERACT Ultrasound Working Group

Objectives: To identify and synthesize the evidence for the use and measurement properties of musculoskeletal ultrasound in assessing structural joint damage in patients with rheumatoid arthritis (RA).Methods: A systematic literature search (SLR) of the PubMed, Embase and Cochrane Library was performed. Original articles were included published in English reporting on ultrasound of bone erosion, cartilage damage and the measurement properties of ultrasound according to the OMERACT filter 2.1.Results: Of the 1.495 identified articles 149 were included in the final review, most of which reported on cross-sectional studies and used the OMERACT definitions for ultrasonographic pathology. Among these, bone erosions were assessed in 139 (93.3%), cartilage damage in 24 (16.1%), enthesophytes in 8 (5.4%), osteophytes in 15 (10.1%) and malalignment and ankylosis in a single (0.9%) study, respectively. Most studies (126/149, 84.6%) assessed the joints of the hands. The overwhelming majority of studies (127/149, 85.2%) assessed structural joint damage bilaterally. Validity, reliability and responsiveness were assessed in 21 (14.1%), 34 (22.8%) and 17 (11.4%) studies, respectively.Conclusion: While the results of this SLR suggest that ultrasound is a sensitive, reliable and feasible tool to detect damage in RA, they also highlight the need for further research and validation. Findings of this SLR will inform the next steps of the OMERACT Ultrasound Working Group in developing an ultrasound score for assessing structural joint damage in patients with RA.(c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/

Regular Consumption of a Flavanol-rich Chocolate can Improve Oxidant Stress in Young Soccer Players

The consumption of a diet rich in certain flavonoids, including the flavanol sub-class, has been associated with a reduced risk for vascular disease. We evaluated the effects of the regular consumption (14 d) of a flavanol-containing milk chocolate (FCMC) or cocoa butter chocolate (CBC) on variables related to vascular disease risk, oxidative stress and physical activity. Twenty-eight free-living, young (18–20 years old) male soccer players consumed daily 105 g of FCMC (168 mg of flavanols) or CBC (<5 mg of flavanols), as part of their normal diet. The consumption of FCMC was significantly associated with a decrease in diastolic blood pressure (-5 mm Hg), mean blood pressure (-5 mm Hg), plasma cholesterol (-11%), LDL-cholesterol (-15%), malondialdehyde (-12%), urate (-11%) and lactate dehydrogenase (LDH) activity (-11%), and an increase in vitamin E/cholesterol (+12%). No relevant changes in these variables were associated with CBC consumption. No changes in the plasma levels of (-)-epicatechin were observed following analysis of fasting blood samples. In conclusion, FCMC consumption was associated with changes in several variables often associated with cardiovascular health and oxidant stress. The presence of significant quantities of flavanols in FCMC is likely to have been one of the contributing factors to these results

Fermi Large Area Telescope Observations of the Cygnus Loop Supernova Remnant

We present an analysis of the gamma-ray measurements by the Large Area Telescope(LAT) onboard the \textit{Fermi Gamma-ray Space Telescope} in the region of the supernova remnant(SNR) Cygnus Loop(G74.0$-$8.5). We detect significant gamma-ray emission associated with the SNR in the energy band 0.2--100 GeV. The gamma-ray spectrum shows a break in the range 2--3 GeV. The gamma-ray luminosity is $\sim$ $1 \times 10^{33}$erg s$^{-1}$ between 1--100 GeV, much lower than those of other GeV-emitting SNRs. The morphology is best represented by a ring shape, with inner/outer radii 0$^\circ$.7 $\pm$ 0$^\circ$.1 and 1$^\circ$.6 $\pm$ 0$^\circ$.1. Given the association among X-ray rims, \halpha filaments and gamma-ray emission, we argue that gamma rays originate in interactions between particles accelerated in the SNR and interstellar gas or radiation fields adjacent to the shock regions. The decay of neutral pions produced in nucleon-nucleon interactions between accelerated hadrons and interstellar gas provides a reasonable explanation for the gamma-ray spectrum.Comment: accepted by ApJ, 34 pages, 6 figure

Very low prevalence of ultrasound detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study

Objectives: This study aimed to determine the prevalence of ultrasound detected tendon abnormalities in healthy subjects (HS) across the age range. / Methods: Adult HS (age 18 to 80 years) were recruited in 23 international Outcome Measures in Rheumatology (OMERACT) ultrasound centres and clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexor (DF) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of Rheumatoid Arthritis (RA) patients was taken from the Birmingham BEACON early arthritis inception cohort. / Results: 939 HS and 144 RA patients were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was statistically significant difference in the proportion of TSH and TPD involvement between HS and RA subjects (HS vs RA p<0.001). In HS there was no difference in the presence of ultrasound abnormalities between age groups. / Conclusions: Ultrasound detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease in newly presenting suspected RA

Historical changes in the stomatal limitation of photosynthesis: empirical support for an optimality principle

The ratio of leaf‐internal (ci) to ambient (ca) partial pressure of CO2, defined here as χ, is an index of adjustments in both leaf stomatal conductance and photosynthetic rate to environmental conditions. Measurements and proxies of this ratio can be used to constrain vegetation models uncertainties for predicting terrestrial carbon uptake and water use. We test a theory based on the least‐cost optimality hypothesis for modelling historical changes in χ over the 1951‐2014 period, across different tree species and environmental conditions, as reconstructed from stable carbon isotopic measurements across a global network of 103 absolutely‐dated tree‐ring chronologies. The theory predicts optimal χ as a function of air temperature, vapour pressure deficit, ca and atmospheric pressure. The theoretical model predicts 39% of the variance in χ values across sites and years, but underestimates the inter‐site variability in the reconstructed χ trends, resulting in only 8% of the variance in χ trends across years explained by the model. Overall, our results support theoretical predictions that variations in χ are tightly regulated by the four environmental drivers. They also suggest that explicitly accounting for the effects of plant‐available soil water and other site‐specific characteristics might improve the predictions

Negative regulation of syntaxin4/SNAP-23/VAMP2-mediated membrane fusion by Munc18c <i>In Vitro</i>

Background: Translocation of the facilitative glucose transporter GLUT4 from an intracellular store to the plasma membrane is responsible for the increased rate of glucose transport into fat and muscle cells in response to insulin. This represents a specialised form of regulated membrane trafficking. Intracellular membrane traffic is subject to multiple levels of regulation by conserved families of proteins in all eukaryotic cells. Notably, all intracellular fusion events require SNARE proteins and Sec1p/Munc18 family members. Fusion of GLUT4-containing vesicles with the plasma membrane of insulin-sensitive cells involves the SM protein Munc18c, and is regulated by the formation of syntaxin 4/SNAP23/VAMP2 SNARE complexes. Methodology/Principal Findings Here we have used biochemical approaches to characterise the interaction(s) of Munc18c with its cognate SNARE proteins and to examine the role of Munc18c in regulating liposome fusion catalysed by syntaxin 4/SNAP23/VAMP2 SNARE complex formation. We demonstrate that Munc18c makes contacts with both t- and v-SNARE proteins of this complex, and directly inhibits bilayer fusion mediated by the syntaxin 4/SNAP23/VAMP2 SNARE complex. Conclusion/Significance Our reductionist approach has enabled us to ascertain a direct inhibitory role for Munc18c in regulating membrane fusion mediated by syntaxin 4/SNAP23/VAMP2 SNARE complex formation. It is important to note that two different SM proteins have recently been shown to stimulate liposome fusion mediated by their cognate SNARE complexes. Given the structural similarities between SM proteins, it seems unlikely that different members of this family perform opposing regulatory functions. Hence, our findings indicate that Munc18c requires a further level of regulation in order to stimulate SNARE-mediated membrane fusion

A Qualitative Study of an Integrated Maternity, Drugs and Social Care Service for Drug-using Women

Background: The care of drug-using pregnant women is a growing health and social care concern in many countries. A specialist clinic was established offering multidisciplinary care and advice to pregnant drug users in and around Aberdeen (UK) in 1997. The majority of women stabilise and reduce their drug use. By determining the needs and views of the women more appropriate services and prevention strategies may be developed. There has been little research conducted in this area and none in Scotland. Methods: This is a qualitative study that aimed to gain an understanding of the experiences of women drug users, seeking and receiving prenatal care and drug services from a specialist clinic. Twelve women participated in semi-structured one-to-one interviews. Results: The women preferred the multidisciplinary clinic (one-stop shop) to traditional prenatal care centred within General Practice. The relationships of the clients to the range of Clinic professionals and in hospital were explored as well as attitudes to Clinic care. The study participants attributed success in reducing their drug use to the combination of different aspects of care of the multi-agency clinic, especially the high level prenatal support. It is this arrangement of all aspects of care together that seem to produce better outcomes for mother and child than single care elements delivered separately. Some women reported that their pregnancy encouraged them to rapidly detoxify due to the guilt experienced. The most important aspects of the Clinic care were found to be non-judgemental attitude of staff, consistent staff, high level of support, reliable information and multi-agency integrated care. Conclusion: There is an impetus for women drug users to change lifestyle during pregnancy. The study highlighted a need for women to have access to reliable information on the effects of drugs on the baby. Further research is required to determine whether positive outcomes related to clinic attendance in the prenatal period are sustained in the postnatal period. Early referral to a specialist clinic is of benefit to the women, as they reported to receive more appropriate care, especially in relation to their drug use. A greater awareness of needs of the pregnant drug user could help the design of more effective prevention strategies

Accuracy of synovial fluid analysis compared to histology for the identification of calcium pyrophosphate crystals: An ancillary study of the OMERACT US working group - CPPD subgroup

The aim of this study was to evaluate the accuracy of synovial fluid analysis in the identification of calcium pyrophosphate dihydrate crystals compared to microscopic analysis of joint tissues as the reference standard. This is an ancillary study of an international, multicentre cross-sectional study performed by the calcium pyrophosphate deposition disease (CPPD) subgroup of the OMERACT Ultrasound working group. Consecutive patients with knee osteoarthritis (OA) waiting for total knee replacement surgery were enrolled in the study from 2 participating centres in Mexico and Romania. During the surgical procedures, synovial fluid, menisci and hyaline cartilage were collected and analysed within 48 hours from surgery under transmitted light microscopy and compensated polarised light microscopy for the presence/absence of calcium pyrophosphate crystals. All slides were analysed by expert examiners on site, blinded to other findings. A dichotomic score (absence/presence) was used for scoring both synovial fluid and tissues. Microscopic analysis of knee tissues was considered the gold standard. Sensitivity, specificity, accuracy, positive and negative predictive values of synovial fluid analysis in the identification of calcium pyrophosphate crystals were calculated.15 patients (53% female, mean age 68 yo +/- 8.4) with OA of grade 3 or 4 according to Kellgren-Lawrence scoring were enrolled. 12 patients (80%) were positive for calcium pyrophosphate crystals at the synovial fluid analysis and 14 (93%) at the tissue microscopic analysis. The overall diagnostic accuracy of synovial fluid analysis compared with histology for CPPD was 87%, with a sensitivity of 86% and a specificity of 100%, the positive predictive value was 100% and the negative predictive value was 33%.In conclusion synovial fluid analysis proved to be an accurate test for the identification of calcium pyrophosphate dihydrate crystals in patients with advanced OA