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Background: Collagen is one of the major proteins of the skin and it is particularly important for its strength and resilience. Skin aging is a natural process that is characterized by the decrease and fragmentation of collagen in the dermis. Oral supplementation with collagen peptides has been clinically shown to have a positive effect on the skin condition. However, the mechanisms of aging-related changes synthesized by cells exposed to collagen are currently not well understood. Therefore, in this in vitro study, the mechanisms associated with collagen, elastin, and versican in human dermal fibroblasts were investigated after exposure to collagen peptides., Methods: The effects of different concentrations of collagen peptides on cell viability and metabolism were analyzed. For gene expression analysis, human dermal fibroblasts were treated with collagen peptides. This was then followed by RNA extraction and DNA synthesis. Gene expressions of collagen type 1 (COL1A1), elastin (ELN), and versican (VCAN) were quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR). In addition, collagen levels were analyzed by confocal scanning laser microscopy using immunostaining., Results: Collagen peptides tested in the study increased the expression of the relevant COL1A1, ELN, and VCAN genes in human dermal fibroblasts ( p  < 0.005). Furthermore, confocal microscopy showed increased collagen expression in the dermal fibroblast culture after treatment with the collagen peptides ( p  < 0.005)., Conclusion: These data provide cell-based evidence for the beneficial effects of exposure to collagen peptides on the skin's collagen content and on the molecules that provide firmness and elasticity. This may support the hypothesis that collagen peptides are important for maintaining extracellular matrix (ECM) structure and skin regeneration., Competing Interests: MP and RN-U were employed by PB Leiner, part of Tessenderlo Group NV. SD, MP, and RN-U are working for the funding stakeholder. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dierckx, Patrizi, Merino, González, Mullor and Nergiz-Unal.)

There is a growing interest in muscle characteristics of the lumbar multifidus related to low back pain, but findings between studies are inconsistent. One of the issues explaining these conflicting findings might be the use of two-dimensional measures of cross-sectional area and thickness of the lumbar multifidus in most studies, which might be a suboptimal representation of the entire muscle volume. A three-dimensional volumetric assessment, combined with standardized imaging and processing measurement protocols, is highly recommended to quantify spinal muscle morphology. Three-dimensional freehand ultrasonography is a technique with large potential for daily clinical practice. It is achieved by combining conventional two-dimensional ultrasound with a motion-tracking system, recording the position and orientation of the ultrasound transducer during acquisition, resulting in a three-dimensional reconstruction. This study investigates intra- and interprocessor reliability for the quantification of muscle volume of the lumbar multifidus based on three-dimensional freehand ultrasound and its validity, in 31 patients with low back pain and 20 healthy subjects. Two processors manually segmented the lumbar multifidus on three-dimensional freehand ultrasound images using Stradwin software following a well-defined method. We assessed the concurrent validity of the measurement of multifidus muscle volume using three-dimensional freehand ultrasound compared with magnetic resonance imaging in 10 patients with low back pain. Processing reliability and agreement were determined using intraclass correlation coefficients, Bland-Altman plots, and calculation of the standard error of measurement and minimal detectable change, while validity was defined based on correlation analysis. The processing of three-dimensional freehand ultrasound images to measure lumbar multifidus volume was reliable. Good to excellent intraclass correlation coefficients were found for intraprocessor reliability. For interprocessor reliability, the intraclass correlation coefficients were moderate to good, emphasizing the importance of processing guidelines and training. A single processor analysis is preferred in clinical studies or when small differences in muscle volume are expected. The correlation between magnetic resonance imaging and three-dimensional freehand ultrasound measurements of lumbar multifidus volume was moderate to good but with a systematically smaller multifidus volume measured on three-dimensional freehand ultrasound. These results provide opportunities for both researchers and clinicians to reliably assess muscle structure using three-dimensional freehand ultrasound in patients with low back pain and to monitor changes related to pathology or interventions. To allow implementation in both research and clinical settings, guidelines on three-dimensional freehand ultrasound processing and training were provided., (© 2023 Anatomical Society.)

Introduction: The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare condition. Its treatment remains a challenge for clinicians, and often yields mixed results., Case: We report the case of a 51-year-old Caucasian woman who presented with SAPHO syndrome with mainly axial involvement. She had been treated with sulfasalazine and anti-inflammatory drugs for many years without any success. A few weeks after starting treatment with tofacitinib, both clinical and biological parameters dramatically improved. Imaging also showed considerable regression of the vertebral and pelvic lesions. However, tofacitinib had to be discontinued due to the occurrence of pulmonary embolism. Consequently, recurrence of bone pain and biologic inflammation was rapidly observed., Conclusions: Anti-JAKs are an interesting treatment option in the management of SAPHO syndrome that need further clinical trials and assessment for validating response., (© 2024. The Author(s).)

Introduction: This study sought to analyze the benefit of an early induction therapy with a biological disease-modifying anti-rheumatic drugs (bDMARD) during the first year of treatment with a 5-year follow-up in early rheumatoid arthritis (ERA)., Methods: We included ERA patients from the UCLouvain Brussels cohort who met the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 classification criteria and were naïve to DMARDs. ERA patients were divided into two groups according to whether they received an induction bDMARD therapy or a standard therapy with methotrexate (MTX). Clinical response after the induction treatment at 6 and 12 months followed by a MTX maintenance therapy at 36 and 60 months was evaluated., Results: Data from 470 ERA patients were collected, 189 received a bDMARD and 281 initiated MTX alone. In the bDMARD group, disease activity and HAQ were higher at baseline. A total of 391 patients were followed up to 5 years. We then divided each group into two subgroups according to the last treatment they received at 5 years: bDMARD > MTX (n = 95), bDMARD > bDMARD (n = 59); MTX > MTX (n = 134), MTX > bDMARD (n = 103). During the induction, we observed a clinical response with a large number of patients achieving DAS28-CRP remission. According to a treat-to-target (T2T) approach, remission rate was stable on MTX monotherapy or rescued by the addition or prolongation of a bDMARD. Interestingly, bDMARD followed by a MTX maintenance therapy experienced a stable and sustained DAS28-CRP remission rate in 53% of the ERA patients at year 5., Conclusions: Long-term remission is an achievable goal in ERA. Our results suggest that a bDMARD induction therapy followed by MTX maintenance therapy could be an interesting option., (© 2023. The Author(s).)

Introduction: Magnetic resonance imaging (MRI) is the standard to quantify size and structure of lumbar muscles. Three-dimensional volumetric measures are expected to be more closely related to muscle function than two-dimensional measures such as cross-sectional area. Reliability and agreement of a standardized method should be established to enable the use of MRI to assess lumbar muscle characteristics., Objectives: This study investigates the intra- and inter-processor reliability for the quantification of (1) muscle volume and (2) fat fraction based on chemical shift MRI images using axial 3D-volume measurements of the lumbar multifidus in patients with low back pain., Methods: Two processors manually segmented the lumbar multifidus on the MRI scans of 18 patients with low back pain using Mevislab software following a well-defined method. Fat fraction of the segmented volume was calculated. Reliability and agreement were determined using intra-class correlation coefficients (ICC), Bland-Altman plots and calculation of the standard error of measurement (SEM) and minimal detectable change (MDC)., Results: Excellent ICCs were found for both intra-processor and inter-processor analysis of lumbar multifidus volume measurement, with slightly better results for the intra-processor reliability. The SEMs for volume were lower than 4.1 cm³. Excellent reliability and agreement were also found for fat fraction measures, with ICCs of 0.985-0.998 and SEMs below 0.946%., Conclusion: The proposed method to quantify muscle volume and fat fraction of the lumbar multifidus on MRI was highly reliable, and can be used in further research on lumbar multifidus structure., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Drug-induced sarcoidosis-like disease is a rare side effect of anti-tumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA) patients. The most commonly involved organs in such condition are the lungs, skin, and lymph nodes. The aim of this study is to report the number of cases and the clinical manifestations of sarcoidosis induced by anti-TNF in our RA UCLouvain Brussels cohort., Methods: All case records of RA patients ever treated with a TNF inhibitor and presenting anti-TNF induced sarcoidosis in our rheumatology centers from 2000 to 2021 were retrospectively reviewed., Results: Our RA UCLouvain Brussels cohort includes 2492 patients. Among them, 697 patients have been or are exposed to a TNF inhibitor. Only four patients with sarcoidosis induced by anti-TNF were identified and reviewed. Patient 1 was classified as incomplete Heerfordt syndrome. Patient 2 was a case of sarcoid-like granulomatosis manifesting as life-threatening hypercalcemia, acute kidney injury and atypical parenchymal pneumopathy. Patients 3 and 4 developed pulmonary sarcoidosis with hilar adenopathies. The TNF inhibitor was etanercept for the first three patients and infliximab for the last one. The time occurrence of sarcoidosis was highly variable after anti-TNF exposure. All patients recovered after glucocorticoid treatment and the discontinuation of the anti-TNF agent., Conclusions: This case highlights this rare paradoxical side effect and the variability of the clinical presentation. Further studies should analyze the immunopathology of such conditions., (© 2022. The Author(s).)

Objectives: To evaluate the proportion of patients with early RA (ERA) who had or had not initiated glucocorticoids, to analyse the baseline characteristics, and to assess the clinical benefit and side effects of glucocorticoids during 5 years of follow-up., Methods: We included patients with ERA from the UCLouvain Brussels cohort who met the ACR/EULAR 2010 classification criteria and were naïve to conventional DMARDs (cDMARDs). We retrospectively collected patient characteristics prior to the introduction of cDMARDs with or without glucocorticoids. Efficiency and serious adverse events were analysed at 6, 12, 36 and 60 months., Results: Data from 474 eligible ERA patients were collected; 180 patients initiated glucocorticoids compared with 294 who did not. At baseline, the increased CRP was the main factor that favoured the initiation of glucocorticoids followed by smoking, absence of ACPA, prescription of MTX as a monotherapy and age. Five years' follow-up of DAS28-CRP, HAQ or visual analog score (VAS) pain values did not differ between the two groups. We also analysed a subgroup of 139 patients who received >1 g of prednisolone during the 5-year period. We confirmed the same baseline differences and observed in addition more men and higher DAS-28CRP values. During the 5 years' follow-up, DAS-28CRP, VAS pain and HAQ remained significantly higher in this subgroup. More severe infections were also reported., Conclusion: In our ERA cohort, the initiation of glucocorticoid treatment did not bring additional benefit for the short- and long-term control of the disease. Glucocorticoid was more prescribed in seronegative RA patients with a higher level of inflammation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background/purpose: Studies have demonstrated that rheumatoid arthritis (RA) patients who achieve low disease activity or remission are able to taper biological disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to evaluate the proportion of patients in whom bDMARDs can be tapered in daily practice and to analyse the characteristics of these patients. Other objectives were to analyse which bDMARDs are more suitable for dose reduction and the cost savings., Results: Data from 332 eligible RA patients from our Brussels UCLouvain cohort were retrospectively analysed; 140 patients (42.1%) received a tapered regimen, and 192 received stable doses of bDMARDs. The age at diagnosis (43.1 vs 38.7 years, p = 0.04), health assessment questionnaire (HAQ) score (1.3 vs 1.5, p = 0.048), RF positivity rate (83.3 vs 72.9%, p = 0.04) and disease duration at the time of bDMARD introduction (9.7 vs 12.1 years, p = 0.034) were significantly different between the reduced-dose and stable-dose groups. Interestingly, relatively more patients receiving a tapered dose were treated with a combination of bDMARDs and methotrexate (MTX) (86.7% vs 73.8%, p = 0.005). In our cohort, anti-TNF agents were the most commonly prescribed medications (68%). Only 15 patients experienced a flare during follow-up. Adalimumab, etanercept and rituximab were the most common bDMARDs in the reduced-dose group and were associated with the most important reductions in annual cost., Conclusion: In daily practice, tapering bDMARDs in RA patients who have achieved low disease activity or remission is an achievable goal in a large proportion of patients, thereby reducing potential side effects and annual drug-associated costs. The combination of bDMARDs with MTX could improve the success of dose reduction attempts., Trial Registration: This retrospective non-interventional study was retrospectively registered with local ethics approval.

Introduction: Auxins are hormones that regulate plant growth and development. To accurately quantify the low levels of auxins present in plant and soil samples, sensitive detection methods are needed. In this study, the design and construction of two different whole cell auxin bioassays is illustrated. Both use the auxin responsive element HpaA as an input module but differ in output module. The first bioassay incorporates the gfp gene to produce a fluorescent bioassay. Whereas the second one utilizes the genes phzM and phzS to produce a pyocyanin producing bioassay whose product can be measured electrochemically., Results: The fluorescent bioassay is able to detect 4-hydroxyphenylacetic acid (4-HPA) and 2-phenylacetic acid (PAA) concentrations from 60 μM to 3 mM in a dose-responsive manner. The pyocyanin producing bioassay can detect 4-HPA concentrations from 1.9 to 15.625 μM and PAA concentrations from 15.625 to 125 μM, both in a dose-responsive manner., Conclusion: A fluorescent whole cell auxin bioassay and an electrochemical whole cell auxin bioassay were constructed and tested. Both are able to detect 4-HPA and PAA at concentrations that are environmentally relevant to plant growth.

In this project we report on the angiotensin I-converting enzyme (ACE)-inhibitory activity of a bovine gelatin hydrolysate (Bh2) that was submitted to further hydrolysis by different enzymes. The thermolysin hydrolysate (Bh2t) showed the highest in vitro ACE inhibitory activity, and interestingly a marked in vivo blood pressure-lowering effect was demonstrated in spontaneously hypertensive rats (SHR). In contrast, Bh2 showed no effect in SHR, confirming the need for the extra thermolysin hydrolysis. Hence, an angiotensin I-evoked contractile response in isolated rat aortic rings was inhibited by Bh2t, but not by Bh2, suggesting ACE inhibition as the underlying antihypertensive mechanism for Bh2t. Using mass spectrometry, seven small peptides, AG, AGP, VGP, PY, QY, DY and IY or LY or HO-PY were identified in Bh2t. As these peptides showed ACE inhibitory activity and were more prominent in Bh2t than in Bh2, the current data provide evidence that these contribute to the antihypertensive effect of Bh2t.