Joint Disease Research Articles

A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression

RNA interference (RNAi) and oxidative stress inhibition therapeutic strategies have been extensively utilized in the treatment of osteoarthritis (OA), the most prevalent degenerative joint disease. However, the synergistic effects of these approaches on attenuating OA progression remain largely unexplored. In this study, matrix metalloproteinase-13 siRNA (siMMP-13) was incorporated onto polyethylenimine (PEI)-polyethylene glycol (PEG) modified Fe3O4 nanoparticles, forming a nucleic acid nanocarrier termed si-Fe NPs. Subsequently, a poly(vinyl alcohol) (PVA) crosslinked phenylboronic acid (PBA)-modified hyaluronic acid (HA) hydrogel (HPP) was used to encapsulate the si-Fe NPs, resulting in a bifunctional hydrogel (si-Fe-HPP) with reactive oxygen species (ROS)-responsive and RNAi therapeutic properties. Studies in vitro demonstrated that si-Fe-HPP exhibited excellent biocompatibility, anti-inflammatory effects and prolonged stable retention time in knee joint. Intra-articular injection of si-Fe-HPP significantly attenuated cartilage degradation in mice with destabilization of the medial meniscus (DMM)-induced OA. The si-Fe-HPP treatment not only notably alleviated synovitis, osteophyte formation and subchondral bone sclerosis, but also markedly improved physical activity and reduced pain in DMM-induced OA mice. This study reveals that si-Fe-HPP, with its ROS-responsive and RNAi abilities, can significantly protect chondrocytes and attenuate OA progression, providing novel insights and directions for the development of therapeutic materials for OA treatment.Graphical

Occlusal Appliance Therapy for Temporomandibular Joint Disorders: Mechanisms, Efficacy, and Limitations

Disorders of the temporomandibular joint (TMJ) are chronic conditions that involve pain, muscle spasm, and dysfunction of the joint and surrounding structures. Occlusal appliances have come to be regarded as essential tools in the non-surgical treatment of these disorders as they help in the management of symptoms and protection of teeth and the structures of the TMJ. In various types of reviews of occlusal appliances, including stabilization splints, anterior and posterior bite planes, repositioning devices, and soft appliances, are discussed in detail with regard to their mechanism of action, indications, and limitations. Improvements in the material and the fabrication method, such as printing, have enhanced CAD/CAM systems accuracy and comfort, as well as the patients’ cooperation in the use of these appliances. Thus, combining occlusal appliances with other treatments, including physiotherapy and Botox, offers a systemic approach to TMJ treatment, dealing with both appliances mechanical help and muscular factors. reduction Although there are certain risks involved, like occlusal changes and discomfort, which need close observation and patient counselling, of occlusal pain, muscle hyperactivity, and joint loading. This review focuses on the need to choose the right appliance, make the right fabrication and to ensure that there is a follow up to check on the progress of the patient. Further developments and multi-disciplinary work will continue to improve the effectiveness and applicability of occlusal appliances in the treatment of TMJ disorders.

Targeting Chondrocyte Hypertrophy as Strategies for the Treatment of Osteoarthritis

Osteoarthritis (OA) is a common joint disease characterized by pain and functional impairment, which severely impacts the quality of life of middle-aged and elderly individuals. During normal bone development, chondrocyte hypertrophy is a natural physiological process. However, in the progression of OA, chondrocyte hypertrophy becomes one of its key pathological features. Although there is no definitive evidence to date confirming that chondrocyte hypertrophy is the direct cause of OA, substantial experimental data indicate that it plays an important role in the disease’s pathogenesis. In this review, we first explore the mechanisms underlying chondrocyte hypertrophy in OA and offer new insights. We then propose strategies for inhibiting chondrocyte hypertrophy from the perspectives of targeting signaling pathways and tissue engineering, ultimately envisioning the future prospects of OA treatment.

Clinical Assessment of Puressentiel® Muscles and Joints Gel Aromatherapy in the Management of Osteoarthritis-Related Knee Pain

Introduction: Knee osteoarthritis (OA) is a degenerative joint disease that affects millions globally, causing chronic pain and limited mobility. Pharmacological treatments for OA-related knee pain come with risks, making alternative or complementary therapies attractive. This post-market trial evaluates the efficacy of Puressentiel® Muscles and Joints gel, an aromatherapy gel with 14 essential oils, in managing OA-related knee pain. Method: In this 12-week open-label trial (NCT04736563), participants aged 45–90 with OA-related knee pain applied Puressentiel® Muscles and Joints gel twice daily for 4 weeks, following a 4-week run-in period without treatment. Pain, joint stiffness, and function were assessed using the Western Ontario McMaster Universities Arthritis Index (WOMAC) and Visual Analog Scale (VAS) at baseline, 4 weeks, 8 weeks, and 12 weeks, and oral analgesic intake was recorded daily. Results: Significant improvements in WOMAC and VAS scores were observed during treatment (p = 0.0262; p < 0.0001, respectively) and sustained 4 weeks post-treatment (p = 0.0190; p < 0.0001, respectively). Paracetamol intake significantly decreased from baseline to the end of treatment (p = 0.0230), though anti-inflammatory intake did not change significantly. No adverse events were reported. Conclusion: Puressentiel® Muscles and Joints gel was well-tolerated, improved WOMAC and VAS scores, and reduced paracetamol use, presenting a viable natural option for pain management in knee OA.

Prevalence and Significance of the Presence of Anti-transglutaminase and Anti-endomysium Antibodies in Patients with Early Inflammatory Joint Disease.

Celiac disease (CD) affects the small intestine, leading to a progressive disappearance of intestinal villi, and can be found in association with several other autoimmune and inflammatory conditions. The main objective of this study was to determine the prevalence and the clinical significance of anti-transglutaminase and anti-endomysium antibodies in patients diagnosed with early rheumatoid arthritis (RA) and spondyloarthritis (SpA). We measured anti-transglutaminase and anti-endomysium antibodies in biobanked serum samples at inclusion in two French prospective multicenter cohorts of patients with suspected early rheumatoid arthritis (ESPOIR, n = 713) and spondyloarthritis (DESIR, n = 709). Results were compared with the clinical, laboratory, and radiographic findings obtained in patients during a 10-year follow-up period. In the DESIR cohort, anti-transglutaminase antibodies were evidenced at low levels (less than three times the upper limit of normal) in 2/709 (0.42%) patients and anti-endomysium antibodies in 0/709 (0%). In the ESPOIR cohort, anti-transglutaminase antibodies were evidenced in 6/713 (0.84%) patients and anti-endomysium antibodies in 1/713 (0.14%). Only the latter patient was confirmed to have celiac disease. Interestingly, this patient was ultimately diagnosed with Sjögren's disease, an autoimmune condition known to be associated with an increased risk of celiac disease. The very low identified prevalence of anti-transglutaminase and anti-endomysium antibodies suggests a negligible risk of celiac disease in patients with early-stage RA or SpA, which are among the most common inflammatory rheumatic conditions. Consequently, routine screening for celiac disease via these antibodies in patients presenting with early inflammatory rheumatic conditions should not be performed except in case of clinical suspicion of celiac disease.

Intra-Articular Administration of Ganglioside Sugars Protects Cartilage from Progressive Degeneration in an Instability OA Rabbit Model.

Osteoarthritis (OA) is a degenerative joint disease that has no cure, and current therapies are intended to minimize pain. There is, therefore, a need for effective pharmacologic agents that reverse or slow the progression of joint damage. We report herein on an investigation of the effects of intra-articular injections of ganglioside sugars on the progression of OA in an experimental rabbit model. Knee OA was induced Japanese in White rabbits by anterior cruciate ligament transection (ACLT). Ganglioside sugars at concentrations of 0.1, 0.3, and 0.9 mg/ml were then intra-articularly injected as a possible treatment for OA. Controls received intra-articular injections of saline. Knees were assessed macroscopically, histologically, and mechanically at 13 weeks after ACLT induction. Macroscopically, knees of the groups that received ganglioside sugars at concentrations of 0.3 and 0.9 mg/ml exhibited milder cartilage degradation compared to the controls. Consistent with these results, histological scores for these knees were significantly higher than the corresponding values for the control knees. Lectin histochemistry staining revealed that the treatment with ganglioside sugars at concentrations of 0.3 and 0.9 mg/ml was associated with a remarkable increase in the levels of GalNAc-positive chondrocytes in cartilage. Coefficient of friction testing also demonstrated that cartilages treated with ganglioside sugars had a lower coefficient of frictions than the values for the control group. Intra-articular injections of ganglioside sugars prevented cartilage degeneration in an OA-instability model. These results highlight the promising therapeutic potential for using ganglioside sugars in the treatment of progressive OA.

Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: preclinical development and first-in-human intra-articular validation as therapeutics for knee osteoarthritis

Osteoarthritis (OA) is a joint disease characterized by articular cartilage degradation. Persistent low-grade inflammation defines OA pathogenesis, with crucial involvement of pro-inflammatory M1-like macrophages. While mesenchymal stromal cells (MSC) and their small extracellular vesicles (sEV) hold promise for OA treatment, achieving consistent clinical-grade sEV products remains a significant challenge. This study aims to develop fully characterized, reproducible, clinical-grade batches of sEV derived from umbilical cord (UC)-MSC for the treatment of OA while assessing its efficacy and safety. Initially, a standardized, research-grade manufacturing protocol was established to ensure consistent sEV production. UC-MSC-sEV characterization under non-cGMP conditions showed consistent miRNA and protein profiles, suggesting their potential for standardized manufacturing. In vitro studies evaluated the efficacy, safety, and potency of sEV; animal studies confirmed their effectiveness and safety. In vitro, UC-MSC-sEV polarized macrophages to an anti-inflammatory M2b-like phenotype, through STAT1 modulation, indicating their potential to create an anti-inflammatory environment in the affected joints. In silico studies confirmed sEV's immunosuppressive signature through miRNA and proteome analysis. In an OA mouse model, sEV injected intra-articularly (IA) induced hyaline cartilage regeneration, validated by histological and μCT analyses. The unique detection of sEV signals within the knee joint over time highlights its safety profile by confirming the retention of sEV in the joint. The product development of UC-MSC-sEV involved refining, standardizing, and validating processes in compliance with GMP standards. The initial assessment of the safety of the clinical-grade product via IA administration in a first-in-human study showed no adverse effects after a 12 month follow-up period. These results support the progress of this sEV-based therapy in an early-phase clinical trial, the details of which are presented and discussed in this work. This study provides data on using UC-MSC-sEV as local therapy for OA, highlighting their regenerative and anti-inflammatory properties and safety in preclinical and a proof-of-principle clinical application.Graphical

Artificial intelligence-enhanced diagnosis of degenerative joint disease using temporomandibular joint panoramic radiography and joint noise data

This study aimed to develop an artificial intelligence (AI) model for the screening of degenerative joint disease (DJD) using temporomandibular joint (TMJ) panoramic radiography and joint noise data. A total of 2631 TMJ panoramic images were collected, resulting in a final dataset of 3908 images (2127 normal (N) and 1781 DJD (D)) after excluding indeterminate cases and errors. AI models using GoogleNet were evaluated with six different combinations of image data, clinician-detected crepitus, and patient-reported joint noise. The model that integrated all joint noise data with imaging demonstrated the highest performance, achieving an F1-score of 0.72. Another model, which incorporated both imaging and crepitus, also achieved the same F1-score but had lower D recall (0.55 vs. 0.67) and N precision (0.71 vs. 0.74). The AI models outperformed orofacial pain specialists when provided with imaging alone or in combination with all joint noise data. These findings suggest that AI-enhanced DJD diagnosis using TMJ panoramic radiography and joint noise data offers a promising approach for early detection and improved patient care. The results underscore AI’s capability to integrate diverse diagnostic factors, providing a comprehensive and accurate assessment that surpasses traditional methods.

Clinical application of visual minimally invasive acupotomy

Visual minimally invasive acupotomy is applicable for the diseases with the pathological characteristics of soft tissue injury, including disorders of spine, four limbs and joints, peripheral nerve compression and chronic soft tissues. The diseases with superior effect obtained are cervicogenic headache, lumbar disc herniation, carpal tunnel syndrome and flexor tendon stenosing tenosynovitis. Under the guidance with ultrasound, visual minimally invasive acupotomy is advantaged at preoperative diagnosis, intraoperative guidance and postoperative evaluation in clinical practice so that it is precise, safe and reliable in clinical treatment. Visual minimally invasive acupotomy is essentially a kind of "ultra-minimally invasive" technique in treatment, focusing on the self-rehabilitation of the body induced by external treatment measures. It is highly complementary to the repair and reconstruction of minimally invasive surgery of modern medicine in clinical application.

Relationship Between the Gut Microbiome, Tryptophan-Derived Metabolites, and Osteoarthritis-Related Pain: A Systematic Review with Meta-Analysis

Introduction: Osteoarthritis (OA) is the most prevalent form of arthritis and affects over 528 million people worldwide. Degenerative joint disease involves cartilage degradation, subchondral bone remodeling, and synovial inflammation, leading to chronic pain, stiffness, and impaired joint function. Initially regarded as a “wear and tear” condition associated with aging and mechanical stress, OA is now recognized as a multifaceted disease influenced by systemic factors such as metabolic syndrome, obesity, and chronic low-grade inflammation. Recent studies have focused on the gut-joint axis to investigate how the gut microbiome modulates inflammation and pain in OA. Materials and Methods: A systematic review was conducted following the PRISMA guidelines and was registered with PROSPERO (CRD42024556265). This review included studies involving adults with symptomatic OA and analyzed the relationship between the gut microbiome and OA-related pain. Randomized and non-randomized clinical trials, case reports, editorials, and pilot studies were excluded. Searches were performed in PubMed, Cochrane Library, and Web of Science without publication date restrictions, and filtered for “observational studies”. The study selection and data extraction were performed by two independent researchers, and the risk of bias was assessed using appropriate tools. Results: Five observational studies were included in the systematic review, and three were included in the meta-analysis. Two studies reported an association between different tryptophan metabolites and pain levels in patients with OA. Two other studies demonstrated a correlation between lipopolysaccharide levels and pain in OA. A fifth study confirmed the relationship between Streptococcus relative abundance of Streptococcus spp. and knee pain. These results were not supported by a meta-analysis, which found no significant association between the presence of pain in OA and the presence of bacilli of the genus Streptococcus or plasma markers of the tryptophan pathway. Conclusions: Current evidence indicates a potential link between gut microbiome dysbiosis and OA-related pain. However, methodological limitations preclude definitive conclusions. Further research using advanced techniques and larger cohorts is needed to validate and extend these findings and elucidate the underlying mechanisms. Targeted manipulation of the gut microbiome may be a valuable strategy for pain management in OA patients.

Supplementary Treatment for Alleviating Pain and Enhancing Functional Ability in Geriatric Patients with Osteoarthritis

Background and Objectives: A degenerative joint disease that primarily affects elderly individuals, osteoarthritis (OA) causes pain, decreased mobility, and a lower quality of life. Procaine is regarded as a “veteran” medicine due to its extensive clinical use, although it remains a molecule of interest, as researchers are uncovering new biological and pharmacological effects through innovative experimental methods. This study evaluates the efficacy of the “procaine complex”, developed in our country, in alleviating pain and improving functionality in elderly individuals with osteoarthritis of the knee and hip. Materials and Methods: We conducted an assessment of a longitudinal short-term study involving 177 patients aged 65 and older, who were randomly divided into two groups. One group received physical therapy and “procaine complex” periarticular injections (n = 101), while the other group received just physical therapy (n = 76). We assessed pain using a visual analog scale (VAS), in addition to functional evaluations using the Lequesne Index, Activities of Daily Living (ADL), and Instrumental ADL (IADL) scores. We evaluated these through a CGA (complex geriatric assessment), the walk test, “Up and Go” test, Mini Mental State (MMSE) and Geriatric Depression Scale (GDS) for cognitive status. We analyzed all the data from this study using PSPP v3 software. Results: The procaine complex treatment group exhibited a significant reduction in pain (p < 0.001) and improvement in daily activities (p < 0.001) relative to the control group. However, there was no notable difference in walking test scores (p = 0.171). No substantial detrimental effects were identified. The procaine complex did not surpass physical therapy in reducing depressive disorders, but both groups showed some enhancement in this regard. Conclusions: This study demonstrates an innovative approach to pain management by integrating periarticular “procaine complex” injections with physical therapy. This provides elderly individuals experiencing osteoarthritis pain and functional limitations with a secure and efficacious alternative to surgery, or may diminish years of disability.

Associated Anatomic Abnormalities in Patients Undergoing Rotational Tibial Osteotomies for Patellofemoral Pathology and Implications for the Level of Correction.

Tibial rotational deformity is a known risk factor for patellofemoral joint (PFJ) disorders. However, it is commonly associated with other abnormalities which affect the PFJ. The purpose of this study was to describe the prevalence of associated factors known to affect PFJ in patients undergoing rotational tibial osteotomy and their implication for the correction level. All patients with PFJ disorder, who underwent rotational tibial osteotomy between July 2009 and February 2020, were included. Patients were excluded if there were no preoperative computed tomography (CT)/magnetic resonance imaging (MRI). Scans were analyzed by 2 observers. Parameters of interest were femoral version, tibial torsion, trochlear dysplasia, lateral trochlear inclination (LTI), tibial tuberosity-trochlear groove (TT-TG) distance, Insall-Salvati (IS), and Caton Deschamps Index (CDI). The search resulted in 80 knees, which had a mean femoral version of 21.0 ± 11.7, tibial torsion of 45.9 ± 9.1, TT-TG of 18.3 ± 5.5, and LTI of 11.4 ± 14.7. In total, 42.5% had TT-TG value of ≥ 20 mm. Patella alta/baja was found in 54% based on CDI or IS >1.2 and <0.8. High-grade trochlear dysplasia was found in 25%. In total, 29% had a tibial torsion abnormality but normal TT-TG and patella height. In total, 18% had abnormal TT-TG but normal patellar height. Based on the associated abnormalities of patella height and tubercle lateralization, 18% of the population were suitable for supratubercle osteotomy, and 29% of patients were suitable for diaphyseal or distal tibial osteotomy. A tibial tubercle osteotomy was required in 54% of patients, making a through-tubercle approach the most appropriate option for most patients. Radiological cross-sectional study.

Association of Anatomical Features of the Petrotympanic Fissure and Presence of Foramen of Huschke With Temporomandibular Disorders.

The foramen of Huschke (FH) and the petrotympanic fissure (PTF) are anatomical structures that can influence temporomandibular joint disorders (TMD) by potentially affecting the movement and function of the mandibular condyle. This study investigates the relationship between patients with TMD and the presence of FH and PTF to enhance diagnostic and therapeutic approaches. This retrospective study analyzed cone beam computed tomography (CBCT) images from 212 patients. Patients were categorised into TMD and control groups based on standardized DC/TMD protocols. An observer, blinded to the patient's clinical status, then analyzed the CBCT images. The CBCT images were evaluated for the presence and characteristics of FH, PTF, and condyle shape and position. A higher incidence of FH and PTF was observed in patients with TMD than in the control group. FH was present on the right side in 33.3% of patients with TMD and 18% of controls and on the left side in 23.8% of patients with TMD and 10.9% of controls. Open and semi-open FPT statistically differed between the TMD and control groups (p < 0.05). The length of FH in patients with TMD was significantly larger (2.11 ± 0.44 mm) than in the controls (1.67 ± 0.56 mm). The position of the condyle showed a statistically significant difference between the groups (p < 0.05). FH and PTF subtypes are significantly associated with TMD, underscoring their importance in clinical practice.

Sirt1 overexpression inhibits chondrocyte ferroptosis via Ftl deacetylation to suppress the development of osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by an imbalance in chondrocyte metabolism. Ferroptosis has been implicated in the pathogenesis of OA. The role of Sirt1, a deacetylase, in mediating deacetylation during ferroptosis in OA chondrocytes remains underexplored. This study aimed to elucidate the mechanisms by which Sirt1 influences chondrocyte ferroptosis in the development of OA. In vitro and in vivo models of OA were established using IL-1β-induced mouse chondrocytes and a destabilization of the medial meniscus (DMM) mouse model, respectively. Ferroptosis was evaluated through measurements of cell viability, lactate dehydrogenase (LDH) release, intracellular levels of Fe2+, glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (ROS), propidium iodide staining, and Western blot analysis. The underlying mechanisms were further investigated using quantitative real-time polymerase chain reaction, Western blotting, immunoprecipitation (IP), co-immunoprecipitation (Co-IP), and glutathione-S-transferase pulldown assays. In vivo validation was performed via Safranin O staining. IL-1β induced ferroptosis and increased histone acetylation, effects that were partially reversed by Sirt1 overexpression. Mechanistically, Sirt1 overexpression upregulated ferritin light polypeptide (Ftl) expression by deacetylating Ftl at the K181 residue. Ftl knockdown inhibited the ferroptosis-enhancing effect of Sirt1 overexpression in chondrocytes. In vivo studies showed that Sirt1 overexpression mitigated the progression of OA and reduced ferroptosis in the DMM-induced OA mouse model. Our findings confirm that Sirt1 overexpression promotes Ftl expression through deacetylation at the K181 site, thereby suppressing chondrocyte ferroptosis and attenuating the progression of OA. These results suggest a potential therapeutic target for OA treatment.

In situ swelling of low-friction, high load-bearing self-bending bilayer hydrogels inspired by articular cartilage.

The articular cartilage is characterized by its gradient hierarchical structure, which exhibits excellent lubrication and robust load-bearing properties. However, its inherent difficulty in self-repair after damage presents numerous formidable challenges for cartilage repair. Inspired by the unique structure of articular cartilage, a biomimetic bilayer hydrogel composed of PAM (polyacrylamide) and PAM/SA (sodium alginate) is prepared using a two-step in-situ swelling method. The bilayer hydrogel demonstrates exceptional structural stability due to the interlayer in-situ chemical cross-linking. Compared to monolayer hydrogels, the PAM-PAM/SA bilayer hydrogel demonstrates superior mechanical attributes, exhibiting a compressive strength of 1 MPa and a compressive modulus of 0.22 MPa. Furthermore, exploration of the tribological performance of the PAM-PAM/SA bilayer hydrogel have revealed its low-friction performance under high loads, with a coefficient of friction as low as 0.032. Finally, leveraging the differential swelling properties between the distinct layers of the PAM-PAM/SA bilayer hydrogel, a self-bending biomimetic cartilage capable of conforming to complex joint surfaces is fabricated. This highly lubricating, mechanically robust, and conformal biomimetic cartilage provides an effective means for addressing cartilage defects and joint diseases.

Changes in health related quality of life in mothers with inflammatory joint disease from year 2000 to 2020 – a comparative cross-sectional study

Changes in health related quality of life in mothers with inflammatory joint disease from year 2000 to 2020 – a comparative cross-sectional study

Olive oil and castor oil-based self-nanoemulsifying drug delivery system of flurbiprofen can relieve peripheral pain and inflammation through reduction of oxidative stress and inflammatory biomarkers: a comprehensive formulation and pharmacological insights.

Flurbiprofen (FBP) is poorly water-soluble BCS class II drug with anti-inflammatory and analgesic effects, used to treat arthritis and degenerative joint diseases. This study was aimed to develop SNEDDS loaded with FBP. Six SNEDDS using two oils olive oil (F1OLV, F2OLV, F3OLV) and castor oil (F4CAS, F5CAS, F6CAS) with three different Smix ratios consisting of Tween 20 and PEG 400 (1:1, 1:2, 2:1) were prepared and characterized. Compatibility between FBP and polymers was investigated using FTIR. SNEDDS were characterized for physicochemical attributes. Two optimized formulations were investigated at 10mg/kg dose given orally in Wistar rats for analgesic activity by hot plate and tail flick methods, and anti-inflammatory activity by carrageenan induced paw edema method. Anti-inflammatory activity was further explored by motor coordination and motility by Rota rod and cage activity tests. Following anesthesia blood samples were collected before dissection to measure inflammatory mediators and oxidative stress markers. Sciatica nerves and hind paws of rats were also removed for histopathological evaluation.FTIR studies revealed compatibility of FBP with other components. Droplet size of F1OLV, F2OLV, F3OLV was 128.5 ± 0.7 nm, 202.5 ± 1.3 nm, and 541.5 ± 1.7 nm, whereas it was 142.5 ± 1.1 nm, 215.4 ± 1.2 nm and 349.9 ± 1.8 nm for F4CAS, F5CAS, F6CAS. %EE of F1OLV, F2OLV, F3OLV was found 85 ± 4.89%-91 ± 4.67%, whereas the %EE F4CAS, F5CAS, F6CAS was 84 ± 4.15%-90 ± 4.21%. DSC curves of F1OLVand F4CASrevealed amorphous nature of the FBP. SEM showed spherical shape of globules. % of drug released in the pH medium 1.2 for plain FBP, F1OLVand F4CASwas 25%, 59% and 57%. % drug released in the pH 6.8 for plain FBP, F1OLVand F4CASwas 59%, 85% and 83%. Oral administration of FBP-loaded SNEDDS (F1OLV and F4CAS) significantly decreased paw diameter and enhanced motor coordination in rats when compared to the disease control group. This was linked to the ability of FBP to reduce inflammation and oxidative stress, with histological studies indicating decreased tissue damage in SNEDDS treated groups, implying the possibility of tissue recovery. Administration of both formulations started to demonstrate analgesic and anti-inflammatory effects after one hour of administration. In addition to anti-inflammatory effect, both formulations improved motor coordination, motility, and reduced infiltration of inflammatory cells in the inflamed paws. The anti-inflammatory and analgesic activities were attributed to decreased serum levels of IL-6 and TNF-α, increased activity of SOD and reduced nitrite content in sciatic nerves. Histopathological evaluation revealed reduced vascularity, inflammation and synovial hyperplasia. The overall findings suggest that the FBP loaded SNEDDS can be used as carriers for improved delivery of FBP which can effectively be used to cure pain and inflammation.

Enhancing Clinical Insights: New Radiographic Grading for Lumbar Facet Joint Degeneration, A Reliability Study.

Lumbar facet joint diseases can often lead to reduced work efficiency and increased medical costs. As a primary imaging tool in orthopedics, X-rays offer numerous advantages. However, there is no consensus on the classification of lumbar facet joints based on X-ray imaging. This study was conducted for 356 patients between November 2017 and September 2023. A senior radiologist and a senior orthopedic surgeon discussed and established a grading system for lumbar facet joints based on both X-ray and MRI findings. Two double-blind attending spinal surgeons were asked to evaluate and grade the included cases. The intra-rater reliability and inter-rater reliability were evaluated by assessing the weighted kappa (κw) coefficient. The level of inter-rater reliability of MRI for complete agreement was good for Doctor A (κw = 0.792) and Doctor B (κw = 0.869). The inter-rater reliability coefficient for grading lumbar facet joint degeneration based on the radiograph was as follows: for Doctor A (κw = 0.702, session 1; κw = 0.847, session 2) and Doctor B (κw = 0.714, session 1; κw = 0.828, session 2). Moreover, the level of intra-rater reliability based on X-ray for complete agreement was excellent for Doctor A (κw = 0.843) and Doctor B (κw = 0.836). We propose a new grading system for lumbar facet joint degeneration based on X-rays, which serves as a supplement to the Weishaupt and Pathria classifications. This grading system aims to provide clinicians with a more comprehensive understanding of lumbar facet joint degeneration, allowing for the use of a broader range of diagnostic tools to evaluate facet joint degeneration from multiple perspectives. We believe that this grading system can be valuable in assessing potential anatomical changes related to the facet joint, thereby informing modifications to surgical techniques and procedural steps.

Moderate-To-Vigorous Physical Activity Independent of Stationary Time Is Associated With Better Functional Outcomes Over Four-Years in Individuals With or at Risk of Knee Osteoarthritis.

Osteoarthritis is a progressive joint disease that causes pain and disability, impairing physical function. Moderate-to-vigorous physical activity (MVPA) is recommended for knee osteoarthritis, while stationary time, independent of activity, may negatively impact health outcomes. We hypothesised that individuals with the highest MVPA and lowest stationary time would have better long-term function compared to those with the lowest MVPA and highest stationary time, as well as those with high levels of both MVPA and stationary time. Data included 442 participants, with an average age of 66-years and 190-females from the Osteoarthritis Initiative who wore accelerometers to assess MVPA and stationary time. Participants were grouped into tertiles of MVPA and stationary time normalised to total accelerometer wear time. The three groups were: highest activity, lowest stationary (HALS), highest activity, highest stationary (HAHS), and lowest activity, highest stationary (LAHS). Gait speed, the 400m walk test, and five-time repeated chair stand were assessed at baseline and four-year follow-up. Compared to the LAHS group, the HALS and HAHS groups had better performance in gait speed p<0.001, d=0.96-1.06, 400m walk time p<0.001, d=1.21-1.36, and five-time repeated chair stand p<0.001, d=0.54-0.81 at baseline and four-year follow-up. No differences were found between the HALS and HAHS groups at either timepoint. Higher levels of MVPA were associated with better lower-limb functional outcomes in individuals with or at risk of knee osteoarthritis. Higher levels of stationary time do not negatively influence functional performance as long as higher numbers of MVPA levels (∼30min/day) are achieved.

What Matters in Psoriatic Arthritis: A Comparison of Patient and Clinician Perspectives.

This study aimed to expand the understanding of the patient with psoriatic arthritis (PsA) experience and to compare/contrast patient and clinician prioritization of PsA dimensions. We conducted four patients with PsA focus groups across three US rheumatology practices using mixed methods to identify attributes of PsA important to patients. Combination with extant attributes of PsA identified by a steering committee created a comprehensive list of attributes. In separate patient and physician Delphi exercises, participants distributed 100 points across items on the list according to importance as a dimension of PsA. Fifty-one items describing PsA were generated. Thirty-eight patients and 13 clinicians completed the last Delphi rating exercise. Patients distributed points across a wider range of items than physicians. Using group mean score per item, prioritization was compared between groups. Items with the top 10 mean scores for both groups included arthritis, disease activity, pain, fatigue, physical function, and spine symptoms. Other prioritized domains showed disparity: access to care, daily activities, stiffness, future health uncertainty, and sleep quality for patients versus specific disease skin and joint manifestations, comorbidities, structural damage, and disease management goals for clinicians. Although concordance between patient and clinician perspectives regarding "what matters" in PsA was seen, significant areas of discordance were uncovered. Patients highlighted concerns about care access and uncertainty about the future and impact on aspects of life beyond physical symptoms, issues not usually discussed in a clinical visit. These differential prioritizations highlight opportunities for improvement in patient-clinician communications and delineate the need for more patient-centered research.