Search

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger’s hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10−7–7.31 × 10−6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10−7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10−6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D’ = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.

In joint surgery, evaluation of the relative positions and angles among joint structures (bones, ligaments, muscle, and cartilages, etc.) in range of motion, lifting and weight bearing of the joint is required. However, current volume visualization techniques provide only static 3D images of anatomic structures in volume data. We propose a method to manipulate (reposition, resize and bend) the joint structures in a volume, by which surgeons can visualize and evaluate the critical positions or angles of the joint structures, and thus plan surgery to correct the morphologic pathology of the joint structures. We also propose a system with a real-time cutting simulation function together with the proposed structure manipulation functions by which surgeons can rehearse and verify joint surgery.

This paper proposes the design and control of passive and active motion of lower limb rehabilitation system. The dynamic model of the rehabilitation machine is firstly derived for further controller design. Then, an intelligent sliding-mode control (ISMC) system which involved recurrent Hermite neural network (RHNN) estimator to estimate the unknown external disturbance and uncertainty is proposed to track the angular position and velocity in the passive motion. In the active motion, the position-based impedance control is implemented to achieve human-machine compliance.

Background Chronic rhinosinusitis (CRS) is an inflammatory disease of the sinuses and mucosa with unclear pathogenesis. Interleukin (IL)-21 is mainly expressed in activated cluster of differentiation (CD)4+ T cells and has potent regulatory effects on the immune system. Objective This study is to determine whether IL-21 in the blood is correlated with CRS. Methods The blood samples from CRS patients and normal controls were analyzed in correlation with clinical features. The eosinophil percentage was counted, and serum levels of total immunoglobulin E (IgE) and IL-21 were analyzed by enzyme-linked immunosorbent assay (ELISA). In addition, IL-21 and interferon (IFN)-γ secreted from stimulated peripheral blood mononuclear cells (PBMCs) were measured by ELISA, and their mRNA expression levels were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Disease severity was scored based on computed tomography (CT) scan, nasal endoscopy, and global osteitis scoring scale (GOSS). Results A total of 55 CRS and 37 healthy subjects were recruited. The average levels of serum total IgE were 20 kU/L in normal group, 290 kU/L in CRS with nasal polys (CRSwNP), and 187 kU/L in CRS without nasal polys (CRSsNP). IL-21 levels were 28 pg/mL in normal group, 54 pg/mL in CRSwNP, and 71 pg/mL in CRSsNP. Both IgE and IL-21 were significantly elevated in both CRS patient subgroups. However, no significant difference was found between these two patient subgroups. The serum IL-21 levels correlated well with the disease severity in the patients. In addition, the secreted IL-21 was enhanced significantly in the patient's PBMCs stimulated by phytohemagglutin (PHA). Conclusion IL-21 could be a target for diagnosis and treatment of CRS.

Tracheal bronchus is a congenital anatomical variant of patients with accessory bronchus in the right upper lobe deriving directly from the supracarinal trachea. Pre-operative consultation with the anesthesiologist is important for patient safety and can avoid adverse effects induced by endotracheal intubation. In this report, we described a case of tracheal bronchus in which general anesthesia was performed for video-assisted thoracoscopic surgery. We discussed some of the issues surrounding to complications in tracheal bronchus.

Dendritic cells (DCs) play an essential role in immunity and are used in cancer immunotherapy. However, these cells can be tuned by tumors with immunosuppressive responses. DC-specific intercellular adhesion molecule 3-Grabbing Nonintegrin (DC-SIGN), a C-type lectin expressed on DCs, recognizes certain carbohydrate structures which can be found on cancer cells. Nasopharyngeal carcinoma (NPC) is an epithelial cell-derived malignant tumor, in which immune response remains unclear. This research is to reveal the molecular link on NPC cells that induces the immunosuppressive responses in DCs. In this article, we report identification of annexin A2 (ANXA2) on NPC cells as a ligand for DC-SIGN on DCs. N-linked mannose-rich glycan on ANXA2 may mediate the interaction. ANXA2 was abundantly expressed in NPC, and knockdown of ANXA2 suppressed NPC xenograft in mice, suggesting a crucial role of ANXA2 in NPC growth. Interaction with NPC cells caused DC-SIGN activation in DCs. Consequently DC maturation and the proinflammatory interleukin (IL)-12 production were inhibited, and the immunosuppressive IL-10 production was promoted. Blockage of either DC-SIGN or ANXA2 eliminated the production of IL-10 from DCs. This report suggests that suppression of ANXA2 at its expression or glycosylation on NPC may improve DC-mediated immunotherapy for the tumor.

This paper proposes the design and control of continuous passive motion (CPM) machine based on constraint-induced movement therapy (CIMT). First, the dynamic model of the CPM machine is derived for further controller design by the principal of virtual work. Then, an intelligent sliding-mode control (ISMC) system which involved recurrent Hermite neural network (RHNN) estimator to estimate the unknown external disturbance and uncertainty is proposed to track the angular position and velocity of the CPM machine.

In this paper, we present the design and control of continuous passive motion (CPM) machine based on Constraint-Induced Movement Therapy (CIMT) for a patient who needs knee rehabilitation. First, the dynamic model of the CPM machine is derived by the principal of virtual work in dynamics. Then, an intelligent sliding-mode control (ISMC) system which involved recurrent Chebyshev neural network (RCNN) estimator to estimate the unknown external disturbance and uncertainty online is proposed to track the angular position and velocity of the CPM machine. Furthermore, we prove that the proposed ISMC system is asymptotically stable via Lyapunov theory. Finally, the experimental results are illustrated to demonstrate that the ISMC system can effectively reduce chattering phenomenon and precisely track reference trajectory of the CPM machine.

The carbohydrate polymer, hyaluronan, is a major component of the extracellular matrix in animal tissues. Exogenous hyaluronan has been used to treat osteoarthritis (OA), a degenerative joint disease involving inflammatory changes. The underlying mechanisms of hyaluronan in OA are not fully understood. Pro-inflammatory interleukin (IL)-1β downregulates peroxisome proliferator-activated receptor gamma (PPARγ), and increases expression of matrix metalloproteinases (MMPs) which are responsible for the degeneration of articular cartilage. The effects of low- and high-molecular-weight hyaluronan (oligo-HA and HMW-HA) on the inflammatory genes were determined in human SW-1353 chondrosarcoma cells. HMW-HA antagonized the effects of IL-1β by increasing PPARγ and decreasing cyclooxygenase (COX)-2, MMP-1, and MMP-13 levels. It promoted Akt, but suppressed mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NFκB) signaling, indicating anti-inflammatory effects. In contrast, the cells had overall opposite responses to oligo-HA. In conclusion, HMW-HA and oligo-HA exerted differential inflammatory responses via PPARγ in IL-1β-treated chondrosarcoma cells.

To investigate the therapeutic potential of naturally occurring cinnamophilin against cartilage degradation and its action mechanisms, its effects on matrix metalloproteinase (MMP)-1 and -13 induction were examined in the human SW1353 chondrocytic cell line. Human chondrocytes (SW1353) were stimulated with interleukin (IL)-1β, and then mitogen-activated protein kinase (MAPK) and c-Jun activations, inhibitory κB-α (IκB-α) degradation, and MMP-1, and 13 expressions were assayed by a Western blot analysis. Cinnamophilin strongly inhibited MMP-1 and -13 induction in IL-1β-treated (30 ng/mL) SW1353 cells in a concentration-dependent manner, and it also reduced MAPK family members including extracellular signal-regulated kinase (ERK), p38 MAPKs, and c-Jun N-terminal kinase. Moreover, nuclear factor (NF)-κB signaling activation through IκB-α degradation, IκB kinase (IKK)-α/β, and p-65 phosphorylation was restored by cinnamophilin upon IL-1β stimulation. Importantly, results showed that IL-1β-induced activation of phosphorylated (p)-c-Jun in chondrocytes was significantly inhibited by cinnamophilin. These results indicate that cinnamophilin inhibited MMP-1 and -13 expressions in IL-1β-treated chondrocytes through either NF-κB or ERK/p38 MAPK downregulation and/or suppressing p-c-Jun pathways. Furthermore, these findings suggest that cinnamophilin may have the potential for chondroprotection against collagen matrix breakdown in cartilage of diseased tissues such as those found in arthritic disorders.

Aim of the study This study examined the modulating effects of Clematis chinensis Osbeck (Ranunculaeae) on pro-inflammatory and degradative mediators associated with inflammatory arthritis. Materials and methods Primary human chondrocytes (PHC) were stimulated with IL-1β or lipopolysaccharide (LPS) to induce the enhanced release of prostaglandin E 2 (PGE 2 ), metalloproteinase (MMP-3 and -13), and cyclooxygenase-2 (COX-2) protein expression. The 18 F-FDG microPET imaging system was used to evaluate the anti-arthritic effects of Clematis chinensis in vivo . Results The acetone extracted Clematis chinensis (CC6) contained the most total saponins compared to other solvent's extracts and showed significant and dose-dependent inhibitory effects on PGE 2 , MMP-3, -13, and COX-2 productions by LPS-stimulated PHC. Furthermore, CC6 also exerted inhibitory effects on 2- 18 F-fluoro-2-deoxy- d -glucose ( 18 F-FDG) uptake when assessed by positron emission tomography (PET) uptake in the joints and serum PGE 2 of rabbits with knee joints injected with LPS. Conclusion The results suggest the significant chondroprotective effects of Clematis chinensis are through its anti-inflammatory and MMPs inhibitory abilities. Meanwhile, we established a new analysis method to evaluate the Chinese herbal anti-arthritic effects.

Background Intramedullary nailing is widely accepted as the gold standard for most metaphyseal fractures of the long bones. Infections after intramedullary nailing have increased and cause recalcitrant metaphyseal osteomyelitis. Usually, multiple surgeries combined with adjuvant administration of local and systemic antibiotics are required to achieve infection control. The recurrence rate is still high and often causes poor limb function. Enhancement of local antibiotic concentrations through different delivery systems has been developed as an effective solution for eliminating musculoskeletal infections. Our study was conducted to evaluate the efficacy of antibiotic-loaded acrylic cement rods in managing infected intramedullary nailing. Methods Twelve patients with metaphyseal osteomyelitis following intramedullary nailing were enrolled. The causative organisms were identified in eight patients, including six methicillin-resistant Staphylococcus aureus , one methicillin-susceptible S aureus , and one methicillin-resistant S aureus and Prevotella intermedia mixed infection. All patients were treated with radical reaming debridement, copious intramedullary lavage, insertion of an impregnated acrylic cement rod, and systemic antibiotic administration. Results The average follow-up duration was 59.1 months. None of the 12 patients showed a relapse of infections. Four patients had nonunion of the old fracture site and received subsequent revisional internal fixation and bone grafting. All of them achieved solid bony union within 18 weeks. Conclusions Insertion of antibiotic-loaded acrylic cement rods combined with adequate debridement, lavage, and systemic antibiotic administration significantly contribute to infection control after intramedullary nailing.

Objective: To investigate alterations of integrin αv, survival and apoptosis signaling pathways in uterine leiomyomas. Materials and Methods: In a prospective study of 50 women with uterine leiomyomas that had been pathologically confirmed, specimens were obtained laparoscopically from 2007 to 2009. The expressions of integrin αv signaling pathways (Ras/Raf/ERK1/2, Akt and cleaved caspase-3), surface microstructures by surface electron microscopy and immunohistochemical findings were assessed. Results: The study yielded novel results: (1) the integrin αv expression approached a low level (mRNA 0.39 ± 0.06, protein 0.47 ± 0.08) with coherent alterations of its downstream signaling molecules (Ras, p-c-Raf, p-ERK1/2) (p < 0.001); (2) smoother surface microstructures of uterine leiomyomas were correlated with low integrin αv expressions, and (3) survival signaling and apoptosis signaling were significantly down- and upregulated respectively (p < 0.001). Conclusion: Integrin αv and related survival signaling pathways were downregulated, but the apoptosis was upregulated in uterine leiomyomas. Benign smooth-contoured tumors may have low integrin expressions and cancer invasion potentials.

Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 +/- 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p0.01), but cleaved caspase-9 and caspase-3 showed no significant changes in either group. TEM findings showed irreversible and reversible inner-structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.

Breast asymmetries and scoliosis influence the results of augmentation mammaplasty. Although a variety of methods have been proposed to resolve breast asymmetries, to date, no simple preoperative algorithm has been proposed for predicting the breast volume and decreasing breast asymmetries in the place of subjective or expensive evaluation. The relationship between the scoliosis and breast volume asymmetry was further analyzed statistically in this study.The study enrolled 60 scoliotic patients from 780 patients undergoing augmentation mammaplasty between January 2000 and March 2008. The average follow-up period was 2 years. The inclusion criteria required hypoplastic breasts, a difference in bilateral breast volumes greater than 20 ml, and scoliosis with a Cobb angle greater than 10 degrees . The authors' surgical algorithm demonstrated an anthropomorphic equation for predicting breast volume and selecting the correct implant size.Pearson regression analysis showed that the breast volume asymmetry difference was significantly correlated with the severity of scoliosis (Cobb angle) (correlation coefficient, 0.901). No correlation between the difference in pre- and postoperative nipple and inframammary levels and the severity of scoliosis was noted. Augmentation mammaplasty significantly decreased the breast asymmetry differences (volume and nipple level) (p0.001). The average preoperative estimated breast volume was 45.3 ml for the smaller breast and 88.4 ml for the larger breast.This study found that the severity of scoliosis showed significant correlation with the breast volume asymmetry differences. Augmentation mammaplasty for breast asymmetries decreased not only the volume difference but also the difference in nipple levels.

Paradoxical anterior movement of the femoral condyles after total knee arthroplasty (TKA) often attenuates the extension mechanism and causes a suboptimal outcome. The medial-pivot implant design aimed to confine anterior movement and emulate physiologic knee kinematics. In our study, a consecutive series of 58 medial-pivot TKA were enrolled with a minimum 5-year follow-up. The Knee Society score improved from 30.5 to 91.1 in objective and from 36.7 to 82.3 in functional scale. The average range of motion was 115.4°. The medial-pivot TKA provided significant improvement in the postoperative range of motion, objective Knee Society score, pain scale, and functional score (P < .05) statistically. A larger sample and longer follow-up are recommended to draw definitive conclusions of this new implant design.

Medical robotics has high potential to bring patients real benefits due to its high accuracy positioning capability. However a patient's organ movement is still a challenge for medical robotics in achieving the expected high positioning accuracy. In orthorpaedic surgery, the target object is hard tissue. Obtaining accurate positioning is usually easier than with a soft tissue target. In the past, the solution was to use a mechanical clamper to fix and prevent the bone from moving. However, the invasive bone clamping approach has several drawbacks, such as additional damage to the bone, large errors for a loose bone, and constraints of ligament adjustment etc. Therefore, in this paper, an unconstrained virtual bone clamper has been proposed. Its aim is to provide the same bone freezing function as a traditional bone clamp, but it is implemented by software. The drawbacks of a physical bone clamp can be avoided. Experimental results on plastic sawbones resection demonstrate that using the virtual c...

Background With respect to interleukin (IL)-1β concentration, the disease-modifying effects of glucosamine HCl (GLN) on IL-1β-treated chondrocytes followed a dose-dependent manner and were traditionally conducted under normoxic conditions not generally encountered by chondrocytes in vivo. Purposes To demonstrate the beneficial effects of GLN on IL-1β-induced matrix metalloproteinase (MMP) expression in chondrosarcoma cells in a dose-dependent manner, but at different concentration ranges of IL-1β; additionally, to determine how hypoxia affects GLN's beneficial effects after dose-dependent application. Methods Under normoxic and hypoxic conditions, human chondrosarcoma cells (SW1353) induced by high and low IL-1β concentrations were respectively treated with low and high concentration ranges of GLN. mRNA and protein expression for MMPs and glucose transporter protein (GLUT)-1 were examined by reverse transcription–polymerase chain reaction and Western blot analysis. Results High concentrations of GLN could reduce mRNA and protein expressions of MMPs induced by low concentration of IL-1β; whereas low concentrations of GLN could reduce the inflammatory response upregulated by high concentrations of IL-1β. The data might substantiate the beneficial effects in clinical application of lower plasma concentrations of GLN achievable by oral administration. Furthermore, the effects were compared under hypoxic conditions to mimic real conditions encountered in human cartilage under normoxia. Upregulation of HIF-1α protein levels under hypoxia was observed. The level of MMP protein expression induced by IL-1β was lower under hypoxic conditions. Instead, inhibition of MMPs by GLN appeared to be more apparent. Finally, GLUT-1 protein expression of SW1353 was upregulated under IL-1β and hypoxia treatment. Conclusion Glucose transporter, most likely GLUT-1, inducible by HIF-1α, might play an important role in the therapeutic efficacy of a lower plasma concentration of GLN on osteoarthritis achievable by oral administration.

Burring surgery is mainly implemented for fine or critical structures and widely used in orthopedic, oral and maxillofacial, ENT and neurosurgery departments to delicately cut or polish bones, joints or other tissues. This paper describes a volume manipulation method that extends a voxel with multiple values to represent accurate burred changes on tissue surfaces. Tissue surface reconstruction is implemented for the local burred surface to provide a real-time visual response. A burring force vector for a haptic response is calculated by detecting which parts of a bur contact tissue and summated from tissue removal loads on the contacted parts. A spine surgery example showed that rough surface features by gross cutting or smooth features by fine cutting can be clearly demonstrated and high haptic reality can be achieved by our simulations. The burring surgery simulator with the accurate visual and haptic responses can be an effective rehearsing and training tool.

This paper describes a three-dimensional reconstruction method to provide real-time visual responses for volume (constituted by tomographic slices) based surgery simulations. The proposed system uses dynamical data structures to record tissue triangles obtained from 3D reconstruction computation. Each tissue triangle in the structures can be modified or every structure can be deleted or allocated independently. Moreover, triangle reconstruction is optimized by only deleting or adding vertices from manipulated voxels that are classified as erosion (in which the voxels are changed from tissue to null) or generation (the voxels are changed from null to tissue). Therefore, by manipulating these structures, 3D reconstruction can be locally implemented for only manipulated voxels to achieve the highest efficiency without reconstructing tissue surfaces in the whole volume as general methods do. Three surgery simulation examples demonstrate that the proposed method can provide time-critical visual responses even under other time-consuming computations such as volume manipulations and haptic interactions.

The purpose of this study was to investigate the possible involvement of synovium in cartilage destruction in osteoarthritis (OA) patients. Using human primary synovial fibroblasts (HPSFs), we examined the effects of glucosamine (GLN) on the regulation of the expression of matrix metalloproteinases (MMP-1, -2, and -13) and chemokines (IL-8, MCP-1, and RANTES) as well as the involvement of MAPK signal pathways (JNK, ERK, and p-38) and the transcription factor of NF-kappaB on the present or absence of interleukin (IL)-1beta. Our experiments showed that protein production and mRNA expressions of MMP-1, MMP-3, MMP-13, IL-8, MCP-1, and RANTES were downregulated by treatment with glucosamine in HPSFs. The results further showed that GLN could inhibit IkappaBalpha phosphorylation and IkappaBalpha degradation leading to inhibition of the translocation of NF-kappaB to nuclei. However, GLN upregulated MAPKs pathways in HPSFs cells with or without IL-1beta. The results suggest that the inhibition of MMP-1, -3, and -13 expressions as well as IL-8, MCP-1, and RANTES productions by GLN might mediate suppression of NF-kappaB signal pathways, and HPSFs seem to have a potential functions as an alternative source of MMPs and chemokines for inducing the degradation of cartilage in OA.

This paper describes a PC based hand rehabilitation system equipped with a commercial haptic device. The proposed system uses a 3D hierarchical hand model to describe the transformation between the wrist with any MCP joint, and the transformations between an MCP or PIP joint with a PIP or DIP joint on the same finger. Through this hand model, a 3D hand image with dynamic rotation of any joint can be demonstrated in real-time. The system also uses the 6D input of the haptic device and the accumulation of transformation matrices between the related joints to estimate the rotational angle of the rehabilitated joint. The system can detect the force and the range of joint motion in the active rehabilitation by the estimated angle and the 3D output force of the haptic device. The detected force and the range of motion are then used to control and achieve high efficient passive rehabilitation. A rehabilitation example of the PIP joint of the index finer demonstrates the attachment, set-up of the haptic device to the rehabilitated joint and shows the rehabilitation can be improved by the controlled passive rehabilitation.

Combined effects of hyaluronate and indomethacin in the treatment of rabbits with antigen-induced arthritis (AIA) were evaluated by assessing joint swelling, C-reactive protein (CRP) and prostaglandin E(2) (PGE(2)) levels with periodic intra-articular (ia) injections of hyaluronate alone (HA group) and with either a low or high concentration of indomethacin (LI-HA or HI-HA group). End-point analyses included matrix metalloproteinases-3 (MMP-3) activity and macroscopic and histological joint examinations. Results demonstrated that treatment in LI-HA and HI-HA groups resulted in statistically significant suppression of CRP, PGE(2, )and MMP-3 in comparison with those of HA group. Inhibition of serum CRP was only observed in LI-HA group. The order of serum MMP-3 inhibition was LI-HAHI-HAHA. Based on macroscopic and histological analyses of pannus formation, hyperplasia, inflammation, joint leakage and erosion, and loss of proteoglycan, the only statistically significant improvement was shown in LI-HA group compared to HA group and HI-HA group compared to control group.

Background Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly. However, few agents with high efficacy and low side effects have been developed to treat OA. In this study, we evaluated the effects of the alginate extract named CTX in OA cell and rabbit models. Results CTX was formulated by hydrolyzing sodium alginate polymers with alginate lyase and then mixing with pectin. HPLC was used to analyze the CTX content. Human chondrosarcoma SW1353 cells treated with interleukin-1β were used as OA model cells to investigate the effects of CTX on chondrocyte inflammation and anabolism. CTX at concentrations up to 1000 μg/ml exerted low cytotoxicity. It inhibited the gene expression of proinflammatory matrix metalloproteinases (MMPs) including MMP1, MMP3 and MMP13 in a dose-dependent manner and increased the mRNA level of aggrecan, the major proteoglycan in articular cartilage, at 1000 μg/ml. Thirteen-week-old New Zealand White rabbits underwent a surgical anterior cruciate ligament transection and were orally treated with normal saline, glucosamine or CTX for up to 7 weeks. Examinations of the rabbit femur and tibia samples demonstrated that the rabbits taking oral CTX at a dosage of 30 mg/kg/day suffered lesser degrees of articular stiffness and histological cartilage damage than the control rabbits. Conclusions The gene expression profiles in the cell and the examinations done on the rabbit cartilage suggest that the alginate extract CTX is a pharmaco-therapeutic agent applicable for OA therapy.

This paper describes a haptic device equipped surgical simulator that provides visual and haptic responses for amputation surgery. This simulator, based on our reported volume (constituted from CT slices) manipulation algorithms, can compute and demonstrate bone changes for the procedures in various orthopedic surgeries. The system is equipped with a haptic device. The position and attitude the haptic device are transformed into the volume to simulate and render the oscillating virtual saw together with the virtual bones. The system then judges if every saw tooth immersing in (cutting) any bone. The load for removing the bone chip on a cutting tooth is calculated according to the feed rate, oscillating speed, saw geometry and bone type. The loads on all the saw teeth are then summed into the three positional forces that the haptic device generates and thus the user feels. The system provides real-time visual and haptic refresh speeds for the sawing procedures. A simulation example of amputation surgery demonstrates the sawing haptic and visual feelings of the sawing procedure are consistent and the simulated sawing force resembles the real force. Therefore, this prototype simulator demonstrates the effectiveness as a surgical simulator to rehearsal the surgical procedures, confirm surgical plains and train interns and students.

Neck contractures after burn produce restrictions in motion and unacceptable aesthetic outcomes. Proper planning and tissue selection is essential to minimize donor site morbidity while optimizing outcomes. A classification system and treatment algorithm aids in achieving this goal. Between December 1999 and January 2003, 40 burn patients underwent release and reconstruction with free perforator flaps. Neck extensibility and zone of injury were evaluated. Choice of reconstruction was based on available tissue, restriction degree and zones involved. Cervical territories were classified according to movement restrictions and amount of improvement. Reconstructive territories were classified as central above (CA), central below (CB), central above and below (CAB) and lateral (L). Single, split, double and preexpanded free flaps were used for the reconstructions. Maximal gain in motion was noted at 4 weeks and maintained for the average 11 months follow-up. Types of reconstructive territories showed significant effects on range of motion while etiology and time between injury and reconstruction showed no impact on the functional outcome. Classification of neck territories aids in improving outcomes while minimizing donor morbidity. The central above territory, when reconstructed with free flaps, yielded the most rewarding improvement. A classification and treatment algorithm aids in achieving significant improvements in range of neck motion while taking into consideration the donor sites.

From the studies on the involvement of iNOS in arthritis, it is clear that attention has focused primarily on rheumatoid arthritis (RA) and osteoarthritis (OA). To date, little is known about the role of iNOS in the pathophysiology of gouty arthritis (GA). Here, we investigated the significance of iNOS expression in cell culture system as well as in GA patients. Gouty crystals monosodium urate (MSU) appeared to up-regulate inducible nitric oxide synthase (iNOS) mRNA and protein expression in a concentration- and time-dependent manner in RAW264.7 macrophages. This increase of iNOS expression is attributable to the activation of multiple signaling pathways. Evidence for this was initially established by inhibitor treatment of cells in the presence of MSU. While the JAK inhibitor AG490, the PI3K inhibitor LY294002, and the NFkappaB inhibitor PDTC abrogated almost completely the expression of iNOS induced by MSU, the ERK1/2 inhibitor PD98059 was only partially effective. Furthermore, the effect of MSU on the activation of PI3K/Akt, JAK/STAT, ERK1/2, and NFkappaB signaling molecules was carefully examined. Moreover, it was shown that GAS and NFkappaB motifs are required for iNOS expression mediated by MSU. In addition, synovial tissues obtained from GA patients displayed enhanced expression of iNOS when compared with normal synovium. Taken together, these findings provide the first evidence for the potential importance of iNOS in the pathogenesis of GA as well as RA and OA, and in turn raise the possibility that iNOS may be an ideal target for preventive therapy in human arthritis.

This paper describes a three-dimensional (3D) reconstruction method and an automatic diagnosis method for spinal diseases using unaligned transverse slices that have arbitrary angles and intervals but do not intersect to each other at regions of interest. The 3D reconstruction method extends the marching cube algorithm to generate triangulated isosurfaces for these unaligned slices. The automatic spinal disease diagnostic method analyses boundaries of discs and vertebral bodies on unaligned transverse slices to estimate the presence and extent of disc herniation and canal compression, and deformities in the spinal curve. The prototype system can be used as a qualitative and quantitative tool for the diagnosis of various spinal diseases using unaligned transverse slices.

This paper describes an image analysis method that uses automatic algorithms for the evaluation of 3D geometry of vertebral bones and spinal anatomic curve in the diagnosis of compression and burst fractures. The method uses a radial B-spline curve to approximate the ellipse-like vertebral body on a transverse section with a concave feature to evaluate the compression of the canal, and infers the anatomic curve of a vertebral body by linearly regressing the centers of B-spline approximate ellipse-like boundaries of the transversal sections passing the vertebral body. This method, then, calculates the reduced angle and height for recovering the compression fracture by comparing the regressed centerlines of neighboring bodies of the fracture body with the normal spinal anatomic curve. The prototype system can be used as a qualitative and quantitative tool for the diagnosis of compression and burst fractures using transverse sections, and for the instruction to plan accurate surgical procedures. An example demonstrates the fractured spine can be accurately diagnosed and instructed to operate by our method that achieved anatomic stability, released the syndrome of nerve compression and bone pain.

In this study, the three-dimensional virtual reality simulation system described herein provides preoperative simulation to verify that the osteotomy and fusion procedures chosen to treat musculoskeletal defects are appropriate. The system also provides an excellent means of training surgeons in new operations without putting patients at risk, and may be especially useful for difficult surgical procedures often performed in orthopedics, craniofacial disease, or plastic and reconstructive surgery departments. The system can be used to teach intern and train resident doctors, and is a planning tool for visiting staff.

Background Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly adults. However, few long-lasting pharmacotherapeutic agents with low side effects have been developed to treat OA. We evaluated the therapeutic effects of intra-articular injections of hydrogels containing hyaluronic acid (HA) and doxycycline (DOX) in a rabbit OA model. Results Thirteen week old New Zealand White rabbits undergone a partial meniscectomy and unilateral fibular ligament transection were administered with either normal saline (NT), HA, DOX or HA-DOX hydrogels on day 0, 3, 6, 9 and 12; animals were also examined the pain assessment in every three days. The joint samples were taken at day 14 post-surgery for further histopathological evaluation. The degree of pain was significantly attenuated after day 7 post-treatment with both HA and HA-DOX hydrogels. In macroscopic appearance, HA-DOX hydrogel group showed a smoother cartilage surface, no or minimal signs of ulceration, smaller osteophytes, and less fissure formation in compare to HA or DOX treatment alone. In the areas with slight OA changes, HA-DOX hydrogel group exhibited normal distribution of chondrocytes, indicating the existence of cartilage regeneration. In addition, HA-DOX hydrogels also ameliorated the progression of OA by protecting the injury of articular cartilage layer and restoring the elastoviscosity. Conclusion Overall, from both macroscopic and microscopic data of this study indicate the injectable HA-DOX hydrogels presented as a long-lasting pharmacotherapeutic agent to apply for OA therapy.

To investigate the therapeutic potential of naturally occurring cinnamophilin against cartilage degradation and its action mechanisms, its effects on matrix metalloproteinase (MMP)-1 and -13 induction were examined in the human SW1353 chondrocytic cell line. Human chondrocytes (SW1353) were stimulated with interleukin (IL)-1β, and then mitogen-activated protein kinase (MAPK) and c-Jun activations, inhibitory κB-α (IκB-α) degradation, and MMP-1, and 13 expressions were assayed by a Western blot analysis. Cinnamophilin strongly inhibited MMP-1 and -13 induction in IL-1β-treated (30 ng/mL) SW1353 cells in a concentration-dependent manner, and it also reduced MAPK family members including extracellular signal-regulated kinase (ERK), p38 MAPKs, and c-Jun N-terminal kinase. Moreover, nuclear factor (NF)-κB signaling activation through IκB-α degradation, IκB kinase (IKK)-α/β, and p-65 phosphorylation was restored by cinnamophilin upon IL-1β stimulation. Importantly, results showed that IL-1β-induced activation of phosphorylated (p)-c-Jun in chondrocytes was significantly inhibited by cinnamophilin. These results indicate that cinnamophilin inhibited MMP-1 and -13 expressions in IL-1β-treated chondrocytes through either NF-κB or ERK/p38 MAPK downregulation and/or suppressing p-c-Jun pathways. Furthermore, these findings suggest that cinnamophilin may have the potential for chondroprotection against collagen matrix breakdown in cartilage of diseased tissues such as those found in arthritic disorders.

Background Improving the quality of medical education is a key goal of government policy in Taiwan. The aim of this study was to reflect the responses of medical education from the perspective of graduating medical students in Taiwan. This is the first survey study of medical education in Taiwan. Methods Using the Medical School Graduation Questionnaire from the Association of American Medical Colleges (AAMC), we distributed 406 questionnaires to medical students of four medical schools in their last semester, and received 270 back (response rate, 66.5%). There were 11 medical schools in Taiwan. Most questions were assessed on a 5-point Likert scale. Results Students identified genetics, biochemistry, and ethics as the three most important premedical subjects preparing them for medical education and gross anatomy, physiology, and pharmacology as the three most helpful basic science subjects preparing them for clinical clerkships and electives. Most Taiwanese students were satisfied with their learning experience in internal medicine. Only 55.9% of students were confident that they had acquired the clinical skills required to become a resident, and 70.7% were satisfied with the quality of their medical education. Conclusion The study offers preliminary results on the views of graduating students on the medical education system in Taiwan. In particular, our government and medical educators need to continuously put more effort into building students’ confidence in their clinical skills.

Purpose Moral orientation can affect ethical decision-making. Very few studies have focused on whether medical education can change the moral orientation of the students. The purpose of the present study was to document the types of moral orientation exhibited by medical students, and to study if their moral orientation was changed after preclinical education. Methods From 2007 to 2009, the Mojac scale was used to measure the moral orientation of Taiwan medical students. The students included 271 first-year and 109 third-year students. They were rated as a communitarian, dual, or libertarian group and followed for 2 years to monitor the changes in their Mojac scores. Results In both first and third-year students, the dual group after 2 years of preclinical medical education did not show any significant change. In the libertarian group, first and third-year students showed a statistically significant increase from a score of 99.4 and 101.3 to 103.0 and 105.7, respectively. In the communitarian group, first and third-year students showed a significant decline from 122.8 and 126.1 to 116.0 and 121.5, respectively. Conclusion During the preclinical medical education years, students with communitarian orientation and libertarian orientation had changed in their moral orientation to become closer to dual orientation. These findings provide valuable hints to medical educators regarding bioethics education and the selection criteria of medical students for admission.

Background Osteoarthritis (OA) is characterized by the degradation of articular cartilage, marked by the breakdown of matrix proteins. Studies demonstrated the involvement of chemokines in this process, and some may potentially serve as diagnostic markers and therapeutic targets; however, the underlying signal transductions are not well understood. Methods We investigated the effects of the CC chemokine eotaxin-1 (CCL11) on the matrix metalloproteinase (MMP) expression and secretion in the human chondrocyte cell line SW1353 and primary chondrocytes. Results Eotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Inhibitors of extracellular signal-regulated kinase (ERK) and p38 kinase were able to repress eotaxin-1-induced MMP-3 expression. On the contrary, Rp-adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPs), a competitive cAMP antagonist for cAMP receptors, and H-89, a protein kinase A (PKA) inhibitor, markedly enhanced eotaxin-1-induced MMP-3 expression. These results suggest that MMP-3 expression is specifically mediated by the G protein-coupled eotaxin-1 receptor activities. Interestingly, little amount of MMP-3 protein was detected in the cell lysates of eotaxin-1-treated SW1353 cells, and most of MMP-3 protein was in the culture media. Furthermore we found that the eotaxin-1-dependent MMP-3 protein secretion was regulated by phospholipase C (PLC)-protein kinase C (PKC) cascade and c-Jun N-terminal kinase (JNK)/mitogen-activated protein (MAP) kinase pathways. These data indicate a specific regulation of MMP-3 secretion also by eotaxin-1 receptor activities. Conclusions Eotaxin-1 not only induces MMP-3 gene expression but also promotes MMP-3 protein secretion through G protein-coupled eotaxin-1 receptor activities. Chemokines, such as eotaxin-1, could be a potential candidate in the diagnosis and treatment of arthritis.

In facial contouring surgery, surgeons operate to change facial bone morphology and obtain esthetic feminine face. Face appearance after surgery is required to evaluate; therefore, simulations for facial bone and soft tissue procedures are both required. This study develops a soft tissue manipulation method based on volume data to simulate face peeling and healing. Inte- grating with our reported bone surgical simulation methods, the proposed simulator can provide high quality illustrations for the simulations of various modalities of facial contouring surgery.

Vitis thunbergii Sieb. and Zucc. var. taiwaniana Lu is an endemic plant in Taiwan used as a dietary supplement for bone health. In this study, human chondrocytes were induced to produce COX-2, MMP-3, -13, and PGE(2) by LPS. An (18)F-FDG microPET imaging system was used to evaluate the anti-inflammatory arthritic effects in vivo. Six stilbenes, resveratrol (1), (+)-epsilon-viniferin (2), ampelopsin C (3), ampelopsin A (4), (-)-vitisin B (5), and ()-vitisin A (6), were isolated from the stem part of V. thunbergii, which displayed the strongest PGE2 inhibition. Among these compounds, 1 significantly decreased COX-2 activity, PGE(2), MMP-3, and -13 production in vitro, and (18)F-FDG uptake and serum PGE(2) in rabbits in vivo. Anti-inflammatory effects were enhanced through the combined usage of 1 and other oligostilbenes. Taken together, the synergistic effects of 1 and oligostilbenes resulted in stem part extracts with lower 1 content displaying the better anti-inflammatory arthritis effects.