Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

Posterior ankle impingement disguised as peroneal tendon subluxation in young athletes – a case report

Posterior ankle impingement is a cause of posterior ankle pain common in those who perform frequent plantarflexion activities. Three young patients presented with posterior ankle pain which was initially attributed to peroneal tendon subluxation. However, detailed physical exam and imaging confirmed the diagnosis of posterior ankle impingement as the actual cause of pain. The peroneal tendon subluxation was not causal but an unrelated co-incidental finding. After failed prolonged conservative management (rest, immobilization and physical therapy), the patients underwent posterior ankle arthroscopic debridement for the impingement resulting in return to prior sporting activity without limitation and no recurrence of pain at 19 months follow-up. Posterior ankle impingement diagnosis could be masked by co-incidental asymptomatic peroneal tendon subluxation in pediatric patients.     

胫前动脉踝上穿支皮瓣修复足踝部软组织缺损19例

目的探讨胫前动脉踝上穿支皮瓣修复足踝部软组织缺损的临床疗效。方法回顾性研究2018年4月至2019年6月采用胫前动脉踝上穿支皮瓣修复足踝部软组织缺损19例的资料,其中男11例,女8例;年龄为21~75岁,平均39岁。根据前踝上穿支皮瓣解剖学基础,按照足踝部软组织缺损大小和形状,在小腿下端前外侧设计并切取皮瓣转位修复创面。切取胫前动脉踝上穿支皮瓣面积为6.0 cm×5.0 cm^14.0 cm×8.0 cm,均为带蒂皮瓣转位。根据皮瓣成活、感染控制、弹性色泽、外观形态、供区瘢痕、皮肤感觉、患者认可等情况,对患者足踝部软组织缺损的修复情况进行综合评价。结果本组19例皮瓣全部成活,软组织缺损、肌腱、骨质及钢板外露均得以修复。供区均I期愈合。术后门诊随访2~16个月,皮瓣血运良好,颜色接近周围正常皮肤,臃肿不明显,患者对外观表示满意;供区皮片愈合良好,无明显增生、挛缩及溃疡,踝关节功能良好。结论胫前动脉踝上穿支皮瓣是修复足踝部软组织缺损较为理想的方法之一,手术操作简便,穿支较恒定,血供可靠,具有一定的临床应用价值。     

How current risk assessment and risk management methods for drinking water in The Netherlands cover the WHO water safety plan approach

In the Netherlands, safe and sufficient drinking water is provided to the general population by ten drinking water companies. To guarantee safe drinking water the World Health Organization (WHO) developed a Water Safety Plan (WSP), a Risk Assessment and a Risk Management (RA/RM) framework. The objective of the study was to identify legally required RA approaches, to document application of RA/RM activities at Dutch drinking water companies and to determine to what extent these RA/RM activities as a whole cover all the elements of the WHO WSP approach. This study could be of interest to both managers of large water utilities and decision makers.The assessment was performed by means of a policy review and interviews with two to four staff members involved in RA/RM from all ten Dutch drinking water companies combined with a joint workshop. The drinking water companies are well aware of the potential hazards and risks that can influence the drinking water quality. To guarantee the supply of safe and sufficient drinking water, the Dutch drinking water sector uses six different legally required RA/RM approaches. This study shows that by using the six legally required RA/RM approaches, all WSP steps are covered. WSP entails a generic risk assessment for identifying all hazards and hazardous events from source to tap, whereas the six legally required RA/RM each focus on specific risks at an advanced level. Each risk assessment provides information on specific hazards and hazardous events covering a part of the water supply chain. These legal requirements are complemented with additional RA/RM activities at sector and water company level such as codes of practices and standard operating procedures. The outcomes of all RA/RM approaches combined provide information from source to tap. When using multiple RA/RM approaches, it is crucial to share and combine information derived from the different activities.     

颈前入路相关结构三维可视化研究

目的：建立颈前入路相关结构的三维可视化模型。方法：选取首例中国数字化可视人体数据集中第3颈椎上缘至第7颈椎下缘的连续薄层断面图像。运用3D—DOCTOR软件，在计算机上分割重建该手术入路相关的解剖结构并立体显示。结果：成功重建并立体显示第3～7颈椎、椎间盘、脊髓、颈神经、椎动脉、颈长肌、喉（气管）、咽（食管）、颈总动脉（颈内、外动脉）、颈内静脉、迷走神经和胸锁乳突肌等解剖结构的位置关系，建立了颈前入路相关结构的三维可视化模型。结论：在颈部三维可视化模型基础上，参照颈前入路手术步骤可逐层显示该手术相关的重要结构．为该手术的术前训练和模拟提供形态学依据。     

神经导航辅助下经单鼻腔蝶窦入路切除垂体腺瘤

目的评价神经导航系统在经单鼻腔蝶窦人路垂体腺瘤切除手术中的应用。方法24例病人术前行MRI或CT连续薄层扫描,将影像学资料输入Brain LAB Vector Vision神经导航系统进行三维重建,标记出肿瘤及重要结构后,设计最佳手术入路,术中在导航的引导下定位蝶窦前壁、鞍底、海绵窦、颈内动脉和斜坡等结构,切除肿瘤。结果24例患者均在神经导航引导下经鼻蝶入路顺利到达肿瘤部位；注册误差0．3～2．0mm,平均(1．21±0．39)mm；肿瘤全切除19例,次全切除3例,大部分切除2例；术后19例病人症状有不同程度的改善,5例无变化,术后无严重并发症出现。结论神经导航辅助下经鼻蝶垂体腺瘤切除术具有定位准确、创伤小等优点．效果良好。