From Low-Grade Inflammation in Osteoarthritis to Neuropsychiatric Sequelae : A Narrative Review

Nowadays, osteoarthritis (OA), a common, multifactorial musculoskeletal disease, is considered to have a low-grade inflammatory pathogenetic component. Lately, neuropsychiatric sequelae of the disease have gained recognition. However, a link between the peripheral inflammatory process of OA and the development of neuropsychiatric pathology is not completely understood. In this review, we provide a narrative that explores the development of neuropsychiatric disease in the presence of chronic peripheral low-grade inflammation with a focus on its signaling to the brain. We describe the development of a pro-inflammatory environment in the OA-affected joint. We discuss inflammation-signaling pathways that link the affected joint to the central nervous system, mainly using primary sensory afferents and blood circulation via circumventricular organs and cerebral endothelium. The review describes molecular and cellular changes in the brain, recognized in the presence of chronic peripheral inflammation. In addition, changes in the volume of gray matter and alterations of connectivity important for the assessment of the efficacy of treatment in OA are discussed in the given review. Finally, the narrative considers the importance of the use of neuropsychiatric diagnostic tools for a disease with an inflammatory component in the clinical setting.publishersversionPeer reviewe

Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk

Funding Information: This study was supported by Rīga Stradiņš University Internal Research Grant Nr. 6-ZD-22/3/2022 “Identification of specific osteoarthritis phenotypes and disease endotypes tackled using the molecular and cellular assessment of the synovium-cartilage-bone interplay by correlation-based network analysis”. The article processing charge was covered by Rīga Stradiņš University Research Department. Publisher Copyright: © 2023 by the authors.Osteoarthritis (OA) is a chronic, progressive, severely debilitating, and multifactorial joint disease that is recognized as the most common type of arthritis. During the last decade, it shows an incremental global rise in prevalence and incidence. The interaction between etiologic factors that mediate joint degradation has been explored in numerous studies. However, the underlying processes that induce OA remain obscure, largely due to the variety and complexity of these mechanisms. During synovial joint dysfunction, the osteochondral unit undergoes cellular phenotypic and functional alterations. At the cellular level, the synovial membrane is influenced by cartilage and subchondral bone cleavage fragments and extracellular matrix (ECM) degradation products from apoptotic and necrotic cells. These "foreign bodies" serve as danger-associated molecular patterns (DAMPs) that trigger innate immunity, eliciting and sustaining low-grade inflammation in the synovium. In this review, we explore the cellular and molecular communication networks established between the major joint compartments-the synovial membrane, cartilage, and subchondral bone of normal and OA-affected joints.publishersversionPeer reviewe

Eradication of damaged keratinocytes in cutaneous lichen planus forms demonstrated by evaluation of epidermal and follicular expression of CK15, indices of apoptosis and regulatory protein S100

Publisher Copyright: © 2016, Versalius University Medical Publisher.All rights reserved.The study of cytoskeleton arrangement and its contribution to survival of cell-to-cell contacts appears to be essential for understanding of numerous cellular and tissue processes. Applying CK15, S100 labeling and TUNEL reaction to cutaneous lichen planus subtypes, we found CK15 expression in the outer and inner root sheath of hair follicles, the basal epidermal layer, and eccrine glands. Its follicular expression was decreased in nearby inflammatory infiltrates. The CK15 immu-nopositivity was mostly described as weak (92.3%) for lichen planus but equally subdivided into weak, moderate and strong in lichen planopilaris (χ2 = 32.514; df = 4; p < 0.001). The greatly varying apoptotic index was the highest in the lichen planopilaris involving the scalp: 81.2 ±10.7; 87.8 ±10.7 and 88.0 ±10.5 for the basal, spinous and upper epidermal layers, respectively. S100 positive epidermal and follicular cells did not differ in the lesions demonstrated in the study groups; still immunoreactivity was more pronounced in the scalp region of lichen planopilaris. Damage of cell-to-cell contacts was confirmed by electron microscopy. Apart from immunocyte-mediated keratinocyte death, cytoskeleton-based injury and loss of cell-to-cell and matrix contacts may be of great importance, leading to eradication of degrading cells and thus contributing to the pathogenesis of lichen planus.publishersversionPeer reviewe

Evaluation of Clinical Manifestations of Hemorrhoidal Disease, Carried Out Surgeries and Prolapsed Anorectal Tissues : Associations with ABO Blood Groups of Patients

Funding Information: This research received funding (Nr. 6-DN-20/2/2023) from Riga Stradiņš University Department of Doctoral Studies for the purchase of reagents and coverage of the article processing charge. Publisher Copyright: © 2023 by the authors.Hemorrhoidal disease (HD) is a chronic multifactorial disease. Increased abdominal pressure, along with hyperperfusion, neovascularization, overexpression of inflammatory mediators, and dysbiosis, contributes to the development of HD. The deterioration of the anchoring connective tissue with reduced collagen content and altered collagen ratios, dilatation of blood vessels and thrombosis, muscle injury, and inflammation gradually lead to clinically manifesting prolapse and bleeding from hemorrhoids. The associations of the ABO blood types with a disease have been investigated for the upper gastrointestinal tract only. This study aimed to evaluate HD clinical manifestations, surgeries carried out, and the status of prolapsed anorectal tissues by exploring the associations with the patients’ ABO blood groups. Clinical and various morphological methods, combined with extensive bioinformatics, were used. The blood type 0, grade III and IV HD individuals constituted the largest group in a moderately-sized cohort of equally represented males and females studied and submitted to surgical treatment of hemorrhoids. There were significantly more complaints reported by HD females compared to males (p = 0.0094). The Longo technique appeared mostly used, and there were proportionally more surgeries performed below the dentate line for HD individuals with blood type 0 compared to other blood type patients (24% vs. 11%). HD males were found to present with significantly more often inflamed rectal mucosa (p < 0.05). Loosening and weakening of collagenous components of the rectal wall combined with vascular dilation and hemorrhage was found to differ in 0 blood type HD individuals compared to other types. HD males were demonstrated to develop the ruptures of vascular beds significantly more often when compared to HD females (p = 0.0165). Furthermore, 0 blood type HD males were significantly more often affected by a disease manifested with tissue hemorrhage compared to the 0 blood type HD females (p = 0.0081). Collectively, the local status of chronically injured anorectal tissue should be considered when applying surgical techniques. Future studies could include patients with HD grades I and II to gain a comprehensive understanding of the disease progression, allowing for a comparison of tissue changes at different disease stages.Peer reviewe

Worldwide Disease — Haemorrhoids. How much do we know?

Publisher Copyright: © 2021 Sciendo. All rights reserved.Haemorrhoids are highly vascular cushions of connective tissue in the anal canal, which are normal structures of the human body. Haemorrhoidal disease in clinical practice means that there is an abnormal enlargement of the anal cushions when these transform into “anal nodules”, bleed and/or prolapse. Haemorrhoidal disease is very common. Despite numerous studies undertaken and knowledge accumulated on the aetiology and pathogenesis of haemorrhoidal disease in the last decade, the specific mechanisms responsible for the development of the disease are not thoroughly understood. The pathophysiology is most likely multifactorial and complex, manifested by muscle weakness, intrarectal prolapse, changes in vascular pressure and flow in blood vessels, malformations, sphincter damage and failure, venostasis, inflammatory reactions, endothelin and collagen abnormalities, matrix metalloproteinases activity, etc. Currently, treatment guidelines for the haemorrhoidal disease are based on Goligher's classification. The classification of haemorrhoidal disease should be submitted to revision by including aetiological factors, the dynamism of prolapse, symptomatology, enteropathogenesis, and gender characteristics. The present review is focused on recent data gained by exploring the anatomy, pathophysiology, classification, theories explaining the development of haemorrhoids, as well as aetiological invasive and surgical treatment modalities.publishersversionPeer reviewe

What we need to learn when exploring the mixed basal cell carcinoma of head and neck

Publisher Copyright: © 2021 Sciendo. All rights reserved.Coexistence of different histopathological types of basal cell carcinomas (BCC) in the same anatomical localisation is rare, and, therefore, is engaging for histopathologists and clinicians. In many cases, the determination of a neoplasm type remains difficult, since BCC may consist of more than one histopathological subtype. Mixed BCCs often present with an aggressive course and recurrence when compared to other subtypes of a tumour. Furthermore, tumours of this type are associated with time-consuming treatment and not a very satisfactory cosmetic result, thus worsening the quality of the patient’s life. Several clinical studies have been published regarding the histopathologically diverse tumours developed in the same anatomical region; however, largely peculiarities of mixed BCCs are not explored sufficiently. The purpose of this study was to substantiate the use of dermoscopy and morphology, assessing mixed type BCC of the head and neck. The tumours were removed with a surgical excision of 1 cm margins, and the tumour sites were assessed in a 24-month-long follow-up period. The dermoscopic characteristics of mixed and aggressive BCC are analysed in this study. Finally, to better estimate the invading cone of the tumour, a complex morphology, which included collagen type IV and podoplanin immunohistochemistry, and electron microscopy were used.publishersversionPeer reviewe

Etiology, Risk Factors and Clinical Outcomes in Infective Endocarditis Patients Requiring Cardiac Surgery

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Background: Infective endocarditis, which may be caused by various microbial agents, severely affects the innermost layer of the heart and often leads to poor clinical outcomes. The purpose of this study was to investigate the etiology, risk factors and short and long-term outcomes of infective endocarditis caused by various bacterial agents in patients requiring cardiac surgery. Methods: One hundred and forty-four patients aged 18 years or above with indications for cardiac surgery due to S. aureus, Streptococcus spp., E. faecalis or coagulase-negative staphylococci caused infective endocarditis were included in this study. Results: S. aureus, Streptococcus spp., E. faecalis and coagulase-negative staphylococci were the causative agents of infective endocarditis in 44 (30.6%), 35 (24.3%), 33 (22.9%) and 32 (22.2%) patients, respectively. The presence of bicuspid aortic valve was the most common predisposing factor confirmed in 19 (23.5%), whereas intravenous drug usage was the most common in 17 (11.8%) patients. No significant differences in intrahospital mortality due to infective endocarditis caused by various bacterial agents were found, however, the worsening of long-term prognosis of endocarditis caused by S. aureus when compared to E. faecalis was confirmed (p = 0.03). The presence of S. aureus was associated with significantly higher rates of embolic complications (p = 0.003). The presence of coagulase-negative staphylococci was associated with prosthetic valve endocarditis (p = 0.015) and perivalvular complications (p = 0.024). Conclusions: In contrast to E. faecalis, the presence of S. aureus determines the worsening of the long-term mortality from infective endocarditis. Perivalvular complications are associated with the presence of coagulase-negative staphylococci.publishersversionPeer reviewe

Long-term complications evidenced studying the explanted Gore® HELEX® atrial septal defect occluder seven years after implantation : a case report

We present the results of the first morphological study of a Gore® HELEX® Septal Occluder 30 mm that was explanted seven years after interventional implantation due to a significant left-to-right shunt (7 mm) which resulted from the stretching of the concomitant patent foramen ovale by the occluder after atrial septal defect closure. Complete endothelialization of the surface of the device, the formation of the connective tissue around the implant, minor chronic inflammation, the appearance of foreign body giant cells and weakened myocardial cells adjacent to the implant as well as enhanced expression of matrix metalloproteinases were demonstrated.publishersversionPeer reviewe

Hydroxyapatite ceramics for restoration of alveolar bone

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Plasma levels of Th17-associated cytokines and selenium status in autoimmune thyroid diseases

© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.INTRODUCTION: The contribution of Th17 cytokines to autoimmune thyroid disease (AITD) is generally accepted. However, the roles of Th17 cells in the initiation and progression of Hashimoto's thyroiditis (HT) and Graves' disease (GD) remain unclear. Selenium deficiency, along with genetic predisposition and environmental factors, may have a role in thyroid autoimmunity. AIM: We aimed to assess (1) the Th17 immune response by measuring plasma levels of Th17- and Treg-associated cytokines and (2) the selenium status in treatment-naïve Latvian patients with newly diagnosed GD or HT. METHODS: Eleven GD patients, 41 HT patients, and 26 healthy subjects were recruited for this study. Plasma levels of IL-17a, IL-22, IL-23, IL-6, and IL-10 were detected by xMAP technology, while selenium was detected fluorometrically. RESULTS AND CONCLUSIONS: No significant differences in IL-17a, IL-22, IL-23, IL-6, or IL-10 levels were found among the HT patients, GD patients, and controls. In the HT patients, IL-17a levels were positively correlated with IL-22, IL-23, IL-6, and IL-10, while IL-22 was correlated with IL-6, IL-23, and IL-10. In the GD patients, IL-17a levels were positively correlated with IL-22, IL-23, and IL-10; IL-22 was positively correlated with IL-23, IL-6, and IL-10; FT3 was positively correlated with IL-17a, IL-23, and IL-10; and FT4 was positively correlated with IL-17a and IL-10 levels. Plasma selenium levels were negatively correlated with antithyroid peroxidase antibody titers in the HT patients. Although no difference in selenium levels was observed between the AITD patients and controls, the selenium status of the Latvian patients with GD or HT was at a suboptimal level.publishersversionPeer reviewe