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Background:Bone remodeling is a constant process maintained by the balance between osteoclast-triggered bone resorption and osteoblast-mediated bone formation. In inflammatory arthritis, such as rheumatoid arthritis (RA), the pro-inflammatory environment favors osteoclast differentiation and skews the balance towards resorption, leading to progressive bone erosion and bone loss. O-GlcNAcylation is a post-translational modification, which transfers a single N-acetylglucosamine molecule to the serine or threonine of the target protein. The modification is accomplished by a single pair of enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Unlike other glycosylation, O-GlcNAcylation occurs in multiple cellular compartments, including the nucleus. Although O-GlcNAcylation is one of the most common modifications, its role in bone homeostasis is still poorly understood.Objectives:We aimed to investigate the role of O-GlcNAcylation in osteoclastogenesis under pro-inflammatory milieus. We also focused on dissecting the signaling pathways affected by O-GlcNAcylation during osteoclast differentiation.Methods:We examined the levels of O-GlcNAc during in vitro osteoclastogenesis by western blotting. The levels of O-GlcNAc in tissue from RA patients and experimental arthritis were detected by immunofluorescence. Pharmacological inhibition and genetic knockout were used to manipulate O-GlcNAcylaiton during osteoclastogenesis. RNA sequencing was performed to study O-GlcNAc-mediated pathways.Results:We demonstrate the dynamic changes in O-GlcNAcylation during osteoclastogenesis. The elevated O-GlcNAcylation was found in the early differentiation stages, whereas its downregulation was detected in the maturation process. TNFα elaborates the dynamic changes in O-GlcNAcylation, which further intensifies osteoclast differentiation.Targeting OGT by selective inhibitor and genetic knockout restrain O-GlcNAcylation and hinder the expression of the early differentiation marker Nfatc1. Inhibition of OGA, which forces high levels of O-GlcNAcylation throughout the differentiation, reduces the formation of multinucleated mature osteoclasts. Consistent with our in vitro data, suppressing OGT and OGA both ameliorate bone loss in experimental arthritis. We detected a reduced number of TRAP-expressing precursors and mature osteoclasts in the mice subjected to OGT inhibition. While inhibiting OGA only lowers the number of TRAP+F4/80– mature osteoclasts without affecting the number of TRAP+F4/80+ precursors.Transcriptome profiling reveals that O-GlcNAcylation regulates several biological processes. Increased O-GlcNAcylation promotes cytokine signaling and oxidative phosphorylation. The downregulation of O-GlcNAcylation is essential for cytoskeleton organization and cell fusion.Conclusion:We demonstrate that the dynamic changes of O-GlcNAcylation are essential for osteoclast differentiation. These findings reveal the therapeutic potential of targeting O-GlcNAcylation in pathologic bone resorption.Disclosure of Interests:Chih-Wei Chen: None declared, Yi-Nan Li: None declared, Thuong Trinh-Minh: None declared, ZHU Honglin: None declared, Alexandru-Emil Matei: None declared, Xiao Ding: None declared, Cuong Tran Manh: None declared, Xiaohan Xu: None declared, Christoph Liebel: None declared, Ruifang Liang: None declared, Min-Chuan Huang: None declared, Neng-Yu Lin: None declared, Andreas Ramming Speakers bureau: Boehringer Ingelheim, Roche, Janssen, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Grant/research support from: Pfizer, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Jörg H.W. Distler Shareholder of: 4D Science, Speakers bureau: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Consultant of: Actelion, Active Biotech, Anamar, ARXX, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi and UCB, Grant/research support from: Anamar, Active Biotech, Array Biopharma, aTyr, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, Novartis, Sanofi-Aventis, RedX, UCB, Employee of: FibroCure

This study investigated satellite cells and their related molecular events adapted to light moderate endurance training in the white gastrocnemius muscle of the rat. The white gastrocnemius muscle of male Sprague-Dawley rats that had been trained for 4 weeks and 8 weeks, with control rats being analysed alongside them, was selected for analysis (n=3 per group). The training protocol consisted of treadmill running at 20 m · min -1 for 30 min on a 0% grade, for 3 days · week -1 . Immunohistochemical staining coupled with image analysis was used for quantification. To provide deeper insight into the cell layer, 40 sections per rat, corresponding to 120 values per group, were obtained as a mean value for statistical comparison. The results indicated that at week 4, training effects increased the vascular endothelial growth factor (VEGF) content and c-met positive satellite cell numbers. At week 8, the training effect was attenuated for VEGF and c-met satellite cell numbers, but it increased in the muscle fibre area. Additionally, c-met positive satellite cell numbers correlated with VEGF content (r = 0.79, p

Objective: Because of ethnic differences in metabolic syndrome (MS) criteria, this study aimed to investigate the MS prevalence among patients with schizophrenia or schizoaffective disorder in Taiwan. Method: We recruited 650 patients with schizophrenia or schizoaffective disorder from 36 psychiatric institutions. The MS prevalence was assessed based on the modified Adult Treatment Panel (ATP) III criteria for Asians. Results: The overall MS prevalence was 34.9%, with 38.9% in female and 31.5% in male patients respectively. The difference of MS prevalence between our sample and the general population was marked in male patients under 40 years of age and in female patients under 50 years old. Body mass index ≥24 and age over 40 years old are two important risk factors of MS. Female and polypharmacy had marginal significance with the presence of MS. Conclusion: Patients with schizophrenia or schizoaffective disorder in Taiwan had a high prevalence of MS, which appeared early in their lives.

In this study, a simple and cheap way to solve the drift problem is presented which describes the relation of drift and gate voltage. Constant various gate voltages are biased in sensing layers with reference electrode. It obviously shows a strong relation of gate drifts and gate stress voltages. When the gate voltage is controlled as 0.5 V, the drift voltage of SiO2 gate ISFET will decrease from 56.12 to 2.94 mV in ten hours measurement. The improvement of drift voltage reaches 94.8%. When the gate voltage is controlled as -1 V, the drift voltage of ZrO2 gate ISFET will also decrease from -57.94 to 0.76 mV. The improvement of drift voltage reaches 98.7%. This may result from the gate electric field affecting the ions to diffusive into the gate insulator. By this way, we can commercialize the ISFET with a very low drift rate in a simple way.

Objective To compare parental knowledge, attitudes, concerns, and first-aid practices for children experiencing febrile convulsions (FC). Subjects and methods A questionnaire was mailed to 326 FC parents from 11 emergency departments in southern Taiwan. Results A total of 109 first- and 107 recurrent-FC parents responded 1-3 months after the FC. Most incorrectly believed an electroencephalogram (EEG) or computed tomography (CT) was necessary; immunization should be postponed, and overestimated the risk of subsequent epilepsy. Parents were concerned about further attacks in the night, fever episodes, and frequently measured the child's body temperature. During the first episode, objects were inserted into the child's mouth and they were rushed to a hospital. One third lowered the child's body temperature, and 15% positioned the children on their side. For subsequent seizures, 80% anticipated rushing the child to a hospital, and 44% would put objects into the child's mouth. In comparison, although the recurrent-FC parents had higher scores in knowledge and attitudes than the first-FC parents, low knowledge scores (40% correct) were seen in both groups. No significant differences were found on parental concerns, performed/anticipated first aid for FC. Conclusion Most FC parents had inadequate knowledge, high concerns, and improper first-aid practices. This suggests that parents with either first- or recurrent-FC children need information, emotional support, and first-aid demonstrations.

Objective To evaluate long-term effects of educational interventions on parental concerns for children with febrile convulsions (FC). Subjects and methods 209 FC parents were recruited from southern Taiwan, and assigned into program or pamphlet groups by their choices. A questionnaire was used to examine the parental concerns at 4 time points: prior to the interventions, 3 months, 1 year, and 2 years after the interventions. Results The concern scores were high before the interventions. Parents concerned that their child is apt to get a fever, has further seizures in the night, that FC results in potential brain damage and is life threatening. After interventions the concern scores were significantly lower for the program group than for the pamphlet group. The educational program was the most significant factor that influenced the change in parental concerns. The recurrence of FC did not significantly influence the change in the concern trajectory in the program group but showed a significant difference in the pamphlet group. Conclusion FC parental concerns decreased as time passed particularly in the program group. The educational program was the significant factor that influenced the change of concern trajectories, and the recurrent/non-recurrent factor influenced the change of concern only in pamphlet group. FC parental concerns should be assessed, and information given combined with emotional support.

The health of the corneal endothelium is essential in maintaining the clarity of the transplanted human cornea. Immune-mediated endothelial rejection is a complex series of events, which may culminate in the decompensation of the donor button. It is the commonest instigator of failure in penetrating corneal transplantation.Methods This retrospective case note review of 203 penetrating keratoplasties with adequate follow-up data during a 5-year study period from 1 January 2000 to 31 December 2003 at Manchester Royal Eye Hospital, were used for analysis.Results Forty-three of the 203 donor grafts underwent at least one single episode of immune-mediated endothelial rejection, an incidence of 21% over a 5-year follow-up. Recipient's age was inversely associated with the risk of rejection. The average age for the cohort of 58.7 years and average age for rejecting patients of 47.6 years were strongly significantly different (P=0.009). Rejection in keratoconic patients accounted for 30% of cases. Death to enucleation time (P=0.03) was also associated with an increased risk of rejection.Conclusion Although penetrating keratoplasty is an effective long-term treatment option for improving visual function, the endothelial rejection rate in our study was 21% over a mean follow-up of over 5 years. Host vascularisation, regrafts, younger recipient age group, and donor factors were found to be significantly associated with a risk of rejection. Rejection in keratoconic recipients was more common than expected.Eye advance online publication, 17 April 2009; doi:10.1038/eye.2009.72.

PURPOSE: Allograft rejection is the main cause of graft failure in human corneal transplantation, for which underlying pathomechanism is not yet clear. We compared gene expression in the peripheral blood of patients who after undergoing corneal transplantation experienced graft rejection with those patients who accepted grafts. METHODS: Sixty-six patients who underwent corneal transplantation were studied including 18 patients who suffered subsequent graft rejection. cDNA array technology was used to survey and quantify transcript expression. A semiquantitative reverse transcriptase-PCR (RT-PCR) was used to confirm the gene expression pattern measured by a cDNA array of selected genes. RESULTS: Among 265 genes present on the array, eight genes were found to be differentially expressed. Four genes (Rac 2, RhoA, paxillin, and CD18) were further analysed by semiquantitative RT-PCR, and significant differences in mRNA expression levels in the rejection group were confirmed. CONCLUSIONS: Our study demonstrated that the expression of Rac2 mRNA was upregulated in the peripheral blood of patients experiencing corneal transplantation rejection compared to those patients who had no rejection episodes. In addition, three genes, RhoA, paxillin, and CD18, showed decreased expression in rejecting patients. cDNA array technology provides a potentially useful approach to identify novel genes that might participate in pathogenic pathways during corneal graft rejection.

In this paper, the equations of motion of a swinging roller-follower cam for rise-dwell-fall-dwell (RDFD) case are derived by applying Hamilton’s principle and the assumed mode method. The cycloidal displacement (sinusoidal acceleration) motion is used to describe the rise and the fall motions of the follower. The corresponding cam profile is determined using theory of envelopes. The follower rod is considered to be flexible and modeled as a Rayleigh beam including axial and transverse deflections. The roller rolls in the cam groove. The contact point between the cam and the roller is an unknown point though it is restrained in the cam groove. The contact point position depends not only on the rigid-body motions of the cam system but also the flexible vibrations of the follower rod. Two geometric constraints are formulated to restrict the roller motion and added to the Hamilton’s principle with Lagrange multipliers. The numerical integration method is applied to solve the non-linear differential-algebraic equations to obtain the vibration responses of the cam system. The numerical results for the studied cases show that the follower vibrates significantly especially for the case of high rotation speed of cam. The follower still vibrates during the dwell interval. The parameter effects including the cam rotation speed, the follower length and cross-sectional radius, and the total rise on the vibration behavior have been investigated.Copyright © 2008 by ASME

The authors derive and verify the concept of antenna focusing by a planar 'microstrip reflectarray' antenna. Experimental results from schematically distributed patch radiators with microstrip delay lines are consistent with the simulation results. The advantages and disadvantages of such an antenna are described. The measured overall antenna efficiency is approximately 48% at scan angles up to 30 degrees . These results demonstrate the feasibility of such an antenna.< >