Identification of 4‐aryl‐1H‐pyrrole[2,3‐b]pyridine derivatives for the development of new B‐Raf inhibitors

During the last years, a significant interest in the identification of new classes of B‐Raf inhibitors has emerged. In this study, which was conceived within an effort that culminated in the recent report of the first dual inhibitors of B‐Raf and Hsp90, we describe the identification of four compounds based on 4‐aryl‐1H‐pyrrole[2,3‐b]pyridine scaffold as interesting starting points for the development of new B‐Raf inhibitors. Structure–activity relationships and predicted binding modes are discussed. Moreover, the novelty of the newly identified structures with respect to currently known B‐Raf inhibitors was assessed through a ligand‐based dissimilarity assessment. Finally, structural modifications with the potential ability to improve the activity toward B‐Raf are put forward.     

“One-piece” patient-specific reconstruction plate for double-barrel fibula-based mandibular reconstruction

Segmental mandibular defects require reconstruction. The fibula flap serves as a versatile flap in restoring mandibular contour and bony height. With the advances in computer-aided design and additive manufacturing technology, an innovative “one-piece” patient-specific reconstruction plate to facilitate double-barrel fibula flap shaping and bone securing was developed; the plate is described in this study. The “one-piece” plate is fabricated with individualized specifications and is mainly composed of three components: the long-bar reconstruction plate, a short-bar plate, and connecting bars. Our initial experiences showed that mandibular reconstructive surgery was greatly facilitated by the “one-piece” reconstruction plate for double-barrel fibula flap reconstruction and achieved satisfactory outcomes. A well-designed clinical trial is required to confirm the superiority of the “one-piece” reconstruction plate in the future. ClinicalTrials.gov registration: NCT03057223.     

The use of virtual communities of practice to improve interprofessional collaboration and education: findings from an integrated review

The recent growth in online technology has led to a rapid increase in the sharing of health related information globally. Health and social care professionals are now using a wide range of virtual communities of practice (VCoPs) for learning, support, continuing professional education, knowledge management and information sharing. In this article, we report the findings from a review of the literature that explored the use of VCoPs by health and social care professionals to determine their potential for interprofessional education and collaboration. We employed integrated review methods to search and identify relevant VCoP articles. We undertook searches of PubMed and Google Scholar from 2000, which after screening, resulted in the inclusion of 19 articles. A thematic analysis generated the following key issues related to the use of VCoPs: ‘definitions and approaches’, ‘technological infrastructure’, ‘reported benefits’, ‘participation issues’, ‘trust and privacy and ‘technical ability’. Based on the findings from this review, there is some evidence that VCoPs can offer an informal method of professional and interprofessional development for clinicians, and can decrease social and professional isolation. However, for VCoPs to be successful, issues of privacy, trust, encouragement and technology need to be addressed.     

虚拟现实技术在护理领域的应用研究进展

综述了虚拟现实技术在护理领域的应用意义和现状,并对其未来应用进行了展望。     

Human hippocampus and viewpoint dependence in spatial memory

Virtual reality was used to sequentially present objects within a town square and to test recognition of object locations from the same viewpoint as presentation, or from a shifted viewpoint. A developmental amnesic case with focal bilateral hippocampal pathology showed a massive additional impairment when tested from the shifted viewpoint compared with a mild, list length-dependent, impairment when tested from the same viewpoint. While the same-view condition could be solved by visual pattern matching, the shifted-view condition requires a viewpoint independent representation or an equivalent mechanism for translating or rotating viewpoints in memory. The latter mechanism was indicated by control subjects' response latencies in the shifted-view condition, although the amnesic case is not impaired in tests of mental rotation of single objects. These results show that the human hippocampus supports viewpoint independence in spatial memory, and suggest that it does so by providing a mechanism for viewpoint manipulation in memory. In addition, they suggest an extremely sensitive test for human hippocampal damage, and hint at the nature of the hippocampal role in episodic recollection.     

Role of the cerebellum in reaching movements in humans. I. Distributed inverse dynamics control

This study focuses on the role of the motor cortex, the spinal cord and the cerebellum in the dynamics stage of the control of arm movement. Currently, two classes of models have been proposed for the neural control of movements, namely the virtual trajectory control hypothesis and the acquisition of internal models of the motor apparatus hypothesis. In the present study, we expand the virtual trajectory model to whole arm reaching movements. This expanded model accurately reproduced slow movements, but faster reaching movements deviated significantly from the planned trajectories, indicating that for fast movements, this model was not sufficient. These results led us to propose a new distributed functional model consistent with behavioural, anatomical and neurophysiological data, which takes into account arm muscles, spinal cord, motor cortex and cerebellum and is consistent with the view that the central nervous system acquires a distributed inverse dynamics model of the arm. Previous studies indicated that the cerebellum compensates for the interaction forces that arise during reaching movements. We show here how the cerebellum may increase the accuracy of reaching movements by compensating for the interaction torques by learning a portion of an inverse dynamics model that refines a basic inverse model in the motor cortex and spinal cord.     

Noise-Optimized Virtual Monoenergetic Dual-Energy CT Improves Diagnostic Accuracy for the Detection of Active Arterial Bleeding of the Abdomen

Purpose

To evaluate diagnostic accuracy of a noise-optimized virtual monoenergetic imaging (VMI+) reconstruction technique for detection of active arterial abdominal bleeding on dual-energy (DE) CT angiography compared with standard image reconstruction.

Validation of an immersive virtual reality system for training near and far space neglect in individuals with stroke: a pilot study

Background: Unilateral spatial neglect (USN) is defined as impaired ability to attend and see on one side, and when present, it interferes seriously with daily life. These symptoms can exist for near and far spaces combined or independently, and it is important to provide effective intervention for near and far space neglect.

Objective: The purpose of this pilot study was to propose an immersive virtual reality (VR) rehabilitation program using a head-mounted display that is able to train both near and far space neglect, and to validate the immediate effect of the VR program in both near and far space neglect.

Methods: Ten USN patients underwent the VR program with a pre–post design and no control. In the virtual environment, we developed visual searching and reaching tasks using an immersive VR system. Behavioral inattention test (BIT) scores obtained pre- and immediate post-VR program were compared.

Results: BIT scores obtained pre- and post-VR program revealed that far space neglect but not near space neglect improved promptly after the VR program. This effect for far space neglect was observed in the cancelation task, but not in the line bisection task.

Conclusions: Positive effects of the immersive VR program for far space neglect are suggested by the results of the present pilot study. However, further studies with rigorous designs are needed to validate its clinical effectiveness.     

苦参黄酮抑制血管新生活性成分的虚拟筛选

血管新生是一个动态的、多步骤的过程,现在已知大约70种疾病与血管新生紊乱相关。作者前期研究及文献报道均表明苦参黄酮类成分有明显抑制血管新生的作用,但其药效物质基础和作用机制尚未明确。该研究应用分子对接技术虚拟筛选苦参黄酮抑制血管新生的药效物质,搜集现已分离鉴定的126个苦参黄酮类化合物组成配体数据库,选择VEGF-a,TEK,KDR等6个与血管新生密切相关的靶点组成受体数据库,以DrugBank中对各靶点有抑制作用并已上市的小分子药物为参照,设定各靶点对应的已上市小分子药物最低打分为阈值,应用Discovery Studio 2.5(DS2.5)软件的LibDock模块进行分子对接,虚拟筛选出打分高于阈值且排名前10%的化合物共37个。对比分析了原配体、已上市药物和苦参黄酮作用于各靶点的主要活性位点,初步揭示了苦参黄酮抑制血管新生的作用机制,为研发血管新生抑制剂类药物提供了一定的参考。