Synovial Inflammation as an Essential Feature of Osteoarthritis: Unravelling the Role of Viral Agents and Associations with Cognitive and Mental Health Outcomes. Doctoral Thesis
Notice bibliographique
Résumé
Osteoarthritis (OA) remains the most prevalent joint disorder worldwide, particularly affecting individuals over the age of 50. Although numerous pathogenetic mechanisms contribute to the initiation and progression of articular cartilage degeneration, synovial inflammation plays a significant role in the disease process. While the degree of inflammation in OA is less pronounced and not systemic as seen in inflammatory arthritides, its involvement constitutes a critical element in the pathogenesis, progression, and persistence of the disease. The effects of synovial inflammation extend beyond the stimulation of catabolic processes, encompassing the acceleration of cellular senescence and potential contributions to neuropsychiatric disturbances, including mood and cognitive alterations. While inflammation in OA has been previously investigated, the complex and multifactorial nature of its triggers, such as latent viral infections, requires further study. Moreover, the potential associations between synovial inflammation and depressive symptoms or cognitive decline remain insufficiently understood and warrant comprehensive investigation. In this study, two independent cohorts of 54 and 50 individuals undergoing joint replacement surgery were analysed. In the first cohort, a focused investigation on the persistence of parvovirus B19 (B19V) and human herpesvirus 7 (HHV-7) in the synovial membrane and their potential impact on inflammation was conducted using the Krenn synovitis histological scoring system. Immunohistochemical analyses were performed to evaluate the expression of tumour necrosis factor alpha (TNF-α) and transforming growth factor-beta (TGF-β) in synovial tissue and to investigate their association with viral presence. Nonetheless, HHV-7-positive samples showed a significant correlation between CD4+ lymphocyte infiltration and TNF-α expression, suggesting immune cell-specific responses to latent viral presence. Additionally, the role of S100 protein expression in the inflammatory process was assessed, showing a positive correlation. This integrative approach aimed to elucidate the contribution of chronic viral persistence and local immune responses to the synovial pathology observed in OA. The second cohort was evaluated for synovial inflammation and its correlation with urinary biomarkers, using ELISA method: C-telopeptide of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP), TNF-α, TGF-β1 and neuropsychological assessments, including Montreal Cognitive Assessment (MoCA), Patient Health Questionnaire-9 (PHQ-9), and Generalised Anxiety Disorder-7 (GAD-7) tests. In the second cohort, histologically confirmed synovitis scores varied widely and correlated with urinary TGF-β1 levels. Cognitive (MoCA) and affective (PHQ-9, GAD-7) scores showed significant associations with synovial inflammation, particularly in patients with moderate-to-high inflammatory grades. Cluster analysis revealed distinct inflammatory phenotypes with gender-linked variations in symptom severity and cognitive and affective symptom outcomes. The Doctoral Thesis was developed at RSU AAI Joint Laboratory of Electron Microscopy and the RSU Department of Internal Diseases, Latvia. Defence of the Doctoral Thesis will take place at the public session of the Promotion Council of Clinical Medicine on 18 December 2025 at 14.00 in the Hippocrates Lecture Theatre, 16 Dzirciema Street, Rīgas Stradiņš University and remotely via online platform Zoom. This Doctoral Thesis was developed with the support of the Fundamental and Applied Research grant No lzp-2018/1-0149 “Interdisciplinary study on the effects of inflammatory joint diseases on neurocognitive function” and support of European grant “Reducing networking gaps between Rīga Stradiņš University (RSU) and internationally-leading counterparts in viral infection-induced autoimmunity research” (VirA)”. 3.2. Clinical Medicine; Sub-Sector – Internal Medicine. Keywords: Synovial inflammation; HHV-7; Parvo-B19; cognitive decline; depression; anxiety.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».