Objective To produce consensus-based scoring systems for ultrasound (US) tenosynovitis and to assess the intraobserver and interobserver reliability of these scoring systems in rheumatoid arthritis ...(RA). Methods We undertook a Delphi process on US-defined tenosynovitis and US scoring system of tenosynovitis in RA among 35 rheumatologists, experts in musculoskeletal US (MSUS), from 16 countries. Then, we assessed the intraobserver and interobserver reliability of US in scoring tenosynovitis on B-mode and with a power Doppler (PD) technique. Ten patients with RA with symptoms in the hands or feet were recruited. Ten rheumatologists expert in MSUS blindly, independently and consecutively scored for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two finger flexor tendons and two ankle tendons of each patient in two rounds in a blinded fashion. Intraobserver reliability was assessed by Cohen's κ. Interobserver reliability was assessed by Light's κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. Results Four-grade semiquantitative scoring systems were agreed upon for scoring tenosynovitis in B-mode and for scoring pathological peritendinous Doppler signal within the synovial sheath. The intraobserver reliability for tenosynovitis scoring on B-mode and PD mode was good (κ value 0.72 for B-mode; κ value 0.78 for PD mode). Interobserver reliability assessment showed good κ values for PD tenosynovitis scoring (first round, 0.64; second round, 0.65) and moderate κ values for B-mode tenosynovitis scoring (first round, 0.47; second round, 0.45). Conclusions US appears to be a reproducible tool for evaluating and monitoring tenosynovitis in RA.
Objective The primary objective of this prospective case-control study was to assess the diagnostic value of several intra-articular and periarticular ultrasound (US)-detected abnormalities in the ...upper and lower limbs in gout. The secondary objective was to test the concurrent validity of US abnormalities using as gold standard the microscopic demonstration of monosodium urate (MSU) crystals. Methods Ninety-one men with gout and 42 age-matched controls were prospectively recruited. All patients with gout and controls underwent US assessment of several US abnormalities in 26 joints, six bursae, eight tendons, 20 tendon compartments, four ligaments, and 18 articular cartilages by experts in US blinded to the patients’ group. Patients with gout and controls with US abnormalities were asked to undergo US-guided aspiration for microscopic identification of MSU crystals. Interobserver and intraobserver reliability of the US assessment was evaluated in a web-based exercise. Results The assessment of one joint (ie, radiocarpal joint) for hyperechoic aggregates (HAGs), two tendons (ie, patellar tendon and triceps tendon) for HAGs and three articular cartilages (ie, first metatarsal, talar and second metacarpal/femoral) for double contour sign showed the best balance between sensitivity and specificity (84.6% and 83.3%, respectively). Intraobserver reliability was good (mean κ 0.75) and interobserver reliability was moderate (κ 0.52). The aspirated material from HAGs was positive for MSU crystals in 77.6% of patients with gout and negative in all controls. Conclusions Our results suggest that US bilateral assessment of one joint, three articular cartilages and two tendons may be valid for diagnosing gout with acceptable sensitivity and specificity.
The basal ganglia (BG) represent a critical center of the nervous system for sensorial discrimination. Although it is known that Huntington’s disease (HD) affects this brain area, it still remains ...unclear how HD patients achieve paradoxical improvement in sensorial discrimination tasks. This paper presents a computational model of the BG including the main nuclei and the typical firing properties of their neurons. The BG model has been embedded within an auditory signal detection task. We have emulated the effect that the altered levels of dopamine and the degree of HD affectation have in information processing at different layers of the BG, and how these aspects shape transient and steady states differently throughout the selection task. By extracting the independent components of the BG activity at different populations, it is evidenced that early and medium stages of HD affectation may enhance transient activity in the striatum and the substantia nigra pars reticulata. These results represent a possible explanation for the paradoxical improvement that HD patients present in discrimination task performance. Thus, this paper provides a novel understanding on how the fast dynamics of the BG network at different layers interact and enable transient states to emerge throughout the successive neuron populations.
The majority of operations carried out by the brain require learning complex signal patterns for future recognition, retrieval and reuse. Although learning is thought to depend on multiple forms of ...long-term synaptic plasticity, the way this latter contributes to pattern recognition is still poorly understood. Here, we have used a simple model of afferent excitatory neurons and interneurons with lateral inhibition, reproducing a network topology found in many brain areas from the cerebellum to cortical columns. When endowed with spike-timing dependent plasticity (STDP) at the excitatory input synapses and at the inhibitory interneuron-interneuron synapses, the interneurons rapidly learned complex input patterns. Interestingly, induction of plasticity required that the network be entrained into theta-frequency band oscillations, setting the internal phase-reference required to drive STDP. Inhibitory plasticity effectively distributed multiple patterns among available interneurons, thus allowing the simultaneous detection of multiple overlapping patterns. The addition of plasticity in intrinsic excitability made the system more robust allowing self-adjustment and rescaling in response to a broad range of input patterns. The combination of plasticity in lateral inhibitory connections and homeostatic mechanisms in the inhibitory interneurons optimized mutual information (MI) transfer. The storage of multiple complex patterns in plastic interneuron networks could be critical for the generation of sparse representations of information in excitatory neuron populations falling under their control.
This study aims to investigate ultrasound (US) findings on salivary glands (SG) in patients with Sjögren syndrome (SS) vs. other connective tissue diseases (CTDs) and to assess the relationship of ...SGUS abnormalities with autoantibody profile in both groups. We enrolled 81 patients, 45 diagnosed with SS (39 with primary SS, 6 with secondary SS) and 36 diagnosed with other CTDs. All patients underwent a prospective evaluation of sicca symptoms, a Schirmer’s test, and a B-mode US assessment of the parotid and submandibular glands, all blinded to the diagnosis. Each SG was semi-quantitatively scored 0–3; a grade ≥ 2 was considered pathological. SGUS involvement was classified as normal or pathological at the patient level and for each pair at the gland level. In addition, a total SGUS score of 0–12 and a parotid/submandibular score of 0–6 were calculated for each patient. Autoimmunity laboratory data were also obtained. All SGUS scores were higher in SS patients than in those with CTD (
p
< 0.001) and significantly more SS patients showed a pathological global (
p
< 0.001), parotid (
p
< 0.001), or submandibular (
p
= 0.001) US score compared with CTD patients. In SS patients, the presence of autoantibodies was significantly associated with pathological SGUS and higher scores, particularly at the parotid level, while in CTD patients, xerostomia and a pathological Schirmer’s test were associated with pathological US and higher scores at the submandibular level (
p
< 0.05). SGUS showed a different grade of abnormality, site involvement, and associated autoantibody profile in SS patients as compared with other CTD.
Key Points
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Patients with SS and other CTDs showed different grades of SGUS abnormality
.
•
Patients with SS and other CTDs showed different gland involvement and associated autoantibody profiles
.
•
Anti-Ro60 and anti-Ro52 Ro60 positivity were associated with the severity of parotid involvement in SS patients.
Immunotherapy has changed the paradigm of cancer treatments. In this way, several combinatorial strategies based on monoclonal antibodies (mAb) such as anti (a)-PD-1 or anti (a)-PD-L1 are often ...reported to yield promising clinical benefits. However, the pharmacokinetic (PK) behavior of these mAbs is a critical issue that requires selective analytical techniques. Indeed, few publications report data on a-PD1/a-PD-L1 exposure and its relationship with therapeutic or toxic effects. In this regard, preclinical assays allow the time profiles of antibody plasma concentrations to be characterized rapidly and easily, which may help to increase PK knowledge. In this study, we have developed and validated two in-house ELISAs to quantify a-PD-1 and a-PD-L1 in plasma collected from tumor-bearing mice. The linear range for the a-PD-1 assay was 2.5–125 ng/mL and 0.11–3.125 ng/mL for the a-PD-L1 assay, whereas the intra-and inter-day precision was lower than 20% for both analytes. The PK characterization revealed a significant decrease in drug exposure after administration of multiple doses. Plasma half-life for a-PD-1 was slightly shorter (22.3 h) than for a-PD-L1 (46.7 h). To our knowledge, this is the first reported preclinical ELISA for these immune checkpoint inhibitors, which is sufficiently robust to be used in different preclinical models. These methods can help to understand the PK behavior of these antibodies under different scenarios and the relationship with response, thus guiding the choice of optimal doses in clinical settings.
To propose a reduced joint power Doppler US (PDUS) assessment and provide preliminary evidence of its validity, feasibility, reliability and sensitivity to change compared with a comprehensive (i.e. ...44 joints) PDUS assessment in evaluating synovitis in JIA.
This multicentre study included 42 children with active JIA with ≥4 clinically involved joints requiring modified therapy. At each visit, clinical and PDUS assessments were performed blinded. Each joint was scored for greyscale (GS) synovitis and power Doppler signal according to a 4-point semiquantitative scale with calculation of US composite indices and US composite joint counts. A process of data reduction based on the frequency of US joint involvement was performed to obtain a reduced PDUS assessment. The relationship between the comprehensive and the reduced PDUS assessments was investigated by Spearman's coefficient at all visits, as well as the relationship between changes in the two PDUS assessments during follow-up. In addition, the metric properties of the comprehensive and the reduced PDUS assessments were tested.
The 10-joint PDUS assessment, including bilateral knee, ankle, wrist, elbow and the second MCP joints, detected 100% of children with GS synovitis and power Doppler signal. The two PDUS assessments were highly correlated at all visits. The reduced model had a higher responsiveness than the comprehensive model. Intraobserver and interobserver agreement was good for both US findings.
The 10-joint PDUS assessment is valid and feasible for assessment of synovitis in JIA in clinical practice.
Pro-inflammatory cytokines such as leptin and IL-6 play an important role in the development of cardiovascular risk. Determine the relationship between leptin and IL-6 concentrations with ...cardiovascular risk in patients with rheumatoid arthritis. We determined IL-6 and leptin levels in 77 patients with the diagnosis of rheumatoid arthritis. The cardiovascular risk was calculated using the modified Framingham scale. Statistical analysis was performed using SPSS 22 considering a significant
p
< 0.05. Serum leptin concentrations and cardiovascular risk (CVR) factors were compared and found that there was a significant difference between higher leptin values and disease activity (
p
0.047), obesity (
p
0.038), positive rheumatoid factor (
p
0.009), tobacco (
p
0.009), and metabolic syndrome (
p
0.001). Likewise, a significant relationship was found between lower leptin concentrations and hydroxychloroquine consumption (
p
= 0.023). We found significant difference between IL-6 concentrations and disease activity (
p
0.028), hypertriglyceridemia (
p
0.023), LDL-C (
p
0.029), and smoking (0.005). Similarly, an association between hydroxychloroquine consumption and low concentrations of IL-6 was found (
p
0.005). Framingham CVR was calculated and the result obtained was multiplied by 1.5. The 35.2% of the population studied had a low Framingham CVR, 38.9% moderate, and 25.9% presented a high risk. We compared the level of CVR and serum leptin and IL-6 concentrations, finding that the highest CVR was the leptin and IL-6 values. There is a positive association between CVR and serum leptin concentrations. It is also significantly associated with traditional and non-traditional risk factors.
The reactivation of very large landslides may cause severe damage to society. Its prevention and management requires detailed information on the geometry and structure of these landslides, but the ...use of standard techniques (boreholes) may be prohibitive from an economic point of view. To overcome these difficulties, geophysical techniques are of special interest because they allow for studying very large areas at a reasonable cost. In this paper, we present a case study wherein the analysis of ambient noise allowed us to produce a model of a large landslide near Granada (southern Spain). The geometry and location of the failure zone, as well as the assessment of the state of involved materials, were estimated by combining two available boreholes and different geophysical techniques (downhole tests and the spectral analysis of ambient noise, horizontal to vertical spectral ratios (HVSR) and the frequency-wavenumber (f-k) methods). The results have allowed us to differentiate between values within the landslide mass with respect to those of stable materials, and to perform for the first time a comprehensive geological model of this unstable mass. Differences were also observed within the landslide mass (earth flow vs. slide zones), which are attributed to differences in the degree of alteration and the disturbance of the internal structure of materials constituting the landslide mass. These results show that techniques based on the measurement of ambient noise are of special interest for studying very large, highly remolded landslide masses.
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