Evaluation of efficacy and safety of glucosamine sulfate, chondroitin sulfate, and their combination regimen in the management of knee osteoarthritis: a systematic review and meta-analysis.

AIM: This study was aimed to assess the efficacy and safety of two oral Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOAs)-Glucosamine Sulfate, Chondroitin Sulfate, and their combination regimen in the management of knee osteoarthritis (KOA). METHODS: This systematic review was conducted according to PRISMA 2020 guidelines. A detailed literature search was performed from 03/1994 to 31/12/2022 using various electronic databases including PubMed, Embase, Cochrane Library, and Google Scholar, using the search terms-Glucosamine sulfate (GS), Chondroitin sulfate (CS), Knee osteoarthritis, Joint pain, Joint disease, and Joint structure, for literature concerning glucosamine, chondroitin, and their combination in knee osteoarthritis treatment. Cochrane Collaboration's Risk assessment tool (version 5.4.1) was used for assessing the risk of bias and the quality of the literature. The data was extracted from the included studies and subjected to statistical analysis to determine the beneficial effect of Glucosamine Sulfate, Chondroitin Sulfate, and their combination. RESULTS: Twenty-five randomized controlled trials (RCTs) were included in this systematic review. In short, exclusively 9 RCTs for GS, 13 RCTs for CS, and 3 RCTs for the combination of GS and CS. All these studies had their treatment groups compared with placebo. In the meta-analysis, CS showed a significant reduction in pain intensity, and improved physical function compared to the placebo; GS showed a significant reduction in tibiofemoral joint space narrowing. While the combination of GS and CS showed neither a reduction in pain intensity, nor any improvement in the physical function. However, the combination exhibited a non-significant reduction in joint space narrowing. In the safety evaluation, both CS and GS have shown good safety profile and were well tolerated. CONCLUSION: This meta-analysis revealed that the CS (with decreased pain intensity and improvement in the physical function), and GS (with significant reduction in the joint space narrowing) have significant therapeutic benefits. However, their combination did not significantly improve the symptoms or modify the disease. This may be due to the limited trials that are available on the combination of the sulfate forms of the intervention. Hence, there is a scope for conducting multicentric randomised controlled trials to evaluate and conclude the therapeutic role of CS and GS combination in the management of KOA.

Elbow Joint Stiffness Functional Scales Based on Hill's Muscle Model and Genetic Optimization.

The ultimate goal of rehabilitation engineering is to provide objective assessment tools for the level of injury and/or the degree of neurorehabilitation recovery based on a combination of different sensing technologies that enable the monitoring of relevant measurable variables, as well as the assessment of non-measurable variables (such as muscle effort/force and joint mechanical stiffness). This paper aims to present a feasibility study for a general assessment methodology for subject-specific non-measurable elbow model parameter prediction and elbow joint stiffness estimation. Ten participants without sensorimotor disorders performed a modified "Reach and retrieve" task of the Wolf Motor Function Test while electromyography (EMG) data of an antagonistic muscle pair (the triceps brachii long head and biceps brachii long head muscle) and elbow angle were simultaneously acquired. A complete list of the Hill's muscle model and passive joint structure model parameters was generated using a genetic algorithm (GA) on the acquired training dataset with a maximum deviation of 6.1% of the full elbow angle range values during the modified task 8 of the Wolf Motor Function Test, and it was also verified using two experimental test scenarios (a task tempo variation scenario and a load variation scenario with a maximum deviation of 8.1%). The recursive least square (RLS) algorithm was used to estimate elbow joint stiffness (Stiffness) based on the estimated joint torque and the estimated elbow angle. Finally, novel Stiffness scales (general patterns) for upper limb functional assessment in the two performed test scenarios were proposed. The stiffness scales showed an exponentially increasing trend with increasing movement tempo, as well as with increasing weights. The obtained general Stiffness patterns from the group of participants without sensorimotor disorders could significantly contribute to the further monitoring of motor recovery in patients with sensorimotor disorders.

Anatomical factors influencing temporomandibular joint clicking in young adults: temporomandibular joint structure disorder or lateral pterygoid muscle dysfunction?

Objective: This study aimed to investigate the selected anatomical factors that can potentially influence temporomandibular joint (TMJ) clicking in young adults by assessing TMJ structures and lateral pterygoid muscle (LPM) function using magnetic resonance imaging (MRI). Methods: The patients were divided into four groups: the healthy control group; the clicking on mouth opening group; the clicking on mouth closing group; and the clicking on mouth opening and closing group. Additionally, we used clinical palpation to evaluate the masticatory muscles' functional state and employed MRI using the OCOR-T1WI-FSE-CLOSED, OSAG-PDW-FSE-CLOSED, and OSAG-PDW-FSE-OPEN sequences to analyze the texture of the lateral pterygoid muscle (LPM). Results: The proportion of any articular disc or condylar morphology class did not differ significantly between the TMJ clicking and HC groups. The articular disc position did not differ significantly between the TMJ clicking and HC groups. In the TMJ clicking group, the presence of masticatory muscle dysfunction differed significantly between the clicking and non-clicking sides. Moreover, the LPM accounted for the highest proportion among masticatory muscles with tenderness in all TMJ clicking subgroups (77.78%-100%). Therefore, in the TMJ clicking group, the LPM texture was less defined, more uniform in gray scale, and more similar to local texture (p < 0.0001). Conclusion: The occurrence of TMJ clicking in young adults is unrelated to the TMJ structure but related to the function of masticatory muscles, particularly the LPM.

Fully Floatable Mortise-and-Tenon Architecture for Synergistically Photo/Sono-Driven Evaporation Desalination and Plastic-Enabled Value-Added Co-Conversion of H2O and CO2.

Establishing an advanced ecosystem incorporating freshwater harvesting, plastic utilization, and clean fuel acquisition is profoundly significant. However, low-efficiency evaporation, single energy utilization, and catalyst leakage severely hinder sustainable development. Herein, a nanofiber-based mortise-and-tenon structural Janus aerogel (MTSJA) is strategically designed in the first attempt and supports Z-scheme catalysts. By harnessing of the upper hydrophilic layer with hydrophilic channels embedding into the hydrophobic bottom layer to achieve tailoring bottom wettability states. MTSJA is capable of a fully-floating function for lower heat loss, water supply, and high-efficiency solar-to-vapor conversion. Benefiting from the ultrasonic cavitation effect and high sensitivity of materials to mechanical forces, this is also the first demonstration of synergistic solar and ultrasound fields to power simultaneous evaporation desalination and waste plastics as reusable substrates generating fuel energy. The system enables persistent desalination with an exceptional evaporation rate of 3.1 kg m-2 h-1 and 82.3% efficiency (21 wt.% NaCl solution and 1 sun), and realizes H2, CO, and CH4 yields with 16.1, 9.5, and 3 µmol h-1 g-1, respectively. This strategy holds great potential for desalination and plastics value-added transformation toward clean energy and carbon neutrality.

Tibiofemoral knee osteoarthritis progresses symmetrically by knee compartment in the GOGO cohort.

Objective: To evaluate the degree of symmetry of knee osteoarthritis (OA) structural severity and progression of participants with a mean follow-up time of 3.8 years. Design: Participants from the Genetics of Generalized Osteoarthritis (GOGO) study (n = 705) were selected on the basis of radiographic evidence of OA in at least 1 knee, availability of radiographs at baseline and follow-up, and no history of prior knee injury or surgery. Incidence and progression of osteoarthritis were determined by radiographic Kellgren-Lawrence (KL) grade; compartmental OA progression was determined by change in joint space width of lateral and medial tibiofemoral compartments. Total OA progression was the sum of change in KL grade of both knees. Results: Compared with left knees, right knees had more severe KL grades at baseline (p = 0.0002) and follow-up (p = 0.0004), McNemar's χ2 = 34.16 and 26.08, respectively; however, both knees progressed similarly (p = 0.121, McNemar's χ2 = 10.09). Compartmental changes were symmetric across knees: medial r = 0.287, p = 0.0002; lateral r = 0.593, p = 0.0002. Change in joint space width in the medial compartment was negatively correlated with change in the lateral compartment of the same knee (left knees: r = -0.293, p = 0.021; right knees: r = -0.195, p = 0.0002). Conclusions: Although right knees tended to have more severe OA at both baseline and follow-up, radiographic progression did not differ by knee and compartmental progression correlated across knees. Given this trend in generalized OA, the risk of progression for both knees should be considered, even if only one knee has radiographic OA at baseline.

A Fenchone Derivative Effectively Abrogates Joint Damage Following Post-Traumatic Osteoarthritis in Lewis Rats.

BACKGROUND: In a previous report, we have identified the cannabinoid receptor 2 (CB2) agonist HU308 to possess a beneficial effect in preventing age and trauma-induced osteoarthritis (OA) in mice. The effects of HU308 were largely related to the capacity of this compound to induce cartilage anabolism which was dependent on the CREB/SOX9 axis, and exhibited pro-survival and pro-proliferative hallmarks of articular cartilage following treatment. Here, we utilized the novel cannabinoid-fenchone CB2 agonists (1B, 1D), which were previously reported to render anti-inflammatory effects in a zymosan model. METHODS: Initially, we assessed the selectivity of CB2 using a Gs-protein receptor cAMP potency assay, which was also validated for antagonistic effects dependent on the Gi-protein receptor cAMP pathway. Based on EC50 values, 1D was selected for a zymosan inflammatory pain model. Next, 1D was administered in two doses intra-articularly (IA), in a post-traumatic medial meniscal tear (MMT, Lewis rats) model, and compared to sham, vehicle, and a positive control consisting of fibroblast growth factor 18 (FGF18) administration. The histopathological assessment was carried out according to the Osteoarthritis Research Society International (OARSI) guidelines for rat models following 28 days post-MMT. RESULTS: The G protein receptor assays confirmed that both 1B and 1D possess CB2 agonistic effects in cell lines and in chondrocytes. Co-administering a CB2 antagonists to 25 mg/kg 1D in a paw inflammatory pain model abolished 1D-related anti-swelling effect and partially abolishing its analgesic effects. Using an MMT model, the high dose (i.e., 24 µg) of 1D administered via IA route, exhibited reduced cartilage damage. Particularly, this dose of 1D exhibited a 30% improvement in cartilage degeneration (zonal/total tibial scores) and lesion depth ratios (44%), comparable to the FGF18 positive control. Synovitis scores remained unaffected and histopathologic evaluation of subchondral bone damage did not suggest that 1D treatment changed the load-bearing ability of the rats. Contrary to the anabolic effect of FGF18, synovial inflammation was observed and was accompanied by increased osteophyte size. CONCLUSION: The structural histopathological analysis supports a disease-modifying effect of IA-administered 1D compound without any deleterious effects on the joint structure.

[Effect of FVIII doses on joint structure and function in adolescents with severe hemophilia A: mid-term results of a prospective cohort study].

OBJECTIVE: To explore the clinical phenotype and changes in joint structure and function in adolescent patients with severe hemophilia A under different doses of FVIII. OBJECTIVE: Forty- three adolescents with severe hemophilia A aged 4-18 years were divided into on-demand group (n=7), low-dose group (FVIII dose of 10-15 U/kg, 2-3 times a week, and ≤30 U/kg a week; n=17), and intermediate-dose group (FVIII dose of 15-20 U/kg, 2-3 times a week, and 45-60 U/kg a week (n=19). The 3 groups were compared for their clinical bleeding phenotype, annual bleeding rate (ABR), annual joint bleeding rate (AJBR), annual the most severe joint bleeding rate, joint imaging scores (ultrasound HEAD-US score and IPSG MRI score), Hemophilia Joint Health Score (HJHS) and Functional Independence Score in Hemophilia (FISH) within 24 months. OBJECTIVE: Compared with that in on-demand group, the ABR was significantly reduced in the low- and intermediate-dose groups (P=0.004 and 0.000, respectively), and was reduced by 32.87% in the intermediate-dose group as compared with the low-dose group. The AJBR (P < 0.01) and annual the most severe joint bleeding rate (P < 0.05) also differed significantly among the 3 groups. The number of bleeding episodes increased progressively with time in the on-demand group, remained stable in the low- dose group, and tended to decrease in the intermediate-dose group. The imaging scores of the most severe joints showed lesion progression in all the 3 groups. The ultrasound scores, which increased steadily in the on-demand group, showed significantly lowered increment rates in the low- and intermediate-dose groups (P=0.002 and 0.000, respectively). The MRI scores showed also delayed increment in the low- and intermediate-dose groups as compared with the on-demand group (P=0.041 and 0.000, respectively), and the increment was accelerated in the on-demand and low-dose group but remained stable in the intermediate-dose group. The increment of the HJHS scores was significantly higher in the on-demand group than in the lowand intermediate-dose groups (P=0.003 and 0.000, respectively), and the scores increased at a steady rate in the on-demand group but tended to decrease in the latter two groups. The FISH score was decreased by 0.29±3.09 in the on-demand group but was increased significantly in the low- and intermediate-dose groups compared with the on-demand group (P=0.000). OBJECTIVE: In Chinese adolescents with severe hemophilia A, low- and intermediate-dose FVIII prophylaxis, especially at the intermediate dose, is better than on- demand treatment for protecting joint structure and function.

A unique methionine-rich protein-aragonite crystal complex: Structure and mechanical functions of the Pinctada fucata bivalve hinge ligament.

The bivalve hinge ligament holds the two shells together. The ligament functions as a spring to open the shells after they were closed by the adductor muscle. The ligament is a mineralized tissue that bears no resemblance to any other known tissue. About half the ligament is composed of a protein-rich matrix, and half of long and extremely thin segmented aragonite crystals. Here we study the hinge ligament of the pearl oyster Pinctada fucata. FIB SEM shows that the 3D organization is remarkably ordered. The full sequence of the major protein component contains a continuous segment of 30 repeats of MMMLPD. There is no known homologous protein. Knockdown of this protein prevents crystal formation, demonstrating that the integrity of the matrix is necessary for crystals to form. X-ray diffraction shows that the aragonite crystals are more aligned in the compressed ligament, indicating that the crystals may be actively contributing to the elastic properties. The fusion interphase that joins the ligament to the shell nacre is composed of a prismatic mineralized tissue with a thin organic-rich layer at its center. Nanoindentation of the dry interphase shows that the elastic modulus of the nacre adjacent to the interphase gradually decreases until it approximates that of the interphase. The interphase modulus slightly increases until it matches the ligament. All these observations demonstrate that the ligament shell complex is a remarkable biological tissue that has evolved unique properties that enable bivalves to open their shell effectively innumerable times during the lifetime of the animal. STATEMENT OF SIGNIFICANCE: The hinge ligament shell complex is a unique functioning structural tissue whose elastic properties enable the shell to open without expending energy. Methionine-rich proteins are not known elsewhere raising fundamental questions about secondary and tertiary structures contributing to its elastic properties. The segmented and extremely thin aragonite crystals embedded in this matrix may also have unexpected elastic materials properties as they flex during compression. The structure of the interphase comprises a fascinating biological joint that connects two very different materials. The interphase materials, including the nacre, are graded with respect to elastic modulus so as to approximately match the connecting components. The interphase incorporates a thin organic rich layer that presumably functions as a gasket. This study raises many fundamental questions relevant to the diverse fields of protein chemistry, biomineralization and biological materials.