Objectives:Describe the classic presentation and typical physical exam findings associated with juvenile idiopathic arthritis.Explain the imaging findings associated with JIA and the most common tests for the evaluation of juvenile idiopathic arthritis.Outline the imaging findings associated with JIA and the most common tests for the evaluation of juvenile idiopathic arthritis.Review the importance of collaboration amongst the interdisciplinary team to improve outcomes for patients affected by juvenile idiopathic arthritis.Access free multiple choice questions on this topic.
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of idiopathic inflammatory arthritis affecting children younger than 16 years of age and lasting six weeks or longer. The terminology of chronic arthritis in children has evolved from juvenile chronic arthritis (JCA) and juvenile rheumatoid arthritis (JRA) to JIA since 1995. According to the consensus conference of the International League of Associations for Rheumatology (ILAR) in 2001, there are seven JIA categories: a) oligoarthritis; b) rheumatoid factor (RF) positive polyarthritis; c) RF negative polyarthritis; d) systemic arthritis; e) psoriatic arthritis; f) enthesitis-related arthritis; g) undifferentiated arthritis. These subtypes have distinct phenotypes, genetic predispositions, pathophysiology, laboratory findings, disease course, and prognosis. Although chronic arthritis is mandatory for all subtypes, the extraarticular and the systemic manifestations characterized every specific subtype. Recently, a new preliminary data-driven classification for JIA is proposed and being formally validated by the Pediatric Rheumatology International Trial Organization (PRINTO).
To identify the relevant neural circuits in juvenile zebrafish aged 21 days, we generated unbiased maps of recent neuronal activity after shoaling with real or virtual conspecifics (Fig. 1a). Virtual conspecifics were projected black dots moving either with fish-like biological motion, or continuously, which are highly attractive and weakly attractive, respectively2 (Fig. 1b). We then recorded a snapshot of neuronal activity by rapid fixation and labelling of c-fos (official gene symbol, fosab) mRNA21 using third-generation in situ hybridization chain reaction22 (HCR) analysis in the forebrain, midbrain and anterior hindbrain (Fig. 1a,c and Extended Data Fig. 1). Visual inspection of the registered and merged c-fos signal from all of the animals identified 31 distinct clusters with robust activity in response to one or more stimulus conditions (Fig. 1c and Extended Data Fig. 1).
Our c-fos labelling method highlights putative visual input pathways for social affiliation. Biological motion probably enters the brain through the TeO and DT27, therefore providing an opportunity to investigate sensory detection of this social cue. To understand stimulus selectivity of individual neurons in these visual areas, we turned to volumetric two-photon calcium imaging of juvenile brain activity in response to presentation of virtual conspecifics.
As TeO and DT-BPNs are activated by fish-like motion, we hypothesized that this pathway is necessary for shoaling. To test this hypothesis, we ablated TeO and DT in juvenile animals and analysed effects on free-swimming interactions with virtual conspecifics.
Adult, juvenile and larval zebrafish (Danio rerio) were housed and handled according to standard procedures. All animal experiments were performed under the regulations of the Max Planck Society and the regional government of Upper Bavaria (Regierung von Oberbayern), approved protocols: ROB-55.2Vet-2532.Vet 03-15-16, ROB-55.2Vet-2532.Vet 02-16-31, and ROB55.2Vet-2532.Vet 02-16-122. Experimental animals were outcrosses to TL or TLN (nacre) unless otherwise noted. The following transgenic lines were used: Tg(elavl3:H2B-GCaMP6s)jf545, SAGFF(lf)81c (TeO Gal4 line)46, Tg(UAS-E1B:NTR-mCherry)c26447, Et(fos:Gal4-VP16)s1026t (DT Gal4 line)48, Tg(UAS:BGi-epNTR-TagRFPT-utr.zb3)mpn420 (this study).
To align functional regions of interest (ROIs) from 2P data to a common reference frame, a two-step strategy was used. First, average frames of all imaging planes were registered to individual z-stacks using template matching. Converted ROI locations in z-stack coordinates were then transformed to the larval and juvenile common reference frames by running the ANTs command antsApplyTransformsToPoints with the matrices from the z-stack registrations.
J.M.K. and K.S. performed two-photon imaging experiments. J.M.K. performed laser ablations, registration of two-photon and HCR data. M.J. segmented the EM volume with FFNs. D.F. proofread and traced presegmented EM data. I.S. performed HCR staining and imaging. F.S. generated the EM data and performed EM brain area registration. S.S. performed pilot HCR in situ experiments in juvenile fish. J.C.D. helped with the two-photon hardware and remote focusing, and advised on microscopy and analysis. J.L. performed behaviour experiments, transgenesis and brain area segmentation. J.M.K., K.S., D.F. and J.L. analysed the data. J.M.K., K.S., D.F., H.B. and J.L. interpreted the data. J.M.K., D.F., H.B. and J.L. wrote the paper with input from all of the authors. All of the authors reviewed and edited the manuscript. H.B. and J.L. supervised the project.
a, Top view of the embedding preparation for 2-photon imaging of juvenile zebrafish. To enable active respiration, agarose columns are cut out in front of the mouth and gills. The tail is also freed to improve oxygen uptake through the skin. Oxygenated water in the imaging chamber is constantly renewed with a peristaltic pump. b, Side view of the preparation and remote focusing system. The imaging chamber, consisting of a small petri dish, is placed in a large petri dish filled with water. Diffusive paper serving as a screen and a small spacer are placed between the large and small petri dish. The large petri dish is placed on a custom-made sample holder. A cold mirror is placed under the preparation to reflect projector images onto the screen. The input beam to the remote focusing system (red), passes through a half-wave plate and is reflected by a polarizing beam splitter. The beam is enlarged by two lenses, passes through a quarter-wave plate, and is focused by an objective onto a mirror mounted to a custom piezo stage. The piezo moves the mirror and thus adjusts the effective focal distance of the reflected beam, which ultimately changes the collimation of the beam at the main objective, changing the focus. The second pass through the quarter-wave plate on the return trip results in a change of polarization compared with the input beam, so the reflected beam now continues straight through the polarizing beam splitter, reaching the microscope. To bypass the remote focusing path, the input half-wave plate can be rotated so the input beam instead passes through the polarizing beam splitter, hits a mirror and passes through a quarter-wave plate twice, and then is reflected into the microscope. The detection path is standard and is not depicted. 153554b96e