BackgroundSafety activities have been initiated at many hospitals in Taiwan, but little is known about the safety culture at these hospitals. The aims of this study were to verify a safety culture survey instrument in Chinese and to assess hospital safety culture in Taiwan.MethodsThe Taiwan Patient Safety Culture Survey was conducted in 2008, using the adapted Safety Attitude Questionnaire in Chinese (SAQ-C). Hospitals and their healthcare workers participated in the survey on a voluntary basis. The psychometric properties of the five SAQ-C dimensions were examined, including teamwork climate, safety climate, job satisfaction, perception of management, and working conditions. Additional safety measures were asked to assess healthcare workers' attitudes toward their collaboration with nurses, physicians, and pharmacists, respectively, and perceptions of hospitals' encouragement of safety reporting, safety training, and delivery delays due to communication breakdowns in clinical areas. The associations between the respondents' attitudes to each SAQ-C dimension and safety measures were analyzed by generalized estimating equations, adjusting for the clustering effects at hospital levels.ResultsA total of 45,242 valid questionnaires were returned from 200 hospitals with a mean response rate of 69.4%. The Cronbach's alpha was 0.792 for teamwork climate, 0.816 for safety climate, 0.912 for job satisfaction, 0.874 for perception of management, and 0.785 for working conditions. Confirmatory factor analyses demonstrated a good model fit for each dimension and the entire construct. The percentage of hospital healthcare workers holding positive attitude was 48.9% for teamwork climate, 45.2% for perception of management, 42.1% for job satisfaction, 37.2% for safety climate, and 31.8% for working conditions. There were wide variations in the range of SAQ-C scores in each dimension among hospitals. Compared to those without positive attitudes, healthcare workers with positive attitudes to each SAQ dimension were more likely to perceive good collaboration with coworkers, and their hospitals were more likely to encourage safety reporting and to prioritize safety training programs (Wald chi-square test, p < 0.001 for all).ConclusionsAnalytical results verified the psychometric properties of the SAQ-C at Taiwanese hospitals. The safety culture at most hospitals has not fully developed and there is considerable room for improvement.

Background:The epitope and the TNF␣ inhabitation mechanism of Adalimumab remain unclear. Results: The crystal structure of the TNF␣ in complex with Adalimumab is reported at a resolution of 3.1 Å. Conclusion:The epitope of Adalimumab provided information that Adalimumab may have clinical advantage compared with Infliximab. Significance: These data reveal the Adalimumab's mechanism of TNF␣ inhibition and its advantages compared with other TNF inhibitors in clinical practice. TNF␣-targeting therapy with the use of the drugs Etanercept, Infliximab, and Adalimumab is used in the clinical treatment of various inflammatory and immune diseases. Although all of these reagents function to disrupt the interaction between TNF␣ and its receptors, clinical investigations showed the advantages of Adalimumab treatment compared withEtanercept and Infliximab. However, the underlying molecular mechanism of action of Adalimumab remains unclear. In our previous work, we presented structural data on how Infliximab binds with the E-F loop of TNF␣ and functions as a TNF␣ receptorbinding blocker. To further elucidate the variations between TNF␣ inhibitors, we solved the crystal structure of TNF␣ in complex with Adalimumab Fab. The structural observation and the mutagenesis analysis provided direct evidence for identifying the Adalimumab epitope on TNF␣ and revealed the mechanism of Adalimumab inhibition of TNF␣ by occupying the TNF␣ receptor-binding site. The larger antigenantibody interface in TNF␣ Adalimumab also provided information at a molecular level for further understanding the clinical advantages of Adalimumab therapy compared with Infliximab.TNF is an immunity-modulating cytokine required for immune processes. The unregulated activities of TNFs can lead to the development of inflammatory diseases. Excess amounts of TNF␣ expressed in cells are associated with the development of immune diseases, including rheumatoid arthritis, Crohn's disease, psoriatic arthritis, and inflammatory bowel disease (1, 2). The function of TNF␣ requires smooth interaction with its two receptors, TNF receptor 1 (TNFR1) 4 and TNF receptor 2 (TNFR2). Blocking the interaction between TNF␣ and TNFRs has successfully been developed as a therapy in treating inflammatory or autoimmune diseases (3,4). TNF␣ neutralization therapies, including the use of a soluble TNFR2-Fc recombinant (Etanercept), a mouse-human chimera mAb (Infliximab), or a human mAb (Adalimumab), have been introduced in the past decades for the management of rheumatoid arthritis and other immune diseases (5).Although all of these TNF␣ blockers function by interrupting the TNF␣-TNFR interaction, information on whether the different TNF␣ inhibitors have similar clinical efficacy remains controversial because of the lack of randomized clinical trial meta-analyses. In the early stages of clinical usage of Infliximab, its discontinuation was reported to result in loss of response. This largely affected patients who received long term treatment and later discontinued use (6). Approximately 10% of...

Background: Although infliximab has high efficacy in treating TNF␣-associated diseases, the epitope on TNF␣ remains unclear. Results: The crystal structure of the TNF␣ in complex with the infliximab Fab is reported at a resolution of 2.6 Å. Conclusion: TNF␣ E-F loop plays a crucial role in the interaction. Significance: The structure may lead to understanding the mechanism of mAb anti-TNF␣.

Orientation of the hip cup is important in total hip arthroplasties. Orientation includes abduction (inclination) and anteversion. Anteversion can be considered as true (anatomic) and planar (radiographic) anteversion. Some measurement methods either are too complicated or are less precise. We developed a new protractor to measure cup orientation using postoperative anteroposterior radiographs centered at the hip. The new protractor measures true and planar anteversion and abduction easily and precisely. We verified its accuracy using a software simulator and simulated 45 radio- graphs of total hip arthroplasties with 15 different anteversions ranging from 15 degrees -29 degrees and 45 actual radiographs of total hip arthroplasties. We then measured the planar ante- version with our method and the method of Lewinnek et al. Maximal errors were 3 degrees and 2.61 degrees , respectively, and mean errors were 0.96 degrees and 1.2 degrees , respectively. The standard deviations were 0.74 degrees with our method and 0.57 degrees with the method of Lewinnek et al. For the real radiographs, the mean of absolute difference between the two methods was 1.34 degrees , and the standard deviation was 1.13 degrees . We found no difference between the two methods and no difference in our findings compared with those of Pradhan.

Objective. Osteonecrosis is one of the major debilitating skeletal disorders. Most patients with osteonecrosis of the femoral head eventually need surgery, usually total hip arthroplasty (THA), within a few years of onset. Previous studies showed that alendronate has a pharmacologic effect in reducing osteoclast activity and that it significantly reduced the incidence of collapse of the femoral head in the osteonecrotic hip. The purpose of this study was to determine the cumulative incidence of THA in patients with osteonecrosis of the femoral head and the time-to-event after treatment with alendronate versus placebo during the study period. Methods.A 2-year multicenter, prospective, randomized, double-blind study was performed. From June 2005 to December 2006, 64 patients were enrolled and randomly assigned to the alendronate or placebo group. In patients with bilateral hip osteonecrosis who met the inclusion criteria, both hips were counted in the analyses. Five patients were excluded from the analysis because they did not comply with any of the study regimens. Seven patients were ineligible because they were not diagnosed as having stage IIC or stage IIIC disease according to the University of Pennsylvania system. Thus, a total of 52 patients (65 hips) were assessed in this study. Disease progression was evaluated by radiography and magnetic resonance imaging (MRI). The Harris Hip Score and the Short Form 36 health survey were used to rate hip function and quality of life, respectively.Results. There was no significant difference in radiographic and MRI data between the 2 study groups. Four of 32 hips in the alendronate treatment group underwent THA, while 5 of 33 hips in the placebo group had THA (P ‫؍‬ 0.837). No differences were noted in disease progression, Harris Hip Scores, or Short Form 36 scores between the 2 groups.Conclusion. Alendronate has no obvious effect on preventing the necessity for THA, reducing disease progression, or improving life quality.Nontraumatic osteonecrosis is frequently caused by prolonged treatment with glucocorticoids, excessive alcohol intake, systemic lupus erythematosus, or sickle cell disease, or it is idiopathic in origin. The disease is one of the most debilitating skeletal complications (1-7), yet its cause remains a subject of controversy. Each year, ClinicalTrials.gov identifier: NCT00265252.

There is an urgent need for improved therapy for advanced ovarian carcinoma, which may be met by administering immune-modulatory monoclonal antibodies (mAbs) to generate a tumor-destructive immune response. Using the ID8 mouse ovarian cancer model, we investigated the therapeutic efficacy of various mAb combinations in mice with intraperitoneal (i.p.) tumor established by transplanting 3 × 106 ID8 cells 10 days previously. While most of the tested mAbs were ineffective when given individually or together, the data confirm our previous finding that 2 i.p. injections of a combination of anti-CD137 with anti-PD-1 mAbs doubles overall survival. Mice treated with this mAb combination have a significantly increased frequency and total number of CD8+ T cells both in the peritoneal lavage and spleens, and these cells are functional as demonstrated by antigen-specific cytolytic activity and IFN-γ production. While administration of anti-CD137 mAb as a single agent similarly increases CD8+ T cells, these have no functional activity, which may be attributed to up-regulation of co-inhibitory PD-1 and TIM-3 molecules induced by CD137. Addition of the anti-cancer drug cisplatin to the 2 mAb combination increased overall survival >90 days (and was probably curative) by a mechanism which included a systemic CD8+ T cell response with tumor specificity and immunological memory. Strikingly, combined treatment of cisplatin and CD137/PD-1 mAb also gave rise to the long-term survival of mice with established TC1 lung tumors. A similar combination of the 2 mAbs and cisplatin should be considered for clinical ‘translation’.

BackgroundOsteoarthritis (OA) is a degenerative joint disease that affects the cartilage, synovium, and subchondral bone and is the leading cause of disability in older populations. Specific diagnostic biomarkers are lacking; hence, treatment options for OA are limited. Synovial inflammation is very common in OA joints and has been associated with both OA’s symptoms and pathogenesis. Confirming the role of the synovium in OA pathogenesis is a promising strategy for mitigating the symptoms and progression of OA. CX3CL1 is the only member of the CX3C class of chemokines that combines the properties of chemoattractants and adhesion molecules. CX3CL1 levels in the synovium and serum were both discovered to be positively associated with OA pathogenesis. CX3CL1 and its receptor CX3CR1 belong to a family of G protein-coupled receptors. Matrix metalloproteinases (MMPs), which are responsible for matrix degradation, play a crucial role in OA progression. The relationship between CX3CL1 and MMPs in the pathophysiology of OA is still unclear.MethodsCX3CL1-induced MMP-3 production was assessed with quantitative real-time PCR and ELISA. The mechanisms of action of CX3CL1 in different signaling pathways were studied using western blot analysis, quantitative real-time PCR and ELISA. Neutralization antibodies of integrin were achieved to block the CX3CR1 signaling pathway. Luciferase assays were used to study NF-κB promoter activity.ResultsWe investigated the signaling pathway involved in CX3CL1-induced MMP-3 production in osteoarthritis synovial fibroblasts (OASFs). CX3CL1 was found to induce MMP-3 production in a concentration-dependent and time-dependent manner. Using pharmacological inhibitors and CX3CR1 small interfering RNA to block CX3CR1 revealed that the CX3CR1 receptor was involved in the CX3CL1-mediated upregulation of MMP-3. CX3CL1-mediated MMP-3 production was attenuated by c-Raf inhibitors (GW5074) and MEK/ERK inhibitors (PD98059 and U0126). The OASFs were stimulated using CX3CL1-activated p65 phosphorylation.ConclusionsOur results demonstrate that CX3CL1 activates c-Raf, MEK, ERK, and NF-κB on the MMP-3 promoter through CX3CR1, thus contributing to cartilage destruction during OA.

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