多线路接入医院网络实现多种应用的实践研究

选用思科ASA5550作为接入设备，对电信互联网、医保专用网、联通互联网实施接口配置，对这些外来线路进行统一规划后再与内部网络连接，以达到安全网络管理与规范管理的效果。同时解决了因多条线路接入导致网络拓扑复杂、设备成本高等问题。     

Cognitive rehabilitation after severe acquired brain injury: current evidence and future directions

Severe acquired brain injury (SABI) is damage to the brain, occurring after birth from traumatic or non-traumatic causes, and often resulting in deterioration of physical, cognitive, and emotional functions. Cognitive rehabilitation (CR) is aimed to help brain-injured or otherwise cognitively impaired individuals to restore normal functioning, or to compensate for cognitive deficits. Over the last years, the development of new technologies in the field of CR has led to a growing use of computer-based cognitive tools in patients with SABI. This review aims to investigate the efficacy of CR in individuals suffering from SABI, and evaluates the role of virtual reality and other innovative technologies in improving behavioural and functional outcomes. The current evidence for CR in the treatment of SABI-related deficits does not allow conclusive results to be achieved and further research is needed to identity the patient and treatment factors that contribute to successful outcomes.     

In silico identification,synthesis and biological evaluation of novel tetrazole inhibitors of MurB

In the context of antibacterial drug discovery resurgence, novel therapeutic targets and new compounds with alternative mechanisms of action are of paramount importance. We focused on UDP‐N‐acetylenolpyruvylglucosamine reductase (i.e. MurB), an underexploited target enzyme that is involved in early steps of bacterial peptidoglycan biosynthesis. On the basis of the recently reported crystal structure of MurB in complex with NADP⁺, a pharmacophore model was generated and used in a virtual screening campaign with combined structure‐based and ligand‐based approaches. To explore chemical space around hit compounds, further similarity search and organic synthesis were employed to obtain several compounds with micromolar IC₅₀ values on MurB. The best inhibitors in the reported series of 5‐substituted tetrazol‐2‐yl acetamides were compounds 13 , 26 and 30 with IC₅₀ values of 34, 28 and 25 μm , respectively. None of the reported compounds possessed in vitro antimicrobial activity against Staphylococcus aureus and Escherichia coli.     

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.     

Interfacing a haptic robotic system with complex virtual environments to treat impaired upper extremity motor function in children with cerebral palsy

Objective: To investigate the ability of the New Jersey Institute of Technology Robot Assisted Virtual Rehabilitation (NJIT-RAVR) system training to elicit changes in upper extremity (UE) function in children with hemiplegia secondary to cerebral palsy.

Methods: Nine children (mean age 9 years, three males) participated in three pilots. Subjects trained 1 hour, 3 days a week for 3 weeks. Two groups performed this protocol as their only intervention. The third group also performed 5–6 hours of constraint-induced movement therapy.

Results: All subjects participated in a short programme of nine, 60-minute training sessions without adverse effects. As a group, subjects demonstrated statistically significant improvements in Melbourne Assessment of Unilateral Upper Limb Function Test, a composite of three timed UE tasks and several measurements of reaching kinematics. Several subjects demonstrated clinically significant improvements in active shoulder abduction and flexion as well as forearm supination.

Conclusion: Three small pilots of NJIT-RAVR training demonstrated measurable benefit with no complications, warranting further examination.     

Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre,multinational study using virtual microscopy

Puppa G, Senore C, Sheahan K, Vieth M, Lugli A, Zlobec I, Pecori S, Wang L M, Langner C, Mitomi H, Nakamura T, Watanabe M, Ueno H, Chasle J, Conley S A, Herlin P, Lauwers G Y & Risio M
(2012) Histopathology  61, 562–575 Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy Aims: Despite the established prognostic relevance of tumour budding in colorectal cancer, the reproducibility of the methods reported for its assessment has not yet been determined, limiting its use and reporting in routine pathology practice. Methods and results: A morphometric system within telepathology was devised to evaluate the reproducibility of the various methods published for the assessment of tumour budding in colorectal cancer. Five methods were selected to evaluate the diagnostic reproducibility among 10 investigators, using haematoxylin and eosin (H&E) and AE1‐3 cytokeratin‐immunostained, whole‐slide digital scans from 50 pT1–pT4 colorectal cancers. The overall interobserver agreement was fair for all methods, and increased to moderate for pT1 cancers. The intraobserver agreement was also fair for all methods and moderate for pT1 cancers. Agreement was dependent on the participants’ experience with tumour budding reporting and performance time. Cytokeratin immunohistochemistry detected a higher percentage of tumour budding‐positive cases with all methods compared to H&E‐stained slides, but did not influence agreement levels. Conclusions: An overall fair level of diagnostic agreement for tumour budding in colorectal cancer was demonstrated, which was significantly higher in early cancer and among experienced gastrointestinal pathologists. Cytokeratin immunostaining facilitated detection of budding cancer cells, but did not result in improved interobserver agreement.     

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.     

Extension to the use of tolerance intervals for the assessment of individual bioequivalence

For the determination of bioequivalence, researchers have recently shifted their emphasis from average bioequivalence alone to average and individual bioequivalence. Existing methods for assessing average bioequivalence were first developed for the standard 2 × 2 crossover design, but these methods are easily generalized to the two-treatment, ρ-period crossover designs (e.g., TRR, RTT, and TTRR, RRTT, TRRT, RTTR). With respect to individual bioequivalence, Westlake (1,2) implemented the use of parametric and distribution-free tolerance intervals for assessing individual bioequivalence. Anderson and Hauck (3) described what they call the test of individual equivalence ratios (TIER) for the same purpose. Note that these methods have been applied and/or developed only for the standard 2 × 2 crossover design. The present work extends the method of using parametric tolerance intervals for assessing individual bioequivalence.     

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects

PurposeFixed-combination drug products (FCDPs) for patients with type 2 diabetes mellitus (T2DM) may show efficacy comparable to their individual components (ICs) while improving adherence to treatment. This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR.MethodsThis randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18–55 years. The primary objective was to evaluate the fed-state bioequivalence of a dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP and a dapagliflozin 10-mg/saxagliptin 5-mg/metformin 1000-mg XR FCDP relative to the ICs. Secondary objectives included the evaluation of the effect of food on the pharmacokinetic (PK) parameters of saxagliptin, dapagliflozin, and metformin in both FCDPs and characterization of the PK parameters of the active metabolite of saxagliptin, 5-hydroxy saxagliptin, in healthy subjects. PK parameters (AUC_0–∞, AUC_0–t, and C_max) were used to assess the bioequivalence of the 2 FCDPs with their ICs. The C_max and AUC_0–t of the study drugs were compared between female and male subjects to assess sex differences in exposure. Safety and tolerability of both FCDPs and ICs were also assessed with adverse events, vital signs (systolic and diastolic blood pressures and pulse rate), 12-lead ECG, physical examinations, and laboratory assessments.FindingsBoth dapagliflozin/saxagliptin/metformin XR FCDPs were bioequivalent to their ICs. For the dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP, the 90% CI for the geometric mean ratio of dapagliflozin C_max was slightly above the 80%–125% bioequivalence limit, which is unlikely to be clinically relevant. Food delayed the absorption of the study drugs in both FCDPs, which is unlikely to have a clinically relevant impact on efficacy. In both cohorts, exposure was higher in female subjects compared with male subjects, potentially due to the lower body weight of the female subjects. The safety profile and tolerability of the FCDPs were similar to those of their ICs, and no deaths or serious adverse events were reported.ImplicationsThese data support the use of the dapagliflozin/saxagliptin/metformin XR FCDP in patients with T2DM. ClinicalTrials.gov identifier: NCT03169959.