The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology

BACKGROUND: In 2001, the European League Against Rheumatism developed and disseminated the first guidelines for musculoskeletal (MS) ultrasound (US) in rheumatology. Fifteen years later, the dramatic expansion of new data on MSUS in the literature coupled with technological developments in US imaging has necessitated an update of these guidelines.OBJECTIVES: To update the existing MSUS guidelines in rheumatology as well as to extend their scope to other anatomic structures relevant for rheumatology.METHODS: The project consisted of the following steps: (1) a systematic literature review of MSUS evaluable structures; (2) a Delphi survey among rheumatologist and radiologist experts in MSUS to select MS and non-MS anatomic structures evaluable by US that are relevant to rheumatology, to select abnormalities evaluable by US and to prioritise these pathologies for rheumatology and (3) a nominal group technique to achieve consensus on the US scanning procedures and to produce an electronic illustrated manual (ie, App of these procedures).RESULTS: Structures from nine MS and non-MS areas (ie, shoulder, elbow, wrist and hand, hip, knee, ankle and foot, peripheral nerves, salivary glands and vessels) were selected for MSUS in rheumatic and musculoskeletal diseases (RMD) and their detailed scanning procedures (ie, patient position, probe placement, scanning method and bony/other landmarks) were used to produce the App. In addition, US evaluable abnormalities present in RMD for each anatomic structure and their relevance for rheumatology were agreed on by the MSUS experts.CONCLUSIONS: This task force has produced a consensus-based comprehensive and practical framework on standardised procedures for MSUS imaging in rheumatology

Transcriptome Alteration in the Diabetic Heart by Rosiglitazone: Implications for Cardiovascular Mortality

BACKGROUND: Recently, the type 2 diabetes medication, rosiglitazone, has come under scrutiny for possibly increasing the risk of cardiac disease and death. To investigate the effects of rosiglitazone on the diabetic heart, we performed cardiac transcriptional profiling and imaging studies of a murine model of type 2 diabetes, the C57BL/KLS-lepr(db)/lepr(db) (db/db) mouse. METHODS AND FINDINGS: We compared cardiac gene expression profiles from three groups: untreated db/db mice, db/db mice after rosiglitazone treatment, and non-diabetic db/+ mice. Prior to sacrifice, we also performed cardiac magnetic resonance (CMR) and echocardiography. As expected, overall the db/db gene expression signature was markedly different from control, but to our surprise was not significantly reversed with rosiglitazone. In particular, we have uncovered a number of rosiglitazone modulated genes and pathways that may play a role in the pathophysiology of the increase in cardiac mortality as seen in several recent meta-analyses. Specifically, the cumulative upregulation of (1) a matrix metalloproteinase gene that has previously been implicated in plaque rupture, (2) potassium channel genes involved in membrane potential maintenance and action potential generation, and (3) sphingolipid and ceramide metabolism-related genes, together give cause for concern over rosiglitazone's safety. Lastly, in vivo imaging studies revealed minimal differences between rosiglitazone-treated and untreated db/db mouse hearts, indicating that rosiglitazone's effects on gene expression in the heart do not immediately turn into detectable gross functional changes. CONCLUSIONS: This study maps the genomic expression patterns in the hearts of the db/db murine model of diabetes and illustrates the impact of rosiglitazone on these patterns. The db/db gene expression signature was markedly different from control, and was not reversed with rosiglitazone. A smaller number of unique and interesting changes in gene expression were noted with rosiglitazone treatment. Further study of these genes and molecular pathways will provide important insights into the cardiac decompensation associated with both diabetes and rosiglitazone treatment

Disposable sensors in diagnostics, food and environmental monitoring

Disposable sensors are low‐cost and easy‐to‐use sensing devices intended for short‐term or rapid single‐point measurements. The growing demand for fast, accessible, and reliable information in a vastly connected world makes disposable sensors increasingly important. The areas of application for such devices are numerous, ranging from pharmaceutical, agricultural, environmental, forensic, and food sciences to wearables and clinical diagnostics, especially in resource‐limited settings. The capabilities of disposable sensors can extend beyond measuring traditional physical quantities (for example, temperature or pressure); they can provide critical chemical and biological information (chemo‐ and biosensors) that can be digitized and made available to users and centralized/decentralized facilities for data storage, remotely. These features could pave the way for new classes of low‐cost systems for health, food, and environmental monitoring that can democratize sensing across the globe. Here, a brief insight into the materials and basics of sensors (methods of transduction, molecular recognition, and amplification) is provided followed by a comprehensive and critical overview of the disposable sensors currently used for medical diagnostics, food, and environmental analysis. Finally, views on how the field of disposable sensing devices will continue its evolution are discussed, including the future trends, challenges, and opportunities

Oriented degradation of the genome of cyanophage AN-23 after exposure to NaCl.

The low tolerance of cyanophage AN-23 to NaCl at more than 0·05 M has been investigated. When isolated from clarified lysates that had been exposed to NaCl in the presence of added DNAse I, the phage genomic DNA consisted of a series of discrete fragments. The fragments were recovered from low melting temperature agarose electrophoresis gels and used for restriction analysis. Comparison of the restriction cleavage products with a restriction map of the 46 kbp AN-23 genome has shown that the fragments are generated by removal of DNA from one end of the linear genome in steps of about 3 kbp. The data are consistent with a model in which NaCl triggers the ejection of the phage genome from the capsid

Inter & Intra-Observer Reliability Of Grading Ultrasound Videoclips With Hand Pathology In Rheumatoid Arthritis By Using Non- Sophisticated Internet Tools (LUMINA Study)

Aim: To evaluate the inter- and intraobserver agreement of a group of European rheumatologist ultrasonographers in grading musculoskeletal ultrasound videoclips posted on the Internet by using a non-sophisticated electronic environment. Methods: Forty short movie clips (less than 30 secs) were made available over the Internet to all participants. Normal and pathological RA hand joints and tendons were included in the movie clips. In the first phase 30 investigators from European countries were invited to evaluate the clips and to interpret/grade them. No instruction session was held prior to the initiation of the study. For synovitis the requested scoring system included 0 to3 grades and for tenosynovitis a binary variable 0/1; separate evaluations were performed for gray scale (GS) and Power Doppler (PD) examinations. In the second phase the responders were asked to grade the same clips in a different order without having access to their first grading scale. Light's k and Cohen's k were used to analyse inter- and intraobserver reliability. Results: Twenty two European rheumatologists agreed to finalise both study phases. Mean Cohen's. for intraobserver reliability was 0.614/0.689 for tenosynovitis GS/PD and 0.523/0.621 for synovitis GS/PD. Light's k for interobserver reliability was 0.503 for tenosynovitis evaluation and 0.455 for global (synovitis and tenosynovitis) evaluation. Mean global overall agreement was 84.95% (90.2% for global synovitis). Conclusions: An over-the-net US evaluation and grading has shown moderate to good reliability. The results could be improved if a training session is added at the beginning of the study

ANXUR receptor-like kinases coordinate cell wall integrity with growth at the pollen tube tip via NADPH oxidases

It has become increasingly apparent that the extracellular matrix (ECM), which in plants corresponds to the cell wall, can influence intracellular activities in ways that go far beyond their supposedly passive mechanical support. In plants, growing cells use mechanisms sensing cell wall integrity to coordinate cell wall performance with the internal growth machinery to avoid growth cessation or loss of integrity. How this coordination precisely works is unknown. Previously, we reported that in the tip-growing pollen tube the ANXUR receptor-like kinases (RLKs) of the CrRLK1L subfamily are essential to sustain growth without loss of cell wall integrity in Arabidopsis. Here, we show that over-expression of the ANXUR RLKs inhibits growth by over-activating exocytosis and the over-accumulation of secreted cell wall material. Moreover, the characterization of mutations in two partially redundant pollen-expressed NADPH oxidases coupled with genetic interaction studies demonstrate that the ANXUR RLKs function upstream of these NADPH oxidases. Using the H₂O₂-sensitive HyPer and the Ca²⁺-sensitive YC3.60 sensors in NADPH oxidase-deficient mutants, we reveal that NADPH oxidases generate tip-localized, pulsating H₂O₂ production that functions, possibly through Ca²⁺ channel activation, to maintain a steady tip-focused Ca²⁺ gradient during growth. Our findings support a model where ECM-sensing receptors regulate reactive oxygen species production, Ca²⁺ homeostasis, and exocytosis to coordinate ECM-performance with the internal growth machinery

Predictors of mortality in solid-organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: the impact of cytomegalovirus disease and lymphopenia

Treatment of carbapenemase-producing Enterobacterales bloodstream infections (CPE-BSI) in solid-organ transplant recipients (SOT) is challenging. The objective of this study was to develop a specific score to predict mortality in SOT recipients with CPE-BSI. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% CI 0.76-0.88) and classified patients into three strata: 0-7 (low mortality), 8-11 (high mortality) and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy versus combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted HR 2.82, 95% CI 1.13-7.06, P=0.03) and high (HR 9.93, 95% CI 2.08-47.40, P=0.004) mortality risk strata. A score-based algorithm is provided for therapy guidance