- 作者列表："Grabowski J","Goldin A","Arthur LG","Beres AL","Guner YS","Hu YY","Kawaguchi AL","Kelley-Quon LI","McAteer JP","Miniati D","Renaud EJ","Ricca R","Slidell MB","Smith CA","Sola JE","Sømme S","Downard CD","Gosain A","Valusek P","St Peter SD","Jagannathan N'","Dasgupta R
BACKGROUND:There is growing concern regarding the impact of general anesthesia on neurodevelopment in children. Pre-clinical animal studies have linked anesthetic exposure to abnormal central nervous system development, but it is unclear whether these results translate into humans. The purpose of this systematic review from the American Pediatric Surgical Association (APSA) Outcomes and Evidence-Based Practice (OEBP) Committee was to review, summarize, and evaluate the evidence regarding the neurodevelopmental impact of general anesthesia on children and identify factors that may affect the risk of neurotoxicity. METHODS:Medline, Cochrane, Embase, Web of Science, and Scopus databases were queried for articles published up to and including December 2017 using the search terms "general anesthesia and neurodevelopment" as well as specific anesthetic agents. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to screen manuscripts for inclusion in the review. A consensus statement of recommendations in response to each study question was synthesized based upon the best available evidence. RESULTS:In total, 493 titles were initially identified, with 56 articles selected for full analysis and 44 included for review. Based on currently available developmental assessment tools, a single exposure to general anesthesia does not appear to have a significant effect on general neurodevelopment, although prolonged or multiple anesthetic exposures may have some adverse effects. Exposure to general anesthesia may affect different domains of development at different ages. Regional anesthetic techniques with the addition of dexmedetomidine and/or some intravenous agents may mitigate the risks of neurotoxicity. This approach may be performed safely in some patients and can be considered as an option in selected short procedures. CONCLUSION:There is no conclusive evidence that a single short anesthetic in infancy has a detectable neurodevelopmental effect. Data do not support waiting until later in childhood to perform general anesthesia for single short procedures. With the complexities and nuances of different anesthetic methods, patients and procedures, the planning and execution of anesthesia for the pediatric patient is generally best accomplished by an anesthesiologist, ideally a pediatric anesthesiologist. TYPE OF STUDY:Systematic review of level 1-4 studies. LEVEL OF EVIDENCE:Level 1-4 (mainly level 3-4).
背景: 全身麻醉对儿童神经发育的影响越来越受到关注。临床前动物研究已经将麻醉剂暴露与中枢神经系统发育异常联系起来，但尚不清楚这些结果是否转化为人类。这项来自美国儿科外科协会 (APSA) 结果和循证实践 (OEBP) 委员会的系统综述的目的是回顾、总结和评估关于全身麻醉对儿童神经发育影响的证据，并确定可能影响神经毒性风险的因素。 方法: Medline，Cochrane，Embase，Web of Science和Scopus数据库使用搜索术语 “全身麻醉和神经发育” 以及特定麻醉剂查询截至2017年12月 (包括12月) 发表的文章。系统评价和荟萃分析 (PRISMA) 指南的首选报告项目用于筛选纳入审查的手稿。针对每个研究问题的建议的共识声明基于最佳可用证据进行合成。 结果: 共有493个标题被初步识别，其中56篇文章被选择进行全面分析，44篇被纳入审查。根据目前可用的发育评估工具，单次暴露于全身麻醉似乎对全身神经发育没有显著影响，尽管长时间或多次麻醉暴露可能有一些不良影响。暴露于全身麻醉可能在不同年龄影响不同的发育领域。添加右美托咪定和/或一些静脉注射药物的区域麻醉技术可以减轻神经毒性的风险。这种方法可以在一些患者中安全地进行，并且可以被认为是在选定的短程序中的选择。 结论: 没有确凿的证据表明婴儿期单一短麻醉剂具有可检测的神经发育作用。数据不支持等到儿童期晚些时候才进行单次短期手术的全身麻醉。由于不同麻醉方法、患者和程序的复杂性和细微差别，儿科患者的麻醉计划和执行通常最好由麻醉师完成，理想的是儿科麻醉师。 研究类型: 1-4级研究的系统回顾。 证据级别: 1-4级 (主要为3-4级)。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.