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Richard Kim Elaine Tan Emily Wang Amit Mahipal Dung-Tsa Chen Biwei Cao Fadzai Masawi Cindy Machado James Yu Dae Won Kim 《The oncologist》2020,25(12):e1893-e1899
Lessons Learned
- The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
- Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
- The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.
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Dana Franzen-Klein Mark Jankowski Charlotte L. Roy Hoa Nguyen-Phuc Da Chen Lorin Neuman-Lee 《Journal of toxicology and environmental health. Part A》2020,83(2):45-65
ABSTRACTDomestic chickens (Gallus gallus domesticus) were exposed to imidacloprid by gavage once daily for 7 consecutive days at 0, 0.03, 0.34, 3.42, 10.25, and 15.5 mg/kg/day (n = 20 per group; 5 6-week-old males, 5 6-week-old females, 5 9-week-old males, and 5 9-week-old females). The severity and duration of neurobehavioral abnormalities were recorded. Components of the innate and adaptive immune system were assessed with 7 standard functional assays. Temporary neurobehavioral abnormalities were observed in a dose-dependent manner, including muscle tremors, ataxia, and depressed mentation. Based upon mean clinical severity scores, the no observed adverse effect level (NOAEL) was 3.42 mg/kg/day, and the lowest observed adverse effect level (LOAEL) was 10.25 mg/kg/day. The effective dose value for the presence of any neurobehavioral abnormalities in 50% of the test group (ED50) was 4.62 ± 0.98 mg/kg/day. The ED50 for an adjusted score that included both severity and duration of neurobehavioral abnormalities was 11.24 ± 9.33 mg/kg/day. These ED50 values are equivalent to a 1 kg bird ingesting 29 or 70 imidacloprid treated soybean seeds respectively. Immunotoxicity was not documented, possible causes include the assays were insensitive, relevant immune functions were not examined, or imidacloprid is not immunotoxic at this dosing schedule in this species. Neurobehavioral abnormalities were a more sensitive indicator of the sublethal effects of imidacloprid than immunotoxicity. 相似文献
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A mixed‐method study of effects of a therapeutic play intervention for children on parental anxiety and parents' perceptions of the intervention 下载免费PDF全文
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Shengxuan Cao Chen Wang Xin Ma Xu Wang Jiazhang Huang Chao Zhang Li Chen Xiang Geng Kan Wang 《Journal of orthopaedic research》2019,37(8):1860-1867
Patients with mechanic ankle instability experience increased tibiotalar and subtalar joint laxity. However, in vivo joint kinematics in functional ankle instability (FAI) patients and lateral ankle sprain (LAS) copers, especially during dynamic activities, are poorly understood. Ten FAI patients, 10 LAS copers, and 10 healthy controls were included in this study. A dual fluoroscopic imaging system was used to analyze the tibiotalar and subtalar joint kinematics during stair descent. Five key poses of stair descent were analyzed. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint positions in each degree of freedom were compared among the three groups. The tibiotalar joints of FAI patients and LAS copers were significantly more inverted than those of healthy controls during the foot strike (p = 0.016, = 0.264). The subtalar joints of FAI patients were significantly more anteriorly translated (pose 2, p = 0.003, = 0.352; pose 3, p < 0.001, = 0.454; pose 4, p = 0.004, = 0.334), inverted (pose 4, p = 0.027, = 0.234; pose 5,p = 0.034, = 0.221), and externally rotated (pose 4, p = 0.037, = 0.217; pose 5; p = 0.004, = 0.331) than those of healthy controls during the mid‐stance and the heel off. The FAI patients showed excessive tibiotalar inversion and subtalar joint hypermobility during stair descent. Meanwhile, the LAS copers maintained subtalar joint stability, and only showed excessive tibiotalar inversion in foot strike. These data provide insight into the mechanisms behind the development of FAI after initial LAS. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1860–1867, 2019 相似文献
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Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow? aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100?mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5?±?1 days, 8?±?1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100?mg/d aspirin intake and began to recover during 4–6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r?=?0.614, p?<?0.01); PL-11 vs. VerifyNow (r?=?0.829, p?<?0.01); PL-11 vs. TEG (r?=?0.697, p?<?0.001). There was no significant bias between PL-11 and LTA at baseline (bias?=?1.94%, p?=?0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias?=?24.02%, p?<?0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA?>?20%, the cut-off values for each method were, respectively: PL-11?>?50%, VerifyNow?>?533 ARU, TEG?>?60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11. 相似文献
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目的:观察抑郁症大鼠模型脑组织不同部位神经营养因子水平的变化及抗抑郁药物使用后改变。方法:将成年SD大鼠30只分为正常对照组、模型对照组、药物干预组,每组10只,雌雄对半;正常组正常养殖,模型组采用慢性不可预知应激结合孤养方式制备抑郁模型大鼠4周。药物干预组采用模型组造模过程4周后给予药物(氟西汀)给入,自实验开始之后每周观察大鼠体重、糖水消耗、旷场实验指标的变化,最后采用荧光定量PCR法观察大鼠脑部BDNF因子及Trkb的表达。结果:与正常对照组大鼠相比,模型组大鼠体重增加缓慢、糖水消耗减少、旷场试验各项指标较正常组间差异具有统计学意义;荧光定量PCR结果显示:模型组较对照组各脑区BDNF及Trkb受体表达减少,药物干预组脑区BDNF及Trkb受体表达显著高于模型对照组。结论:脑部BDNF因子及Trkb的表达在抑郁症发生与治疗中有所改变。 相似文献
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