Severe Joint Damage Research Articles

Recurrent septic arthritis caused by Gemella morbillorum: a case report and literature review

Gemella morbillorum is a gram-positive coccus that is part of the normal microbiota of the human oral cavity and gastrointestinal tract. It is an opportunistic pathogen that can cause invasive infections, including septic arthritis. Septic arthritis caused by Gemella morbillorum is relatively rare, but when it occurs, it can lead to severe joint damage and other complications if not promptly diagnosed and treated. Here, we report a case of recurrent septic arthritis caused by Gemella morbillorum.

Managing of Post-traumatic Knee Arthritis by Total Knee Arthroplasty: Case Report and Literature Review

Introduction: Post-traumatic knee osteoarthritis (PTOA) develops rapidly after injuries from sports, accidents, or falls. Unlike primary osteoarthritis, PTOA escalates quickly, causing severe joint damage and impairments. Early intervention is crucial to alleviate pain, restore function, and prevent further deterioration. Delayed treatment worsens symptoms and increases the need for invasive procedures like total knee arthroplasty (TKA). Case Presentation: A 29-year-old patient with a year of left knee pain, swelling, and difficulty straightening had no history of rheumatic or autoimmune diseases. Examination showed osteophytes, indicating osteoarthritis. He underwent TKA with no complications, achieving a satisfactory outcome: good range of motion, improved quality of life, and an Oxford Knee Score of 42. Discussion: PTOA typically follows trauma to the joint surface, with severity often correlating with the impact intensity. In this case, the patient’s rapid development of osteoarthritis, despite his young age and lack of pre-existing conditions, may suggest a genetic predisposition. Knee arthroplasty was chosen to restore function, aligning with research showing comparable outcomes for post-traumatic and primary osteoarthritis patients, though post-trauma cases can have higher complication rates due to comorbidities. Conclusion: Effective management of PTOA is crucial due to its rapid progression and significant impact on joint function and quality of life. Early intervention is key to preventing severe damage and reducing the need for invasive treatments. While TKA can be effective, its success depends on the severity of the condition. Timely management and preventive strategies are vital to improving outcomes and maintaining joint health. Keywords: post traumatic osteoarthritis, total knee arthroplasty, quality of life, early intervention, case report

To Assess the Functional outcome of Inflammatory arthritis of Knee following a Total Knee Replacement in a Tertiary Care Centre

Introduction : Inflammatory arthritis, particularly RA, can lead to significant joint destruction and functional impairment, necessitating interventions such as TKA. Despite medical therapy, severe joint damage may occur, warranting surgical intervention. This study assesses the functional outcomes post-TKA in patients having inflammatory arthritis. Materials and Methods: Patients who received TKA for inflammatory arthritis were included in this prospective observational cohort research, specifically RA, between 2019 and 2023 at Saveetha Medical College, Chennai. Clinical, radiological, and functional results have been assessed using the American Knee Society scoring system. IBM SPSS version 22.0 was utilized for analysis of data, p < 0.05 is the threshold for statistical significance. Results:Twenty TKAs have been performed for RA, with all patients successfully followed up. The mean age of the patients was 58.5 years, and the majority were female. Before TKA, the average length of RA was 7.24 years, and all patients were in stage IV illness. Preoperative and postoperative knee society scores showed significant improvement, with average scores of 58.15 and 96.15, respectively. Functional scores also demonstrated substantial enhancement post-TKA, with an average increase of 130%. Radiological assessment revealed no evidence of lysis in any patient. Conclusion: Significant inverse relationship among the postoperative functional score and the length of the disease and the involvement of other joints. Utilizing the American Knee Society and functional scoring systems allows for objective prediction of surgical success. This can motivate surgeons and treating physicians to enhance care for RA patients.

Self-immunological disease aid diagnosis with ConvSANet and Eu-clidean distance

BackgroundAnkylosing spondylitis (AS), Osteoarthritis (OA), and Sjögren's syndrome (SS) are three prevalent autoimmune diseases. If left untreated, which can lead to severe joint damage and greatly limit mobility. Once the disease worsens, patients may face the risk of long-term disability, and in severe cases, even life-threatening consequences. ResultIn this study, the Raman spectral data of AS, OA, and SS are analyzed to auxiliary disease diagnosis. For the first time, the Euclidean distance(ED) upscaling technique was used for the conversation from one-dimensional(1D) disease spectral data to two-dimensional(2D) spectral images. A dual-attention mechanism network was then constructed to analyze these two-dimensional spectral maps for disease diagnosis. The results demonstrate that the dual-attention mechanism network achieves a diagnostic accuracy of 100 % when analyzing 2D ED spectrograms. Furthermore, a comparison and analysis with s-transforms(ST), short-time fourier transforms(STFT), recurrence maps(RP), markov transform field(MTF), and Gramian angle fields(GAF) highlight the significant advantage of the proposed method, as it significantly shortens the conversion time while supporting disease-assisted diagnosis. Mutual information(MI) was utilized for the first time to validate the 2D Raman spectrograms generated, including ED, ST, STFT, RP, MTF, and GAF spectrograms. This allowed for evaluation of the similarity between the original 1D spectral data and the generated 2D spectrograms. SignificantThe results indicate that utilizing ED to transform 1D spectral data into 2D images, coupled with the application of convolutional neural network(CNN) for analyzing 2D ED Raman spectrograms, holds great promise as a valuable tool in assisting disease diagnosis. The research demonstrated that the 2D spectrogram created with ED closely resembles the original 1D spectral data. This indicates that ED effectively captures key features and important information from the original data, providing a strong descript.

Total knee and hip replacement in rheumatoid arthritis: A current trend

Total joint replacement (TJR) is a surgical procedure widely used in severe destructive joint damage. TJR of the knee and hip joint (TKR and THR respectively) occupies an important place in the complex treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), and can significantly reduce pain and improve function in patients with severe structural joint damage due to an ineffectiveness of conservative therapy. In recent years, due to the development of the modern concept of active treatment of RA (treat-to-target) and the introduction of new classes of anti-inflammatory drugs, such as biologic disease modifying antirheumatic drugs and JAK inhibitors, the need for TJR in RA has begun to decrease. At the same time, the aging of the population, the increase in the number of patients with OA and the lack of generally approved pathogenetic therapy determine the increase of TKR/THR incidence in this disease. This review presents the long-term dynamics of the incidence of TKR and THR according to the national registers of different countries. The issues of the complication risks in patients with RA and OA, current recommendations for anti-rheumatic therapy in RA in the perioperative period are also considered.

CD8 T cell-derived perforin regulates macrophage-mediated inflammation in a murine model of gout.

Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow-derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage.

Targeting the serum marker interleukin 9 improves the underlying characterization and immune homeostasis in rheumatoid arthritis.

Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are serological markers used for diagnosing rheumatoid arthritis (RA), an autoimmune disease characterized by inflammatory joint damage. However, there is a subset of RA patients who test negative for both RF and ACPA, known as seronegative rheumatoid arthritis (SNRA). The levels of serum markers were examined in both clinical samples and a rat model of type II collagen-induced RA (CIA). The effect of interleukin 9 (IL-9) on RA was investigated using recombinant rat IL-9 (rrIL-9), anti-rat IL-9 neutralizing monoclonal antibody (mAb), and control IgG antibody in the CIA rat. The severity of arthritis was assessed. Treg and Th17 cells, M1 and M2 macrophages, and inflammatory cytokine levels were analyzed. We observed higher levels of IL-9 in clinical samples from SNRA patients compared to the normal group. Rat models of CIA exhibit increased arthritis scores, weight loss, paw swelling, and severe joint damage. IL-9 was the most sensitive serum marker for the diagnosis of RA in serum assays of CIA rats. IL-9 increased arthritis scores and cartilage damage, whereas treatment with IL-9 inhibitors produced the opposite effect. IL-9 inhibitors promoted Treg/Th17 homeostasis, decreased M1 macrophages, increased M2 macrophages, and decreased levels of inflammatory cytokines in joint tissues. These results suggest that IL-9 has potential as a diagnostic marker for SNRA. Inhibition of IL-9 could reduce the severity of arthritis in CIA rats by ameliorating inflammation and modulating the Treg/Th17 immune balance, M2 and M1 macrophage activation.

A review of carbon fiber-reinforced polymer composite used to solve stress shielding in total hip replacement

<abstract> <p>Arthroplasty is generally used to treat advanced osteoarthritis or other degenerative joint diseases. However, it can also be considered in younger patients with severe joint damage that seriously limits their function and quality of life. Young patients are at risk of aseptic mobilization and bone resorption due to the uneven distribution of stress on the contact surface between the prosthesis and the femur that generates the stress-shielding phenomenon. To overcome this occurrence, it is necessary to use biocompatible materials with a stiffness that is similar to bone. Composite hip prostheses, consisting of continuous fiber-reinforced polymers, play a progressively key role in the development of prosthetic devices. Composite materials can be designed more carefully than monolithic stems (single-phase materials such as metals), allowing for the development of more effective tissue substitutes. Our purpose of this review was to analyze the state of the art in the use of carbon femoral prostheses. In particular, the major mechanical properties of reinforcement (fiber) and matrix were outlined with their applications in the prosthetic field.</p> </abstract>

Gender Differences in Clinical Characteristics of Rheumatoid Arthritis

The most prevalent type of autoimmune inflammatory arthritis is rheumatoid arthritis (RA). Sex hormones are strongly associated in the pathogenesis and progression of RA. Hence, the core objective of this study was to compare the clinical features of RA among men and women. We consecutively recruited 23 men and 23 age-matched women with RA from our rheumatology clinic. Subjects were evaluated for their disease activities, radiographic joint damages and functional capacities. The above assessment was performed using DAS-28, Modified Sharp Score (MSS) and European League Against Rheumatism (EULAR) response criteria; respectively. The mean age for the male and female patients were 60.87 + 12.5 and 60.70 + 11.73, respectively. We found that the female subjects had significantly higher c-reactive protein (CRP) levels (p=0.05). The HAQ-DI(p<0.02) and MSS scores (p<0.001) of women were substantially higher than those of males. HAQ-DI and MSS remained to be independently associated with female gender in multivariate analysis, with p values of 0.017 and 0.014, respectively. The findings of this study suggested that in RA, compared to men, women had more severe joint damage and functional disability.

The possibility of a favourable outcome and reversibility of severe ankle joint damage on the example of a clinical observation

The problem of aseptic talus necrosis consists of the following features: a) manifestation of the disease in the form of acute articular syndrome without typical symptoms; b) inevitable serious consequences in the form of disfiguring deforming arthrosis of the ankle joint, development of gross deformities of the rearfoot, etc., resulting in disability. The lack of methods for monitoring the dynamics of the disease also plays an important role. This is particularly so with such an important issue as the substantiation of stopping immobilization and allowing the load on the foot in order to avoid collapsed talus and subsequent complications. It is believed that treatment started before radiographic changes helps to avoid severe complications, but for a number of reasons patients arrive already at the stage of late severe destructive changes. All of the above explains the high relevance of the problem of treatment of patients with aseptic talus necrosis. The importance of the presented clinical case and the value of this information can be considered several points: its example demonstrates the possibility of early diagnosis of severe talus damage cause by aseptic necrosis; based on objective data, a substantiation was made for allowing the load on the leg with body weight in the complex of rehabilitation measures; the possibility of regression of pathological changes associated with aseptic talus necrosis and the dynamics of the course of aseptic talus necrosis with a favorable outcome were demonstrated, which is confirmed by modern research methods. Thus, the need for magnetic resonance imaging has been confirmed for all referred patients with a clinical picture of local articular syndrome in the ankle joint, the possibility of complete regression of avascular necrosis symptoms in case of conservative treatment at the early stages and the possibility of resolving the load on the leg in the complex of rehabilitation treatment have been demonstrated.

Enzyme targeted delivery of sivelestat loaded nanomicelle inhibits arthritic severity in experimental arthritis

AimsRheumatoid arthritis (RA) is chronic inflammatory disorder mainly affects the lining of articular cartilage of synovial joints characterized by severe inflammation and joint damage. The expression of proteolytic enzymes like MMP-2 and Neutrophil Elastase (NE) worsens the RA condition. To address this concern, we have synthesized dual enzyme targeted chlorotoxin conjugated nanomicelles loaded with sivelestat as broad spectrum treatment for RA. Materials and methodsConjugation of the chlorotoxin over nanomicelle and incorporation of sivelestat in nanomicelle provide it dual targeting potential. The sivelestat loaded nanomicelle (SLM) evaluated for the drug release and in-vitro cytocompatibility. Further, investigated its in-vivo anti-arthritic potential on collagen-induced arthritis in wistar rats. Key findingsThe microscopic observation of SLM showed spherical ball like appearance with size ranging from 190 to 230 nm. SLM showed good drug loading and encapsulation efficiency along with no cytotoxicity against healthy cell lines. In-vivo therapeutic assessment on collagen induced arthritis rat model showed potential chondroprotection. The microscopic visualization of articular cartilage by staining showed that it restores the cartilage integrity and lowers the expression of pro-inflammatory enzymes showed by Immunohistochemistry and Immunofluorescence. We observed that, it restrain the mediators of synovial inflammation by simultaneous inhibition of the proteolytic enzymes involved in swelling, cartilage destruction and joint damage which provides strong chondroprotection. SignificanceWe report that significant alleviation of inflammation and inhibition of proteolytic enzymes together might provide enhanced potential for the treatment and management of RA.

Sexual dimorphism of the synovial transcriptome underpins greater PTOA disease severity in male mice following joint injury

Osteoarthritis is a disease with sex-dependent prevalence and severity in both humans and animal models. We sought to elucidate sex differences in synovitis, mechanical sensitization, structural damage, bone remodeling, and the synovial transcriptome in the anterior cruciate ligament rupture (ACLR) mouse model of post-traumatic osteoarthritis (PTOA). Male and female 12-week-old C57/BL6J mice were randomized to Sham or noninvasive ACLR with harvests at 7d or 28d post-ACLR (n=9 per sex in each group - Sham, 7d ACLR, 28d ACLR). Knee hyperalgesia, mechanical allodynia, and intra-articular MMP activity (via intravital imaging) were measured longitudinally. Trabecular and subchondral bone remodeling and osteophyte formation were assessed by µCT. Histological scoring of PTOA and synovitis and anti-MMP13 immunostaining were performed. NaV1.8-Cre;tdTomato mice were used to document localization and sprouting of nociceptors. Bulk RNA-seq of synovium in Sham, 7d, and 28d post-ACLR, and contralateral joints (n=6 per group per sex) assessed injury-induced and sex-dependent gene expression. Male mice exhibited more severe joint damage at 7d and 28d and more severe synovitis at 28d, accompanied by 19% greater MMP activity, 8% lower knee hyperalgesia threshold, and 43% lower hindpaw withdrawal threshold in injured limbs compared to female injured limbs. Females had injury-induced catabolic responses in trabecular and subchondral bone, whereas males exhibited 133% greater normalized osteophyte volume relative to females and sclerotic remodeling of trabecular and subchondral bone. NaV1.8+ nociceptor sprouting in subchondral bone and medial synovium was induced by injury and comparable between sexes. RNA-seq of synovium demonstrated similar injury-induced transcriptomic programs between the sexes at 7d, but only female mice exhibited a transcriptomic signature indicative of synovial inflammatory resolution by 28d, whereas males had persistent pro-inflammatory, pro-fibrotic, pro-neurogenic, and pro-angiogenic gene expression. Male mice exhibited more severe overall joint damage and pain behavior after ACLR, which was associated with persistent activation of synovial inflammatory, fibrotic, and neuroangiogenic processes, implicating persistent synovitis in driving sex differences in murine PTOA.

Topology Optimization of a Femoral Stem in Titanium and Carbon to Reduce Stress Shielding with the FEM Method

Arthroplasty is commonly performed to treat advanced osteoarthritis or other degenerative joint conditions; however, it can also be considered for young patients with severe joint damage that significantly limits their functionality and quality of life. Young patients are still at risk of aseptic mobilization and bone resorption due to the phenomenon of stress shielding that causes an uneven distribution of tensions along the femoral contact surface prosthesis. This phenomenon can be limited by choosing the material of the prosthesis appropriately or by varying its stiffness, making sure that its mechanical behavior simulates that of the femur as much as possible. The aim of this study is to evaluate the mechanical strength of a prosthesis optimized both in shape and material and compare the results with a standard titanium prosthesis. Methods: Through three-dimensional modeling and the use of finite element method (FEM) software such as ANSYS, the mechanical behavior of traditional prosthesis and prosthesis optimized topologically respecting the ASTM F2996-13 standard. Results: With topological optimization, there is a stress reduction from 987 MPa to 810 MPa with a mass reduction of 30%. When carbon fiber is used, it is possible to further reduce stress to 509 MPa. Conclusions: The reduction in stress on the femoral stem allows an optimal distribution of the load on the cortical bone, thus decreasing the problem of stress shielding.

Ultrasound Evaluation of Tendinopathy in Hemophiliac Patients for the Purpose of Rehabilitation Indications.

Hemophilia is a inherited bleeding disorder that is characterized by intra-articular bleeding (hemarthrosis). The aim of the study was to evaluate the state of the satellite tendons of the target joints in the patient with hemophilic arthropathy and propose rehabilitation treatment with eccentric exercises. The tendons of the joints mainly affected by hemophilic arthropathy were evaluated by ultrasound. The ultrasound evaluation is associated with the use of evaluation clinical scales, such as the Hemophilia Joint Health Score (HJHS), the Functional Independence Score in Hemophilia (FISH), the Hemophilia Activity List (HAL), the DASH, the VISA-A, the VISA-P, and the VAS scale. In 20 patients with hemophilic arthropathy, the thickness of the tendons that were examined was normal. In six subjects with severe joint damage, echostructural alterations were present, and signs of hyperemia and neo-vascularization were detected on color Doppler, as well as the presence of intratendinous calcifications. The tendons of the target joints in patients with hemophilic arthropathy are compromised by the indirect biomechanical damage caused by the joint disease, and rehabilitation treatment with eccentric exercises can be considered safe and effective in improving the tenso-elastic properties of the tendons.

Treatment for Acute Anterior Cruciate Ligament Tear in Young Active Adults

BackgroundAnterior cruciate ligament (ACL) injury of the knee is common in young active adults and often has severe and sometimes lifelong consequences. The clinical management of this injury remains debated. A prior trial of early versus delayed optional ACL repair showed no differences in outcomes at 2 years.MethodsWe present the 11-year follow-up of a randomized clinical trial involving 121 young active adults (mean age 26yo, 74% male) with an acute sports-related ACL tear. We compared patient-reported and radiographic outcomes between those randomized to receive early ACL reconstruction (ACLR) followed by exercise therapy (N=62) and those treated with early exercise therapy plus optional delayed ACLR (N=59). The primary end point at 11 years was change from baseline in the mean of four subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) — pain, symptoms, function in sports and recreation, and knee-related quality of life (KOOS4; range of scores, 0 [worst] to 100 [best]; minimal important change=9).ResultsIn all, 88% of the cohort followed up at 11 years (53/62 in the early vs. 54/59 in the optional late ACL repair groups), and 52% of those assigned to optional delayed ACLR underwent ACLR. Mean improvement in KOOS4 from baseline to 11 years was 46 points for those assigned to early ACLR plus exercise therapy and 45 points for those assigned to exercise therapy plus optional delayed ACLR (between-group difference, 1.6 points; 95% confidence interval [CI], −8.8 to 5.6; P=0.67 after adjustment for baseline score, full analysis set). About two thirds of the full cohort reported meeting the case definition for a “patient-acceptable symptom state” (KOOS4 patient-acceptable symptom state threshold value=79), whereas 44% had developed radiographic osteoarthritis of their injured knee. Mean summed incident radiographic osteoarthritis feature scores, scores range from 0 to 30 where higher scores indicate more severe joint damage, were 2.4 for the group assigned to early ACLR and 1.0 for the group assigned to exercise therapy plus optional delayed ACLR (mean difference, 1.0; 95% CI, 0.1 to 1.9).ConclusionsAt 11-year follow-up, among young active adults with acute ACL tears assigned to early ACLR plus exercise versus initial exercise therapy with the option of delayed ACLR, there were no differences in patient-reported outcomes. (Funded by the Swedish Research Council; ISRCTN number, ISRCTN84752559.)

Nitric Oxide Synthases in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe joint damage and disability. However, the specific mechanism of RA has not been thoroughly clarified over the past decade. Nitric oxide (NO), a kind of gas messenger molecule with many molecular targets, is demonstrated to have significant roles in histopathology and homeostasis. Three nitric oxide synthases (NOS) are related to producing NO and regulating the generation of NO. Based on the latest studies, NOS/NO signaling pathways play a key role in the pathogenesis of RA. Overproduction of NO can induce the generation and release of inflammatory cytokines and act as free radical gas to accumulate and trigger oxidative stress, which can involve in the pathogenesis of RA. Therefore, targeting NOS and its upstream and downstream signaling pathways may be an effective approach to managing RA. This review clearly summarizes the NOS/NO signaling pathway, the pathological changes of RA, the involvement of NOS/NO in RA pathogenesis and the conventional and novel drugs based on NOS/NO signaling pathways that are still in clinical trials and have good therapeutic potential in recent years, with an aim to provide a theoretical basis for further exploration of the role of NOS/NO in the pathogenesis, prevention and treatment of RA.

Rheumatoid arthritis.

It is difficult to determine from ancient writings, old human specimens, and from Art over the centuries, as to when Rheumatoid Arthritis first appeared. It may be a relatively modern condition, as it was reasonably well described in the seventeenth century. Augustin Jacob Landre-Beauvais (1772-1840), University of Paris is credited, with the first clear description of the disease in his thesis. In 1859 Sir Alfred Baring Garrod (1819-1907), the "father of rheumatology", gave the disease its current name which was finally adapted in Britain by the Ministry of Health in 1922. Some forms of Juvenile Arthritis are related to adult Rheumatoid Arthritis (aka Still's disease). If untreated Rheumatoid arthritis can result in severe destructive joint damage and often there are associated severe systemic complications. Disease modifying agents have benefited the disease management, but it was the discovery of the anti TNF-alpha agents in the 1990s, and subsequently many additional Biologic agents, which have greatly changed the clinical outcome in Rheumatoid Arthritis.

Wheel Running Exacerbates Joint Damage after Meniscal Injury in Mice, but Does Not Alter Gait or Physical Activity Levels.

Exercise and physical activity are recommended to reduce pain and improve joint function in patients with knee osteoarthritis (OA). However, exercise has dose effects, with excessive exercise accelerating OA development and sedentary behaviors also promoting OA development. Prior work evaluating exercise in preclinical models has typically used prescribed exercise regimens; however, in-cage voluntary wheel running creates opportunities to evaluate how OA progression affects self-selected physical activity levels. This study aimed to evaluate how voluntary wheel running after a surgically induced meniscal injury affects gait characteristics and joint remodeling in C57Bl/6 mice. We hypothesize that injured mice will reduce physical activity levels as OA develops after meniscal injury and will engage in wheel running to a lesser extent than the uninjured animals. Seventy-two C57Bl/6 mice were divided into experimental groups based on sex, lifestyle (physically active vs sedentary), and surgery (meniscal injury or sham control). Voluntary wheel running data were continuously collected throughout the study, and gait data were collected at 3, 7, 11, and 15 wk after surgery. At end point, joints were processed for histology to assess cartilage damage. After meniscal injury, physically active mice showed more severe joint damage relative to sedentary mice. Nevertheless, injured mice engaged in voluntary wheel running at the same rates and distances as mice with sham surgery. In addition, physically active mice and sedentary mice both developed a limp as meniscal injury progressed, yet exercise did not further exacerbate gait changes in the physically active mice, despite worsened joint damage. Taken together, these data indicate a discordance between structural joint damage and joint function. Although wheel running after meniscal injury did worsen OA-related joint damage, physical activity did not necessarily inhibit or worsen OA-related joint dysfunction or pain in mice.

Transverse Connectivity and Durability Evaluation of Hollow Slab Bridges Using Surface Damage and Neural Networks: Field Test Investigation

Prefabricated concrete hollow slab bridges are widely used in short- and medium-span highway bridges in China due to the advantages of high production quality, installation convenience, and low construction cost. Field investigation shows that severe hinge joint damage occurred during the service life, and mechanical performance of the bridges also deteriorated with the weakened joints. It is important to accurately evaluate the performance of hollow slab bridges to ensure the safety of the highway system. In this paper, transverse connectivity and durability of the concrete hollow slab bridges are investigated in a field test using the surface damage and neural networks. Hollow slab bridges in the Wu-He highway system were taken as the background bridge. Surface damage was visually checked and statistically analyzed. Static load test was conducted to evaluate the transverse connectivity of the hinge joints based on the girder responses. The hollow slab bridges were then demolished, and a total of 75 concrete girder segments were cut off. Durability of the girders was evaluated based on the conditions of concrete and rebars, and the analytic hierarchy process along with the fuzzy comprehensive evaluation method was employed. Results showed that there were two main types of the defects in the hollow slab bridges, i.e., the transverse cracks on the bottom plates of the girders and the longitudinal cracks in the hinge joints. The distribution of the deflection of each girder was non-uniform due to the weakening of the transverse connectivity, and the girders in the background bridges were within the moderate deterioration condition after 25 years’ service life. An evaluation method of the hollow slab girders using the neural networks and surface damage was verified by the field test data. The maximum crack width at different locations of the bridges was used in the input layer of the neural network, and the hinge joint damage or the durability was considered as the output results. The prediction error of the method in the test set was within 15.0% for the hinge joint damage and within 40% for the durability result of the girder, indicating the feasibility of the evaluation method.

Identification of essential genes and immune cell infiltration in rheumatoid arthritis by bioinformatics analysis

Rheumatoid arthritis (RA) is a common autoimmune disease that can lead to severe joint damage and disability. And early diagnosis and treatment of RA can avert or substantially slow the progression of joint damage in up to 90% of patients, thereby preventing irreversible disability. Previous research indicated that 50% of the risk for the development of RA is attributable to genetic factors, but the pathogenesis is not well understood. Thus, it is urgent to identify biomarkers to arrest RA before joints are irreversibly damaged. Here, we first use the Robust Rank Aggregation method (RRA) to identify the differentially expressed genes (DEGs) between RA and normal samples by integrating four public RA patients’ mRNA expression data. Subsequently, these DEGs were used as the input for the weighted gene co-expression network analysis (WGCNA) approach to identify RA-related modules. The function enrichment analysis suggested that the RA-related modules were significantly enriched in immune-related actions. Then the hub genes were defined as the candidate genes. Our analysis showed that the expression levels of candidate genes were significantly associated with the RA immune microenvironment. And the results indicated that the expression of the candidate genes can use as predictors for RA. We hope that our method can provide a more convenient approach for the early diagnosis of RA.