How does a cadaver model work for testing ultrasound diagnostic capability for rheumatic-like tendon damage?

To establish whether a cadaver model can serve as an effective surrogate for the detection of tendon damage characteristic of rheumatoid arthritis (RA). In addition, we evaluated intraobserver and interobserver agreement in the grading of RA-like tendon tears shown by US, as well as the concordance between the US findings and the surgically induced lesions in the cadaver model. RA-like tendon damage was surgically induced in the tibialis anterior tendon (TAT) and tibialis posterior tendon (TPT) of ten ankle/foot fresh-frozen cadaveric specimens. Of the 20 tendons examined, six were randomly assigned a surgically induced partial tear; six a complete tear; and eight left undamaged. Three rheumatologists, experts in musculoskeletal US, assessed from 1 to 5 the quality of US imaging of the cadaveric models on a Likert scale. Tendons were then categorized as having either no damage, (0); partial tear, (1); or complete tear (2). All 20 tendons were blindly and independently evaluated twice, over two rounds, by each of the three observers. Overall, technical performance was satisfactory for all items in the two rounds (all values over 2.9 in a Likert scale 1-5). Intraobserver and interobserver agreement for US grading of tendon damage was good (mean κ values 0.62 and 0.71, respectively), with greater reliability found in the TAT than the TPT. Concordance between US findings and experimental tendon lesions was acceptable (70-100 %), again greater for the TAT than for the TPT. A cadaver model with surgically created tendon damage can be useful in evaluating US metric properties of RA tendon lesions

Dual oscillator model of the respiratory neuronal network generating quantal slowing of respiratory rhythm

We developed a dual oscillator model to facilitate the understanding of dynamic interactions between the parafacial respiratory group (pFRG) and the preBötzinger complex (preBötC) neurons in the respiratory rhythm generation. Both neuronal groups were modeled as groups of 81 interconnected pacemaker neurons; the bursting cell model described by Butera and others [model 1 in Butera et al. (J Neurophysiol 81:382–397, 1999a)] were used to model the pacemaker neurons. We assumed (1) both pFRG and preBötC networks are rhythm generators, (2) preBötC receives excitatory inputs from pFRG, and pFRG receives inhibitory inputs from preBötC, and (3) persistent Na+ current conductance and synaptic current conductances are randomly distributed within each population. Our model could reproduce 1:1 coupling of bursting rhythms between pFRG and preBötC with the characteristic biphasic firing pattern of pFRG neurons, i.e., firings during pre-inspiratory and post-inspiratory phases. Compatible with experimental results, the model predicted the changes in firing pattern of pFRG neurons from biphasic expiratory to monophasic inspiratory, synchronous with preBötC neurons. Quantal slowing, a phenomena of prolonged respiratory period that jumps non-deterministically to integer multiples of the control period, was observed when the excitability of preBötC network decreased while strengths of synaptic connections between the two groups remained unchanged, suggesting that, in contrast to the earlier suggestions (Mellen et al., Neuron 37:821–826, 2003; Wittmeier et al., Proc Natl Acad Sci USA 105(46):18000–18005, 2008), quantal slowing could occur without suppressed or stochastic excitatory synaptic transmission. With a reduced excitability of preBötC network, the breakdown of synchronous bursting of preBötC neurons was predicted by simulation. We suggest that quantal slowing could result from a breakdown of synchronized bursting within the preBötC

Using Expression and Genotype to Predict Drug Response in Yeast

Personalized, or genomic, medicine entails tailoring pharmacological therapies according to individual genetic variation at genomic loci encoding proteins in drug-response pathways. It has been previously shown that steady-state mRNA expression can be used to predict the drug response (i.e., sensitivity or resistance) of non-genotyped mammalian cancer cell lines to chemotherapeutic agents. In a real-world setting, clinicians would have access to both steady-state expression levels of patient tissue(s) and a patient's genotypic profile, and yet the predictive power of transcripts versus markers is not well understood. We have previously shown that a collection of genotyped and expression-profiled yeast strains can provide a model for personalized medicine. Here we compare the predictive power of 6,229 steady-state mRNA transcript levels and 2,894 genotyped markers using a pattern recognition algorithm. We were able to predict with over 70% accuracy the drug sensitivity of 104 individual genotyped yeast strains derived from a cross between a laboratory strain and a wild isolate. We observe that, independently of drug mechanism of action, both transcripts and markers can accurately predict drug response. Marker-based prediction is usually more accurate than transcript-based prediction, likely reflecting the genetic determination of gene expression in this cross

Reliability of ultrasonography in detecting shoulder disease in patients with rheumatoid arthritis.

OBJECTIVE: To assess the intra and interobserver reproducibility of musculoskeletal ultrasonography (US) among rheumatologists in detecting destructive and inflammatory shoulder abnormalities in patients with rheumatoid arthritis (RA) and to determine the overall agreement between US and MRI. METHODS: A total of 14 observers examined 5 patients in 2 rounds independently and blindly of each other. US results were compared with MRI. Overall agreement of all findings, of positive findings on MRI, as well as intra and interobserver reliabilities, were calculated. RESULTS: Overall agreement between US and MRI was seen in 79% with regard to humeral head erosions (HHE), in 64% with regard to posterior recess synovitis (PRS), in 31% with regard to axillary recess synovitis (ARS), in 64% with regard to bursitis, in 50% with regard to biceps tenosynovitis (BT), and in 84% for complete cuff tear (CCT). Intraobserver and interobserver kappa was 0.69 and 0.43 for HHE, 0.29 and 0.49 for PRS, 0.57 and 1.00 for ARS, -0.17 and 0.51 for bursitis, 0.17 and 0.46 for BT and 0.52 and 0.6 for CCT, respectively. The intraobserver and interobserver kappa for power Doppler (PD) was 0.90 and 0.70 for glenohumeral signals and 0.60 and 0.51 for bursal signals, respectively. CONCLUSIONS: US is a reliable imaging technique for most shoulder pathology in RA especially with regard to PD. Standardisation of scanning technique and definitions of particular lesions may further enhance the reliability of US investigation of the shoulder

Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR "Train the trainers" course

OBJECTIVE: To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging "gold standard". METHODS: The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. RESULTS: Taking an agreement in US examination of 10 out of 14 experts into account, the overall kappa for all examined joints was 0.76. Calculations for each joint region showed high kappa values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). kappa Values for bone lesions, bursitis, and tendon tears were high (kappa = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). CONCLUSION: Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US

No association between striatal dopamine transporter binding and body mass index: A multi-center European study in healthy volunteers

INTRODUCTION: Dopamine is one among several neurotransmitters that regulate food intake and overeating. Thus, it has been linked to the pathophysiology of obesity and high body mass index (BMI). Striatal dopamine D(2) receptor availability is lower in obesity and there are indications that striatal dopamine transporter (DAT) availability is also decreased. In this study, we tested whether BMI and striatal DAT availability are associated. METHODS: The study included 123 healthy individuals from a large European multi-center database. They had a BMI range of 18.2-41.1kg/m(2) and were scanned using [(123)I]FP-CIT SPECT imaging. Scans were analyzed with both region-of-interest and voxel-based analysis to determine the binding potential for DAT availability in the caudate nucleus and putamen. A direct relation between BMI and DAT availability was assessed and groups with high and low BMI were compared for DAT availability. RESULTS: No association between BMI and striatal DAT availability was found. CONCLUSION: The lack of an association between BMI and striatal DAT availability suggests that the regulation of striatal synaptic dopamine levels by DAT plays no or a limited role in the pathophysiology of overweight and obesity.status: publishe

Interobserver reliability in musculoskeletal ultrasonography: results from a "Teach the Teachers" rheumatologist course.

OBJECTIVE: To assess the interobserver reliability of the main periarticular and intra-articular ultrasonographic pathologies and to establish the principal disagreements on scanning technique and diagnostic criteria between a group of experts in musculoskeletal ultrasonography. METHODS: The shoulder, wrist/hand, ankle/foot, or knee of 24 patients with rheumatic diseases were evaluated by 23 musculoskeletal ultrasound experts from different European countries randomly assigned to six groups. The participants did not reach consensus on scanning method or diagnostic criteria before the investigation. They were unaware of the patients' clinical and imaging data. The experts from each group undertook a blinded ultrasound examination of the four anatomical regions. The ultrasound investigation included the presence/absence of joint effusion/synovitis, bony cortex abnormalities, tenosynovitis, tendon lesions, bursitis, and power Doppler signal. Afterwards they compared the ultrasound findings and re-examined the patients together while discussing their results. RESULTS: Overall agreements were 91% for joint effusion/synovitis and tendon lesions, 87% for cortical abnormalities, 84% for tenosynovitis, 83.5% for bursitis, and 83% for power Doppler signal; kappa values were good for the wrist/hand and knee (0.61 and 0.60) and fair for the shoulder and ankle/foot (0.50 and 0.54). The principal differences in scanning method and diagnostic criteria between experts were related to dynamic examination, definition of tendon lesions, and pathological v physiological fluid within joints, tendon sheaths, and bursae. CONCLUSIONS: Musculoskeletal ultrasound has a moderate to good interobserver reliability. Further consensus on standardisation of scanning technique and diagnostic criteria is necessary to improve musculoskeletal ultrasonography reproducibility