Intervertebral disc degeneration in warmblood horses: Histological and biochemical characterization

Gross morphology of healthy and degenerated intervertebral discs (IVDs) is largely similar in horses as in dogs and humans. For further comparison, the biochemical composition and the histological and biochemical changes with age and degeneration were analyzed in 41 warmblood horses. From 33 horses, 139 discs and 2 fetal vertebral columns were evaluated and scored histologically. From 13 horses, 73 IVDs were assessed for hydration, DNA, glycosaminoglycans, total collagen, hydroxyl-lysyl-pyridinoline, hydroxylysine, and advanced glycation end-product (AGE) content. From 7 horses, 20 discs were assessed for aggrecan, fibronectin, and collagen type 1 and 2 content. Histologically, tearing of the nucleus pulposus (NP) and cervical annulus fibrosus (AF), and total histological score (tearing and vascular proliferation of the AF, and chondroid metaplasia, chondrocyte-like cell proliferation, presence of notochordal cells, matrix staining, and tearing of the NP) correlated with gross degeneration. Notochordal cells were not seen in IVDs of horses. Age and gross degeneration were positively correlated with AGEs and a fibrotic phenotype, explaining gross degenerative changes. In contrast to dogs and humans, there was no consistent difference in glycosaminoglycan content and hydration between AF and NP, nor decrease of these variables with age or degeneration. Hydroxylysine decrease and collagen 1 and AGEs increase were most prominent in the NP, suggesting degeneration started in the AP. In caudal cervical NPs, AGE deposition was significantly increased in grossly normal IVDs and total collagen significantly increased with age, suggesting increased biomechanical stress and likelihood for spinal disease in this part of the vertebral column.

Three-Dimensional In Vitro Lymphangiogenesis Model in Tumor Microenvironment

Lymphangiogenesis is a stage of new lymphatic vessel formation in development and pathology, such as inflammation and tumor metastasis. Physiologically relevant models of lymphatic vessels have been in demand because studies on lymphatic vessels are required for understanding the mechanism of tumor metastasis. In this study, a new three-dimensional lymphangiogenesis model in a tumor microenvironment is proposed, using a newly designed macrofluidic platform. It is verified that controllable biochemical and biomechanical cues, which contribute to lymphangiogenesis, can be applied in this platform. In particular, this model demonstrates that a reconstituted lymphatic vessel has an in vivo–like lymphatic vessel in both physical and biochemical aspects. Since biomechanical stress with a biochemical factor influences robust directional lymphatic sprouting, whether our model closely approximates in vivo, the initial lymphatics in terms of the morphological and genetic signatures is investigated. Furthermore, attempting an incorporation with a tumor spheroid, this study successfully develops a complex tumor microenvironment model for use in lymphangiogenesis and reveals the microenvironment factors that contribute to tumor metastasis. As a first attempt at a coculture model, this reconstituted model is a novel system with a fully three-dimensional structure and can be a powerful tool for pathological drug screening or disease model.

Analysis of the influence parameters spine-pelvic balance on the risk of development degeneration and degenerative disease of adjacent segments after lumbar spine rigid fixation

Introduction An increase in the load on adjacent segments causes changes in the parameters of the spinal-pelvic balance and, as a consequence, the development of the so-called biomechanical «stress». Such pressures are a key link in the pathogenesis of degeneration, and in the presence of clinical and neurological manifestations of the latter and adjacent segment degenerative disease (ASD/ASDd).Objective of this study was to assess the effect of the parameters of the spinal pelvic balance on the risk of developing ASD/ASDd after dorsal decompression-stabilizing interventions (DDSI).Material and Methods The study included medical records of patients who underwent DDSI for lumbar spine degenerative diseases. Clinical and instrumental parameters were assessed.Results Based on the inclusion criteria, 98 patients (48 with signs of ASD/ASDd and 50 without) were included in the study. The average postoperative follow-up period for the respondents was 46.6 ± 9.8 months. If PI/ LL parameters were <10 and the ratio of segmental and global lumbar lordosis (LIV-SI/LI-SI) was 50% or more, the incidence of ASD/ASDd was significantly lower in patients who underwent rigid lumbar stabilization surgery.Conclusion The values of PI/LL parameters and the ratio of segmental and global lumbar lordosis are obvious risk factors for the development of ASD/ASDd after rigid lumbar spine DDSI.

The mechanical regulation of RNA binding protein hnRNPC in the failing heart

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by re-expressing fetal contractile proteins via transcriptional and post-transcriptional processes, like alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is upregulated and relocates to the sarcomeric Z-disk upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates to the translation machinery. Alterations in hnRNPC expression and localization can be mechanically determined and affect the AS of numerous mRNAs involved in mechanotransduction and cardiovascular diseases, like Hippo pathway effector YAP1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by impacting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNAs homeostasis mechanoregulation in pathological conditions.

Biomechanics in Removable Partial Dentures: A Literature Review of FEA-Based Studies

The present study was aimed at reviewing the studies that used finite element analysis (FEA) to estimate the biomechanical stress arising in removable partial dentures (RPDs) and how to optimize it. A literature survey was conducted for the English full-text articles, which used only FEA to estimate the stress developed in RPDs from Jan 2000 to May 2021. In RPDs, the retaining and supporting structures are subjected to dynamic loads during insertion and removal of the prosthesis as well as during function. The majority of stresses in free-end saddle (FES) RPDs are concentrated in the shoulder of the clasp, the horizontal curvature of the gingival approaching clasp, and the part of the major connector next to terminal abutments. Clasps fabricated from flexible materials were beneficial to eliminate the stress in the abutment, while rigid materials were preferred for major connectors to eliminate the displacement of the prosthesis. In implant-assisted RPD, the implant receive the majority of the load, thereby reducing the stress on the abutment and reducing the displacement of the prosthesis. The amount of stress in the implant decreases with zero or minimal angulation, using long and wide implants, and when the implants are placed in the first molar area.

Biomechanical Stress in Obturator Prostheses: A Systematic Review of Finite Element Studies

Aim. This systematic review is aimed at investigating the biomechanical stress that develops in the maxillofacial prostheses (MFP) and supporting structures and methods to optimize it. Design and Methods. A literature survey was conducted for full-text English articles which used FEA to examine the stress developed in conventional and implant-assisted MFPs from January 2010 to December 2020. Results. 87 articles were screened to get an update on the desired information. 74 were excluded based on a complete screening, and finally, 13 articles were recruited for complete reviewing. Discussion. The MFP is subjected to stress, which is reflected in the form of compressive and tensile strengths. The stress is mainly concentrated the resection line and around the apices of roots of teeth next to the defect. Diversity of designs and techniques were introduced to optimize the stress distribution, such as modification of the clasp design, using materials with different mechanical properties for dentures base and retainer, use of dental (DI) and/or zygomatic implants (ZI), and free flap reconstruction before prosthetic rehabilitation. Conclusion. Using ZI in the defective side of the dentulous maxillary defect and defective and nondefective side of the edentulous maxillary defect was found more advantageous, in terms of compression and tensile stress and retention, when compared with DI and free flap reconstruction.

Biomechanical stress in the context of competitive sports training triggers enthesitis

Objective To evaluate the influence of mechanical stress on the development of immediate enthesitis. Methods The BEAT study is an interventional study that assessed entheses in competitive badminton players before and immediately after a 60-min intensive training session. Power Doppler (PD) signal and Gray scale (GS) changes were assessed in the insertion sites of both Achilles tendon, patellar tendons, and lateral humeral epicondyles and quantified using a validated scoring system. Results Thirty-two badminton players were included. One hundred ninety-two entheseal sites were examined twice. The respective empirical total scores for PD examination were 0.1 (0.3) before and 0.5 (0.9) after training. Mean total GS scores were 2.9 (2.5) and 3.1 (2.5) before and after training, respectively. The mean total PD score difference of 0.4 between pre- and post-training was significant (p = 0.0014), whereas no significant difference for the mean total GS score was observed. Overall, seven participants (22%) showed an increased empirical total PD score. A mixed effects model showed a significant increase of PD scores after training, with a mean increase per site of 0.06 (95% CI 0.01 to 0.12, p = 0.017). Conclusions Mechanical stress leads to rapid inflammatory responses in the entheseal structures of humans. These data support the concept of mechanoinflammation in diseases associated with enthesitis.

Prosthodontic rehabilitation of residual mandibular defect with Fixed removable Hybrid prosthesis- A case report

Ameloblastoma is a rare, benign tumor of odontogenic epithelium that was recognized in 1827 by Cusack and renamed ameloblastoma in 1930 by Ivey and Churchill. Ameloblastomas can be found both in the maxilla and mandible with a greater predilection of about 80% in the mandible with the posterior ramus area being the most frequent site. While chemotherapy, radiation therapy, curettage and liquid nitrogen have been effective in some cases of ameloblastoma, surgical resection remains the most definitive treatment for this condition. Rehabilitation of residual mandibular defect post resection is a challenge due to long span compromised ridge condition and the absence of dentition. In such scenario, a fixed-removable prosthesis allows rapid return to excellent function by providing favorable biomechanical stress distribution along with restoration of esthetics, phonetics and ease of postoperative care and maintenance.This paper presents successful Prosthodontic rehabilitation of a patient with a large residual mandibular defect secondary to surgical resection for ameloblastoma using fixed-removable hybrid prosthesis.

Genetic and environmental determinants of diastolic heart function

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between ventricular stiffness and heart failure. Our results provide novel insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and tractable targets in heart failure.

AB0495 BIOMECHANICAL STRESS IN THE CONTEXT OF COMPETITIVE SPORTS TRAINING TRIGGERS ENTHESITIS

Background:Preclinical models have indicated that biomechanical stress can trigger entheseal inflammation (1). Furthermore, enthesitis is a hallmark of psoriatic arthritis (PsA) and spondyloarthritis (SpA), suggesting that mechanoinflammation is an important step in their pathogenesis (2). However, the relation between mechanical stress and enthesitis in humans is poorly investigated. Competitive badminton is a demanding stop-and-go sport that strains entheseal sites in particular and provides an opportunity to assess the impact of physical activity on the development of an instant inflammatory response in the entheses.Objectives:To evaluate the influence of mechanical stress on the development of immediate enthesitis.Methods:BEAT (Badminton Enthesitis Arthrosonography Study) is an interventional study that assessed entheses in competitive badminton players before and immediately after a 60-minute intensive training session by ultrasound. Power Doppler (PD) signal and Gray-Scale (GS) changes were evaluated at the insertions sites of both Achilles tendon, patellar tendons and lateral humeral epicondyles and quantified using a validated scoring system (3). Pre- and post-training scores were compared using linear mixed-effects models. We used interaction terms to assess possible differential effects on patellar, elbow and Achilles entheses.Results:Thirty-two badminton players (22 men, 10 women) with an average age of 31.1±13.0 years were included (Table 1). On average, they had been playing badminton for 16.2±10.1 years. 192 entheseal sites were examined twice. The respective empirical total scores for PD examination were 0.1 (0.3) before and 0.5 (0.9) after training (Figure 1). Mean total GS scores were 2.9 (2.5) and 3.1 (2.5) before and after training, respectively. The mean total PD score difference of 0.4 between pre- and post -training was significant with a p value of 0.0014, whereas the p value for the mean total GS score difference of 0.2 was 0.63. Overall, seven participants (22%) showed an increased empirical total PD score. A mixed-effects model showed a significant increase of PD scores after training, with a mean increase per site of 0.06 (95%CI 0.01 to 0.12, p=0.017).Table 1.Baseline characteristicsDemographic characteristicsN, total32Females, N (%)10 (31.3)Age, years (mean ± SD)36.1 ± 13.0Height, cm (mean value ± SD)178.6 ± 9.9Body weight, kg (mean value ± SD)74.7 ± 13.5Smoking, N (%)11 (34.4)Alcohol, N (%)24 (75.0)Concomitant DiseasesInflammatory bowel disease, N (%)0Psoriasis, N (%) 0Uveitis, N (%)0Diabetes mellitus, N (%)0Hypertension, N (%)2 (6.3)Sports historyYears Badminton (mean ± SD)16.2 ± 10.1Figure 1.Ultrasound scores before and after training Figure 1. A Spaghetti plots depicting inividual Gray-Scale and Power Doppler ultrasound scores before and after trainingConclusion:Mechanical stress leads to rapid inflammatory responses in the entheseal structures of humans. These data support the concept of mechanoinflammation in diseases associated with enthesitis. However, while such responses may be self-contained in healthy subjects, they may be prolonged and more pronounced in certain risk groups, such as patients with PsA or SpA.References:[1]Cambré I, et al. Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis. Nature Communications. 2018; 9:4613.[2]Schett G, et al. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol. 2017; 13:731-741.[3]Balint PV, et al. Reliability of a consensus-based ultrasound definition and scoring for enthesitis in spondyloarthritis and psoriatic arthritis: an OMERACT US initiative. Annals of the Rheumatic Diseases. 2018; 77:1730.Disclosure of Interests:David Simon: None declared., Arnd Kleyer: None declared., Sara Bayat: None declared., Johannes Knitza: None declared., Larissa Valor: None declared., Marina Schweiger: None declared., Georg Schett: None declared., Koray Tascilar: None declared., Axel Hueber Grant/research support from: Novartis Research Grant.