Uncertain Associations of Major Bleeding and Concurrent Use of Antiplatelet Agents and Chinese Medications: A Nested Case-Crossover Study

Despite the evidence that some commonly used Chinese medications (CMs) have antiplatelet/anticoagulant effects, many patients still used antiplatelets combined with CMs. We conducted a nested case-crossover study to examine the associations between the concomitant use of antiplatelets and CMs and major bleeding using population-based health database in Taiwan. Among the cohort of 79,463 outpatients prescribed antiplatelets (e.g., aspirin and clopidogrel) continuously, 1,209 patients hospitalized with new occurring bleeding in 2012 and 2013 were included. Those recruited patients served as their own controls to compare different times of exposure to prespecified CMs (e.g., Asian ginseng and dong quai) and antiplatelet agents. The periods of case, control 1, and control 2 were defined as 1–4 weeks, 6–9 weeks, and 13–16 weeks before hospitalization, respectively. Conditional logistic regression analyses found that concurrent use of antiplatelet drugs with any of the prespecified CMs in the case period might not significantly increase the risks of bleeding over that in the control periods (OR = 1.00, 95% CI 0.51 to 1.95 and OR = 1.13, 95% CI 0.65 to 1.97). The study showed no strong relationships between hospitalization for major bleeding events and concurrent use of antiplatelet drugs with the prespecified CMs

EXPLORING E-LEARNING BEHAVIOR THROUGH LEARNING DISCOURSES

As many studies predict e-learning behaviors through intention, few of them investigate user’s learning behaviors directly. In addition to intention, individual’s e-learning behaviors may be influenced by technology readiness and group influences, such as social identity and social bond. This research-in-progress study explores how e-learning behaviors vary with intention, technology readiness, social identity and social bond. Our investigation was based on analyzing the speech acts embedded in fourteen learners’ online discourses in an eighteen-week e-learning course. We then compared how speech acts varied among groups with different degree of intention, technology readiness, social identity, and social bond. Our findings contribute e-learning research by clarifying how intention, technology readiness, social identity, and social bond influence learning behaviors in e-learning context

High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

<p>Abstract</p> <p>Background</p> <p>This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1) expression on response to cisplatin-based induction chemotherapy (IC) followed by concurrent chemoradiation (CCRT) in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) patients.</p> <p>Methods</p> <p>Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records.</p> <p>Results</p> <p>The 12-month progression-free survival (PFS) and 2-year overall survival (OS) rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p < 0.001) and 2-year OS (74.2 vs. 44.4%, p = 0.023) rates. Multivariate analysis showed that for patients who did not chew betel nuts and had low expression of ERCC1 were independent predictors for prolonged survival.</p> <p>Conclusions</p> <p>Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.</p

Characteristics, survival, and related factors of newly diagnosed colorectal cancer patients refusing cancer treatments under a universal health insurance program

BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer worldwide. Few studies have addressed the causes and risks of treatment refusal in a universal health insurance setting. METHODS: We examined the characteristics and survival associated with treatment refusal in patients with newly diagnosed colorectal cancer in Taiwan during 2004–2008. Treatment refusal was defined as not undergoing any cancer treatment within 4 months of confirmed cancer diagnosis. Patient data were extracted from four national databases. Factors associated with treatment refusal were identified through logistic regression using the generalized estimating equation method, and survival analysis was performed using the Cox proportional hazards model. RESULTS: Of the 41,340 new colorectal cancer cases diagnosed, 3,612 patients (8.74%) refused treatment. Treatment refusal rate was higher in patients with less urbanized areas of residence, lower incomes, preexisting catastrophic illnesses, cancer stages of 0 and IV, and diagnoses at regional and district hospitals. Logistic regression analysis revealed that patients aged >75 years were the most likely to refuse treatment (OR, 1.87); patients with catastrophic illnesses (OR, 1.66) and stage IV cancer (OR, 1.43) had significantly higher refusal rates. The treatment refusers had 2.66 times the risk of death of those who received treatment. Factors associated with an increased risk of death in refusers included age ≥75 years, insured monthly salary ≥22,801 NTD, low-income household or aboriginal status, and advanced cancer stage (especially stage IV; HR, 11.33). CONCLUSION: Our results show a lower 5-year survival for colorectal patients who refused treatment than for those who underwent treatment within 4 months. An age of 75 years or older, low-income household status, advanced stages of cancer, especially stage IV, were associated with higher risks of death for those who refused treatment

Timosaponin AIII Suppresses Hepatocyte Growth Factor-Induced Invasive Activity through Sustained ERK Activation in Breast Cancer MDA-MB-231 Cells

Background. The aim of this study was to investigate the mechanisms by which Timosaponin AIII (TAIII) is able to inhibit HGF-induced invasion activity in the triple negative breast cancer cell line MDA-MB-231. Methods. After pretreatment with different concentrations (10−6~10−8 M) of TAIII, the cells were treated with hepatocyte growth factor (HGF, 15 ng/mL). At different time intervals after coincubation, various parameters, including the expression of c-Met, ERK, COX2, and MMP-9, which were assessed by Western blotting or by real-time PCR, were analyzed. In addition, invasive activity was also monitored. Results. HGF was found to induce c-MET activation and ERK activation, together with increased COX2 protein expression; these changes were followed by a subsequent increase in invasive activity. TAIII was found to suppress HGF-induced invasive activity and COX2 gene expression in a concentration-dependent manner (10−6~10−8 M) in parallel with increases in the phosphoforms of c-Met and ERK after TAIII treatment. The mechanisms by which TAIII suppresses HGF-induced invasive activity were demonstrated to include sustained cytoplasmic and nuclear ERK activation; these led to a suppression of nuclear ATF2 activation, which was followed by downregulation of COX2 and MMP-9 transcription. Conclusion. TAIII suppresses HGF-induced invasive activity in MDA-MB-231 cells via sustained ERK activation

The dimer interface of the SARS coronavirus nucleocapsid protein adapts a porcine respiratory and reproductive syndrome virus-like structure

AbstractWe have employed NMR to investigate the structure of SARS coronavirus nucleocapsid protein dimer. We found that the secondary structure of the dimerization domain consists of five α helices and a β-hairpin. The dimer interface consists of a continuous four-stranded β-sheet superposed by two long α helices, reminiscent of that found in the nucleocapsid protein of porcine respiratory and reproductive syndrome virus. Extensive hydrogen bond formation between the two hairpins and hydrophobic interactions between the β-sheet and the α helices render the interface highly stable. Sequence alignment suggests that other coronavirus may share the same structural topology

Role of pirenoxine in the effects of catalin on in vitro ultraviolet-induced lens protein turbidity and selenite-induced cataractogenesis in vivo

Purpose: In this study, we investigated the biochemical pharmacology of pirenoxine (PRX) and catalin under in vitro selenite/calcium- and ultraviolet (UV)-induced lens protein turbidity challenges. The systemic effects of catalin were determined using a selenite-induced cataractogenesis rat model. Methods: In vitro cataractogenesis assay systems (including UVB/C photo-oxidation of lens crystallins, calpain-induced proteolysis, and selenite/calcium-induced turbidity of lens crystallin solutions) were used to screen the activity of PRX and catalin eye drop solutions. Turbidity was identified as the optical density measured using spectroscopy at 405 nm. We also determined the in vivo effects of catalin on cataract severity in a selenite-induced cataract rat model. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) was applied to analyze the integrity of crystallin samples. Results: PRX at 1,000 μM significantly delayed UVC-induced turbidity formation compared to controls after 4 h of UVC exposure (p<0.05), but not in groups incubated with PRX concentrations of <1,000 μM. Results were further confirmed by SDS–PAGE. The absolute γ-crystallin turbidity induced by 4 h of UVC exposure was ameliorated in the presence of catalin equivalent to 1~100 μM PRX in a concentration-dependent manner. Samples with catalin-formulated vehicle only (CataV) and those containing PRX equivalent to 100 μM had a similar protective effect after 4 h of UVC exposure compared to the controls (p<0.05). PRX at 0.03, 0.1, and 0.3 μM significantly delayed 10 mM selenite- and calcium-induced turbidity formation compared to controls on days 0~4 (p<0.05). Catalin (equivalent to 32, 80, and 100 μM PRX) had an initial protective effect against selenite-induced lens protein turbidity on day 1 (p<0.05). Subcutaneous pretreatment with catalin (5 mg/kg) also statistically decreased the mean cataract scores in selenite-induced cataract rats on post-induction day 3 compared to the controls (1.3±0.2 versus 2.4±0.4; p<0.05). However, catalin (equivalent to up to 100 μM PRX) did not inhibit calpain-induced proteolysis activated by calcium, and neither did 100 μM PRX. Conclusions: PRX at micromolar levels ameliorated selenite- and calcium-induced lens protein turbidity but required millimolar levels to protect against UVC irradiation. The observed inhibition of UVC-induced turbidity of lens crystallins by catalin at micromolar concentrations may have been a result of the catalin-formulated vehicle. Transient protection by catalin against selenite-induced turbidity of crystallin solutions in vitro was supported by the ameliorated cataract scores in the early stage of cataractogenesis in vivo by subcutaneously administered catalin. PRX could not inhibit calpain-induced proteolysis activated by calcium or catalin itself, and may be detrimental to crystallins under UVB exposure. Further studies on formulation modifications of catalin and recommended doses of PRX to optimize clinical efficacy by cataract type are warranted

Integration, Launch, and First Results from IDEASSat/INSPIRESat-2 - A 3U CubeSat for Ionospheric Physics and Multi-National Capacity Building

The Ionospheric Dynamics and Attitude Subsystem Satellite (IDEASSat) is a 3U CubeSat carrying a Compact Ionospheric Probe (CIP) to detect ionospheric irregularities that can impact the usability and accuracy of global satellite navigation systems (GNSS), as well as satellite and terrestrial over the horizon communications. The spacecraft was developed by National Central University (NCU) in Taiwan, with additional development and operational support from partners in the International Satellite Program in Science and Education (INSPIRE) consortium. The spacecraft system needed to accommodate these mission objectives required three axis attitude control, dual band communications capable of supporting both tracking, telemetry and command (TT&C) and science data downlink, as well as flight software and ground systems capable of supporting the autonomous operation and short contact times inherent to a low Earth orbit mission developed on a limited university budget with funding agency-imposed constraints. As the first spacecraft developed at NCU, lessons learned during the development, integration, and operation of IDEASSat have proven to be crucial to the objective of developing a sustainable small satellite program. IDEASSat was launched successfully on January 24, 2021 aboard the SpaceX Falcon 9 Transporter 1 flight. and successfully began operations, demonstrating power, thermal, and structural margins, as well as validation of uplink and downlink communications functionality, and autonomous operation. A serious anomaly occurred after 22 days on orbit when communication with the spacecraft were abruptly lost. Communication was re-established after 1.5 months for sufficient time to downlink stored flight data, which allowed the cause of the blackout to be identified to a high level of confidence and precision. In this paper, we will report on experiences and anomalies encountered during the final flight model integration and delivery, commissioning, and operations. The agile support from the international amateur radio community and INSPIRE partners were extremely helpful in this process, especially during the initial commissioning phase following launch. It is hoped that the lessons learned reported here will be helpful for other university teams working to develop spaceflight capacity