Building the cytokinetic contractile ring in an early embryo: Initiation as clusters of myosin II, anillin and septin, and visualization of a septin filament network

The cytokinetic contractile ring (CR) was first described some 50 years ago, however our understanding of the assembly and structure of the animal cell CR remains incomplete. We recently reported that mature CRs in sea urchin embryos contain myosin II mini-filaments organized into aligned concatenated arrays, and that in early CRs myosin II formed discrete clusters that transformed into the linearized structure over time. The present study extends our previous work by addressing the hypothesis that these myosin II clusters also contain the crucial scaffolding proteins anillin and septin, known to help link actin, myosin II, RhoA, and the membrane during cytokinesis. Super-resolution imaging of cortices from dividing embryos indicates that within each cluster, anillin and septin2 occupy a centralized position relative to the myosin II mini-filaments. As CR formation progresses, the myosin II, septin and anillin containing clusters enlarge and coalesce into patchy and faintly linear patterns. Our super-resolution images provide the initial visualization of anillin and septin nanostructure within an animal cell CR, including evidence of a septin filament-like network. Furthermore, Latrunculin-treated embryos indicated that the localization of septin or anillin to the myosin II clusters in the early CR was not dependent on actin filaments. These results highlight the structural progression of the CR in sea urchin embryos from an array of clusters to a linearized purse string, the association of anillin and septin with this process, and provide the visualization of an apparent septin filament network with the CR structure of an animal cell.

The Use of Scoring Hip Osteoarthritis with MRI as an Assessment Tool for Physiotherapeutic Treatment in Patients with Osteoarthritis of the Hip

Rehabilitation programs are considered effective at reducing the impact of osteoarthritis (OA) of the hip; however, studies using reliable measures related to OA biomarkers to assess the effects of rehabilitation are lacking. The objective of this study was to investigate whether an MRI-based (Magnetic Resonance Imaging-based), semi-quantitative system for an OA severity assessment is feasible for the evaluation of the structural changes in the joint observed during a long-term physiotherapy program in patients with hip OA. The study group consisted of 37 adult OA patients who participated in a 12-month physiotherapy program. The Scoring hip osteoarthritis with MRI (SHOMRI) system was used to evaluate the severity of structural changes related to hip OA. Hip disability and the osteoarthritis outcome score (HOOS) and the core set of performance-based tests recommended by Osteoarthritis Research Society International were used for functional assessment. SHOMRI showed excellent inter- and intra-rater agreement, proving to be a reliable method for the evaluation of hip abnormalities. At the 12-month follow-up no statistically significant changes were observed within the hip joint; however, a trend of structural progression was detected. There was a negative correlation between most of the SHOMRI and HOOS subscales at baseline and the 12-month follow-up. Although SHOMRI provides a reliable assessment of the hip joint in patients with OA it showed a limited value in detecting significant changes over time in the patients receiving physiotherapy over a 12-month period.

Structural Lesion Progression of the Sacroiliac Joint and Clinical Features in axSpA During TNFi Reduction: A Retrospective Cohort Study

Objective: In the clinic, some patients with axial spondyloarthritis (axSpA) have to reduce tumor necrosis factor inhibitor (TNFi) for various reasons. However, there are few studies about how to balance the relapse and TNFi reduction. Here we retrospectively analyzed the structural progression of the sacroiliac joint (SIJ) and clinical features in axSpA during TNFi reduction.Methods: A total of 108 patients with axSpA who followed up for 2 years and completed at least baseline, 12-month, and 24-month MRI scans of SIJ were divided into the tapering group (n = 63) and withdrawal group (n = 45) according to whether TNFi was stopped. We divided 2 years into five intervals, calculating the average dose quotient (DQ) for each of 540 intervals from 108 patients. By using generalized estimation equations with inverse probability of treatment weighting, we investigated the unbiased effects of average DQ on structural progression and treatment response.Results: The disease activity (such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, and ASDAS-ESR) and relapse rate were lower in the tapering group at 12 and 24 months (p < 0.05). Δerosion (β = −0.0100, p = 0.00026) and Δthe Spondyloarthritis Research Consortium of Canada (SPARCC; β = −0.0959, p < 0.0001) were negatively correlated with average DQ. The average DQ 30 (74.8%, 80.0%) or 41.6 (76.5%, 83%) was best to discriminate the status of treatment response or the status of bone marrow edema, but considering operability, the average DQ 25 (78.0%, 63.3%) was also acceptable especially for patients with HLA-B27 negative and non-severe fat metaplasia.Conclusion: Complete TNFi withdrawal was not recommended. Our study provided a referable strategy (tapering then maintained the average DQ over 30 or even 25) for patients who need TNFi reduction. Higher dose usage of TNFi was associated with a slower erosion progression of SIJ.

Role of clinical and biochemical inflammation in structural progression of patients with psoriatic arthritis

ObjectiveTo determine the contribution of clinical and biochemical inflammation to structural progression of patients with psoriatic arthritis (PsA).MethodsWe analysed patients from the Infliximab Multinational Psoriatic Arthritis Controlled Trial 2 trial (infliximab vs placebo). We obtained total modified Sharp/van-der-Heijde Scores from baseline and year one images, and swollen joint counts (SJC) and levels of C reactive protein (CRP) throughout the second half of year 1 (5 measurements) from 74 placebo-treated patients. We computed radiographic progression, time-averaged SJC (taSJC) and CRP (taCRP) values and assessed their impact on structural progression by logistic regression analysis. We further categorised patients as ‘active’ (+) or ‘inactive’ (−) based on their taSJC (cut-off point: 2/66 joints) and taCRP (cut-off point: 0.5 mg/dL) and compared radiographic progression across three groups (double inactive, single active, double active).ResultsORs for progression were 1.24 (95 % CI 1.04 to 1.47; p=0.016) for taSJC and 6.08 (95 % CI 1.12 to 33.03; p=0.036) for taCRP. When predictors were dichotomised (+ vs −), differences were maintained between taSJC+ and taSJC− patients (1.05±3.21 and 0.56±2.30, respectively), as well as for taCRP+ vs taCRP− patients (1.14±3.23 and 0.05±2.37, respectively). Progression was intermediate in the presence of abnormalities of one but not the other inflammatory variable, indicating increasing radiographic progression with increasing inflammation (p=0.05).ConclusionIn patients with PsA, both clinical and biochemical inflammation have an impact on structural progression. Overall, progression is smallest in the absence of both clinical and biochemical inflammation, higher when either clinical or biochemical inflammation is present and highest with both clinical and biochemical inflammation.

Spinal Radiographic Progression and Predictors of Progression in Patients With Radiographic Axial Spondyloarthritis Receiving Ixekizumab Over 2 Years

Objective To evaluate the long-term effect of ixekizumab on radiographic changes in the spine in patients with radiographic axial spondyloarthritis (r-axSpA) by measuring change from baseline through 2 years in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and to identify potential predictors of progression. Methods This study evaluates patients from COAST-V (NCT02696785, bDMARD-naive) and COAST-W (NCT02696798, TNFi-experienced) who had mSASSS data at baseline in the originating studies and 108 weeks after baseline in the extension study COAST-Y (NCT03129100). We examined the proportion of patients who did not have spinal radiographic progression through 2 years (108 weeks) of treatment with ixekizumab (80 mg every 2 or 4 weeks) and the change from baseline to year 2 in mSASSS. Potential predictors of spinal radiographic progression were also evaluated. Results Among patients with evaluable radiographs who were originally assigned to ixekizumab (N=230), mean (SD) change in mSASSS from baseline at year 2 was 0.3 (1.8). The proportion of non-progressors over 2 years was 89.6% if defined as mSASSS change from baseline <2 and 75.7% if defined as mSASSS change from baseline ≤0. Predictors of structural progression at year 2 (mSASSS change >0) were age ≥40, baseline syndesmophytes, HLA-B27 positivity and male gender. Week 52 inflammation in SPARCC spine was also a predictor of radiographic progression at year 2 in patients with MRI-data in COAST-V (N=109). Conclusion The majority of patients with r-axSpA receiving ixekizumab had no radiographic progression in the spine through 2 years of treatment. Predictors were generally consistent with previous studies.

METHODS - A randomised controlled trial of METhotrexate to treat Hand Osteoarthritis with Synovitis: study protocol for a randomised controlled trial

Background Hand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis. Methods Ninety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups. Discussion This study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124

Meniscus position and size in knees with versus without structural knee osteoarthritis progression: data from the osteoarthritis initiative

Objective To explore whether and which quantitative 3D measures of medial and/or lateral meniscus position and size are associated with subsequent medial femorotibial structural progression of knee osteoarthritis and to determine the correlation between central slice and total meniscus measures. Materials and Methods Knees with radiographic osteoarthritis from Osteoarthritis Initiative participants with longitudinal medial MRI-based cartilage thickness and radiographic joint space width (JSW) loss over 12 months were selected. These 37 structural progressor knees (64.7 ± 8.0y, 30.2 ± 4.6 kg/m2, 35% men) were matched 1:1 to 37 non-progressor knees (64.6 ± 9.8y, 30.2 ± 4.4 kg/m2, 35% men) without cartilage thickness or JSW loss. Quantitative measures of meniscus position and size were computed from manual segmentations of coronal baseline MRIs. Cohen’s D was used as measure of effect size. Results Maximum extrusion distance of the total medial meniscus and mean extrusion in the central 5 and in the central slice were greater for progressor than non-progressor knees (Cohen’s D 0.58–0.66). No significant differences were observed for medial tibial coverage or mean extrusion (entire meniscus). Among medial meniscus morphology measures, only mean height differed between progressor vs non-progressor knees (Cohen’s D 0.40). Among lateral meniscus measures, height and volume were greater in progressor vs. non-progressor knees (Cohen’s D 0.46–0.83). Mean extrusion measures were highly correlated between the entire meniscus and the central (r = 0.88) or the central 5 (r = 0.93) slices. Conclusions 3D maximum and central medial meniscus extrusion may serve as predictors for subsequent structural progression. Central meniscus extrusion measures could substitute 3D extrusion measurement across the entire meniscus.

Efficacy of intra-articular of high molecular weight hyaluronic acid injections in in osteoarthritis of the knee and hip

Наличие болевого синдрома и нарастание функциональной недостаточности суставов – наиболее частые причины обращения пациентов за медицинской помощью. В настоящее время, учитывая рост распространенности остеоартрита, необходим более активный мультимодальный подход к ведению пациентов с учетом их индивидуальных особенностей и потребностей. Основными целями терапии остеоартрита являются: уменьшение боли, сохранение или улучшение функции суставов, предотвращение нарастания функциональной недостаточности, улучшение качества жизни, связанного со здоровьем, и уменьшение/предотвращение структурного прогрессирования заболевания. В статье представлены данные об одном из эффективных и безопасных методов лечения остеоартрита коленных и тазобедренных суставов – внутрисуставном введении гиалуроновой кислоты, который обеспечивает значительное снижение боли, улучшение функции сустава, способствует снижению потребности в нестероидных противовоспалительных препаратах и замедлению прогрессирования заболевания. Полученные результаты исследований свидетельствуют о хорошем и длительном симптоматическом эффекте препарата, высоком профиле безопасности и возможности его использования в широкой клинической практике. The presence of pain syndrome and an increase in functional insufficiency of the joints are the most frequent reasons for patients seeking medical help. Currently, given the growing prevalence of osteoarthritis, a more active multimodal approach to patient management is needed, taking into account their individual characteristics and needs. The main goals of osteoarthritis therapy are: pain relief; maintaining or improving joint function; preventing the build-up of functional impairment, improving health-related quality of life, and reducing/preventing structural progression of the disease. The article presents data on one of the effective and safe methods of treating osteoarthritis of the knee and hip joints – intra-articular administration of hyaluronic acid, which provides a significant reduction in pain, improvement of joint function; helps to reduce the need for NSAIDs and slow the progression of the disease. The obtained research results indicate a good and long-term symptomatic effect of the drug, a high safety profile and the possibility of its use in wide clinical practice.