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Katherine Dutton,1 Geoffrey Littlejohn21Department of Rheumatology, Townsville Hospital, Douglas, QLD, Australia; 2Department of Medicine, Monash University, Melbourne, VIC, AustraliaAbstract: Complex regional pain syndrome has long been recognized as a severe and high impact chronic pain disorder. However, the condition has historically been difficult to define and classify and little attention has been given to where complex regional pain syndrome sits within other apparently similar chronic pain disorders, such as fibromyalgia and regional pain syndrome. In this review challenges in regard to nomenclature, definitions, and classification of complex regional pain syndrome are reviewed and suggestions are provided about future directions.Keywords: complex regional pain syndromes, fibromyalgia, causalgia, classification

Neural crest cells form diverse cell types, including ectomesenchymal fates (e.g., craniofacial skeleton and fin mesenchyme) and nonectomesenchymal fates (e.g., neurons, glia, and pigment cells). The zebrafish colorless/sox10 (cls) mutants are models for two neurocristopathies: Hirschsprung's disease, characterized by few or no enteric ganglia, and Waardenburg-Shah syndrome, which combines Hirschsprung's disease with loss of pigment, cls mutants have a significant reduction in sensory and sympathetic neurons, putative satellite glia, Schwann cells, and pigment cells. Iontophoretic-labeling experiments have shown that neural crest cell clones in live cls mutant embryos adopt ectomesenchymal fates at the same frequency in cls and wild-type sibling embryos and differentiate after migration to appropriate sites. All other clones in els embryos did not differentiate or migrate normally; instead, they died late by an apoptotic mechanism. This suggests that cls/sox10 has a primary role in specification of nonectomesenchymal fates and that defects in migration, survival, and differentiation are secondary to a defect in specification. We have examined dorsal root ganglia (DRG) neuron formation in cls mutant embryos. DRG neurons are decreased in total number in cls mutants in an anterior to posterior gradient, resulting in a total lack of DRG neurons in the tail. In mouse sox10 mutants a similar gradient has been reported, although reports conflict on the orientation of the gradient. We have used sox10-specific morpholinos to create sox10 hypomorphs to further investigate the role of sox10 in DRG neuron specification.

Objectives: To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of clinical features predicting US synovitis/tenosynovitis., Methods: In a longitudinal multicentre study, SLE patients with physician-diagnosed inflammatory joint pain received intramuscular methylprednisolone 120 mg once. Clinical assessments, patient-reported outcomes and bilateral hand/wrist USs were collected at 0, 2 and 6 weeks. The primary outcome (determined via internal pilot) was the early morning stiffness visual analogue scale (EMS-VAS) at 2 weeks, adjusted for baseline, comparing patients with positive (greyscale ≥2 and/or power Doppler ≥1) and negative US. Post hoc analyses excluded FM., Results: Of 133 patients, 78 had a positive US. Only 53 (68%) of these had one or more swollen joint. Of 66 patients with one or more swollen joint, 20% had a negative US. A positive US was associated with joint swelling, symmetrical small joint distribution and serology. The primary endpoint was not met: in the full analysis set (N = 133) there was no difference in baseline-adjusted EMS-VAS at week 2 [-7.7 mm (95% CI -19.0, 3.5); P = 0.178]. After excluding 32 patients with FM, response was significantly better in patients with a positive US at baseline [baseline-adjusted EMS-VAS at 2 weeks -12.1 mm (95% CI -22.2, -0.1); P = 0.049]. This difference was greater when adjusted for treatment [-12.8 mm (95% CI -22, -3); P = 0.007]. BILAG and SLEDAI responses were higher in US-positive patients., Conclusion: In SLE patients without FM, those with a positive US had a better clinical response to therapy. Imaging-detected synovitis/tenosynovitis may be considered to decide on therapy and enrich clinical trials., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Type I interferon (IFN) responses are broadly associated with autoimmune diseases, including systemic lupus erythematosus (SLE). Given the cardinal role of autoantibodies in SLE, this study was undertaken to investigate whether the findings of a B cell-specific IFN assay correlate with SLE activity., Methods: B cells and peripheral blood mononuclear cells (PBMCs) were stimulated with type I IFN and type II IFN. Gene expression was analyzed, and the expression of pathway-related membrane proteins was determined. A flow cytometry assay for tetherin (CD317), an IFN-induced protein ubiquitously expressed on leukocytes, was validated in vitro and then clinically against SLE diagnosis, plasmablast expansion, and the British Isles Lupus Assessment Group (BILAG) 2004 score in a discovery cohort (n = 156 SLE patients, 30 rheumatoid arthritis [RA] patients, and 25 healthy controls). A second, longitudinal validation cohort of 80 SLE patients was also evaluated for flare prediction., Results: In vitro, a close cell-specific and dose-response relationship between type I IFN-responsive genes and cell surface tetherin was observed in all immune cell subsets. Tetherin expression on multiple cell subsets was selectively responsive to stimulation with type I IFN compared to types II and III IFNs. In patient samples from the discovery cohort, memory B cell tetherin showed the strongest associations with diagnosis (SLE:healthy control effect size 0.11 [P = 0.003]; SLE:RA effect size 0.17 [P < 0.001]), plasmablast numbers in rituximab-treated patients (R = 0.38, P = 0.047), and BILAG 2004. These associations were equivalent to or stronger than those for IFN score or monocyte tetherin. Memory B cell tetherin was found to be predictive of future clinical flares in the validation cohort (hazard ratio 2.29 [95% confidence interval 1.01-4.64]; P = 0.022)., Conclusion: Our findings indicate that memory B cell surface tetherin, a B cell-specific IFN assay, is associated with SLE diagnosis and disease activity, and predicts flares better than tetherin on other cell subsets or whole blood assays, as determined in an independent validation cohort., (© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

We report an interesting case of hepatitis C virus-negative type II cryoglobulinaemic vasculitis (CV) in a patient with a background history of systemic lupus erythematosus. The type II CV became less responsive to traditional treatments over time and culminated in an intensive care unit admission with critical multiorgan failure. A detailed flow cytometric evaluation of the bone marrow proved to be helpful in treatment. It demonstrated that bortezomib was a viable alternative treatment option for the type II CV. The patient received bortezomib and has made a full and durable recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Although the traits of psychopathic personality (psychopathy) have received extensive attention from researchers in forensic psychology, psychopathology, and personality psychology, the relations of these traits to aspects of everyday functioning are poorly understood. Using a large internet survey of members of the general population (N = 3388), we examined the association between psychopathic traits, as measured by a brief but well-validated self-report measure, and occupational choice, political orientation, religious affiliation, and geographical residence. Psychopathic traits, especially those linked to fearless dominance, were positively and moderately associated with holding leadership and management positions, as well as high-risk occupations. In addition, psychopathic traits were positively associated with political conservatism, lack of belief in God, and living in Europe as opposed to the United States, although the magnitudes of these statistical effects were generally small in magnitude. Our findings offer preliminary evidence that psychopathic personality traits display meaningful response penetration into daily functioning, and raise provocative questions for future research.

In humans, mutations in the SOX10 gene are a cause of the auditory-pigmentary disorder Waardenburg syndrome type IV (WS4) and related variants. SOX10 encodes an Sry-related HMG box protein essential for the development of the neural crest; deafness in WS4 and other Waardenburg syndromes is usually attributed to loss of neural-crest-derived melanocytes in the stria vascularis of the cochlea. However, SOX10 is strongly expressed in the developing otic vesicle and so direct roles for SOX10 in the otic epithelium might also be important. Here, we examine the otic phenotype of zebrafish sox10 mutants, a model for WS4. As a cochlea is not present in the fish ear, the severe otic phenotype in these mutants cannot be attributed to effects on this tissue. In zebrafish sox10 mutants, we see abnormalities in all otic placodal derivatives. Gene expression studies indicate deregulated expression of several otic genes, including fgf8, in sox10 mutants. Using a combination of mutant and morphant data, we show that the three sox genes belonging to group E (sox9a, sox9b and sox10) provide a link between otic induction pathways and subsequent otic patterning: they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions. Single-cell labelling experiments indicate a small and transient neural crest contribution to the zebrafish ear during normal development, but this is unlikely to account for the strong defects seen in the sox10 mutant. We discuss the implication that the deafness in WS4 patients with SOX10 mutations might reflect a haploinsufficiency for SOX10 in the otic epithelium, resulting in patterning and functional abnormalities in the inner ear.

This paper describes a system using lensed optical fiber sensors that are arranged in the form of two orthogonal projections. The sensors are placed around a process vessel for upstream and downstream measurements. The purpose of the system is for on-line monitoring of particles and droplets being conveyed by a fluid. The lenses were constructed using a custom heating fixture. The fixture enables the lenses to be constructed with similar radii resulting in identical characteristics with minimum differences in transmitted intensity and emission angle. By collimating radiation from two halogen bulbs, radiation can be obtained by the sensors with radiation intensity related to the nature of the media. Each sensor interrogates a finite section of the measurement section. Each sensor provides a view. Parallel sensors provide a projection. Signal processing is carried out on the measured data in the time and frequency domains to investigate the latent information present in the flow signals.

A survey of the microbiological quality of beef carcasses and boneless beef produced in Australia was conducted during the period June to November 1998. Sponge samples were collected from 1,275 carcasses, and meat samples were drilled from 990 cartons of frozen boneless beef. Carcass and boneless beef samples were respectively collected from 21 and 27 establishments that concentrated on export and from 38 and 3 establishments supplying the Australian domestic market of which 31 were very small plants slaughtering no more than 150 cattle equivalents per week. The mean log total viable counts (TVCs) were 2.42/cm2 and 2.52/g for carcasses and boneless meat, respectively. Escherichia coli was detected on 10.3% of carcasses and 5.1% of boneless beef samples and coagulase-positive staphylococci on 24.3% of carcasses and 17.5% of boneless beef. Salmonella was detected on 0.2% of carcasses and 0.1% of boneless beef and E. coli O157:H7 recovered from 0.1% of carcasses but not detected on 990 boneless beef samples. Mean log TVCs/cm2 differed significantly (P < 0.05) between establishment types. They were lower on carcasses from export establishments (2.20) compared with domestic (2.61) and very small plants (3.10). There were no significant differences in prevalence of Salmonella or E. coli O157:H7 between establishment types. Excision samples were taken from 670 carcasses to make comparisons with the first baseline study of Australian meat, carried out in 1993 to 1994. While there were differences in sampling and microbiological techniques between the two studies that require detailed consideration, there were small but significant improvements in several microbiological criteria for carcasses and boneless meat.

Microbiological quality of sheep carcasses and boneless sheep meat produced in Australia was surveyed during the period June to November 1998. Sponge samples were collected from 917 carcasses, and meat samples were drilled from 467 cartons of frozen boneless meat. Carcass and boneless meat samples were respectively collected from 7 and 10 establishments that concentrated on export, and from 36 and 5 establishments supplying the Australian domestic market of which 31 were very small plants slaughtering cattle and sheep but no more than 1,200 sheep equivalents per week. The mean log total viable counts were 3.55/cm2 and 3.30/g for carcasses and boneless meat, respectively. Escherichia coli was detected on 29.2% of carcasses and 24.5% of boneless meat samples and coagulase-positive staphylococci on 24.1% of carcasses, and 38.6% of boneless meat samples. Salmonella was detected on 0.1% of carcasses and 1.3% of boneless meat samples. E. coli O157:H7 was recovered from 0.7% of carcasses and 1.3% of boneless sheep meat. There were statistically significant differences between establishment types for some microbiological criteria, although there were no significant differences in prevalence of Salmonella or E. coli O157:H7 between establishment types. While there were differences in sampling and microbiological techniques between this study and another conducted in 1993 to 1994 that require detailed consideration, there were small but significant improvements in several microbiological criteria for boneless meat. While data that would allow for comparison of carcass data were not gathered, it is unlikely that improvements in the microbiological quality of boneless sheep meat could accrue without improvements to carcasses.

The zebrafish fkd6 gene is a marker for premigratory neural crest. In this study, we analyze later expression in putative glia of the peripheral nervous system. Prior to neural crest migration, fkd6 expression is downregulated in crest cells. Subsequently, expression appears initially in loose clusters of cells in positions corresponding to cranial ganglia. Double labelling with a neuronal marker shows that fkd6-expressing cells are not differentiated neurones and generally lie peripheral to neurones in ganglia. Later, expression appears associated with the posterior lateral line and other cranial nerves. For the posterior lateral line nerve, we show that fkd6-labeling extends caudally along this nerve in tight correlation with lateral line primordium migration and axon elongation. Expression in colourless mutant embryos is consistent with these cells being satellite glia and Schwann cells.