Alzheimer's Disease THErapy With NEuroaid (ATHENE): A Randomized Double-Blind Delayed-Start Trial

ObjectivesPreclinical and clinical studies indicate a role for MLC901 (NeuroAiD II) in Alzheimer's disease (AD). The primary aim was to investigate its safety as add-on therapy to standard treatment and the secondary aims its effect on cognition and slowing disease progression.DesignRandomized double-blind placebo-controlled delayed-start study.Setting and ParticipantPatients with mild to moderate probable AD by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n = 125), were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months when all patients received MLC901, in a delayed-start design (clinical trial registration: ClinicalTrials.gov, NCT03038035).MethodsThe primary outcome measure was occurrence of serious adverse events (SAEs) at 6 months. Secondary outcomes included the Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS-Cog) and other assessment scales.ResultsThere was no significant difference in the risk of SAEs between early and delayed starters at month (M) 6 (22.6% vs 27.0%, risk difference ?4.4%, 90% CI –16.9% to 8.3%). Similarly, there was no significant difference in the risk of adverse events and the occurrence of stroke or vascular events between early and delayed starters throughout the 12-month study period. Early starters did not differ significantly on ADAS-Cog from delayed starters at M6 [mean difference (MD) ?1.0, 95% CI –3.3 to 1.3] and M12 (MD –2.35, 95% CI –5.45 to 0.74) on intention-to-treat analysis. Other cognitive assessment scales did not show significant differences.Conclusions and ImplicationsThis study of 125 persons with dementia found no evidence of a significant increase in adverse events between MLC901 and placebo, thus providing support for further studies on both efficacy and safety. Analyses suggest the potential of MLC901 in slowing down AD progression, but this requires further confirmation in larger and longer studies using biomarkers for AD.     

Minimum information to report about a flow cytometry experiment on extracellular vesicles: Communication from the ISTH SSC subcommittee on vascular biology

The Extracellular Vesicle Flow Cytometry Working Group ( http://www.evflowcytometry.org ) is formed by members of the International Society for Extracellular Vesicles (ISEV), the International Society for Advancement of Cytometry (ISAC), and the International Society on Thrombosis and Haemostasis (ISTH). This working group of flow cytometry experts develops guidelines for best practices regarding flow cytometry detection of extracellular vesicles. To improve rigor and standardization, this working group published a framework outlining the minimal information to report about a flow cytometry experiment on extracellular vesicles (MIFlowCyt-EV) in the Journal of Extracellular Vesicles, the ISEV journal, in 2020. In parallel, an article explaining MIFlowCyt-EV was published in Cytometry Part A, one of the ISAC journals, and now will be introduced to the ISTH as an SSC Communication in the Journal of Thrombosis and Haemostasis. The goal of this SSC Communication is to explain why flow cytometry is becoming the instrument of choice to characterize single extracellular vesicles, the obstacles that have been identified and (mostly) overcome by developing procedures to calibrate flow cytometers, and the relevance of reporting minimal information to improve reliability and reproducibility of experiments in which flow cytometers are used for characterization of extracellular vesicles.     

讨论式教学法在温病学中的教学设计——以温病的祛湿法为例

文章以温病的治法祛湿法为例,提出讨论式教学法的教学设计,包括建立"三人为师"规则、"发言签"规则,营造讨论气氛,角色分配包括向导、刺头、记录员、法官、汇报人,然后按照"领结模型"展开讨论,最后按照表达意愿、思维技能、学生间互动、内容知识掌握情况等进行评估,旨在培养学生温病学临床思维能力与团队协作能力。     

Assessment of dental implant surface stability at the nanoscale level

ObjectivesTo study the oxide layer stability of certified dental implants of system "P", made based on TiO₂ alloy with carbon coating. To perform a comparative statistical analysis of the obtained data with the available data for the dental implants of systems "A" and "B".MethodsX-ray microtomography and X-ray fluorescence analysis were used to study soft tissue biopsy specimens. Supernatants were studied by dynamic light scattering and transmission electron microscopy when simulating free emission of nanoscale metal oxide particles from the surface of dental implants as well as when simulating physical loading. A comparative analysis of three parameters of nanoscale particles was performed by statistical data analysis. The surface of the "P" system dental implant with surface treatment was analyzed by scanning electron microscopy.ResultsBoth free emission of nanoscale oxide layer particles and yield of nano- and microscale particles during simulation of physical load were confirmed. Statistically significant differences were noted in a comparative analysis of the size and frequency of occurrence of these particles in the supernatants obtained from the surfaces of three dental implant systems. The elemental composition of the particles and the composition and structure of the "P" system dental implants themselves were analyzed.SignificanceThe developed method of dynamic light scattering can be used to compare the stability of the oxide layer of standardized medical products manufactured on the basis of the TiO₂ alloy.     

Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

Center of pressure position in the touches of the star excursion balance test in healthy individuals

BackgroundThe Star Excursion Balance Test (SEBT) is a clinical test that aims to assess postural control. Its interpretation is related to the understanding of the motor specificities required. Adjustments must be made to the center of pressure (COP) to maintain balance during testing movements. Comprehend the specifics of these adjustments for each direction can allow the development of more suitable exercises for balance training. The aim was to compare the positions of the COP on the different directions of the SEBT and correlate the reachs obtained in the SEBT with the distances from the COP to the borders of the base of support (BOS).MethodsSixteen healthy subjects participated in the study. Measurements were made by performing the SEBT over the force platform. The Kruskal-Wallis test followed by Bonferroni's post hoc test was used to compare directions. The Pearson correlation test was used to check the correlation of parametric variables and Spearman correlation test for the nonparametric ones.ResultsThe position of the COP at the touch differs from the anterior direction to the other directions of the SEBT and the performance in this direction is correlated with the proximity of the COP to the anterior limit of the support base. The performances in the other directions did not correlate with the COP position.ConclusionThe requirements of the compensation mechanisms for postural control are different between the directions of the SEBT.     

DCE-MRI诊断原发性肝癌效能和TACE术后评估肿瘤活性应用价值研究*

目的 探讨动态对比增强磁共振成像(DCE-MRI)检查诊断原发性肝癌(PLC)患者的效能及评价疗效的价值。方法 2017年1月～2021年6月我院诊治的肝占位性病变患者68例,均接受DCE-MRI检查,并行穿刺细胞学检查诊断,应用临床流行病学基本技术评估MRI诊断的效能。所有PLC患者接受经皮肝动脉化疗栓塞术(TACE)治疗,术后再次接受MRI检查,评估疗效。结果 DCE-MRI检查显示PLC患者肝内特征性恶性肿瘤表现,T1WI序列为低信号,T2WI序列为高信号,动脉期明显强化,门脉期快速消退,偶见明显的肿瘤包膜;在68例肝占位性病变患者,经穿刺细胞学检查,诊断PLC患者64例,非肿瘤病变4例;DCE-MRI检查诊断的灵敏度、特异度、准确率、阳性和阴性预测值分别为95.2%、75.0%、89.7%、93.8%和25.0%;在TACE术后,MRI检查发现肿瘤被完全灭活18例(28.1%),部分灭活25例(39.1%),肿瘤稳定15例(23.4%),疾病进展6例(9.3%)。结论 DCE-MRI检查在诊断PLC和治疗后疗效判断方面有独特的作用,可指导临床制定治疗方案,价值很大。