B cells are classically considered solely as antibody-producing cells driving humoral immune responses to foreign antigens in infections and vaccinations as well as self-antigens in pathological ...settings such as autoimmunity. However, it has now become clear that B cells can also secrete a vast array of cytokines, which influence both pro- and anti-inflammatory immune responses. Indeed, similarly to T cells, there is significant heterogeneity in cytokine-driven responses by B cells, ranging from the production of pro-inflammatory effector cytokines such as IL-6, through to the release of immunosuppressive cytokines such as IL-10. In this review, focusing on human B cells, we summarize the key findings that have revealed that cytokine-producing B cell subsets have critical functions in healthy immune responses and contribute to the pathophysiology of autoimmune diseases.
The census of exoplanets is incomplete for orbital distances larger than 1 AU. Here, we present 41 long-period planet candidates in 38 systems identified by Planet Hunters based on Kepler archival ...data (Q0–Q17). Among them, 17 exhibit only one transit, 14 have two visible transits, and 10 have more than three visible transits. For planet candidates with only one visible transit, we estimate their orbital periods based on transit duration and host star properties. The majority of the planet candidates in this work (75%) have orbital periods that correspond to distances of 1–3 AU from their host stars. We conduct follow-up imaging and spectroscopic observations to validate and characterize planet host stars. In total, we obtain adaptive optics images for 33 stars to search for possible blending sources. Six stars have stellar companions within 4″. We obtain high-resolution spectra for 6 stars to determine their physical properties. Stellar properties for other stars are obtained from the NASA Exoplanet Archive and the Kepler Stellar Catalog by Huber et al. We validate 7 planet candidates that have planet confidence over 0.997 (3σ level). These validated planets include 3 single-transit planets (KIC-3558849b, KIC-5951458b, and KIC-8540376c), 3 planets with double transits (KIC-8540376b, KIC-9663113b, and KIC-10525077b), and 1 planet with four transits (KIC-5437945b). This work provides assessment regarding the existence of planets at wide separations and the associated false positive rate for transiting observation (17%–33%). More than half of the long-period planets with at least three transits in this paper exhibit transit timing variations up to 41 hr, which suggest additional components that dynamically interact with the transiting planet candidates. The nature of these components can be determined by follow-up radial velocity and transit observations.
Summary Background & aims Fluid thickeners are an important and commonly-used strategy to manage swallowing difficulties however there are no reports of the perceptions and experiences of parents of ...children using thickeners. Methods Semi-structured interviews of 14 parents having a child using fluid thickeners due to swallowing difficulties. Results Parents reported improvements in quality of life and health through the use of thickeners. They also reported persistent difficulties in the use of thickeners. Conclusions Results showed unanimous goodwill and positive attitudes towards thickeners and their observed benefits, tempered by common difficulties with thickeners (variability and unpredictability). There remains scope for improvements of commercial thickeners and in information conveyed to users.
Purpose To evaluate the clinical and radiographic outcomes of a consecutive series of patients who had internal fixation of an acute, nondisplaced scaphoid waist fracture via a limited dorsal ...approach. Methods Twenty consecutive patients had surgical fixation of a nondisplaced scaphoid waist (Herbert B2) fracture via a limited dorsal approach. Eighteen patients were available for follow-up evaluation at a mean duration of 98 weeks after surgery (range, 12–272 wk). Fifteen males and 3 females with a mean age of 25 years (range, 16–62 y) were examined. Wrist range of motion; grip strength; visual analog and numeric pain scores; and a Disabilities of the Arm, Shoulder, and Hand (DASH) outcomes questionnaire were assessed. Postoperative radiographs were reviewed in a blinded fashion to assess the fracture union and screw position. Results Seventeen of 18 fractures healed at a mean duration of 8 weeks. No case of proximal pole avascular necrosis occurred. All patients were satisfied and returned to their pre-injury level of employment. Five of 6 collegiate or professional athletes returned to play without limitations. The mean subjective and visual analog pain scores were 0.3 and 0.4 (maximum of 10 for each scale). The mean DASH score was 6.12 (out of 100), which is consistent with an excellent functional outcome. Central axis screw position was achieved on anteroposterior and lateral radiographs in 17 of 18 patients. Conclusions Fixation of an acute, nondisplaced scaphoid waist fracture via a limited dorsal approach is safe and effective. The limited dorsal approach allows for accurate insertion of the screw in the central scaphoid, which is biomechanically advantageous for fracture union and early restoration of function. Type of study/level of evidence Therapeutic IV.
Initial experience with the use of dynamic sonography of the elbow for diagnosing ulnar nerve dislocation and snapping triceps syndrome is reported. Cases of three consecutive patients who underwent ...sonographic evaluation of the elbow and subsequent open elbow surgery for symptomatic ulnar nerve dislocation were reviewed. Dynamic sonography of the elbow was used to aid in the accurate diagnosis of and differentiation between ulnar nerve dislocation and snapping of the medial triceps muscle.
Purpose: To assess the long-term clinical and radiographic results after a proximal row carpectomy (PRC).
Methods: Twenty patients with various degenerative and posttraumatic disorders of the wrist ...were evaluated. The evaluation consisted of a physical examination, plain radiographs, and completion of a questionnaire that assessed patient satisfaction, return to work status, occupational and recreational activities and restrictions, and pain level.
Results: Two patients (10%) had persistent pain after a PRC requiring a radiocapitate arthrodesis. The remaining 18 patients were evaluated at an average follow-up of 13.1 years (range, 10.0–17.2 y). The average wrist range of motion was 63% and the average maximal grip strength was 83% of the opposite extremity, respectively. Seventeen patients were satisfied with their outcome. One patient complained of persistent pain and was not satisfied but did not want further surgery. All but 2 patients returned to their original occupation and activity level including all 5 patients involved in workers’ compensation. Follow-up radiographs showed flattening of the proximal capitate in 6 patients. Radiocapitate arthrosis was absent/minimal in 13 patients and moderate/severe in 4 patients. The presence of radiographic changes did not correlate with patient satisfaction or degree of wrist pain.
Conclusions: Proximal row carpectomy is a dependable and durable procedure that results in satisfactory pain relief in the majority of patients, maintenance of functional wrist motion and grip strength, high patient satisfaction, and ability to return to work. Progressive symptomatic deterioration of the radiocapitate articulation was not observed.
Abstract Background/Aims Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease in children with methotrexate (MTX) as the first line treatment. However, about 50% of JIA ...patients will not respond well to MTX yet still experience drug side effects. Early prediction to MTX treatment response would be beneficial for patients and families to avoid incurring unnecessary MTX side effects and ongoing uncontrolled inflammation: such validated tools or biomarkers are currently not available. Methods Transcriptional analysis was performed on peripheral blood mononuclear cells (PBMC) from pre-MTX-treated JIA patients (n = 97) of all ILAR JIA subtypes, excluding systemic JIA. RNAseq was performed on total PBMC and sorted immune cell populations: CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD14+ monocytes. Clinical data collected at the time of sampling (baseline) and at the follow-up time (between 3-12 months) were used to define outcomes, measured as change in active joint count (AJC), change in Physician VAS (PhysVAS), and change in cJADAS10. After batch normalisation with ComBat-seq, differential gene expression (DGE) analysis was performed using limma-voom with age, sex, ethnicity, and steroid status included as covariates. Log2 fold changes were utilised to rank genes to implement gene set enrichment analysis (GSEA) by fgsea. Results DGE analysis showed minimal significant differentially expressed (DE) genes that passed 5% false discovery rate (FDR). The greatest number of significant DE genes were observed in CD14+ monocytes, where baseline expression of 13 genes were significantly associated with change in PhysVAS. As alterations of gene expression for a heterogeneous disease such as JIA can be subtle and correlated between genes, GSEA was performed to investigate expression changes at pathway level. Using MSigDb Hallmark pathways, GSEA showed interferon-related and tumor-necrosis-factor pathways as significantly associated with MTX response in all cell types (5% FDR). However, the directionality (up/down regulation) differed between cell lineages, suggesting pathways divergence between T cell and non-T cell lineages. For example, in interferon gamma pathway, up-regulation associated with poor treatment response in T-cells and down-regulation in non-T cells. Preliminary analysis of the leading edge genes of the interferon gamma pathway in the non-T cell lineages showed that many of the genes are driven by interferon alpha, whilst within CD4+ and CD8+ T cells the majority of the leading edge genes are specific to interferon gamma. Conclusion Different directionality of pathways that might be relevant to JIA response to treatment with MTX is observed in different mononuclear cell lineages. This could potentially explain the difficulties of finding biomarkers which correlate with response to treatment from whole blood or PBMC. Shared genes across different interferon-related pathways also suggest that interaction between interferon pathways might be driving the different direction of interferon pathway expression in different cell lineages. Disclosure M. Kartawinata: None. W. Lin: None. B. Jebson: None. K. O'Brien: None. E. Ralph: None. R. Restuadi: None. G.T. Hall: None. S. Castellano: None. C. Wallace: None. L.R. Wedderburn: Grants/research support; LRW Declares in kind contributions to CLUSTER by AbbVie, GSK, UCB, Sobi and Pfizer inc and non renumerated collaborations with Lilly and Novartis.
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