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To investigate the incidence of implant-related pain after medial opening wedge high tibial osteotomy (MOWHTO) using a locking plate, to determine whether implant removal provides pain relief and functional improvement, and to evaluate bone healing and loss of correction after implant removal. Between March 2014 and September 2017, MOWHTO was performed without bone graft. The inclusion criteria were patients who underwent implant removal after MOWHTO and were followed up for a minimum of 2 years. Patients were evaluated for implant removal 1 and 2 years after surgery. Clinical and functional evaluations were conducted to investigate implant-related pain using the visual analog scale, Lysholm score, and Tegner score. The radiographic indices measured were the gap-filling rate, weightbearing line (WBL) ratio, hip-knee-ankle angle (HKAA), medial proximal tibial angle (MPTA), and posterior tibial slope angle (PTSA). A total of 55 patients were enrolled. Fifty-one (92.7%) patients experienced implant-related pain prior to implant removal, with 43 and 8 patients reporting mild pain and moderate pain, respectively. At 1 and 2 years after implant removal, mild pain occurred in 6 (10.9%) and 5 (9.1%) patients, respectively. The remaining patients reported no implant-related pain. Prior to implant removal and 1 year after implant removal, the Lysholm score improved from 77.0 ± 5.6 to 86.8 ± 5.7 (P <.001), and the Tegner score improved from 3.3 ± 1.2 to 3.9 ± 1.3 (P <.001). The mean gap-filling rate was 84.4% ± 9.6% at implant removal, and it significantly increased to 93.7% ± 5.4% and 97.4% ± 2.6% at 1 and 2 years after implant removal, respectively (P <.001). For the WBL ratio, HKAA, MPTA, and PTSA, no statistically significant differences were found after implant removal. The incidence of implant-related pain after MOWHTO using the medial proximal tibial locking plate was high. Implant removal provides pain relief and functional improvement (met minimal clinically important differences). Even after implant removal, bone healing progressed gradually without a loss of correction in all patients. Level IV, case series. [ABSTRACT FROM AUTHOR]

As the process of bone regeneration is preceded by an inflammatory response, the immune system has long been considered important for fracture healing. Despite many studies on the contribution of immune cells to bone-related diseases, the role of immune cells in the regeneration therapy of lost bone is not well understood. In addition, various types of cells are involved in the clinical bone regeneration environment, but most of the osteo-biology studies are conducted in an osteoblast-only environment. Here, we investigated the effects of macrophages and dendritic cells on osteogenic differentiation in a co-culture environment involving human periosteal cell-derived osteoblasts, human monocyte-derived osteoclasts, and myeloid-derived cells. In addition, the cluster of myeloid immune cells involved in the clinical bone regeneration process was analyzed through bone defect rat modeling. We found that specific types of myeloid cells and related cytokines increased osteogenic differentiation. These results were confirmed in experiments using myeloid cells originating from human primitive peripheral blood mononuclear cells and by measuring the colonization of macrophages and dendritic cells in an in vivo bone defect environment. In addition, Next generation sequencing (NGS) analysis was performed through RNA sequencing for osteogenesis caused by macrophages and dendritic cells in vitro , which implemented a clinical bone regeneration environment. The results of these experiments suggest that the role of M2 macrophages or dendritic cells is markedly increased during osteogenic differentiation. Therefore, we propose that the exchange of bioactive factors between macrophages and dendritic cells during the bone formation metabolic process is a crucial step of tissue regeneration rather than limited to the initial inflammatory response. This study indicates that M2 macrophages, among myeloid cells, can be mediators that play a vital role in the effective bone regeneration process and shows the potential as a useful next-generation advanced cell therapy for bone regeneration treatment. [ABSTRACT FROM AUTHOR]

• Based on the Kano model, we classified delighters, satisfiers, and dissatisfiers. • Personal and administrative quality lead to satisfaction and reduce dissatisfaction. • Procedural fairness is negatively related to both satisfaction and dissatisfaction. • Distributive and interactional fairness are positively related to satisfaction. • Satisfaction and dissatisfaction affect continuance intention in an opposite way. While college interdisciplinary programs are widespread in South Korea, little is known about what factors can increase college student satisfaction and/or dissatisfaction or whether satisfaction and dissatisfaction are opposite or different constructs. Thus, applying the Stimulus-Organization-Response theory and Kano model, this study seeks to employ service fairness and service quality as diagnostic tools to predict satisfaction and dissatisfaction, examine the asymmetric effect of those attributes on both emotions, and investigate how those emotions are related to the intention of continuing the program. The following results were produced: (1) personal and administrative quality are positively related to satisfaction and negatively related to dissatisfaction, working as satisfiers; (2) procedural fairness is negatively related to both satisfaction and dissatisfaction, working as a dissatisfier; (3) distributive and interactional fairness are positively related to satisfaction, working as delighters; and (4) satisfaction and dissatisfaction are significantly related to continuance intention in an opposite direction. [ABSTRACT FROM AUTHOR]

Abstract Influenza continues to pose a threat to public health by causing illness and mortality in humans. Discovering host factors that regulate influenza virus propagation is vital for the development of novel drugs. We have previously reported that sphingosine kinase (SphK) 1 promotes influenza A virus (IAV) replication in vitro. Here we demonstrate that the other isoform of SphK, SphK2 promotes the replication of influenza A virus (IAV) in cultured cells, and temporary inhibition of SphK1 or SphK2 enhances the host defense against influenza in mice. IAV infection led to an increased expression and phosphorylation of SphK2 in host cells. Furthermore, pharmacologic inhibition or siRNA-based knockdown of SphK2 attenuated IAV replication in vitro. Notably, oral administration of an SphK2-specific inhibitor substantially improved the viability of mice following IAV infection. In addition, the local instillation of an SphK1-specific inhibitor or an inhibitor that globally blocks SphK1 and SphK2 provided protection to IAV-infected mice. Collectively, our results indicate that both SphK1 and SphK2 function as proviral factors during IAV infection in vivo. Therefore, SphK1 and SphK2 represent potential host targets for therapeutics against influenza. Highlights • Sphingosine kinase (SK) 2 accelerates IAV replication in cultured cells. • IAV infection increases the expression and activation of SK2. • Oral administration of SK2 inhibitor improves the viability of mice following IAV infection. • Transient inhibition of SK1 provides protection to IAV-infected mice. [ABSTRACT FROM AUTHOR]

Background: Pterostilbene is a stilbenoid and major compound and has diverse biological activities, such as antioxidant, anti-cancer, and anti-inflammatory. However, it has not been shown whether pterostilbene affects the mitotic clonal expansion during adipogenesis in 3T3-L1 cells.Purpose: In the present study, we aimed to demonstrate the detailed mechanism of pterostilbene on anti-adipogenesis in 3T3-L1 cells.Methods: Preadipocytes were converted to adipocytes through treatment with MDI (IBMX; 3-isobutyl-1-methylxanthine, DEX; dexamethasone, insulin) in 3T3-L1 cells. Oil Red O staining was performed to measure intracellular lipid accumulation. Western blot analysis was conducted to analyze protein expressions.Results: Our results showed that pterostilbene decreased the lipid accumulation compared to MDI-induced differentiation, using Oil Red O staining. Next, we found that pterostilbene suppressed the expression of C/EBPα, PPARγ, and aP2 as well as the mitotic clonal expansion-associated proteins CHOP10 and C/EBPβ, by western blot analysis. Our results indicated that pterostilbene may repress adipocyte differentiation through the activation of HO-1 expression prior to entering into the mitotic clonal expansion in 3T3-L1 cells. RNA interference was used to determine whether HO-1 acts as a regulator of CHOP10.Conclusion: Our results revealed that pterostilbene induced HO-1 expression which acts as a regulator of CHOP10. Together, we demonstrated that pterostilbene suppresses the initiation of mitotic clonal expansion via up-regulation of HO-1 expression during adipocyte differentiation of 3T3-L1 cells. [ABSTRACT FROM AUTHOR]

Background: Elaeocarpus sylvestris (Lour.) Poir. (Elaeocarpaceae) belongs to a genus of tropical and semitropical evergreen trees, which has known biological activities such as antiviral and immunomodulatory activities. However, its antiviral potential against influenza virus infection remains unknown.Purpose: In this study, we investigated the antiviral activity of the 50% aqueous ethanolic extract of E. sylvestris (ESE) against influenza A virus (IAV) infection, which could lead to the development of novel phytomedicine to treat influenza virus infection.Methods: To investigate the in vitro antiviral activity of ESE and its main ingredients, 1,​2,​3,​4,​6-​penta-​O-​galloyl-β-d-glucose (PGG) and geraniin (GE), the levels of viral RNAs, proteins, and infectious viral particles in IAV-infected MDCK cells were analyzed. Molecular docking analysis was performed to determine the binding energy of PGG and GE for IAV proteins. To investigate in vivo antiviral activity, IAV-infected mice were treated intranasally or intragastrically with ESE, PGG, or GE.Results: ESE and its gallate main ingredients (PGG and GE) strongly inhibited the production of viral RNAs, viral proteins, and infectious viral particles in vitro. Also through the viral attachment on cells, polymerase activity, signaling pathway, we revealed the ESE, PGG, and GE inhibit multiple steps of IAV replication. Molecular docking analysis revealed that PGG and GE could interact with 12 key viral proteins (M1, NP, NS1 effector domain (ED), NS1 RNA-binding domain (RBD), HA pocket A, HA receptor-binding domain (RBD), NA, PA, PB1, PB2 C-terminal domain, PB2 middle domain, and PB2 cap-binding domain) of IAV proteins with stable binding energy. Furthermore, intranasal administration of ESE, PGG, or GE protected mice from IAV-induced mortality and morbidity. Importantly, oral administration of ESE suppressed IAV replication and the expression of inflammatory cytokines such as IFN-γ, TNF-α, and IL-6 in the lungs to a large extent.Conclusion: ESE and its major components (PGG and PE) exhibited strong antiviral activity in multiple steps against IAV infection in silico, in vivo, and in vitro. Therefore, ESE could be used as a novel natural product derived therapeutic agent to treat influenza virus infection. [ABSTRACT FROM AUTHOR]

Purpose: To investigate changes in femoral tunnel diameter, dimension, and volume after anterior cruciate ligament reconstruction with notchplasty. Methods: Porcine knee specimens were divided into 2 groups of 10 specimens each. Group A did not receive notchplasty. A 2-mm notchplasty was conducted in group B. Seven-millimeter-diameter femoral tunnels were drilled and a doubled flexor digitorum profundus tendon was inserted and fixed with an EndoButton (Smith & Nephew, Andover, MA) in each knee specimen. Samples were mounted on a materials testing machine. Each group was preloaded at 10 N and subjected to 20 loading cycles (between 0 and 40 N), followed by 1,000 loading cycles in the elastic region (between 10 and 150 N). High-resolution computed tomography with 1.0-mm slices was conducted with all samples before and after testing. A 3-dimensional model was constructed to evaluate the degree of the tunnel change. Results: In group B the mean longest diameter and dimension of the femoral tunnel significantly increased after the test (P = .005 and P = .001, respectively). The volumetric loss of bony structure after the test in group B was significantly greater than that in group A (P = .039). Meanwhile, no significant difference was found before and after the test in terms of tunnel diameter, dimension, and volumetric loss around the tunnel in group A. Conclusions: The intra-articular orifice of the femoral tunnel was enlarged after the uniaxial cyclic loading test after notchplasty. An enlarged tunnel orifice may lead to a discrepancy between the tunnel and the graft at the tunnel aperture. Clinical Relevance: The data may have an implication that suspensory fixation with a notchplasty has a negative effect on the full graft accommodation at the tunnel aperture. Aperture widening may affect graft positioning, leading to subtle changes in graft biomechanics and laxity. [Copyright &y& Elsevier]

Purpose: The aim of this study was to determine the acromioclavicular (AC) motion and change in length and tension of the coracoclavicular ligament during different positions of shoulder abduction using a 3-dimensional finite element model based on computed tomography images from normal human shoulders. Methods: The right shoulders of 10 living subjects were scanned with a high-resolution computed tomography scanner at 0°, 60°, 120°, and 180° of shoulder abduction. Several modeling programs were used to simulate AC motion. Finite element models of the conoid and trapezoid ligaments were constructed based on each footprint. The tension and length changes of each ligament during shoulder abduction were assessed. Results: The distal clavicle exhibited internal rotation with respect to the medial acromion at 0°, 60°, 120°, and full abduction (3.2° ± 2.9°, 23.2° ± 10.8°, 20.6° ± 3.7°, and 37.1° ± 3.4°, respectively). With horizontal motion, the clavicle translated posteriorly at 60° of abduction (4.4 ± 3.4 mm) and then translated anteriorly at 120° and full abduction (0.4 ± 1.6 mm and 1.9 ± 0.4 mm, respectively). The lengths of the conoid ligament gradually increased at 60° to 180° of shoulder abduction whereas those of the trapezoid ligament remained relatively consistent at 60° to 120° of abduction compared with 0° of abduction. Conclusions: The distal clavicle had a wide range of motion during shoulder abduction, which did not support the concept of synchronous motion with the scapula. The conoid and trapezoid ligaments functioned reciprocally during shoulder abduction. With increasing shoulder abduction, the length of the conoid ligament gradually increased; meanwhile, the trapezoid ligament was relatively consistent and then lax at full abduction. In particular, the conoid ligament may act as a key restraint to prevent excessive retraction of the scapula during shoulder abduction. Clinical Relevance: The data in this study have the potential to suggest that conoid and trapezoid ligaments should be reconstructed separately, and rigid AC fixation in patients with AC separation is not recommended based on the findings of this study. [Copyright &y& Elsevier]

Purpose: The aim of this study was to determine the change in length and tension of the reconstructed anterior cruciate ligament (ACL) double bundles at different knee flexion angles by use of a 3-dimensional finite element model. Methods: The right knees of 12 living subjects were scanned with a high-resolution computed tomography scanner at 0°, 45°, 90°, and 135° of knee flexion. Several modeling programs were used to simulate double-bundle ACL reconstruction. A finite element model of each bundle with a tension of 20 N was put into each tunnel followed by fixation of the bundles. The tension and length changes of each bundle at different knee flexion angles were assessed. Results: For the anteromedial bundle, the length decreased gradually between 45° and 90° of knee flexion and then reached a plateau, whereas the length of the posterolateral bundle significantly decreased at 45° and 90° of flexion but then increased at full flexion. The reaction force of the anteromedial graft slightly decreased at 45° and then remained constant between 90° and 135° of knee flexion. The reaction force of the posterolateral bundle at full extension slightly decreased at 45° and 90° of flexion, followed by a rebound increase at 135°. Conclusions: We found that both bundles functioned throughout the arc of flexion with consistency in tension, although their lengths decreased. The 2 ACL grafts did not function in a reciprocal manner, unlike previous descriptions. Clinical Relevance: The data obtained for length and tension versus flexion angle have the potential to suggest the appropriate knee position for graft fixation and tensioning to be near extension in clinical situations. [ABSTRACT FROM AUTHOR]

Abstract: Sphingosine 1-phosphate (S1P)-metabolizing enzymes regulate the level of bioactive sphingolipids that have curative potential. Recently, S1P-metabolizing enzymes such as sphingosine kinase 1 and S1P lyase were shown to regulate influenza virus replication and the virus-induced cytopathogenicity. The mechanism appeared to employ a JAK/STAT type I interferon signaling pathway that induces anti-viral status. Further, sphingosine analogs altered cytokine responses upon influenza virus infection. This article focuses on recent discoveries about the sphingolipid system that influences on host protection from viral virulence and the involvement of cytokine signaling in its underlying mechanisms. Deciphering the steps of this pathway could help us envision how the modulation of sphingolipid metabolism can be applied as a therapeutic approach to overcome infectious diseases. [Copyright &y& Elsevier]

Background: Adonis amurensis Regel & Radde, commonly found in East Asia, has been traditionally used to treat cardiac insufficiency and edema. Although this plant extract has been shown to regulate cell growth and neovascularization, the anti-cancer mechanism of A. amurensis has not been fully investigated.Purpose: In this study, we aimed to examine the anti-cancer activity of A. amurensis and identify its underlying mechanism.Methods: The growth of cancer cells was evaluated by MTT and hollow fiber assays. A cancer xenograft nude mouse model was used to assess the anti-cancer activities in vivo. Autophagic activity was measured by the detection of autophagosome formation and by performing a monodansylcadaverine (MDC) assay.Result: A. amurensis extract showed potent anti-cancer activity both in vitro and in vivo. Importantly, the treatment of cancer cells with A. amurensis extract dramatically increased the formation of autophagosomes and was involved in the activation of multiple signaling components including AKT, ERK, and MAPK. Furthermore, we isolated an active ingredient, Multioside, which exhibited strong anti-cancer activity through autophagy.Conclusion: A. amurensis displays anti-cancer activity that is mediated by the activation of autophagy, suggesting that A. amurensis could be a useful therapeutic anti-cancer agent. [ABSTRACT FROM AUTHOR]

Background: Obesity develops when dietary energy intake exceeds energy expenditure, and can be associated with metabolic syndrome. Recent studies have shown that dietary phytochemicals can promote energy expenditure by inducing the browning of white adipose tissue (WAT).Purpose: This study investigated whether cardamonin induces the browning of 3T3-L1 adipocytes through the activation of protein kinase A (PKA).Methods: Anti-obesity potential of cardamonin was evaluated in 3T3-L1 adipocytes. Adipocyte-specific genes were observed using western blot, qPCR analysis and immunocytochemistry.Results: Cardamonin treatment inhibited lipid droplet accumulation and reduced the expression of the adipogenic proteins C/EBPα and FABP4, and the lipogenic proteins LPAATθ, lipin 1, DGAT1, SREBP1, and FAS. Cardamonin also induced the expression of the browning marker genes PRDM16, PGC1α, and UCP1 at the mRNA and protein levels, and induced mRNA expression of CD137, a key marker of beige adipocytes. It also increased the expression of the β-oxidation genes CPT1 and PPARα at the mRNA and protein levels. In addition, cardamonin increased PKA phosphorylation and the mRNA and protein expression of the downstream lipolytic enzymes adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL).Conclusion: Our findings demonstrate novel effects of cardamonin to stimulate adipocyte browning, suppress lipogenesis, and promote lipolysis, implying it may have potential as an anti-obesity agent. [ABSTRACT FROM AUTHOR]

Abstract: The adsorption mechanisms of metal cations on the surfaces of clay minerals and other minerals are important for understanding their fate in contaminated soils and in waste water treatment. The reactions of Cu2+ and Pb2+ heavy metal cations with layered double hydroxide (LDH), has been investigated in aqueous solutions to elucidate their removal behaviors by LDH. The reaction of aqueous CuCl2 solution with Mg/Al-LDH resulted in precipitation of Cu hydroxide chloride (Cu7Cl4(OH)10·H2O) along with slight decomposition of Mg/AI-LDH. On the other hand, the reaction of aqueous PbCl2 solution led to steady decomposition of Mg/Al-LDH structure along with the formation of various Pb precipitates such as carbonate chloride (PbCO3PbCl2) and hydroxide chloride (Pb(OH)Cl). Experimental techniques such as X-ray diffraction, X-ray photoelectron spectroscopy and cation removal isotherms were used to decipher the mechanism of uptake. This study indicates that LDH removes Cu2+ and Pb2+ transition metal cations from aqueous solution mainly by surface adsorption and precipitation. [Copyright &y& Elsevier]

• Elderly patients in urology receive potentially inappropriate medications (PIMs). • 73.7% of patients with lower urinary tract symptoms received PIMs at least once. • The average number of PIMs used per patient was 1.31 ± 1.25 (0–7). • Number of chronic diseases and polypharmacy were predictive factors for PIMs. To investigate polypharmacy and potentially inappropriate medications (PIMs) in elderly patients visiting the urology department for lower urinary tract symptoms (LUTS). We retrospectively analyzed digital medical records of individuals over the age of 65 who visited the urology department for LUTS. This cross-sectional study was conducted in 10 hospitals located in South Korea, between September 2017 and December 2017. All prescribed medications were analyzed using electronic medical records. The updated 2015 Beers criteria were used to identify and assess the appropriateness of the prescribed drugs in elderly patients. We analyzed a total of 2143 patients aged over 65 years from 10 institutions. The mean age was 74.2 ± 6.26 years (65–97), 1634 (76.2%) were men. Patients took a mean of 6.48 ± 2.46 medications (range 0–18), and polypharmacy was found in 1762 patients (82.2%). The number of patients who received PIMs at least once was 1579 (73.7%). The average number of PIMs used per patient was 1.31 ± 1.25 (0–7). PIM use ratio was 18.9 ± 0.15% (0–67%). The number of chronic diseases, and concurrent medication and polypharmacy were predictive factors associated with PIM use. Our multi-institutional results show that a substantial proportion of elderly patients took PIMs when visiting the urology department. Factors associated with PIMs were the number of chronic diseases and polypharmacy. Medication use in elderly patients, especially in urology, should be monitored carefully. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) continues to threaten human health. To date, two classes of antiviral drugs have been approved to treat IAV infection, but the continuous emergence of the drug-resistant IAV mutant reinforces the need to develop new antiviral drugs. In this study, we aimed to investigate the anti-IAV activity of an aqueous mixture of Agrimonia pilosa and Galla rhois extracts (APRG64). We demonstrated that APRG64 significantly reduced the IAV-induced cytopathic effect, the transcription/expression of viral proteins, and the production of infectious viral particles. Among nine major components of APRG64, apigenin was identified as the main ingredient responsible for the anti-IAV activity. Interestingly, APRG64 and apigenin inhibited the cell attachment and entry of virus and polymerase activity. Importantly, intranasal administration of APRG64 or apigenin strongly reduced viral loads in the lungs of IAV-infected mice. Furthermore, oral administration of APRG64 significantly reduced the level of viral RNAs and the expression level of pro-inflammatory cytokines in the lungs, which protected mice from IAV-induced mortality. In conclusion, APRG64 could be an attractive antiviral drug to treat IAV infection. [Display omitted] • APRG64 and its compound apigenin inhibit IAV replication. • APRG64 reduces pulmonary viral burden and the level of inflammatory cytokines. • Oral administration of APRG64 protects mice from IAV-induced mortality. [ABSTRACT FROM AUTHOR]

Purpose: Our objective was to evaluate the effectiveness of arthroscopic distal clavicle resection in cases presenting with pain and subtle instability after neglected grade II acromioclavicular (AC) joint dislocation. Methods: From February 1998 to May 2006, 17 patients with symptomatic AC instability following chronic grade II AC joint injury were studied. Sixteen patients were male and one female, with a mean age of 48 years. An all-arthroscopic procedure comprising disk removal and distal clavicle resection was performed in all cases. All patients were reviewed clinically, preoperatively and at final follow-up (mean 38 months) using the pain score on a visual analog scale and the Constant score. Strength was measured using an Isobex digital strength analyzer. Patient's personal satisfaction after the procedure was documented as excellent, good or poor. Postoperative AC joint radiographs were routinely obtained in all patients to measure the amount of clavicle resection. Results: Two patients underwent additional reconstructive surgery for disabling pain and dysfunction even after the arthroscopic resection procedure. The remaining 15 patients were analyzed. The pain scores improved significantly ( p = 0.03). The mean pain score was 5.8 (range 5-9) before treatment and 1.6 (range 0-3) at follow-up. The Constant scores had improved significantly at the final follow-up ( p = 0.001). The median Constant score increased from 46 (range 36-69) preoperatively to 71 (range 48-84) postoperatively. Strength had improved at the last follow-up. Eleven patients were satisfied and six were not satisfied with this procedure at the final follow-up. Conclusions: Arthroscopic distal clavicle resection statistically improved the pain score, Constant score and strength for grade II AC injury with subtle distal clavicle instability. However, six patients (33.5 %) were not satisfied subjectively. This procedure seemed to be a reasonable initial treatment option with lower morbidity. [ABSTRACT FROM AUTHOR]

[Display omitted] Agrimonia pilosa (AP), Galla rhois (RG), and their mixture (APRG64) strongly inhibited SARS-CoV-2 by interfering with multiple steps of the viral life cycle including viral entry and replication. Furthermore, among 12 components identified in APRG64, three displayed strong antiviral activity, ursolic acid (1), quercetin (7), and 1,2,3,4,6-penta- O -galloyl- β - d -glucose (12). Molecular docking analysis showed these components to bind potently to the spike receptor-binding-domain (RBD) of the SARS-CoV-2 and its variant B.1.1.7. Taken together, these findings indicate APRG64 as a potent drug candidate to treat SARS-CoV-2 and its variants. [ABSTRACT FROM AUTHOR]