Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson’s disease: A single-arm,open-label,prospective, multicenter study

Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A_2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A_2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.

Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.

Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.

Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.

Trial registration: UMIN-CTR (UMIN000020288).     

Cryoablation: physical and molecular basis with putative immunological consequences

Abstract

Cryoablation (CA) is unique as the singular energy deprivation therapy that impacts all cellular processes. CA is independent of cell cycle stage and degree of cellular stemness. Importantly, CA is typically applied as a non-repetitive (single session) treatment that does not support adaptative mutagenesis as do many repetitive therapies. CA is characterized by the launch of multiple forms of cell death including (a) ice-related physical damage, (b) initiation of cellular stress responses (kill switch activation) and launch of necrosis and apoptosis, (c) vascular stasis, and (d) likely activation of ablative immune responses. CA is not without limitation related to the thermal gradient formed between cryoprobe surface (～?185°C) and the distal surface of the freeze zone (～0°C) requiring freeze margin extension beyond the tumor boundary (up to ～1?cm). This limitation is mitigated in part by commonly applied dual freeze thaw cycles and the use of freeze sensitizing adjuvants. This review will (1) identify the cascade of damaging effects of the freeze–thaw process, its physical and molecular-based relationships, (2) a likely immunological involvement (abscopic effect), and (3) explore the use of freeze-sensitizing adjuvants necessary to limit freezing beyond the tumor margin.     

疫情期间雨课堂在西医院校针灸教学中的应用

疫情当前,为科学防护、有效应对,现我校转变传统的课堂教学为以“雨课堂”为授课平台的线上教学。针灸学属于西医院校中医学必修课内容,对于大多数西医院校的学生,针灸教学内容相对抽象、繁杂。本文将雨课堂这种新的教学模式应用于针灸课程中,通过“课前-课上-课后”的“3段式导学”,充分调动学生主动学习针灸的积极性,活跃课堂气氛,学生可以个性化调整学习节奏,同时为教师提供数据性的反馈结果,及时科学地调整教学内容。在保障学生可以足不出户、安全有效完成教学任务的同时,还可提升教学质量。本研究探讨了雨课堂线上授课在针灸教学中的优势,构建了一次传统文化与现代网络技术的火花碰撞,以期促进针灸教学的课程改革。     

纤维支气管镜下支气管结核冷冻疗法对肉芽增殖型支气管结核的疗效与安全性

目的 研究纤维支气管镜下支气管结核冷冻疗法对肉芽增殖型支气管结核的疗效与安全性.方法 选取扬州市第三人民医院2015年6月至2019年5月收治的肉芽增殖型支气管结核患者60例,根据治疗方案不同分为两组:对照组(n=30)给予常规规范抗结核治疗,观察组(n=30)在对照组基础上给予纤维支气管镜下冷冻治疗.观察两组治疗4周后疗效、痰菌转阴时间及治疗前和治疗4周后第一秒用力呼气量(FEV1)、降钙素原(PCT)、血沉(ESR)、超敏C反应蛋白(CRP)水平及治疗期间不良反应(如胸痛、出血、呼吸困难等)情况.结果 观察组总有效率高于对照组,痰菌转阴时间短于对照组,差异均有统计学意义(P<0.05),但两组不良反应发生率比较,差异无统计学意义(P>0.05).两组治疗后FEV1较治疗前上升,PCT、CRP、ESR较治疗前下降,观察组上述指标治疗前后差值大于对照组(P<0.05).结论 纤维支气管镜下支气管结核冷冻治疗肉芽增殖型支气管结核疗效显著,可抑制炎症因子释放,缩短痰菌转阴时间,安全性好.     

An optimal control model for cloud seeding in a deterministic and stochastic environment

To promote artificial rain in India and other such developing countries, in this article, we have proposed and analyzed a nonlinear mathematical model for cloud seeding by considering that aerosols are introduced proportional to the density of water vapors present in the atmosphere. The model is analyzed using Lyapunov's stability theory of differential equations. To reduce the cost of cloud seeding, an optimal control strategy is designed by incorporating four control parameters. We have shown the existence and uniqueness of solution of this optimal control problem, using Pontryagins Maximum Principle. To minimize the cost in making artificial rain, the optimal control problem provides the strategy for the rate of introduction of aerosols in the atmosphere. To capture the effects of environmental noise on control strategies, the model in deterministic framework is converted into stochastic framework. In this regard, the Hamilton-Jacobi-Bellman equation for stochastic control cost function has been formed. The stochastic analysis implies that the control strategy is effective in reducing the cost and increasing rainfall.     

Goat semen cryopreservation with rainbow trout seminal plasma supplemented lecithin-based extenders

The objective of this study was to determine the optimum concentrations of rainbow trout seminal plasma (RTS) supplemented extenders for goat semen quality at post-thaw and after incubation. Five sexually mature Saanen goat (Capra aegagrus hircus) were used for semen collection. Pooled semen was diluted with soybean lecithin-based extender without RTS (control) or supplemented with different concentrations of RTS (1%, 2%, 4% or 8%), at a final concentration of 150 × 10⁶ spermatozoon/ml. Sperm motility, plasma membrane functional integrity (HOST), damaged acrosome (PSA-FITC), mitochondrial activity (rhodamine123) and DNA integrity (TUNEL) were evaluated. Spermatological parameters were evaluated at post-thaw and after 6 hr incubation. RTS8 group preserved sperm motility, acrosomal integrity, plasma membrane functional integrity and mitochondrial function better than the control group (p < .05). The study demonstrated that RTS supplemented lecithin-based extenders have useful effects on goat spermatozoa. In addition, the results of the current study represented the positive effect of using 8% RTS supplemented extender.     

Presynaptic architecture of the larval zebrafish neuromuscular junction

This article shows the ultrastructural architecture of larval zebrafish (Danio rerio) neuromuscular junctions in three dimensions. We compare classical electron microscopy fixation techniques with high‐pressure freezing followed by freeze substitution (HPF/FS) in combination with electron tomography. Furthermore, we compare the structure of neuromuscular junctions in 4‐ and 8‐dpf zebrafish larvae with HPF/FS because this allows for close‐to‐native ultrastructural preservation. We discovered that synaptic vesicles of 4‐dpf zebrafish larvae are larger than those of 8‐dpf larvae. Furthermore, we describe two types of dense‐core vesicles and quantify a filamentous network of small filaments interconnecting synaptic vesicles as well as tethers connecting synaptic vesicles to the presynaptic cell membrane. In the center of active zones, we found elaborate electron‐dense projections physically connecting vesicles of the synaptic vesicle pool to the presynaptic membrane. Overall this study establishes the basis for systematic comparisons of synaptic architecture at high resolution in three dimensions of an intact vertebrate in a close‐to‐native state. Furthermore, we provide quantitative information that builds the basis for diverse systems biology approaches in neuroscience, from comparative anatomy to cellular simulations. J. Comp. Neurol. 523:1984–1997, 2015 © 2015 Wiley Periodicals, Inc.