Pharmacokinetic modeling and simulation of etodolac following single oral administration in dogs

1. Etodolac is a nonsteroidal anti-inflammatory drug with selective cyclooxygenase-2 inhibition to treat pain and inflammation associated with osteoarthritis in humans and dogs. The aim of the study was to investigate the pharmacokinetics of etodolac following single oral administration of 200?mg to 10 healthy beagle dogs.

2. The plasma concentrations of etodolac were detected using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was conducted using the noncompartmental method and modeling approaches.

3. Etodolac was rapidly absorbed (T_max?=?0.85?h, K_a?=?1.49?h^?1) and slowly eliminated (T_1/2?=?39.55?h) following oral administration to the dogs. A two-compartment pharmacokinetic model with first-order absorption and elimination rate constants was successfully explained for the pharmacokinetic aspects of etodolac in dogs. From a Monte Carlo simulation (1000 repetitions), the accumulation index and AUC_τ at steady state were predicted as 1.60 [90% confidence intervals (CI), 1.24–2.81] and 408.18?ng·hr/mL [90% CI, 271.26–590.58?ng·hr/mL], respectively.

4. This study will help to enact a more accurate optimal dosing regimen of etodolac in dogs with osteoarthritis, and may be useful in developing a novel formulation of etodolac for human in the future.

     

Relationship between EMG-detected and ultrasound-detected fasciculations in amyotrophic lateral sclerosis: A prospective cohort study

ObjectivesFasciculation potentials (FP) are an important consideration in the electrophysiological diagnosis of ALS. Muscle ultrasonography (MUS) has a higher sensitivity in detecting fasciculations than electromyography (EMG), while in some cases, it is unable to detect EMG-detected fasciculations. We aimed to investigate the differences of FP between the muscles with and without MUS-detected fasciculations (MUS-fas).MethodsThirty-one consecutive patients with sporadic ALS were prospectively recruited and in those, both needle EMG and MUS were performed. Analyses of the amplitude, duration, and number of phases of EMG-detected FPs were performed for seven muscles per patient, and results were compared between the muscles with and without MUS-fas in the total cohort.ResultsThe mean amplitude and phase number of FP were significantly lower in patients with EMG-detected FP alone (0.39 ± 0.25 mV and 3.21 ± 0.88, respectively) than in those with both FP and MUS-fas (1.22 ± 0.92 mV and 3.74 ± 1.39, respectively; p < 0.0001 and p = 0.017, Welch’s t-test).ConclusionSmall FP may be undetectable with MUS. MUS cannot replace EMG in the diagnostic approach for ALS.SignificanceClinicians should use a combination of EMG and MUS for the detection and quantitative analysis of fasciculation in ALS.     

Improving Surgical Training

Improving Surgical Training is a programme piloting an innovative, evidence-based approach to training. It was developed in response to the Shape of Training report which reviewed postgraduate training and recommended changes in medical education to meet the demands of the modern NHS. A series of initiatives have been developed to enhance the experience for surgical trainees not only to encourage a more focussed and supported method, but also to improve their job satisfaction. The initiatives have combined a greater emphasis on time for training provided by trainers with allocated time for training with multidisciplinary teamworking and the use of technology enhanced learning with simulation of both technical and non-technical skills. The pilot started in 2018 with core training in general surgery and has been expanded to include vascular surgery, urology and trauma and orthopaedics over the last 2 years. Initial feedback from both trainees, trainers and schools of surgery have identified different challenges to aid implementation. The programme is being very carefully evaluated by an independent company as well as careful oversight by the General Medical Council which are paramount to its success.     

中日友好医院分型股骨头坏死腓骨植入治疗的三维有限元分析

文题释义：股骨头坏死中日友好医院分型的有限元分析：根据李子荣等提出的中日友好医院分型，建立股骨头坏死三维模型，分为 M型(内侧型)、C型(中央型)和 L型(外侧型)，其中 L型包括L1型(次外侧型)、L2型(极外侧型)和 L3型(全头型)。通过对建立的模型进行有限元分析，为该分型的保髋治疗提供了一定力学依据，显示外侧柱的存留是精准预防塌陷的重要因素，为进一步实现个体化治疗提供力学基础。 腓骨支撑坏死股骨头保髋手术：是对于早中期股骨头坏死需要保留股骨头患者进行的一种手术方式。首先需对股骨头进行髓芯减压，清除一定坏死骨，空腔填塞松质骨(髂骨为主)，打压结实后植入腓骨(异体或自体)支撑，给坏死区的提供力学支撑及生物学修复，预防股骨头进一步坏死及塌陷。 背景：研究报道股骨头坏死的保髋疗效与外侧柱存留密切相关，中日友好医院分型是根据三柱结构确立的，对股骨头塌陷的预测准确性高。 目的：建立股骨头坏死中日友好医院分型各分型仿真的三维有限元模型，通过有限元分析各分型腓骨植入的力学变化，探讨外侧柱存留对保髋疗效的意义，为该分型的塌陷精准预测提供基础。 方法：建立正常股骨头、中日友好医院分型(M型、C型、L1型、L2型、L3型)股骨头坏死及其腓骨植入3组11种三维有限元模型，运用ANSYS软件进行有限元分析计算，观察各组模型的最大应力值、最大位移值及股骨头内部载荷传递模式。 结果与结论：①坏死组位移最大，应变最大，且因坏死分型不同而位移不同，位移变化如下：M型相似文献   

情景模拟联合案例讨论在急诊护理临床带教中的应用体会

目的探究急诊护理临床带教中采用情景模拟、案例讨论联合教学法效果。方法在本院实习的若干名护生中,选取124名护生分按照教学方法分组,对照组62名实施传统急诊护理带教,观察组62名实施案例讨论、情景模拟联合教学法,对比临床带教效果。结果两组实践与理论成绩相比,观察组成绩更高(P<0.05)。思维、急救及应激能力自我评价相比,观察组的总提高率高于对照组(P<0.05)。实施案例分析结合情景模拟教学模式后,问卷调查中观察组无护生不赞同此模式,非常赞同此教学模式的护生占总人数的90%以上。结论实施案例讨论、情景模拟联合教学模式后,护生急诊护理实践与理论水平均提升,护生我评价较高。     

Actin binding proteins,actin cytoskeleton and spermatogenesis – Lesson from toxicant models

Actin cytoskeleton is crucial to support spermatogenesis in the mammalian testis. However, the molecular mechanism(s) underlying changes of actin cytoskeletal organization in response to cellular events that take place across the seminiferous epithelium (e.g., self-renewal of spermatogonial stem cells, germ cell differentiation, meosis, spermiogenesis, spermiation) at specific stages of the epithelial cycle of spermatogenesis remain largely unexplored. This, at least in part, is due to the lack of suitable study models to identify the crucial regulatory proteins and to investigate how these proteins work in concert to support actin dynamics. Much of the information on the role of actin binding proteins in the literature, namely the actin bundling proteins, actin nucleation proteins and motor proteins, are either findings based on genetic models or morphological analyses. While this information is helpful to delineate the function of these proteins to support spermatogenesis, they are not helpful to identify the regulatory signaling proteins, the signaling pathways and the cascade of events to modulate actin cytoskeleton dynamics. Recent studies based on the use of toxicant models, both in vitro and in vivo, however, have bridged this gap by identifying putative regulatory and signaling proteins of actin cytoskeleton. Herein, we summarize and critically evaluate these findings. We also provide a hypothetical model by which actin cytoskeletal dynamics in Sertoli cells are regulated, which in turn supports spermatid transport across the seminiferous epithelium, and at the blood-testis barrier (BTB) during the epithelial cycle of spermatogenesis.