Medical education during the COVID-19 pandemic: lessons for the orthopedic departments.

BACKGROUND: After the Coronavirus pandemic, many educational routines were stopped for the safety of medical staff. To achieve educational goals, we have implemented new policies in our hospitals. In this study, we aimed to evaluate the effect of such strategies. METHOD: This survey-based study uses questionnaires to assess newly implemented educational strategies. We surveyed 107 medical staff of the orthopedic department of Tehran University of Medical Sciences, including faculty members, residents, and students. The survey contained three series of questionnaires for these groups. RESULTS: The maximum satisfaction for all three groups was observed in the platform and facilities for using e-classes, and the cost- and time-saving capabilities (Respectively, faculty members (FM): 81.8%, residents (R): 95.2%, students/interns (S/I): 87.0%; FM: 90.9%, R: 88.1%, S/I: 81.5%). The new policies have been shown to reduce the stress level of most trainees, increase the quality of knowledge-based education, increase the opportunity for reexamining educational content, expand discussion and research opportunities, and improve work conditions. There was a broad acceptance of the virtual journal clubs and morning reports. However, there were discrepancies between residents and faculty members on issues such as the evaluation of trainees, the new educational curriculum, and flexible shift schedules. Our strategies failed to improve skill-based education and patient treatment status. Most participants indicated that e-learning should be used with face-to-face training post-pandemic (FM: 81.8%, R: 83.3%, S/I: 75.9%). CONCLUSION: Our efforts to optimize the educational system during this crisis have generally improved trainees' work conditions and educational experience. Most participants believed that e-learning and virtual methods should be used alongside traditional training as a complementary component after the pandemic.

Anti-inflammatory effects of PRIMA-1MET (mutant p53 reactivator) induced by inhibition of nuclear factor-κB on rheumatoid arthritis fibroblast-like synoviocytes.

Fibroblast-like synoviocytes (FLSs), the main pathological cells in rheumatoid arthritis (RA), display tumor-like phenotype, including hyper-proliferation, apoptosis resistance, and aggressive phenotype. Excessive proliferation and insufficient apoptosis of RA-FLSs can lead to hyperplastic synovial pannus tissue, excess production of inflammatory mediators, and destruction of joints. In this article, we investigate the effect of PRIMA-1MET on the apoptosis induction and inhibition of pro-inflammatory cytokines in RA-FLSs. Synovial tissue samples were obtained from 10 patients with RA. The FLSs were treated with different concentrations of PRIMA-1MET. The rate of apoptosis and cell survival was assessed by flow cytometry and MTT assay and Real-time quantitative PCR was performed to evaluate the transcription of p53, IL-6, IL-1ß, TNF-α, Noxa, p21, PUMA, Bax, Survivin, and XIAP in treated RA-FLSs. The protein level of p53, IκBα, and phospho-IκBα were measured using Western blotting. The results showed that PRIMA-1MET induced apoptosis in RA-FLSs and increased significantly the expression of Noxa, and decreased significantly IL-6, IL-1ß, p53, and phospho-IκBα expression. PRIMA-1MET can induce apoptosis in RA-FLSs through induction of Noxa expression while p53 was downregulated. Furthermore, PRIMA-1MET treatment results in the suppression of pro-inflammatory cytokine production and NF-κB inhibition. Given the role of p53 and NF-κB in RA-FLSs, PRIMA-1MET can be considered as a new therapeutic strategy for rheumatoid arthritis.

Determination of Normal Reference Values for Meniscal Extrusion Using Ultrasonography During the Different Range of Motion: A Pilot, Feasibility Study.

OBJECTIVES: It is essential to know the normal extrusion measures in order to detect pathological ones. In this study, we aimed to define some normal reference values for meniscal extrusion in the normal knees during different ranges of motion. METHODS: The amount of anterior and posterior portion of meniscal extrusion among 21 asymptomatic volunteers (42 knees) were tracked in 0, 45, and 90° of knee flexion using an ultrasound machine. The repeated measures analysis of variance (ANOVA) was used to show the interaction between the amounts of meniscal extrusion and the different degrees of knee flexion. RESULTS: The anterior portion of the lateral menisci at full knee extension (0.59 ± 1.40) and the posterior portion of the medial menisci during 90° flexion (3.06 ± 2.36) showed the smallest and the highest mean amount of extrusion, respectively. The normal average amounts of anterior extrusion were 1.12 ± 1.17 and 0.99 ± 1.34 mm for medial and lateral menisci, respectively. The posterior meniscal normal extrusions were significantly increasing in both medial and lateral menisci during the survey (F = 20.250 and 11.298; both P values <.001) as they were measured 2.37 ± 2.16 and 1.53 ± 2.18 mm in order. CONCLUSIONS: The medial meniscus can extrude 1.74 ± 1.84 mm normally while this amount was 1.26 ± 1.82 mm for the lateral meniscus. These measures commonly increased with the rising of knee flexion motion. Likewise, the posterior portion showed more extrusion than the anterior portion on both sides. These measures commonly increased with higher knee flexion.

The functional impact of home-based self-rehabilitation following arthroscopic meniscus root repair.

BACKGROUND: Corona virus infectious pandemic makes outdoors rehabilitation a potential hazard. Patient education to perform simple home-based exercises seems to be an interesting and sometimes a mandatory option. This study provides a comparison between the conventional and home-based virtual rehabilitation after surgical repair of medial meniscus root tears. METHODS: In this prospective study, all patients who underwent medial meniscus posterior root repair with a modified trans-tibial pull-out technique from March 2019 to March 2021 were evaluated. Those who underwent surgery after December 2019 were trained to perform self-rehabilitation. The rest had undergone outdoors specialized rehabilitation according to a unified protocol and these were used as a historical control group. All patients were followed up for a minimum of 2 year after surgery. Final Lysholm scores were utilized to compare functional outcomes after considering the effect of age, body mass index and time from surgery by multivariate linear regression analysis. RESULTS: Forty-three consecutive patients with medial meniscal root tears were studied. Thirty-nine (90.7%) were women and 4 (9.3%) were men. The mean age of participants was 53.2 ± 8.1 years. The total Lysholm knee score, and all its items were significantly improved in both groups at a two-year follow-up (p < 0.05), except the "Using cane or crutches" item (p = 0.065). Nevertheless, the final Lysholm knee score improvement was higher in patients who performed outdoors specialized rehabilitation and in patients with shorter time-to-surgery. CONCLUSION: Regardless of age and gender, home-based rehabilitation after meniscal root repair with the modified trans-tibial pull-out technique improved the patients' function at a two-year follow-up. Nonetheless, this effect was still significantly lower than that of the outdoors specialized rehabilitation. Future work is required to clarify basic protocols for home-based tele-rehabilitation programs and determine clinical, radiological and functional results. LEVEL OF EVIDENCE: Level IV, therapeutic, historically controlled study.

Epigenetics in rheumatoid arthritis; fibroblast-like synoviocytes as an emerging paradigm in the pathogenesis of the disease.

Rheumatoid arthritis (RA) is characterized by immune dysfunctions and chronic inflammation that mainly affects diarthrodial joints. Genetics has long been surveyed in searching for the etiopathogenesis of the disease and partially clarified the conundrums within this context. Epigenetic alterations, such as DNA methylation, histone modifications, and noncoding RNAs, which have been considered to be involved in RA pathogenesis, likely explain the nongenetic risk factors. Epigenetic modifications may influence RA through fibroblast-like synoviocytes (FLSs). It has been shown that FLSs play an essential role in the onset and exacerbation of RA, and therefore, they may illustrate some aspects of RA pathogenesis. These cells exhibit a unique DNA methylation profile in the early stage of the disease that changes with disease progression. Histone acetylation profile in RA FLSs is disrupted through the imbalance of histone acetyltransferases and histone deacetylase activity. Furthermore, dysregulation of microRNAs (miRNAs) is immense. Most of these miRNAs have shown an aberrant expression in FLSs that are involved in proliferation and cytokine production. Besides, dysregulation of long noncoding RNAs in FLSs has been revealed and attributed to RA pathogenesis. Further investigations are needed to get a better view of epigenetic alterations and their interactions. We also discuss the role of these epigenetic alterations in RA pathogenesis and their therapeutic potential.

Correction to: "Comparative repair capacity of knee osteochondral defects using regenerated silk fiber scaffolds and fibrin glue with/without autologous chondrocyes during 36 weeks in rabbit model.

The published online of the original version contains mistakes.

Comparative repair capacity of knee osteochondral defects using regenerated silk fiber scaffolds and fibrin glue with/without autologous chondrocytes during 36 weeks in rabbit model.

The reconstruction capability of osteochondral (OCD) defects using silk-based scaffolds has been demonstrated in a few studies. However, improvement in the mechanical properties of natural scaffolds is still challengeable. Here, we investigate the in vivo repair capacity of OCD defects using a novel Bombyx mori silk-based composite scaffold with great mechanical properties and porosity during 36 weeks. After evaluation of the in vivo biocompatibility and degradation rate of these scaffolds, we examined the effectiveness of these fabricated scaffolds accompanied with/without autologous chondrocytes in the repair of OCD lesions of rabbit knees after 12 and 36 weeks. Moreover, the efficiency of these scaffolds was compared with fibrin glue (FG) as a natural carrier of chondrocytes using parallel clinical, histopathological and mechanical examinations. The data on subcutaneous implantation in mice showed that the designed scaffolds have a suitable in vivo degradation rate and regenerative capacity. The repair ability of chondrocyte-seeded scaffolds was typically higher than the scaffolds alone. After 36 weeks of implantation, most parts of the defects reconstructed by chondrocytes-seeded silk scaffolds (SFC) were hyaline-like cartilage. However, spontaneous healing and filling with a scaffold alone did not eventuate in typical repair. We could not find significant differences between quantitative histopathological and mechanical data of SFC and FGC. The fabricated constructs consisting of regenerated silk fiber scaffolds and chondrocytes are safe and suitable for in vivo repair of OCD defects and promising for future clinical trial studies.

Effect of anterior cruciate ligament injury on acceleration response of knee joint.

This study investigated the effect of anterior cruciate ligament (ACL) injury on relative acceleration of the tibia and femur during a number of tests/activities, in order to assess the feasibility of acceleration-based diagnosis of ACL injury using inertial sensors. First, a detailed finite element model of the knee joint was developed to simulate the target tests/activities, and identify those in which a large difference between the maximum acceleration peaks (MAPs) of the healthy and ACL injured knees is likely to be observed. The promising tests/activities were entered in an experimental study, where the relative accelerations of the tibiae and femurs of 20 individuals with unilateral ACL injury, allocated randomly to two groups of conscious and unconscious test conditions, were recorded. Model predictions indicated MAP ratios>1.5 for the ACL-injured to healthy knees, during the anterior drawer, Lachman, and pivot-shift tests, as well as the lunge activity. The experimental MAP results indicated acceptable test-retest reliabilities for all tests (coefficient of variation<0.25), and significant MAP differences (p < 0.05) in the anterior drawer and pivot-shift tests, in both coconscious and unconscious conditions. The individualized MAP results indicated side-to-side differences>2 m/s2 for all subjects during unconscious pivot shift tests, and >0.5 m/s2 for eight cases out of ten during conscious anterior drawer tests. It was concluded that the pivot shift test had a great repeatability and discriminative ability for acceleration-based diagnosis of ACL injury in unconscious condition. For the conscious condition, however, the anterior drawer test was appeared to be most promising.

TAK-242 (Resatorvid) inhibits proinflammatory cytokine production through the inhibition of NF-κB signaling pathway in fibroblast-like synoviocytes in osteoarthritis patients.

BACKGROUND: Fibroblast-like synoviocytes (FLSs) are involved in osteoarthritis (OA) pathogenesis through pro-inflammatory cytokine production. TAK-242, a TLR4 blocker, has been found to have a significant impact on the gene expression profile of pro-inflammatory cytokines such as IL1-ß, IL-6, TNF-α, and TLR4, as well as the phosphorylation of Ikßα, a regulator of the NF-κB signaling pathway, in OA-FLSs. This study aims to investigate this effect because TLR4 plays a crucial role in inflammatory responses. MATERIALS AND METHODS: Ten OA patients' synovial tissues were acquired, and isolated FLSs were cultured in DMEM in order to assess the effectiveness of TAK-242. The treated FLSs with TAK-242 and Lipopolysaccharides (LPS) were analyzed for the mRNA expression level of IL1-ß, IL-6, TNF-α, and TLR4 levels by Real-Time PCR. Besides, we used western blot to assess the protein levels of Ikßα and pIkßα. RESULTS: The results represented that TAK-242 effectively suppressed the gene expression of inflammatory cytokines IL1-ß, IL-6, TNF-α, and TLR4 which were overexpressed upon LPS treatment. Additionally, TAK-242 inhibited the phosphorylation of Ikßα which was increased by LPS treatment. CONCLUSION: According to our results, TAK-242 shows promising inhibitory effects on TLR4-mediated inflammatory responses in OA-FLSs by targeting the NF-κB pathway. TLR4 inhibitors, such as TAK-242, may be useful therapeutic agents to reduce inflammation and its associated complications in OA patients, since traditional and biological treatments may not be adequate for all of them.

Ipsilateral Concurrent Knee Arthroplasty and Tibial Osteotomy with 3D-Printed Patient-Specific Instrumentation: A Case Report.

CASE: A 70-year-old woman presented with knee pain and instability and was diagnosed with advanced knee osteoarthritis and bifocal tibial deformities. The complexity of the case challenged our team to perform a significant sagittal correction (>60°) and restore her ability to walk independently. We performed ipsilateral total knee arthroplasty and anterior closed wedge tibial osteotomy using virtual planning and 3D-printed patient-specific instrumentation. CONCLUSION: Using 2 separate 3D-printed patient-specific cutting guides for this patient with a complex deformity and managing the whole planning process in close collaboration between the surgeons and engineers resulted in a satisfactory postoperative outcome, optimal implant positioning and leg alignment, and minimal soft-tissue damage.

Management of tibial nonunion and osteoarthritis using a 3D-printed titanium cone: A case report.

The use of customized 3D-printed structures has been gaining popularity in non-union management, as it allows for bypassing the defect while promoting osseointegration. Additionally, porous titanium implants minimize stress shielding due to their stiffness and elastic modulus being closer to that of bone. The interconnected channels increase the surface area and provide space for cell adhesion and proliferation. This study presents the case of a 62-year-old female patient with concomitant knee osteoarthritis recalcitrant aseptic atrophic nonunion in the tibial proximal metaphysis. Due to the small distance between the nonunion site and the joint line, nonunion treatment had to be included in the treatment plan, as it would result in a lack of mechanical stability of the tibial component, and techniques such as plating were not an option. A customized 3D-printed porous titanium cone was used to bypass the fracture site and support the stem used with the CCK prosthesis, allowing for simultaneous nonunion and osteoarthritis management.

Effect of curcumin on the expression of NOD2 receptor and pro-inflammatory cytokines in fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients.

BACKGROUND: Previous studies has shown that nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is expressed in Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients which is stimulated by muramyl dipeptide (MDP) present in the joint environment and induces inflammation via the NF-κB pathway. Also, other studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of RA FLSs. In this study, we aim to evaluate the effect of curcumin, a natural anti-inflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines. METHODS: Synovial membranes were collected from ten patients diagnosed with RA and ten individuals with traumatic injuries scheduled for knee surgery. The FLSs were isolated and treated with 40 µM curcumin alone or in combination with 20.3 µM MDP for 24 h. mRNA was extracted, and real-time PCR was performed to quantitatively measure gene expression levels of NOD2, p65, IL-6, TNF-α, and IL-1ß. RESULTS: The study findings indicate that administering MDP alone can significantly increase the mRNA expression levels of IL-6 and IL-1ß in the trauma group and TNF-α in the RA group. Conversely, administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of RA patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression. CONCLUSION: This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for RA patients. Despite the limitations of the study being an investigation of the FLSs of RA patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of RA.

Plantar fasciitis.

Heel pain, mostly caused by plantar fasciitis (PF), is a common complaint of many patients who requiring professional orthopedic care and are mostly suffering from chronic pain beneath their heels. The present article reviews studies done by preeminent practitioners related to the anatomy of plantar fasciitis and their histo-pathological features, factors associated with PF, clinical features, imaging studies, differential diagnoses, and diverse treatment modalities for treatment of PF, with special emphasis on non-surgical treatment. Anti-inflammatory agents, plantar stretching, and orthosis proved to have highest priority; corticosteroid injection, night splints and extracorporeal shock wave therapy were of next priority, in patients with PF. In patients resistant to the mentioned treatments surgical intervention should be considered.

Practical approach to the native distal femur fractures in the elderly: A rapid review over the recent trends.

Significant work has been done in recent years on treatment strategies for distal femur fractures. Inclusive reviews on periprosthetic fractures of distal femur have been carried out recently, but there is a lack of such reviews on the subject of native distal femur fractures in the recent literature. In this narrative review, we are set out to address the latest updates on geriatric non-periprosthetic distal femur fractures, and perform a rapid review over different treatment options, arriving at a summarized proposed treatment algorithm.

MicroRNA-211-5p Overexpression Effect on Endoplasmic Reticulum Stress and Apoptotic Genes in Fibroblast-like Synoviocytes of Rheumatoid Arthritis.

Fibroblast-like synoviocytes (FLSs) play a major role in the pathogenesis of rheumatoid arthritis (RA). Endoplasmic reticulum (ER) stress and dysregulation of unfolded protein response are involved in the resistance to apoptosis of FLSs in RA (RA-FLSs). MicroRNA (MiR)-211 plays an important role in controlling ER stress and apoptotic genes in a PKR-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-dependent manner. We investigated the effect of miR-211-5p overexpression on ER stress and apoptotic genes in RA-FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients. MiR-211-5p and mRNA expression of the selected genes involved in the PERK pathway and apoptosis regulation were measured in RA, trauma, and thapsigargin (Tg)-treated RA-FLSs. Afterward, Tg-treated RA-FLSs following miR-211-5p overexpression were evaluated for miR-211-5p and mRNA levels of the study genes. The expression of miR-211-5p, PERK, BAX, and BCL2 showed no differences between RA and trauma. However, the expression of ATF4 and BCL-XL showed a significant increase in trauma. In addition, the levels of C/EBP homologous protein (CHOP) and MCL1 indicated a significant increase in RA-FLSs. Tg treatment significantly increased the expression of PERK, ATF4, and CHOP in RA-FLSs with no effect on miR-211-5p, BAX, BCL2, BCL-XL, and MCL1. Furthermore, Tg treatment following miR-211-5p overexpression in RA-FLSs showed a significant increase in levels of miR-211-5p with no changes in apoptotic genes. MiR-211-5p overexpression in stimulated RA-FLSs did not alter the levels of selected genes involved in apoptosis regulation. However, more investigations are necessary to determine the ER stress role in apoptosis regulation in RA-FLSs.

Low post-arthroplasty infection rate is possible in developing countries: long-term experience of local vancomycin use in Iran.

BACKGROUND: Utilizing intrawound vancomycin powder in TKA surgery has yielded rather contrasting results in the current literature. Furthermore, CDC criteria, although effective in general, are not specifically designed for post-TKA infections. Here, we present a 7-year experience of vancomycin use in primary TKA in a high-volume tertiary knee center in Iran. Also, new criteria are proposed to detect suspected superficial post-TKA infections. METHODS: This is a retrospective analysis of primary total knee arthroplasties performed in a tertiary knee center, from March 2007 to December 2018, by a single senior knee surgeon. All patients with follow-up periods of less than 1 year were excluded from the study. Since March 2011, all patients received vancomycin (powder, 1 g) before water-tight closure of the joint capsule. A comparison was made between this group and historical control subjects (operated from March 2007 to March 2011). RESULTS: Altogether, 2024 patients were included in the study. The vancomycin and the control groups included 1710 and 314 cases respectively. Patients were mostly women (male to female ratio, 1 to 4), with a mean age of 65.20 (SD = 10.83) years. In the vancomycin group, the rate of suspected SII (1.87%) and PJI (0.41%) was significantly lower than the control group (P = 0.002). CONCLUSIONS: Our experience shows that application of local vancomycin during TKA surgery could be a reasonable infection prevention measure, although prospective randomized studies are required to evaluate its efficacy.

Transformation of fibroblast-like synoviocytes in rheumatoid arthritis; from a friend to foe.

Swelling and the progressive destruction of articular cartilage are major characteristics of rheumatoid arthritis (RA), a systemic autoimmune disease that directly affects the synovial joints and often causes severe disability in the affected positions. Recent studies have shown that type B synoviocytes, which are also called fibroblast-like synoviocytes (FLSs), as the most commonly and chiefly resident cells, play a crucial role in early-onset and disease progression by producing various mediators. During the pathogenesis of RA, the FLSs' phenotype is altered, and represent invasive behavior similar to that observed in tumor conditions. Modified and stressful microenvironment by FLSs leads to the recruitment of other immune cells and, eventually, pannus formation. The origins of this cancerous phenotype stem fundamentally from the significant metabolic changes in glucose, lipids, and oxygen metabolism pathways. Moreover, the genetic abnormalities and epigenetic alterations have recently been implicated in cancer-like behaviors of RA FLSs. In this review, we will focus on the mechanisms underlying the transformation of FLSs to a cancer-like phenotype during RA. A comprehensive understanding of these mechanisms may lead to devising more effective and targeted treatment strategies.

Role of Fibroblast Activation Protein Alpha in Fibroblast-like Synoviocytes of Rheumatoid Arthritis.

Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-ß1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-ß1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs.

Evaluation of TAK-242 (Resatorvid) Effects on Inflammatory Status of Fibroblast-like Synoviocytes in Rheumatoid Arthritis and Trauma Patients.

Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis )RA( pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-ß, IL-6, TNF-α, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikßα and pIkßα) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-ß, IL-6, TNF-α, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikßα and pIkßα by western blot. The baseline expression of IL1-ß, IL-6, TNF-α, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1ß, IL-6, TNF-α, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkßα in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients.

Loop-Post Construct, A Novel Technique for Medial Meniscus Root Repair.

Surgical reattachment of medial meniscus posterior root tear (MMPRT) with transtibial sutures can delay the presence of medial knee joint compartment osteoarthritis. Most suture configurations are placed five mm away from the torn margin in the meniscal substance which is already degenerated and may decrease the pull out strengths of repair construct. The number of meniscus penetration may also be important considering meniscus tissue damage with more complex suture techniques impose the risk of suture cut out through the meniscus substance. We introduce our loop postsuture construct technique which is simple, cheap and reproducible.